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Pharmacy Prep

Evaluating Exam
Review Book

Misbah Biabani, Ph.D

Toronto Institute of Pharmaceutical Sciences (TIPS) Inc.
Toronto, ON M2N 6K7

2016
Pharmacy Prep
Professional Exams Preparation Center
5460 Yong St. Suites # 209 and 210, Toronto, ON, M2N 6K7
WWW.PHARMACYPREP.COM
416-223-PREP (7737)/647-221-0457
Toronto Institute of Pharmaceutical Sciences Inc.
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Disclaimer

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The information contained in the notes intended as an educational aid only. It is not intended
as medical advice for individual conditions or treatment. It is not a substitute for a medical
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Foreword by
Misbah Biabani, Ph.D
Coordinator, Pharmacy Prep
Toronto Institute of Pharmaceutical Sciences (TIPS) Inc
5460 Yonge St. Suites 209 and 210
Toronto ON M2N 6K7, Canada

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Content
Abbreviations

Part 1. Biomedical Sciences 15%

1. Human Anatomy
2. Gastrointestinal System
3. Nervous System
4. Cardiovascular System
5. Endocrine System
6. Renal System
7. Liver Function and Pathophysiology
8. Respiratory System
9. Urinary System
10. The Eye and Ear
11. Blood and Anemia
12. Biochemistry
13. Fluids, Electrolytes and Nutrition
14. Microbiology
15. Cell and Molecular Biology
16. Pharmacogenetics
17. Immunology and Immunizations
18. Biotechnology
19. Toxicology

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Part 2. Pharmaceutical Sciences 25%

20. Pharmacokinetics
21. Rates and Orders of Reactions
22. Pharmacodynamics
23. Basics of Medicinal Chemistry
24. Medicinal Chemistry and Pharmacology of Autonomic Nervous System Drugs.
25. Medicinal Chemistry and Pharmacology of Histamines, Serotonin, Prostaglandin and
Non-Steroidal Anti-inflammatory Drugs
26. Medicinal Chemistry and Pharmacology of Cardiovascular Drugs
27. Medicinal Chemistry and Pharmacology of Psychiatric & Neurological Drugs
28. Medicinal Chemistry and Pharmacology Endocrine Drugs
29. Medicinal Chemistry and Pharmacology of Respiratory Drugs
30. Medicinal Chemistry and Pharmacology of Musculoskeletal Drugs
31. Medicinal Chemistry and Pharmacology of Antimicrobial Drugs
32. Drug Metabolism
33. Biopharmaceutics
34. Physical Pharmacy
35. Pharmaceutical Excipient
36. Rheology
37. Pharmaceutical Dosage Forms
38. Drug Delivery Systems
39. Pharmaceutical Analysis
Part 3. Social/Behavioural/Administrative Sciences 10%
40. Canadian Healthcare System
41. Canadian Pharmacy Law and Jurisprudence
42. Social and Behavioural and Cognitive Pharmacy
43. Pharmacy Management
44. Pharmacoeconomics
45. The New Drug Approval Process
46. Evidence Based Medicine and Epidemiology
47. Biostatistics
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48. Hospital Pharmacy

Part 4a. Pharmacy Practice (50%)
Professional Practice Skills (15%)-workflow
49. Pharmacy Calculations. Basics
50. Pharmacy Calculations. Dose Calculations
51. Pharmacy Calculations. Dilutions and Allegations
52. Brand and Generic Name Indexes
53. Prescription Processing and Medication Dispensing
54. Safety of Medications in Special Populations
55. Identification and Prevention of Drug Toxicity
56. Professional Pharmacy Communication Skills
57. Bioethics and Professional Ethics
58. Drug Information Resources and Literature Evaluation
59. Medication Errors and Patient Safety Practices
60. Health Promotion and Disease Prevention
61. Collaboration and Teamwork
62. Sterile Preparations
63. Compounding and Storage Conditions
Part 4b. Pharmacy Practice-Clinical Pharmacy (35%)
64. Pharmaceutical Care and Drug Related Problems
65. Adverse Drug Reactions and Management
66. Drug Interactions
67. Clinical Biochemistry
68. Therapeutic Drug Monitoring
69. OTC and Prescription Drugs for Dermatological and Foot Conditions
70. OTC and Prescription Drugs for Ophthalmic, Ear and Mouth Disorders
71. OTC Drugs Antihistamine, Decongestants, Antitussives, Expectorants
72. OTC Drugs for Nausea, Vomiting, Constipation, Diarrhea, Hemorrhoids
73. Analgesics, and Topical Pain Relievers
74. Asthma and Chronic Obstructive Pulmonary Disease (COPD)
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75. Smoking Cessation

76. Insomnia
77. Eating Disorders
78. GERD, Ulcers, Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS)
79. Diabetes Mellitus Type I and Type 2
80. Thyroid Disorders
81. Contraception
82. Gynaecologic and Genitourinary Disorders
83. Rheumatoid Arthritis, Osteoarthritis and Gout arthritis
84. Osteoporosis
85. Hypertension
86. Coronary Artery Diseases
87. Stroke
88. Congestive Heart Failure
89. Cardiac Arrhythmias
90. Peripheral Vascular diseases
91. Anticoagulants
92. Anxiety Disorder
93. Depression
94. Psychosis and Schizophrenia
95. Dementia
96. Seizures and Epilepsy
97. Parkinson’s Disease
98. Antimicrobial Agents
99. Anticancer Drugs and Chemotherapy
100. Pharmacognosy and Natural Products

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1
Human Anatomy
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Anatomy of body movements like abduction, adductions, supine and prone.
• Anatomical planes such as sagittal and midsagittal plane.
• Skeletal bones and joints. Patella (kneecap), hip joints or bowl and socket (ilium, ischium,
pubis), skull bones, knee joints have poplietal spaces.
• Muscles. Flexor and Extensor muscles, Actin and myocin muscle fibers for muscle contraction,
messeter muscles are attached to mandibles.

This chapter reviews essentials and definitions of systemic human anatomy terminology and provide a
basic understanding of how the human body is structured with emphasis on clinical applications. This
chapter also reviews cellular mechanism in human physiology. A special emphasis is on drug-induced
diseases and effects of adverse drug reactions on various organs.

Body Movements (Fig 1.1)

• Abduction. Movement away from the midline of the body.
• Adduction. Movement toward the midline of the body.
• Extension. Lengthening or straightening of a flexed limb.
• Flexion. Bending of a part of the body.
• Dorsiflexion. Backward (upward) bending of the foot.
• Plantar flexion. Bending of the sole of the foot downward toward the ground.
• Pronation. Act of turning the hand so that the palm faces downward.
• Supination. Act of turning the hand so that the palm is uppermost.
• Eversion. Outward turning.
• Fascia. Fibrous membrane separating and enveloping muscles.
• Anterior (ventral). Front side of the body (example. Abdomen is anterior to the spinal cord).
• Posterior (dorsal). Back of the body (example. Spinal cord is posterior to the stomach).
• Lateral view = from the side of the body
• Medial view = from the middle of body (between two legs)
• Deep. Away from the surface.
• Superficial. On the surface (example. Superficial veins can be viewed through skin).
• Proximal. Near the point of attachment to the trunk or near the beginning of a structure (Example.
The proximal end of the stomach is at the esophagus or the proximal end of the upper bone joins
with shoulder bone).
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• Distal. Far from the point of attachment to the trunk or from the beginning of a structure
(Example. The distal end of the stomach is at the small intestine).
• Inferior. Below another structure. Caudal (pertaining to the head) means inferior in human.
(Example. The urinary bladder lies inferior to the kidney)
Fig 1.1

Anatomical planes (Fig 1.1)

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• Sagittal plane: Plane created by an imaginary line that is parallel to the median plane. Separates
the body into right and left portions.
• Midsagittal plane (median plane): Plane created by an imaginary line that divides the body into
right and left halves. Separates the body/body part into equal right/left portions.
• Parasagittal plane: Divides the body into unequal right and left portions.
• Coronal plane/frontal. Divides the body/body part into anterior and posterior portions.
• Transverse plane/horizontal. Divides the body/body part into superior and inferior portions.
• Oblique plane. Passes through the body/body part at an angle.
• Postural. Positional.
• Orthostatic. Standing upright and lying down supine.

Skeletal Joints (Fig 1.2)

Weight bearing joints
• Shoulder joint consists of humerus, scapula, synovial membrane, articular cartilage, articular
capsule, articular liquid, and ligament.
• Knee joint consists of femur (longest bone), tibia, patella, meniscus, articular cavity, serous bag,
and articular capsule & cartilage. Patella (knee cap) bone is present in knee joint. Popliteal spaces
or nerves are present in knee joint.
• Hip joint (socket and ball) consists of ilium, ischium, and pubis.

The major skull bones include frontal, parietal,

sphenoid, temporal, nasal, maxilla, occipital,
zygomatic, and mandible skull have 25 bones, of
which
• Cranial bones (8)
• Facial bones (14)
• Ossicles (ear bones) 3

Cranial bones are nasal cavity, cranial fossae,

sinuses, euthmoid bone, lacrimal bone,sphenoid
bone, zygomatic bone, orbital tissure

Tennis elbow (lateral epicondylosis).

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inflammation and pain of outer side of elbow involving humerus and usu. This results from
excessive use of forearm or twisting.

Muscles
• Trapezius neck
• Triceps bronchi shoulder (anterior).
• Biceps bronchi upper arm (biceps) and thighs.
• Femorus is present in back of thigh and leg.
• Quadriceps --> thighs
• Gluteus medium is in hip.
• Psoas muscle hip
• Largest musclegluteus maximus (which forms part of the buttock).
• Fastest muscle is eyelid elevator.
• Longest single muscle sartorius muscle (which stretches from the pelvis to below the knee
(more than 15 inches or 40 cm long).
• Smallest muscle is stapedius (found inside the middle ear and less than 0.04 inch (1 mm) long).
• Strongest muscle. Masseter muscle (which elevates during mastication. It can exert a force
equivalent in 100 kg (220 lbs).
• Muscles account for 40% of total body weight.
• Triceps are in only in arms.
• Muscle fibers actin and myocin helps in muscle contraction.

Fig 1.3
Types of tissues and functions. Four basic types of
tissues, epithelial (covering), connective (support),
muscle (movement), and nervous
(control/integration).
• Epithelium. It’s functions include covering,
secretion, absorption, and sensitivity.
• Connective tissue. Support. cartilage, bone,
blood, fibrous tissue of ligament (chondrocytes)
• Muscle tissue, skeletal muscle tissue, cardiac
muscle tissue, smooth muscle tissues.
• Nervous. control and integration.

Tissue functions: Protection, absorption, filtration,

excretion, secretion, and sensory reception.

Epithelium tissue present at sites of rapid diffusion, such as the lining of lung alveoli, covering/lining or
glandular, are 2 basic types endocrine "ductless" produce hormones. Exocrine have ducts. sweat, oil,
saliva, bile enzymes, mucin (mucus).
Endothelium tissue present in the lining of blood vessels.
Mesothelium present at sites where very little activity is occurring, such as Bowman's capsule in the
kidney and the lining of major body cavities.

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• Connective Tissue: support protection, insulation, transportation. Characteristics, large extra

cellular matrix. Four basic classes of connective tissue:
• Connective tissue proper. Loose, adipose, areolar storage, support organs or vessels, Dense.
regular, elastic (tendons and ligaments).
• Cartilage. Cushion, structure, support, and laid down before bone.
• Osseous (bone): Bring in beef bone, compact, rigid, and spongy marrow.
• Blood: RBCs, WBCs, and platelets, and plasma matrix.
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Tips
1 Supination 2. flexion 3. Abduction
4 Extension 5. adduction 6. Parasagittal plane
7 Sagittal plane 8. Midsagittal plane 9. Kneecap
10 Biceps bronchi 11 Triceps bronchi 12 dysphagea
13 Joints 14 Hormone glands 15 Blood vessels
16 Extensor muscles 17 Flexor muscles 18 Pubis
19 Ilium 20 Ischium 21 transverse plane
22 Endocrine glands 23 Arteries 24 Skull bones
25 Moving away from body 26 Moving closer to body 27 slicing vertically
28 slicing vertically from 29 Slicing vertically from side lines 30 Slicing horizontal
middle line
31 dysurea 32 Dyspnea

• Adduction  ( )
• Abduction  ( )
• Sagital planes  ( )
• Para sagital plane ( )
• Mid sagital plane  ( )
• Transverse plane  ( )
• Hip joints have  ( )
• Flexor muscles are present in ( )
• Extensor muscles are present in ( )
• Epithelial tissue is present in  ( )
• Endothelial tissues is present in  ( )
• Skull bones are ???
• Movement away from the midline of the body ( )
• Act of turning the hand so that the palm is uppermost ( )
• bending part of the body ( )
• movement toward the midline of the body ( )
• lengthening or straightening of the flexed limb ( )
• found in arms and thighs ( )
• Found in arms only( )
• Separates the body into unequal right and left portions ( )
• Separates the body into equal right and left portions ( )
• Separates the body into right and left portions ()
• It protects the front of the joint ( )
• Difficulty in breathing ( )
• Difficulty in swallowing ( )
• Difficulty in urination ( )
• Found in limbs, foot, arms ( )
• Hip joints have ( )
• Which one is a part of the shoulder?( )
• Popliteal space is present knee ( )

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PharmacyPrep.com Gastrointestinal System

2
Gastrointestinal System
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Stomach secretions (intrinsic factor, HCL, gastrin). Pepsin is digestive enzyme present in
GIT break downs proteins.
• Role of small intestine in absorption of nutrients, drugs and supplements
• Large intestine (colon) bacteria and excessive absorption of water that cause
constipation.
• Disease of GI system like GERD, peptic ulcers, Crohn's disease, ulcerative colitis and
irritable bowel syndrome (IBS) symptoms.
• Food allergens like gluten (celiac), lactose and milk proteins.

This chapter review anatomy, physiology and pathophysiology of the gastrointestinal system, common
disease that occurs in gastrointestinal tract.

Mouth
• Tongue has bony
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attachments (styloid process, hyoid bone) attached to the floor of the mouth by frenulum.
• Posterior exit from mouth guarded by a ring of palatine/lingual tonsils.
• Ducted salivary glands open at various points into the mouth. This process involves teeth (muscles
of mastication move jaws) and tongue (extrinsic and intrinsic muscles).
• Mechanical breakdown, plus some chemical (ptyalin, enzyme in saliva) secretion.
• Saliva amylase does hydrolysis of starch and glycogen into maltose.

Esophagus
• The esophagus is about 10" long.
• Food moves through esophagus by peristalsis.
Stomach

Fig 2.2
• Cardioesophageal sphincter guarding entrance from esophagus.
• Pyloric sphincter guarding the outlet is much better defined.
• Fundus, body and pylorus recognised as distinct regions.
• Stomach secretes both acid and mucus (for self protection).
• Surface area increased by rugae, which serves as temporary store for food.

Stomach secretions
Secretions Purpose Source
Mucus Lubricant, protects surface from acid Mucus Cell
Intrinsic factor Vitamin B 12 absorption (in small intestine Parietal cell
ilium)
Acid (H+) Kills bacteria, breaks down food, converts Parietal cell
pepsinogen.
Pepsinogen Broken down to pepsin (a protease) Chief Cell
Gastrin Stimulates acid secretion (in response G Cell
protein)
*Deficiency of intrinsic factors causes a type megaloblastic anemia i.e. pernicious anemia.

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Gastric acid secretion mechanism. In the parietal cells CO2 and H2O are converted H+ and HCO3-
catalyzed by carbonic anhydrase. The parietal cells secrete HCl into the lumen of the stomach and
concurrently absorb HCO3- into the blood stream.

Gastric acid stimulations. Gastric acid production is stimulated by three mechanisms.

Vagal stimulation. Vagal nerve innervates parietal cells and stimulates H+ secretion directly.

Histamine release. Histamine is released from mast cells in the gastric mucosa and diffuses to nearby
parietal cells.

Gastrin. It is released in response to eating a meal (protein), thus stimulates parietal cells to secrete
H+.

Pathophysiology of gastric acid secretions causes gastric ulcer, duodenal ulcers and Zollinger-Ellison
syndrome.

Gastric emptying Time. The caudad region of stomach contract to propel food into the duodenum.
The rate of gastric emptying time is fastest if gastric content is isotonic.
Fat inhibits gastric emptying time (i.e. increase gastric emptying time).

Small intestine. Consist of duodenum, jejunum, and ileum.

Duodenum. First part of the small intestine.
• C-shaped 10" (inch) long and curves around the head of pancreas and the entry of common
bile duct.
• Highest drug absorption in the body takes place here.
• Pancreases is a large glandular organ attached near the stomach.
• Pancreas secretes intestinal enzymes (pancreatic lipase, amylase, protease), and these helps
in the digestion of carbohydrates.
• Bile secretions are bile salts, bilirubin, phospholipids, cholesterol.

• Jejunum. It is 8 to10 feet long. The majority of food absorption takes place in the jejunum.

Secretion
• Secretin stimulates pancreas to produce watery fluid, high in bicarbonates concentration.
• Pancreozymin stimulates pancreas to produce a viscous fluid low in bicarbonate concentration.

Ileum. It is 12 feet long. Towards the end of the small intestine, accumulations of lymphoid tissue
(Peyer’s patches) are more common here.

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Large Intestines. It is also known as colon.

• Jejunum terminates at caecum.
• Highest basic or pH.
• Animals digest cellulose in colon.
• The large intestine reabsorbs water then eliminates drier residues as feces.
• Its primary purpose is to extract (absorbed) water from feces.
• Colon consists of higher flora and fauna in GI tract 90 to 99% anaerobic bacteria. Example B.
fragilis and C. difficle anaerobic and aerobic E. coli.
• Colon bacterial produce vitamin K 2 .

Diseases of the gastrointestinal system.

Diseases of the Mouth and Jaw
• Oral thrush is caused by Candida albicans, and moniliasis.
• Gingivitis (gum inflammation) is caused by Fusobacterium sp.
• Stomatitis is Inflammation of mouth cavity.

Disease of the Salivary Glands

• Sjogren syndrome (dry mouth, dry eyes) is autoimmune disease, it is associated with rheumatoid
arthritis.

Diseases of the Esophagus.

• Gastro esophageal reflux disease (GERD) is reflux of gastric acid contents into esophagus. Also
referred as heartburn, or regurgitation. Extra esophageal symptoms include cough, laryngitis and
asthmatic syndrome. But the common symptoms are heartburn, regurgitation of acid or bile and
hyper salivation.

Diseases of the stomach.

• Gastritis (inflammation of gastric or stomach lining). Caused by NSAIDS, cigarette smoking, and
heavy alcohol.
• Gastroenteritis. Inflammation of entire GI tract.
• Peptic ulcer. There are two main causes of Helicobacter pylori infections or drug induced
(NSAIDS).

Dyspepsia. Defined as pain or discomfort in the upper abdomen. Symptoms are nausea, fullness, early
satiety, bloating or regurgitation. The dyspepsia could be due to esophagitis, GERD, peptic ulcer (GU or
DU) 15-25%, Reflux esophagitis, 5-15%, gastric or esophageal cancer (<2%).

What is the main cause of dyspepsia?

Diseases of the small intestine.

• Duodenal ulcers are mainly caused by Helicobacter pylori and the second most common reason is
medications like NSAIDs.
• Zollinger Ellison syndrome is excessive secretion of HCl
• Celiac disease is caused by sensitivity to gluten in cereals. This is due to inability of absorption of
gluten (it mainly effects on upper part of small intestine).

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Diseases of the Colon

• Inflammatory bowel disease (IBD). Consist of two conditions, Crohn’s disease and ulcerative colitis.
• IBD symptom are diarrhea, abdominal pain, rectal bleeding and weight loss.
• Ulcerative colitis occurs mainly in colon and Crohn's disease occurs from esophageal to rectum.
• Crohn's disease (small intestine or colon), chronic inflammatory of ileum, and colon, this can lead
to fistula.

Ulcerative colitis Crohn's Disease

Localized to colon Occurs from esophageal to rectum

• Irritable bowel syndrome (IBS). This can cause severe chronic diarrhea, constipation, bloating and
cramps, nausea and vomiting.

• Pseudo membranous colitis. Clostridium difficile over growth (produce exotoxin) cause diarrhea.
• Amebic colitis is caused by Entamoeba histolytica
• Cholera is caused by Vibrio cholera.

Hernia. a perturbation of GI tract at the junction of esophagus and stomach.

Fig 2.3

Digestion and Absorption

Digestive enzymes are classified based on their target substrates
• Proteases and peptidases split proteins into small peptides and amino acids.
• Lipases split fat into three fatty acids and a glycerol molecule.
• Carbohydrases split carbohydrates such as starch and sugars into simple sugars such as glucose.
• Nucleases split nucleic acids into nucleotides.
GI secretions include saliva, gastric secretions, pancreatic secretions and bile.

Carbohydrates digestion
The most common site of carbohydrate absorption is small intestine. Only monosaccharides such as
glucose, fructose, and galactose are absorbed.
Amylase. Hydrolyse starch and glycogen into maltose. There are amylase in saliva and stomach.
• Maltase. Converts maltose into glucose + glucose
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• Sucrase. Converts sucrose into glucose + fructose.

• Trehalase. degrades carbohydrate to glucose.
• Glucosidase. breakdown sucrose and starch to glucose (Acarbose inhibits alpha glucosidase).
• Lipase is released mainly from the pancreases into the GI track to help breakdown fat. (Orlistat,
Xenical inhibit lipase)
• Lactase. Converts lactose (milk) into glucose + galactose.

Pancreatic Secretions (High HCO 3 isotonic, pancreatic lipase, amylase, proteases)

Fig 2.4
Disorder of carbohydrate absorption. Lactose intolerance results from absence of brush border
lactase. Thus non-absorbed lactose cause osmotic diarrhea.
Milk intolerance can results from 2 reasons. 1) Lactose intolerance 2) milk protein allergies

Lipid Absorption. Bile acids emulsify lipids in the small intestine, increase surface for digestion.
Pancreatic lipases, hydrolyse, lipids to fatty acids, monoglycerides, cholesterol and lysolecithin.

Lipid absorption disorders. Malabsorption of lipids thus causing fatty stools, this also referred as
stethorrhea. Stethorrhea can cause by
• Pancreatic diseases such as pancreatitis, and cystic fibrosis.
• Hyper secretion of gastrin
• Ileal resection
• Bacterial overgrowth

Absorption of Proteins. Trypsin and chymotrypsin are secreted by pancreas, which helps in digestion of
proteins.
• Trypsin is secreted in the inactive form as trypsinogen and is converted to trypsin by enzyme
enterokinase.
• Chymotrypsin is secreted in the inactive form as chymotrypsinogen and converted to
chymotrypsin by trypsin.

Absorption of nucleic acid

• Nuclease Nucleic acid into nucleotide.
• Ribonuclease  Hydrolyses RNA
• Deoxyribonuclease  Hydrolyses DNA

Absorption of water (H 2 O). It is isosmotic in the small intestine and gallbladder.

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Absorption of Vitamins and Nutrients. Fat soluble vitamins (ADEK) are absorbed in small intestine
along with other lipids. Vitamin B12 is absorbed in the ileum and requires intrinsic factor.

Absorption of calcium. Mainly occurs in small intestine, which assisted by active form of vitamin D3, 1,
25-dihydroxycholecalciferol, which is produced in kidney. Chronic renal failure or vitamin D deficiency
results in inadequate intestinal Ca2+ absorption, causing rickets in children and osteomalacia in adults.

Absorption of Iron. It is absorbed as heme iron (iron bound to hemoglobin or myoglobin) or as free
Fe2+. In intestinal cells, heme iron is degraded to Fe2+ and released. The free Fe2+ binds to apoferritin
and is transported into the blood.

Transferrin. Free Fe2+ circulates binds transferring and transports it from small intestine to its storage
sites in the liver and from the liver to the bone marrow for the synthesis of hemoglobin.

Cystic fibrosis
• It is multi organ disease but it is mainly associated with pancreatic secretion.
• It results from a defect in Cl- channels that are caused by a mutation in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene.
• Associated with a deficiency of pancreatic enzymes resulting in malabsorption and stethorrhea.

Innervations of GI tract. Autonomic innervations.

Cholinergic
• It is usually excitatory on functions of GI tract.
• It is carried via the vagus and pelvic nerves.
• Vagus nerve innervates the esophagus, stomach, pancreases and upper large intestine
• Pelvic nerve innervates the lower large intestine and rectum, and anus.
Adrenergic
• It usually inhibitory on the functions of GI tract
• Direct post ganglion adrenergic innervations of blood vessels and some smooth muscles.

Tips
Practice answering tips from table:
1. diarrhea 2. constipation 3. Bloating
4. cramps 5. Proteases 6. nuclease
7. 2 glucose 8. Colon 9. gluten present in cereal
10 Alpha glucosidase 11 95-100% anaerobic bacteria 12 Fructose + glucose
13 Peptidase 14 Enterokinase 15 Chymotrypsin
16 Trypsin 17 Vitamin D 3 18 Deficiency of intrinsic factors
19 Parenteral vitamin B 12 20 Alcohol dehydrogenase 21 wheat
22 rye 23 oats

• The most basic part of the GI tract ( )

• Irritable bowel disease symptoms ( )
• The proteins are digested by ( )

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• What converts nucleic acid into nucleotides ( )

• The pernicious anemia is caused by ( )
• What digest peptides into amino acids ( )
• pernicious anemia is treated by ( )
• What converts inactive trypsinogen into trypsin ( )
• What enzyme oxidizes alcohol to aldehyde and acids ( )
• What are the major bacteria present in colon ( )
• Breakdown sucrose & starch to glucose ( )
• Gluten is present in ( )
• Allergic component in milk ( )
• Celiac is caused by ( )
• Soya milk allergies due to ( )
• A patient with chronic renal failure have deficiency of vitamin? ( )
• Pernicious anemia is caused by  ( )
• Pernicious anemia is treated by  ( )
• Maltase breakdowns maltose to  ( )
• Sucrase breakdowns sucrose to  ( )
• Alcohol dehydrogenase: ethanol  acetaldehyde  acetic acid
• Irritable bowel symptoms (IBS) include  ( )
• Alpha glucosidase is  ( )
• Active Vitamin D is  ( )
• What is allergic component in milk?( )
• Bacteria in colon makes --> ( )
• Cystic fibrosis is --> ( )

• Epigastric pain is a symptom of Ulcer. (less likely GERD), GERD is heartburn, this
could be regurgitation of acid into esophagus to throat.

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3
Nervous System
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Blood brain barrier definition and functions
• What section of brain controls voluntary and involuntary movements?
• Types of Neurological disorders. Multiple sclerosis, Chronic spasticity, Bell's Palsy, Neuralgia,
Seizures or epilepsy, Fibromyalgia, and Parkinson's disease.
• Sciatica pain site is buttocks and back of thighs.
• Causes of multiple sclerosis

Fig 3.1

Fig 3.2

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Nervous system divided into central nervous system and peripheral nervous system. The central
nervous system consists of brain and spine.

Brain
• Cerebrum. largest section of brain and controls voluntary (Think and decide what to say) and
involuntary movements.
• Brain stem. Is the posterior part of the brain consist of pons and medulla oblongata and mid brain.
• Cerebellum. Controls balance and modifies body movements. Maintain body coordination and
balance.
• Spinal cord. vertebral column, epidural space, meninges, spinal cord, dorsal vertebra, and spinal
nerve.
• Thalamus. affects sensory levels, awareness and alertness.

Frontal lobe functions

Motor Cognitive Behavior Arousal
Voluntary movements Memory Personality Attention
Planning Initiation Problem solving Social and sexual
Spontaneity Judgment Impulse control
Language Expression Abstract thinking Mood and effect
Eye movements
Occipital lobe.
Eye information is
processed.
Temporal lobe.
Auditory information is
processed.

Vestibular system: Reflex adjustment of head, eyes and postural muscles provide a stable visual image
and steady posture.

Vestibular occular reflexes:

Nystagmus: The direction of the nystagmus is defined as the direction of the fast (rapid eye)
movement. Therefore, the nystagmus occurs in the same direction as the head rotation. Normally
initial rotation of the head causes the eyes to move slowly in the opposite direction to maintain visual
fixation.

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Meninges
• The meninges are three concentric membranes that surround and protect brain and spinal cord.
• The dura mater: outer most membrane
• The arachnoid: middle layer, transparent, flexible
• The pia mater: inner layer, is fine, and delicate

Cerebro Spinal Fluid (CSF): The CSF is outside of the brain and circulates through the cavities inside the
brain called ventricles.

Blood brain barrier: The blood brain barrier (BBB) is the barrier between cerebral capillary blood and
cerebrospinal fluid (CSF). BBB is formed by capillary endothelial cells that line cerebral microvessels
forms tight junctions and lacks large intracellular spaces. Further neural tissue covers capillaries.
Together constitutes forms BBB.

The CSF fills the ventricles and the subarachoid space. Three functions of BBB
• Protects brain from endogenous or exogenous toxins. It prevents escape of neurotransmitters
from CNS into blood circulations.
• Lipids soluble drugs cross faster than water-soluble (polar) drugs.

In capillary lining of BBB have, enzymes such as monoamine oxidase (MAO), cholinesterase and some
other enzymes. These enzymes prevents catecholamine's, serotonin, acetylcholine, to enter into brain.

Peripheral Nervous System. All nerves of the body residing outside of the
brain and spinal cord comprise the peripheral nervous system.
Periphery can be divided into sensory (somatic) and autonomic.
• Ulnar nerve. Passes through the shoulder to wrist.
• Sciatic nerve runs through buttock, thighs down to foot. It divides
into tibial and common fibular nerve. which supplies the muscles of
posterior thigh and all of the leg and foot.
• Intercostal nerve are that anterior divisions of the thoracic spinal
nerves.
• Radial nerve runs through wrist to finger tips. It supplies to muscles
of forearm.
• Popliteal nerve. Passes in knee joint.
• Auxillary nerve (circumflex). It supplies the deltoid and teres minor muscles, shoulder joint, and
skin on back of arm.

The branch of the autonomic nervous system that induces the "flight or fight" response is
the sympathetic.

Ependymal cells are specialized epithelial cells in the CNS that produce cerebrospinal fluid. In general,
positively charged ions (cation) on the inner cell membrane surface of a resting neuron, there is an
accumulation of negative (anionic) charge.

In electrical terms, "potential" is synonymous with " voltage ".

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An "excitable" cell is one that can quickly and dramatically change its resting membrane potential. Two
types of examples of excitable cells include muscle fibers and neuronal cells.
The typical neuronal resting membrane potential measures approximately -70mV. A neuronal impulse
is also referred to as an action potential , which indicates that it is a "moving" region of "voltage
change" that migrates along the neuronal cell membrane. Movement of Cl- into a neuronal cell would
make a neuron less likely to fire an action potential.

Nerve Cell. Nerve cell consists of dendrite, cell body, axon, myelin sheath, and synapse.

Fig 3.2
Fig 3.3

Pathology of neurological disorders

Seizures or epilepsy. Excessive excitation of neurons due to disorderly inhibition of cortical neurons.

Parkinson's disease. Decrease in dopamine or imbalance of dopamine negrostratial pathway.

Extrapyramidal symptoms (EPS is side effect of antipsychotic drugs) = Akathisia, Dystonia,
Parkinsonism, Tardive Dyskinesia. These symptoms are the side effect of antipsychotic drugs like
haloperidol.
Ataxia = lack of muscle coordination in voluntary movements.
Akathisia = restlessness or cannot sit still.
Dyskinesia = involuntary movement or shaking
Dystonia = involuntary muscle spasm
Tardive dyskinesia = involuntary movement of lips, tongue, and chewing motion.

Migraine Headache. Vasodilatation of intracranial extra cerebral blood vessels.

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Vertigo. False sensation of moving or spinning or object moving usually accompanied by nausea and
loss of balance.

Meniere's disease produces sudden episode attack of vertigo along with ringing in ears (tinnitus) and
progressive deafness. Episodes can last from minutes to hours. Associated with nausea and vomiting.
Beta-histine is used for treatment.

Chronic spasticity: Spasticity is an involuntary velocity dependant increase in muscle tone resulting in
injury to motor pathway in brain or spinal cord. It is common in MS, stroke, spinal cord injury and
cerebral palsy. It can impair feeding, dressing, bowel function, hygiene and gait.

Bell's Palsy: Paralysis of lower motor neuron of facial nerve. It is often due to herpes simplex virus
(HSV 1 ) infection causing inflammation and edema.

Multiple Sclerosis: The multiple sclerosis (MS) is characterized by destruction of myelin sheet
(demylenation) and axonal degeneration & loss in CNS. The MS is chronic and can be caused by
autoimmune mediated action.
Treatment. Interferons beta (first line therapy), glatiramer acetate (Immunomodulators similar to
interferon beta), Mitoxantrone, natalizumab, Fingolimod (spingosine-1-phosphate receptor agonist),
Teriflunomide, and laqinimod.

Temperature regulation:
The homeostatic mechanisms regulate body temperature (37.5 °C).
Sympathetic nervous system innervate heat loss by vasodilatation and sweat production. Sympathetic
nervous system innervate adrenal gland than increase metabolic rate.
Thalamus  pituitary gland  thyroid  Increase metabolic rate.
Hyperthermia = >38.2 °C
Hyperpyrexia (fever) = a fever >41.5 °C
Hypothermia = <35 °C, if <32 °C it can cause ventricular arrhythmias.

Malignant hyperthermia is the side effects of drugs that cause fever symptoms. Example. Halothane,
and succinylcholine.
Treatment. Dantrolene 2.5 mg/kg for Q5min

Neuroleptic malignant syndrome (NMS) induced by antipsychotic drugs. Characterized by

hyperthermia and muscle rigidity, autonomic instability e.g. cardiac arrhythmias.

Heat stroke: Core body temp. >40.6 °C

Antipyretics (NSAIDs) reduce fever by inhibiting cyclooxigenase, this inhibits prostaglandin synthesis.
Therefore analgesics decrease set-point temperature. In response that cause heat loss in the form of
sweating, vasodilatation.

Diagnostic techniques:
• Electroencephalograph (EEG); The EEG consist of alternating excitatory and inhibitory synaptic
potential in the pyramidal cells of the cerebral cortex.
• CT scan (computed tomography) of brain. Demonstrates generalized waves of spike and wave
discharge.
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• Cerebrospinal fluid (CSF) sample is taken by Lumbar puncture.

• FMRI:The functional MRI is used brain scanning.

Tips
1. Sciatic nerve 2 Blood brain barrier 3 Adrenal medulla
4 Tardive dyskinesia Protects brain from endogenous 6 Bradykinesia
5 &exogenous toxins
7 Nissl substance 8 Multiple sclerosis 9 Cerebrum
10 it prevents escape of 11 lipid soluble drugs cross faster than
neurotransmitter from CNS H 2 O soluble drugs
into blood circulations
• What is the barrier between cerebral capillary blood and cerebrospinal fluid (CSF) the CSF fills the
ventricles & the subarachnoid space ( )
• A CNS disease where the myelin sheath of motor neurons is degenerating or being destroyed,
which interferes with neuronal impulses ( )
• The nerve that pass through buttocks, thighs down to foot ( )
• What part of brain controls voluntary and involuntary movements ( )
• Inappropriate posture of neck, face and limbs is referred as ( )
• Functions of blood brain barrier ( )
• Slow movement ( )
• The dark granular inside neuronal cell bodies ( )
• Sciatica is  ( )
• Nor epinephrine becomes epinephrine, this reaction is catalyzed by  ( )
• The longest and largest nerve is --> ( )
• Pain from shoulder to arm is called -->Referred pain

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4
Cardiovascular System

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Conduction System of the Heart (fig 4.4)

Fig 4.4

Types of pacemakers
• Natural (main) pacemaker of heart is SA node.
• Latent pacemaker of heart is AV
node, bundles of His and purkinje
Important concept! Fig 4.5
fibres.
Depolarisation and repolarisation?
• Pulse direction. SA node  AV node 
Bundles His  Purkinje fibres

Depolarization (inward current). Carrying +ve charge into cell

Increase Na+ influx into cell

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Decrease K+ efflux out to cell

Repolarization (outward current or hyper polarization). Take +ve charge out of cell
Increase K+ efflux out to cell
Increase Cl- influx into cell

Myocardial action potential curve. Myocardial action potential curve reflects action potential, which
describes electrical activity of five phases. This occurs in atrial and ventricular myocytes and purkinje
fibers.
• Phase 0: Rapid depolarization: Na+ enters the cell
• Phase 1: Early rapid repolarisation: K+ leaves the cell
• Phase 2: Plateau: Ca2+ enters the cell
• Phase 3: Final rapid repolarisation: K+ pumped out of
the cell
• Phase 4: Slow depolarization: K+ inside the cell and
Na+, Ca2+ outside the cell.
Phase 1 to starting phase 3 is absolute refractor period or
effective refractory period. The cell cannot respond to any
stimuli.(NO action potential can be initiated).
During Phase 3 is relative refractory period. The cell
ability to respond stimuli increases or cell can respond
to strong stimuli.

Electrocardiograph Wave Forms. The electrical activity

occurred during depolarization and repolarization
transmitted through electrodes attached to the body
and transformed by an electrocardiograph (ECG) in to
series of waveforms.
• P wave indicates atrial depolarization.
• PR interval indicates the spread of the impulse
from the atria through Purkinje fibres. (beginning
of initial depolarisation of ventricle).
• QRS complex indicates ventricular depolarization.
• ST segment indicates phase 2 of the action potential the absolute refractory period.
• T wave shows phase 3 of the action potential ventricular repolarization.
• Q-T interval. Mechanical contraction of the ventricles (Torse de pointes).
• U wave caused by hypokalemia.

Torsade de pointes. This is also called the Q-T interval. A problem in one of the ion channels can
prolong the Q-T interval. A prolonged Q-T interval can increase risk for a type of arrhythmia called
torsade de pointes.

• Thrombus is blood clot.

• Embolus is moving blood clot.
• Aneurysm is abnormal dilatation of arteries. Can cause stroke.
• Stenosis is constriction or narrowing of opening.

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Atherosclerosis is increased in LDL, progressively hardens the arteries and veins. Cause CAD
(angina, MI), stroke, ischemia, PVD.

• Plaques are progressive accumulation of lipids and inflammatory cells.

site of injuries in arteries results formation of plaques. Sheer stress
may results in plaque rupture, collagen exposure, platelet aggregation,
and clot formation. Examples of diseases that comes from plaques are
angina, myocardial infarction, atrial fibrillation, cerebral stroke, embolism and peripheral vascular
diseases (DVT and PE).

Cardiac oxygen consumption. when increased size of the heart.

Laplace's Law. Laplace's law describes how tension in the vessel wall increases with transmural
pressure. According to Laplace’s law, tension is proportional to the radius of a sphere.

Autonomic
effects on heart rate
and conduction velocity

Inotropic. Force of contraction (The ability of the cardiac muscle to develop force at given muscle
length)
+ve inotropics: Digoxin, ACEI, DHP-CCB
- ve inotropics: BBs, verapamil, diltiazem
Chronotropic. heart rate (the number of action potential that occur per unit time)
+ve chronotropic. DHP-CCB
-ve chronotropic. Amiodarone, BBs, NDHP-CCBs, digoxin, "(ABCD)"
Dromotropic. Conduction
+ ve dromotropic: amitriptyline
- ve dromotropic: Na+& K+ channel blockers

Stroke volume. The volume of blood ejected from the ventricle on each beat.
Ejection fraction. The fraction of end-diastolic volume ejected in each stroke volume.
Ejection fraction = stroke volume/end diastolic volume
Cardiac output = stroke volume x heart rate

Diagnostics
Blood pressure. Sphygmomanometer.
Normal 120/80

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BP is my be diagnosed in 2 office visits if BP average >180/110, or >140/90 mm Hg, in presence of

DM, renal, atherosclerosis, and cerebrovascular.
if the average SBP/DBP is 140-159/90-99 mmHg, treatment is recommended in the presence of risk
factors smoking, FH, truncal obesity, sedentary lifestyle, male >55 yo, female >60yo.

Coronary artery disease.

ECG and biological marker (Troponin and Creatine kinase)

ECG = Electrocardiogram, Measures cardiac rhythms

Echocardiogram. Shows the presence of regional wall motion abnormalities.

Echocardiogram allows for identification of valvular abnormalities and other MI problems.

ECG - used for excluding atrial fibrillation.

MRI, MR angiography (MRA), or CT angiography used for confirmation of degree of arterial occlusion
or neurologic conditions like cerebral ischemia.

Tips
Find answers from the table.
1. Absolute refractory period 2. Repolarization 3 arrhythmia
4. Phase 0 5. Phase 1 to starting phase 3 6 Relative refractory period
7. Phase 3 8. + ve inotropic 9 –ve inotropic
10 Digoxin 11 ACEI 12 Dihydropyridine CCBs
13 Beta blockers 14 stroke 15 brain attack
16 cerebral embolism

• Absence of rhythm ( )
• Drugs that cause +ve inotropic effect ( )
• Rapid depolarization ( )
• Increase in force of contraction ( )
• The cell cannot respond to any stimuli ( )
• The cell ability to respond stimuli increases or cell can respond to strong stimuli ( )
• Decrease in force of contraction ( )
• Excessive negative charge in cell occurs ( )

Select True/False Statements

• A brain attack that occurs when a wandering clot (embolus) or some other particle forms
in a blood vessel usually in the heart and flow into in the brain cerebral vessel is
cardiogenic cerebral embolism. True/False
• Drugs that cause –ve chronotropic effect (digoxin, beta blockers) True/False
• Stroke or brain attack happens when brain cells die because of inadequate blood flow to
the brain (True/False)
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PharmacyPrep.Com Endocrine System

5
Endocrine System
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Hormone of anterior and posterior pituitary gland, thyroid hormone, Insulin, corticosteroid
hormones.
• Hypothyroid and hyperthyroidism symptoms. Lab investigations of serum TSH
• Hypoglycemia and hyperglycemia symptoms.
• Pathophysiology of diabetes and diabetic ketoacidosis
• Hypo corticosteroids (Addison diseases) and hyper corticosteroids (Cushing's disease).
Definitions

• Amniocentesis: surgical puncture of the amniotic sac

• Cystoscopy: process of viewing the urinary bladder
• Dysmenorrhea: Painful periods
• Embryology: study of the growth and development of the human organism
• Gynecologist: specialist in the diseases of the female reproductive system
• Hydrocele: accumulation of water in the scrotum;
• Menorrhagia: Excessive bleeding during menstruation
• Nephritis: Inflammation of the kidney
• Primigravida: first pregnancy
• Spermatogenesis: creation of new sperm
• Urology: study of urinary tract

Endocrine system
Consists of a group of organs that have NO DUCTS and therefore are also known as DUCTLESS
GLANDS that secrete hormones directly into the blood stream..

Major endocrine glands: Pituitary Gland (present under hypothalamus), the master endocrine
gland. Testes, Ovaries, Thyroid Gland (neck), Adrenal Gland (on kidney), Pancreas Gland
(endocrine and exocrine)

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Fig 5.1

Other glands
• Parathyroid Gland (neck)
• Thymus Gland (chest)
• Pineal Gland (brain)

Pituitary Gland
• Located at the base of the brain.
• Consists of two parts: anterior lobe and posterior lobe.
• It is sometimes known as the master gland.
• It controls the functions of other endocrine glands and is in turn controlled by the
hypothalamus.

Endocrine Gland Types of hormone Target tissue Physiologic actions

Hypothalamus Houses releasing and Anterior pituitary Controls release of anterior pituitary
inhibiting hormones hormone
Anterior Pituitary Thyroid-stimulating Thyroid Production of thyroid hormone (T 4 and T 3 ,
gland hormone (TSH) and calcitonin).
Adrenocorticotropic (ACTH) Adrenal cortex Secretion of cortisol
Growth hormone (GH) Bones; soft Stimulates growth of bones and soft tissues
tissues
Follicle-stimulating hormone Females; ovary Promotes growth of ovarian follicle;
(FSH) Stimulates estrogen secretion
Males: Testes Stimulates sperm production
Luteinizing hormone (LH) Females: Ovary Stimulates ovulation
Stimulates progesterone secretion
Males. Testes Stimulates testosterone secretion

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Prolactin Females: breast Promotes breast development; stimulates
milk secretion

Posterior Pituitary Vasopressin (antidiuretic Kidney Causes water retention

gland hormone)
Oxytocin (formed in Uterus Causes contraction
hypothalamus and stored in Breasts Causes ejection of milk
posterior pitutary gland).
Pineal Melatonin Brain; anterior Sets the body’s “time clock”.
pituitary; Causes sleep in response to darkness
reproductive
organs; possibly
other sites.
Thyroid Thyroid hormone (Triiodo T 3 Most cells Increases the metabolic rate; necessary for
and levothyroxine T 4 ), and normal growth and development.
calcitonin. Calcitonin takes Ca from Blood  Bones
Parathyroid Parathyroid hormone Bone; kidney; Increase amount of calcium in the
intestine bloodstream. Decreases amount of
phosphate in the bloodstream
PTH takes Ca from Bones  Blood
Thymus Thymosin T lymphocytes Enhances the production of T lymphocytes
Pancreas Insulin Most cells Promotes use and storage of nutrients
Secreted from beta cells particularly glucose, after eating
Glucagon Most cells Maintains glucose levels in the bloodstream
Secreted from alpha cells during periods of no food
Somastatin and gastrin Digestive system Inhibits digestion and absorption of
Secreted from delta cells nutrients.
F cells? pancreatic Inhibit secretion of insulin, glucagon and
polypeptides gastrin
Adrenal Medulla Epinephrine Kidney Increases Na+ retention and K+ excretion
Adrenal cortex Zona Aldosterone Kidney Increases Na+ retention and K+ secretion
glomerulosa
(out)
Z. fasciculata Cortisol Most cells Increases glucose in the bloodstream

Z. reticularis Androgens Females: bone Puberty growth spurt and sex drive in
and brain females.
Testes (male) Testosterone Male sex organs; Stimulates production of sperm; responsible
body as a whole. for development of sex characteristics.
Promotes sex drive.
Ovaries (female) Estrogen Female sex Stimulate uterine and breast growth;
organs; body as a responsible for sex characteristics.
whole
Progesterone Uterus Prepares for pregnancy

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Physiological effects of some pituitary hormones

• Somatostatin: opposes the effects of Growth Hormone-Releasing Hormone (GHRH)
• Prolactin: It is synthesized and secreted by lactotrope cells in the anterior pituitary gland, breast
and the deciduas.
Effects
• Stimulates the mammary glands to produce milk (lactation).
• Provides the body with sexual gratification after sexual acts
• immune tolerance of the fetus by the maternal organism during pregnancy.

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• Stimulate proliferation of oligodendrocyte precursor cells which differentiate into
oligodendrocytes, the cells responsible for the formation of myelin coatings on axons in the central
nervous system.

Thyroid Gland (Fig 5.3). Secretes thyroid hormones, which in turn control the
body’s metabolic rate.
Thyroxin or Levothyroxine (T 4 )
• Naturally occurs in levo (L) isomer form produced in the
thyroid gland.
• Converted in the liver and other organs to T 3 by
deiodination (deiodinase).
• Controls the rate of metabolism in the body.

• Triiodothyronine (T 3 )
• Metabolically active form.
• Calcitonin (a peptide)
• Secreted by parafollicular cells (C-cells).
• Reduces blood calcium ion concentration by moving Ca from blood to bones.
• Hypocalcemic hormone.
• Used in treatment of osteoporosis associated vertebral fracture.
• Hypercalcemia stimulates calcitonin production.

• Functions of thyroid hormones

• Growth and development
• Proper function of all body system
• Maintenance of all body tissues
• Carbohydrate, fat, protein, and vitamin metabolism (Basal Metabolic Rate)
• Affects the secretion of other hormones (insulin, NE, Epi, cortisol, estrogen and
testosterones.

Mechanism of action
• At the target cell, proteases split protein carrier off from the thyroid hormone and most of
T 4 is deiodinated to T 3.
• T 3 (and probably some T 4 ) enter the cell through membrane transport proteins and bind to
a specific nuclear receptor.

Hypothyroidism Hyperthyroidism
Thyroid gland is under active and Overactive thyroid gland causing an
produces insufficient thyroid hormone. abundance of thyroid hormone.
Thyrotoxicosis is the general term for over
activity of the thyroid gland.
Symptoms Sensitivity to cold Heat intolerance
Dry flaky skin and Coarse hair Profuse sweating
Slowed speech Diffusely enlarged nontender goiter.
Puffy face, hands, feet Nervousness, irritability, anxiety and
Hearing loss insomnia
Decreased libido Weigh loss in spite of increased appetite
Weight gain Tremor and muscle weakness

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Constipation Tachycardia
Impaired memory Diarrhea
Hypertension, bradycardia
Slow return of deep tendon reflexes
Diseases Hashimoto (autoimmune, the most Graves disease (diffuse toxic goiter) the
common type of hypothyroidism. most common form of hyperthyroidism,
Common on in elderly). autoimmune disorder. Antibodies (long-
Myxedema (If untreated Myxedema acting thyroid stimulators) bind to and
and coma may develop. activate TSH receptors.
Dwarfism
Mental retardation Plummer’s disease (toxic nodular goiter)

Serum TSH The most sensitive test for detecting

assay the hypothyroid state.
Sensitive TSH Commonly used in patient receiving Sensitive TSH assay
assay replacement therapy (levothyroxine)
to control treatment.
Free thyroxin This is not separate test but estimation
index (FTI) of free T 4 level mathematical
interpretation of relationship of RT 3 U
and serum T 4 levels.
Serum total Elevated T 4 indicates hyperthyroidism
thyroxine (Free Decreased T 4 indicates hypothyroidism
T4)
Serum total Disproportionate rise indicated
triiodothyronine hyperthyroidism.
(TT 3 ) Useful in early detection and rule out of
hyperthyroidism
Pregnancy Levothyroxine is used to treat. Propylthiouracil the treatment of choice.
Adequate dose thyroxin, necessary for
development of the fetal brain.
Serum TSH >6 mU/L <0.3mU/L
Thyroid function tests (normal serum TSH is 0.3 to 6 mU/L)

Parathyroid Glands. Four tiny glands in the posterior surface of the thyroid gland, which is
positioned on the esophagus, produce parathyroid hormone (PTH), which regulates the calcium
metabolism in the body.

Parathyroid hormone. Reabsorbs calcium in kidney.

Hypoparathyroidism Hyperparathyroidism
Decrease production of PTH Increase production of PTH
Decrease blood calcium Increase blood calcium levels
Increase blood phosphate levels Decrease blood phosphate
Causes convulsions levels
Causes hypokalemia Causes muscle weakness
Causes neuromuscular irritability Causes muscle atrophy
Causes fatigue

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Pancreas. In the pancreas the acini which produces digestive enzymes. Islets produce 3 types of
hormones.
o Insulin produced by beta cells
o Glucagon produced by alpha cells
o Somatostatin produced delta cells (extra pancreatic cells)
Insulin
• Increase glucose uptake into cell.
• Glycogenesis. Increased glycogen storage in liver, and muscle.
• Increase decrease gluconeogenesis. Decrease synthesis of glucose from non-carbohydrate source.
• Lipogenesis. Fat/triglyceride storage (adipose tissue).

Insulin
• Insulin acts on liver, adipose tissue and muscles.
• Produced by beta cells of islets of langerhans.
• Insulin is peptide
• Stored in vesicles in combination with zinc
• 51 amino acid chain
• Half life insulin is 3 to 5 min Controls blood glucose concentration
• Decrease insulin secretion
Insulin function in carbohydrate, protein and fat metabolism
Carbohydrate Protein metabolism: Fat metabolism:
metabolism
Increase glucose uptake Increase RNA and DNA Increase storage of fatty acid in
Decrease glycogenolysis synthesis adipose tissue
Decrease ketogenesis Increased protein synthesis Increase lipogenesis
Decrease glucogenesis Increased cell growth Decrease lipolysis
Increase lipogenesis Increased amino acid
transport

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Glucagon
• Stimulated breakdown of glycogen to glucose (glycogenolysis) in the liver
• Increase blood glucose levels.

DIABETES MELLITUS
This is a primary disorder of carbohydrate metabolism that exhibits the following characteristics. A
defective or deficient insulin secretory response. Glucose underutilization and hyperglycemia.

Types of diabetes:
 Insulin-Dependent/Type 1 (IDDM)
 Non-Insulin Dependent/Type 2 (NIDDM)
 Secondary Diabetes (e.g. pancreatic disease)
 Impaired Glucose tolerance
 Gestational diabetes (i.e. glucose intolerance w/onset during pregnancy)

Diabetic Patient
Insulin or resistance

Influx of glucose inside the cell

Cell starvation * Polyphagia (increased appetite)

Glucose in blood (hyperglycemia)

Osmotic diuresis

Glucose in urine (glycosuria)

* Polyuria (profound loss of water and electrolytes)

* Polydipsia (intense thirst)

Late Complications. Diabetic microangiopathy, atherosclerosis, myocardial infarction, cerebral stroke,

gangrene of the lower extremities.
• Diabetic nephropathy, Progressive proteinuria and chronic renal failure (CRF)
• Diabetic retinopathy, cataract formation or glaucoma
• Diabetic Neuropathy pain (numbness, tingling, pin feeling and burning).Symmetric
peripheral neuropathy affects motor and sensory nerves of the lower extremities.
Schwann cell injury, myelin degeneration, axonal damage.
• Autonomic neuropathy, sexual impotence, bowel and bladder dysfunction.
• Effects of insulin deficiencies. Cataract, retinopathy (blindness), neuropathy, nephropathy
premature atheroma (increase blood fatty acids) and cardiovascular.

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Insulin requirement Insulin requirement

increase decrease
Heavy meals Physical activity
Emotional Stress Exercise
Infections
Pregnancy

Diabetes Insipidus (DI)

• Anti diuretic hormone (vasopressin) deficiency causes diabetes insipidus
• Insufficient ADH due to dysfunction of hypothalamic nuclei (e.g. tumors,
hydrocephalus, histocytosis, trauma).
• Passage of large volumes of dilute urine.

Decrease in ADH causes large volume of dilute urine, Polyurea, Polydipsea, and Polyphagea.
Treatment: Anti diuretic hormone

THYMUS GLAND
• Regulates the development of T-lymphocytes in immune system
PINEAL GLAND
• Small cone shaped gland
• Smallest of all glands located in mid brain
• Large in children and begins to shrink at puberty
• Only brain structure that does not come in a pair
• Produces melatonin and dimethyl tryptamine in the dark
Functions
• Influences circadian rhythms e.g. sleep and temperature
• Sexual development
• metabolism
• Regulates the mating behavior
• Regulates day and night cycle.

Adrenal Gland (Fig 5.4). Two adrenal glands one on top of each kidney.

Inner part (medulla). Secretes epinephrine (adrenalin)

● Epinephrine increases BP, HR, vasoconstriction and blood supply to skeletal muscle.
 Norepinephrine increases effects of epinephrine.

Outer part (cortex)

● Secretes corticosteroids, androgens and mineral corticoids.
 ACTH regulates the secretion of mineral corticoids. e.g. aldosterone helps regulate salt and
water balance by retaining salt and water and excreting potassium.
Glucocorticoids
 Control glucose metabolism and protein synthesis.
 The principle glucocorticoids are cortisol and cortisone.
● Androgens are male sex hormones mainly testosterone.

Functions of ACTH

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• ACTH stimulates the cortex of the adrenal gland and boosts the synthesis of
corticosteroids, mainly glucocorticoids but also mineral corticoids and sex steroids
(androgens).
• ACTH is also related to the circadian rhythm in many organisms.
• The half-life of ACTH in human blood is about 10 minutes.

Hypo corticosteroids. Addison's disease (chronic adrenal insufficiency, or hypocortisolism).

Causes auto immune reaction, HIV and tuberculosis.

Signs and symptoms. Chronic fatigue that gradually worsens, Muscle weakness, weight loss and loss of
appetite, nausea, diarrhea, or vomiting.
Treatment. Replacement of missing cortisol and fludrocortisones.

Hypercorticosteroids. Cushing's syndrome or hypercortisolism or hyperadrenocorticism is caused by

high levels of cortisol in the blood.

Signs and symptoms

• Rapid weight gain

• Moon face
• Buffalo hump
• Reduced libido
• Easy bruising

• Treatment. Removal of adrenals. Post operative steroid replacement (hydrocortisone

or prednisolone).

Other androgens are

• Dehydroepiandrosterone (DHEA).
• Androstenedione (Andro)
• Androstenediol: Androsterone
• Dihydrotestosterone (DHT)
• Androsterone

Ovaries. Produces two hormones estrogen and progesterone.

Estrogen. Controls the development of female sex characteristics and reproductive system
Progesterone. Prepares the lining of the uterus for implantation of a fertilized egg.

Pregnancy test. Human chorionic gonadotropin (hCG) hormone levels are elevated in first 3 months of
pregnancy (first trimester). Progestin's in pregnancy is produced by ovaries, corpus luteum and
placenta.

Dysmenorrhea
• Menstrual pains are referred as dysmenorrhea.
• It is most common from age 20 to 25.
• Primary when no underlying cause is found.
• Secondary when a cause is identified as a gynecological disorder.
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Endometriosis
• Common cause of secondary dysmenorrhea.
 Endometriosis gives pelvic pain, spotting before normal periods and may cause
infertility.

Ovulation cycle and menstruation

• During the menstrual cycle estrogen is produced by the ovarian follicles.
• After ovulation estrogen is produced by the corpus luteum.
• During pregnancy ovulation does not occur. It is suppressed by high levels of
estrogen and progesterone's.

Menstrual cycle

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Menopause. Cessation of menstrual periods is referred as menopause. Occurs when the ovaries stop
producing estrogen. Ovarian follicles are depleted at approximately 51 year of age.
• Most common vasomotor symptoms. Hot flushes, night sweat, mood swings, sleeplessness,
lethargy, and depression. Urogenital atropy (this leads to dryness of the vagina, dyspareunia
(painful intercourse).

Tips
1. adrenal medulla 2. pituitary gland 3. posterior pituitary gland
4. diabetes insipidus 5. glucose 6. H 2 O + CO 2
7. excessive urination 8. outer adrenal cortex 9. sensitivity to cold
10. bradycardia 11 Weight gain 12. Glycogen
13. constipation 14 dry skin 15. weight loss
16. tachycardia 17. diarrhea 18. sensitivity to heat
19. sweating 20. palpitation 21. fatigue
22. polyhagia 23. polyurea 24. Blurred vision
25. polydipsea

• Epinephrine is released from? ( )

• Aldosterone is released from? ( )
• ACTH is secreted by? ( )
• Oxytocin is secreted from? ( )
• ADH is secreted from? ( )
• Deficiency of ADH gives… ( )
• Symptom of diabetes insipidus ( )
• Symptoms of diabetes mellitus ( )
• Symptoms of hypoglycemia ( )
• What hormones are released from posterior pituitary gland? ( )
• Hypothyroidism laboratory investigation include ( )
• Epinephrine is released from? ( )
• Aldosterone is released from? ( )
• Testosterone to 5-hydroxy testosterone is catalyzed by? ( )
• Diabetes mellitus symptoms? ( )
• Hypoglycemia symptoms? ( )
• Symptoms of hyperthyroidism? ( )
• Symptoms of hypothyroidism? ( )
• Symptoms of Cushing syndrome? ( )
• Addison disease is  ( )
• Adrenal gland cancer (pheochromacytoma) may cause…( )

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6
Renal System
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Filtration, Secretion and Reabsorption process.
• Types and causes of acute renal failure. Symptoms of chronic renal disease and acute renal
failure (pre renal acute renal failure is due to lack of blood perfusion).
• Creatinine clearance in renal diseases
• Metabolic acidosis (increase in CO2) and alkalosis (Increase in HCO3).

Fig 6.2
Fig 6.1

Nephron. A nephron is the basic unit of renal function. There is millions of nephron present in each
kidney. Nephron has three major functions.
• Filtration
• The filtration occurs at glomerular or bowman capsules.
• Creatinine clearance is the measure of glomerular filtration rate (eGFR). Normal
creatinine clearance is 80 to 120 mL/min.
• Reabsorption
• Transportation of ions or drugs back into blood from nephron is referred as
reabsorption.

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• Secretion
• Secretion of ions or small molecular drugs into nephron from nephron walls.

Acute Renal Failure (ARF)

The acute renal failure (ARF) is rapid decline in the renal ability to clear the blood of toxic substances,
causing accumulation of metabolic waste products, like blood urea nitrogen.

Three types of ARF

• Prerenal ARF (occurs due to problems in organs liver, heart and blood circulations).
• Intrinsic ARF (occurs due to problems in kidney).
• Post-renal ARF (occurs due to problems in organs after kidney like ureter or bladder).

Prerenal ARF is characterized by inadequate blood circulation (perfusion) to the kidneys, which leaves
them unable to filter the blood properly. Many patients with prerenal ARF are critically ill and
experience shock (very low blood pressure). There is often poor perfusion within many organs, which
may lead to multiple organ failure.
Causes. Some of the most important causes of prerenal ARF are dehydration, heart failure, sepsis
(severe infection), and severe blood loss.

Prerenal ARF is associated with a number of pre-existing medical conditions, such as atherosclerosis
("hardening" of the arteries with fatty deposits), which reduces blood flow. Dehydration caused by
drastically reduced fluid intake or excessive use of diuretics (water pills) is a major cause of prerenal
ARF. Many people with severe heart conditions are kept slightly dehydrated by the diuretics they take
to prevent fluid build up in their lungs, and they often have reduced blood flow (under perfusion) to
the kidneys.

Symptoms of prerenal ARF include the following. Dizziness, dry mouth, Low blood pressure
(hypotension), rapid heart rate, slack skin, thirst, weight loss. Urine output is usually low in people
with prerenal ARF. The patient also may have symptoms of heart or liver disease.

Chronic kidney diseases (CKD). Slow progressive decline in kidney function can cause accumulation of
metabolic waste like BUN. (CrCl >30 and <60 ml/min)
Risk Factors
• High blood pressure
• Atherosclerosis
• Blood loss
• Chronic liver disease
• Heart disease
• Blood sugar (diabetes)
• Autoimmune disease like systemic lupus erythromatus

Chronic kidney disease affects blood.

• ↑ urea and creatinine concentration
• Anemia
• ↑ blood acidity
• ↓ Ca and vitamin D 3 concentration
• ↑ Para thyroid hormone (PTH)

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• Normal or slightly ↑ K concentration

CKD can cause azotemia, anemia, vitamin D 3 deficiency, decrease Ca concentration, and increased
blood activity (acidosis).

CKD can cause decrease drug (metabolite) clearance and drug half-life (T 1/2 ) increase.

Nephrotic syndrome. Severe prolonged loss of protein into urine decrease blood proteins like albumin.
Chronic nephritis syndrome. Glomeruli are damaged and kidney function degenerates over a period of
time. Symptoms are vomiting, nausea, edema, high blood pressure, difficulty in breathing, itchy and
fatigue.

Electrolytes and Disorders

Electrolytes present in blood Na+, K+, Ca2+, Mg2+, Cl-, and CO 3 -.

Electrolytes

Extracellular (interstitial and plasma) Intracellular

Na+, Cl -, Ca2+ K+, Mg2+, Phosphate

Calcium (Ca2+). In normal adults, there are approximately 1400 g of calcium in the body, of which 99%
in bones. The total of 0.1% calcium is present in blood (plasma). The most common source of calcium
is dairy products. Calcium plays an important role in propagation of neuromuscular activity and
regulation of endocrine functions.

Parathyroid hormone (PTH) helps to dissolve calcium ion from bones and moves calcium to blood,
thereby hyper PTH can cause hypercalcemia. Helps in calcium reabsorption in kidney.

Calcitonin is secreted from thyroid gland. It helps in movement of calcium ion from the blood to bone
formation. Thereby hypercalcemia stimulates secretion of calcitonin from thyroid gland.

Vitamin D. The active form of vitamin D is 1, 25-dihydroxy vitamin D 3 (chole-calciferol). It enhances

absorption of calcium when calcium is low in the blood. Calcium is primarily absorbed by carrier-
mediated diffusion at small intestine (jejunum, and duodenum).
* Blood coagulation
* Bone and tooth structural integrity
* Normal values. 8.8 to 10.3 mg/dL or 2.20 to 2.56 mmol/L.

Hypercalcemia
Causes. Malignancy or metastatic bone disease.
• Hyperparathyroidism. Excessive parathyroid hormone secretion. Drugs that cause hypercalcemia
are Thiazide diuretics (Increase Ca reabsorption therefore decrease Ca secretion). Vitamin D
intoxication can cause excessive absorption of Ca.
• Treatment. Hypercalcemia can be treated with drugs such as calcitonin, bisphosphonates,
zolindranoic acid, corticosteroids, and prednisone.

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• PTH Increase Ca2+ reabsorption by activating adenylate cyclase in the distal tubule.

Hypocalcemia
Causes. Due to deficiency of vitamin D.
• Hypoparathyroidism (due to decrease in PTH secretion).
• Drugs that can cause hypocalcemia are corticosteroids. The corticosteroids counteract the effects
of vitamin D. Loop diuretics increase Ca2+ excretion therefore cause hypocalcemia (furosemide,
ethacrinic acid). Excess of phosphate in total parenteral nutrition.

Phosphorus: Phosphorus is an intracellular ion. Phosphorus is found primarily in bone (85%) and soft
tissues (14%).

Hypophosphatemia
• Hyperparathyroidism (excessive PTH) causes hypophosphetemia.
• Hypophosphatemia (seen mostly in primary hyperparathyroidism and malignancy-associated
hypercalcemia). Exacerbates hypercalcemia by increasing renal synthesis of 1,25-
dihydroxycholecalciferol, reducing bone formation and increasing bone resorption.
Hyperphosphatemia
• Occurs due to hypoparathyroidism (low PTH).
• Drugs that prevent bone resorption (death) are referred as antiresorptive agents.
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• Antiresorptive agents are bisphosphonates, clodronate disodium, pamidronate disodium and

zoledronic acid.

Potassium (K+): Potassium distributed primarily in intracellular (98%) and extracellular (2%) in muscle
tissues.
• Major cation in intracellular space.
• Maintenance of proper electrical conduction in cardiac and skeletal muscles (muscle and nerve
excitability).
• Plays a role in acid base equilibrium acidosis.
• Range of normal value 3.5 to 5 mEq/L.

Potassium regulated by.

• Kidneys (renal function)
• Aldosterone
• Arterial pH
• Insulin (insulin decrease K+ in blood by shifting K+ into cell.)
• K+ supplement intake
• Sodium delivery to distal tubule

Hyperkalemia: Aldosterone increase K+ secretion.

Causes. Renal insufficiency and drugs
• Drugs that cause hyperkalemia includes K+ sparing diuretics (Spironolactone, Triamterene,
Amiloride), ACEi, and ARBs etc.
• Adrenal insufficiency (aldosterone hormones)
• During vigorous exercise
• Cellular breakdown (tissue damage, hemolysis, burns, infections)
• Metabolic acidosis, and cardiac arrest.

Hypokalemia
• Malaise (feeling NOT well)
• Confusion
• Dizziness
• ECG changes
• Muscle weakness
• Pain
Causes:
• Excessive mineral corticoid activity
• Vomiting
• Diarrhea

Drugs that cause hypokalemia. Diuretic Thiazide, loop diuretics, and acetazolamide increase secretion
of K+. Corticosteroids, penicillin (piparicillin, ticaracillin), beta 2 agonist, and amphotericin.
• Glucosuria
• Alkalemia
• Administration of insulin and glucose
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Chloride (Cl-)
• The most abundant extracellular anion is Cl- (Na+ is the most abundant extracellular cation).
• Maintenance of acid base balance relationship between Na, and Cl.

Hyperchloremia (Cl- excess) and hypernatremia ( Na+ excess in the blood)

Caused by:
• Renal insufficiency when chloride intake exceeds excretion
• Dehydration
• Excessive salt intake

Hypochloremia
Caused by:
• Excess loss of GI fluids
• Diuretic therapy: Thiazide, and loop diuretics. Hypochloremic alkalosis is caused by: thiazides.
• Fasting
• Adrenal insufficiency

Sodium (Na+)
• Sodium is the predominant cation of the extra cellular fluid (ECF).
• Norma sodium levels (135 to 147 mEq/L or mmol/L).
• Sodium is essential in establishing osmotic pressure relation between intracellular and extra
cellular fluid.

Hyponatremia: Caused by cirrhosis, CHF, nephrosis or the administration of osmotic active solutes
such as albumin or mannitol (osmotic diuretic).

Hypernatremia
Caused by:
• Loss of free water (not body fluid)
• Loss of hypotonic fluid
• Excessive sodium intake
• Drugs that contain (beta lactam, ticaracillin, antacids such as sodium carbonate).

Acid Base Disorders

Body produces two types of acids; volatile (CO 2 ) and non volatile or fixed acids (HCl. phosphoric acid,
sulfuric acid.

Metabolic acidosis
↓ Bicarbonates (HCO 3 -) in blood and↑ CO 2 in blood
pH of blood is reduced in metabolic acidosis (acidic) pH of urine is increased (alkaline).
Carbonic anhydrase, is present in most cells, catalyzes the reversible reaction between CO 2 and
H 2 O --->HCO 3 -
Drugs that cause metabolic acidosis are acetazolamide, amiloride, triamterene, spironolactone
(potassium sparing), and overdose of ASA.

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Treatment. Sodium bicarbonate (NaHCO 3 ).

Metabolic alkalosis
• ↑ Bicarbonates (HCO 3 -) in blood and ↓ CO 2 in blood.
• Drugs and disease that cause metabolic alkalosis. Thiazide and loop diuretics, hypercalcemia, high
concentration of alkali administration, and vomiting.
• Treatment. Ammonium chloride (NH 4 Cl) or ascorbic acid (vitamin C).

Respiratory Acidosis
• This occurs due inadequate ventilation of CO 2 by lungs.
• Predisposing factor for respiratory acidosis such as asthma, beta-blockers, sleep apnea, CNS
depressants, pulmonary edema or embolism, and cardiac arrest.

Respiratory Alkalosis
• Due to increase secretion of CO 2
• Not very common
• Example. Over dose of ASA

Tips _______________________

1. Hypokalemia 2. in kidneys 3. Creatinine clearance

4. ↓HCO 3 ↑CO 2 5. ↑HCO 3 ↓ CO 2 6. Azotemia
7. Renal perfusion 8. Ureter 9. Bladder or prostate
10 Flow rate 11 pH 12 Tonicity
13 Metabolism 14 Hypocalcemia 15 Hypercalcemia

• Excessive blood urea nitrogen in blood ( )

• The most common cause of pre-renal acute renal failure is due to ( )
• What happens in metabolic acidosis? ( )
• What happens in metabolic alkalosis? ( )
• Intrinsic acute renal failure occurs in? ( )
• Post renal acute renal failure can occur in? ( )
• Factors that affect reabsorption ( )
• Glomerular filtration (GFR) measures…( )
• Chronic renal disease may cause…( )
• What renal conditions causes the deficiency of Vit D ( )
• Stimulates secretion of calcitonin from thyroid gland ( )
• albumneurea is --> ( )
• Albumneurea is indicator of --> ( )
• The most common extra cellular cation is--> ( )
• The most common extra cellular anion is--> ( )
• What happens in metabolic acidosis? ( )
• What happens in metabolic alkalosis? ( )
• Write the examples of drugs that cause metabolic acidosis? ( )
• Write the examples of drugs that cause metabolic alkalosis? ( )

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• Pre-renal ARF is due to  ( )

• Site of calcium reabsorption ( )

Select True or False statements

• Normal serum potassium levels  ( )
• If it is defect in renal filtration, CrCl  ( )
• Normal CrCl is  ( )
• In renal disease CrCl is  ( )
• Azotemia or uremia is  ( )
• Potassium sparing diuretics gives  ( )
• Pyuria and dysuria is symptoms of  ( )
• Lactic acidosis is SE of  ( )
• Summary of electrolytes action in kidney (True/ False)
• Proximal convoluted tubule = Reabsorbs Na+, Cl-, Ca2+(True/ False)
• Distal convoluted tubule = Reabsorbs Na+, Cl-, Ca2+(True/ False)
• Thin descending loop of Henle = Reabsorbs H 2 O (True/ False)
• Thick ascending loop of Henle = Reabsorbs: Na+, K+, Cl-, Mg2+, Ca2+ (True)
• Collecting tubule = Reabsorbs Na+ in exchange of K+ or H+ (regulated by aldosterone). Reabsorption
of H 2 O is regulated by ADH (vasopressin). (True)

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www.pharmacyprep.com Liver function and Pathophysiology

7
Liver Functions and Chronic
Liver Diseases
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Causes of chronic liver diseases like ascites (peritonitis).
• Hepatitis A, B, C infections causes of infections
• Hepatitis A and B vaccines and treatment.

Definitions
• Necrosis cellular breakdown example: Acetaminophen
• Steatosis: Hepatocytes filled with small droplet of lipid. Example: Tetracycline’s

Drugs transportation into the bile from the liver

• There are transporters for anions, bile salts, cations, and neutral organic compounds.
• Release small intestine.

• Oral drugs passage to liver. Mesenteric veins  portal veins  liver  hepatic vein 
systemic circulation

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Enterohepatic recirculation
• This term refers to drugs emptied via bile into the small intestine and then reabsorbed from
the intestinal lumen into the systemic circulation.
• It can allow the body to conserve endogenous substances such as bile acids, vitamins D and
B 12 , estrogen etc. It may be responsible for some of the long half-lives of drugs.
• Antibiotic therapy interferes with the process of enterohepatic recirculation by drugs, which
have been conjugated can be hydrolyzed by gut enzymes such as glucuronidase and then
reabsorbed as the active drug or as a metabolite. A decrease in bacterial flora as a
consequence of antibiotic therapy can decrease the amount of sulfatase and glucuronidase
containing bacteria. This could then lead to an increased rate of elimination of the drug.

Chronic liver disease. Ascites, hepatic encephalopathy, cholestatic disease, Wilson’s disease,
alcoholic liver disease and viral hepatitis.

Chronic Liver Disease

Spontaneous Chronic Ascites (Peritonitis) Hepatic encephalopathy

Bacterial Peritonitis cholestasis Treatment. Diuretics Treatment. Lactulose
Treatment: antibiotics Treatment.
Antihistamine or
cholestyramine

Chronic Cholestasis
• Cholestasis is a condition in which obstruction of bile from liver to intestine, it is also
referred to as obstructive jaundice. Symptoms are pruritus (itching) and are due to
hyperbilirubinemia associated with liver diseases. Cholestyramine removes excess of
bilirubin from the body. Antihistamines can be used for non-specific pruritus.
• Jaundice. The jaundice is a yellowish discoloration of skin and whites of eye caused by high
levels of pigment bilirubin in the blood stream. The urine is dark because excessive bilirubin
in blood excreted through kidney. The other characteristic symptoms are pale stools and
generalized itchiness.

Ascites or Hydroperitoneum
• The accumulation of fluid in peritoneal cavity and cause abdominal distention is referred to
as ascites, this is due to high plasma aldosterone levels. Symptoms include abdominal
distention. Ascites is caused due to infections such as tuberculosis, heart failure, cirrhosis,
and portal hypertension, and various cancers.
• Drug of choice is spironolactone is inhibitor of aldosterone, because aldosterone hormone
increases Na/H 2 O retention. Alternate furosemide can be added to enhance diuresis.

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Hepatic Encephalopathy. (Porto Systemic Encephalopathy)

• Condition in which brain function is impaired by presence of toxic
substances, absorbed from colon, which is
normally detoxify and removed by liver. This
condition occurs in severe liver damage such
as liver cirrhosis.
• Symptoms include: Drowsiness, confusion,
difficulty in performing task (e.g. writing) and
coma.
• Drug of choice is lactulose to achieve 2 to 3
bowel movement a day. If no improvement in
1 to 2 days add metronidazole.

Wilsons Disease
• Excessive copper can cause Wilsons disease. The
drug of choice is the penicillamine and treatment is Fig 7.2
lifelong. Pyridoxine (vitamin B 6 ) 25 mg daily should be
given with penicillamine to counteract its antipyridoxine effect.
• Avoid food that has high copper content such as peanuts, chocolate, shellfish, mushrooms,
and liver.

The liver cirrhosis is the destruction of normal liver tissue. The most common cause is due to
alcohol abuse or continued excessive intake of alcohol over long period of time.

Viral Hepatitis. There are 5 types of hepatitis viral infection, hepatitis A, B, C, D, and E. However
the common infections are hepatitis A, B and C.
Most common symptoms of hepatitis are flue like symptoms, loss of appetite, fatigue, mild
fever, muscle or joint aches, nausea and vomiting. Less common symptoms are light colored
stools, jaundice (yellowing of skin, and whites of the eye), generalized itching, internal bleeding,
and altered mental state.

Hepatitis A
• Hepatitis A is acute infection
• Transmits through food contaminations such as water or orofecal
• Vaccine available
• Hepatitis A vaccine is recommended to travelers.

Hepatitis B and C
• Hepatitis B and C are chronic. Hepatitis B is 90% chronic in children and 5% in adults.
• The most common is hepatitis B.
• Hepatitis B is DNA type of virus, where as other hepatitis are RNA type.
• Transmission through body fluids, such as blood transfusion, sexual contact and sharing
needles (drug abuse and spa).
• Hepatitis C is often chronic in adults (acute hepatitis C, is 80% becomes chronic likely
within first year of infection).
• Hepatitis C has NO vaccine.
• Hepatitis B vaccine also protects hepatitis D infections.
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• Interferon alfa (IFN alfa) is the drug of choice to treat acute viral hepatitis and chronic
hepatitis.

Tips

• Causes of ascites include  infections, TB, cancer, GI surgeries, chronic liver disease
• Lactulose is used in what type of chronic liver disorder  hepatic encephalopathy (decrease
NH 3 )
• What type of hepatitis is chronic  B and C
• What is treatment of hepatitis  interferon’s
• Hepatitis A transmits by  water and orofecal
• Hepatitis B and C transmits by  sexual contact
• Ascites is caused by infections, cancer, GI ulcer, TB
• If takes Hep. B vaccine, this also protects HepD

Drugs that can cause hepatotoxicity include:

• Acetaminophen (> 4 g daily)
• Tetracycline (>2 g daily)
• Methotrexate (>25 mg/wk)
• Vitamin A (chronic use over 40,000 U daily)
• Salicylates (chronic use >2 g daily)
• Iron (single dose >1 g)
• Cyclophosphamide
• 6-Mercaptopurines

• Cholestatitis
• Retention of bile acids because of the obstruction of bile ducts.
• Example: Penicillins (isoxazole type)
• Cholestatitis can lead to hyperbilirubinemia
Example: Rifampin
• Bacterial peritonitis: Chronic liver disease, history of fever, abdominal pain.

Tips
1. Penicillamine 2. Ascites 3. Wilsons disease
4. Cholestatitis 5. hepatic 6. Hepatitis B
encephalopathy
7. Hepatitis C 8. Infections 9. Tuberculosis
10 Cancer 11 GI surgeries 12 Chronic liver disease
13 Sexual contact 14 water 15 Orofecal
16 Interferon alfa 17 Portal hypertension 18 Spironolactone

• What type of hepatitis is chronic? ( )

• What is the treatment of hepatitis? ( )
• Hepatitis A transmits by? ( )
• Hepatitis B and C transmits by? ( )

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• Ascites is caused by? ( )

• What is a DNA type of virus ( )
• Accumulation of fluid in peritoneal cavity ( )
• It is caused by excessive copper ( )
• Drug of choice to treat Wilsons disease ( )
• Retention of bile acids because of obstruction of bile ducts ( )
• A type of hepatitis that has no vaccine ( )
• The drug of choice to treat ascites ( )
• Lactulose is used in what type of chronic liver disorder? ( )
• What type of hepatitis is chronic  ( )
• What is treatment of hepatitis  ( )
• Hepatitis A transmits by  ( )
• Hepatitis B and C transmits by  ( )
• Ascitis is caused by ( )
• If takes Hep B vaccine, this also protects ( )

Select True or False statements:

• Cholestatitis: Retention of bile acids because of the obstruction of bile ducts. Example:
Penicillins (isoxazole type) (True/False)
• Cholestatitis can lead to hyperbilirubinemia example: Rifampin (True/False)
• Bacterial peritonitis: Chronic liver disease, history of fever, abdominal pain. (True/False)
• Causes of ascites include  infections, TB, cancer, GI surgeries, chronic liver disease
(True/False)
• Lactulose is used in what type of chronic liver disorder  hepatic encephalopathy (decrease
NH 3 ) (True/False)

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www.pharmacyprep.com Respiratory System

8
Respiratory System
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Tidal volume. The volume inspired or expired with each normal breathing.
• Definition of emphysema is COPD.
• Differences between COPD (terminal bronchioles or alveoli) and asthma (bronchus).

Fig 8.1

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Lung volume:
Tidal volume: Can be measured by Spirometer. (in asthma expiratory flow rate decreased). The
volume inspired or expired with each normal breath.

Residual volume: The volume that remains in the lung after a maximal expiration.
The residual volume cannot measured by spirometer.

Lung capacities:
Total lung capacity: The sum of all four lung volumes (tidal volume, inspiratory lung volume,
expiratory lung volume, residual volume) . The volume in the lungs after maximal inspiration.

Forced expiratory volume (FEV 1 ): The volume of air that can be expired in 1 second after
maximal inspiration. This is measured by spirometer.

Spirometer: Measure volume that has been exhaled at the end of the first second (FEV 1 ). The
spirometer is used for diagnosis of obstructive lung diseases such as asthma and COPD.

Peak flow meter is test to determine asthma severity for patient at home. This test measures
the highest forced expiratory flow.

ASTHMA COPD
Obstructive Obstructive
Site Bronchus or bronchial tubes Alveoli
Cause Inflammation in bronchus Permanent (irreversible) enlargement
alveoli (emphysema) and /or Chronic
bronchitis.
Symptoms Wheezing, cough, sputum, SOB. SOB, dyspnea, fatigue, cough, sputum
Treatment Bronchodilators Bronchodilators (SABD, LABD)
Steroids (ICS, PO, IV) Acute COPD oral steroids (not used?
inhaled corticosteroids) Antibiotics
(pneumonia)
Esinophilic Neutrophilic due to bacterial infections.
Obstruction of airflow is Obstruction of airflow is irreversible
reversible
Immunization Flu vaccine annually Flu vaccine annually and Pneumococcal
Pneumococcal vaccine vaccine Q5-10y in high risk

Lower Respiratory Tract

Physiology Ventilation. Air moves from Atmosphere URTLRTalveoli
Respiration. Gaseous exchange occurs at alveoli capillary membrane.
Factors that • Increased in resistance to air flow
decrease the • Decrease ventilation
respiration • Decrease diffusion
• Mucosal edema.
• Increased bronchial secretion
• Bronchospasm

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Arrangement of • Tracheobronchial tubes have smooth muscle fibers arranged on a

Bronchiole spiral around the tube.
smooth muscles
Disease Asthma, COPD is Emphysema and Bronchitis

Upper respiratory tract

Anatomy Sinus (prenasal cavity in & around the nasal cavity)
Nasal cavity
Pharynx
Larynx
Trachea (past outside thoracic cavity)
Disorders Acute rhinitis
Acute pharyngitis
Acute tonsillitis
Acute laryngitis
Common cold (most prevalent of URI, and NOT life threatening but causes
severe discomfort).
Treatment Antihistamine Runny nose
Decongestants (Sympathomimetics)nasal congestion
AntitussiveCough
Antibiotics Infections
ExpectorantsBring up mucus

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Tips
1 Asthma 2 emphysema 3 dyspnea
4 COPD 5 Spirometer 6 Peak flow meter
• Definition of emphysema?
• Wheezing cough is symptoms of?
• Difficulty in breathing is termed as ( )
• Permanent enlargement of the alveoli is described as ( )
• What respiratory conditions occurs in the bronchus ( )
• What respiratory conditions bronchioles & alveoli ( )
• What device is used to diagnosis of Asthma?
• What device is used to determine asthma severity for patient at home?

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www.pharmacyprep.com Urinary System

9
Urinary System
Questions Alerts!
Common questions in pharmacy exam is to ask!
Urinary tract infection symptoms Bladder (cystitis), Urethra (urethritis), Ureter (ureteritis), kidney
(pyelonephritis). Complicated and uncomplicated UTI.
Symptoms of benign prostatic hyperplasia (BPH).
Types and symptoms of urinary incontinence and over reactive bladder.
Prostate cancer screening is prostate specific antigen (PSA), and Digital rectal exams.

The urinary system includes two kidneys, two ureters, the bladder, two sphincter muscles, and the ure-
thra. Urinalysis is a test that studies the content of urine for abnormal substances such as protein or
signs of infection. Urodynamic tests evaluate the storage of urine in the bladder and the flow of urine
from the bladder through the urethra.

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Urinary Tract Infection

The name of the UTI depends on its location in the urinary tract. An infection in the bladder is called cys-
titis. If the infection is in one or both of the kidneys, the infection is called pyelonephritis. This type of
UTI can cause serious damage to the kidneys if it is not adequately treated.

Pathological defense mechanism of UTI.

Uncomplicated UTI. Occurs in females with normal genitourinary tract. Cystitis, the most common in-
fecting organism is E. coli (80-90%).
Usual presenting symptoms. internal dysurea, frequency, suprapubic discomfort and urgency.
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Complicated UTI. occurs in individuals with functional or structural abnormalities of genitourinary tract.
Virtually all episodes of UTI in men are complicated. E. coli (50%). Patient with cystitis..

Benign prostatic hyperplasia (BPH) is a condition in men that affects the prostate gland, which is part of
the male reproductive system. The prostate is located at the bottom of the bladder and surrounds the
urethra. BPH is an enlargement of the prostate gland that can interfere with urinary function in older
men. It causes blockage by squeezing the urethra, which can make it difficult to urinate. Men with BPH
frequently have other bladder symptoms including an increase in frequency of bladder emptying both
during the day and at night.
Symptoms. Urine obstructions symptoms includes frequent urine, drop by drop, incomplete voiding,
nocturea and also include irritation symptoms.
Treatment. Finasteride 5 mg, or tamsulosin.

Painful bladder syndrome/Interstitial cystitis (PBS/IC) is a chronic bladder disorder also known as fre-
quency-urgency-dysuria syndrome. In this disorder, the bladder wall can become inflamed and irritated.
The inflammation can lead to scarring and stiffening of the bladder, decreased bladder capacity, pin-
point bleeding, and, in rare cases, ulcers in the bladder lining. The cause of IC is unknown at this time.

Kidney stones is the term commonly used to refer to stones, or calculi, in the urinary tract system.
Stones form in the kidneys and may be found anywhere in the urinary system. They vary in size. Some
stones cause great pain while others cause very little. The aim of treatment is to remove the stones,
prevent infection, and prevent recurrence. Both nonsurgical and surgical treatments are used. Kidney
stones affect men more often than women.
Stones (calculi) can form anywhere in urinary tract and may cause pain, bleeding, obstruction of flow of
urine, or an infection. Depending on the site of stone it is referred as kidney stone, ureteral stone, or
bladder stone. The process of stone formation is urolithiasis, renal lethiasis, or nephrolithiasis.

Prostatitis is inflammation of the prostate gland that results in urinary frequency and urgency, burning
or painful urination, a condition called dysuria, and pain in the lower back and genital area, among other
symptoms. In some cases, prostatitis is caused by bacterial infection and can be treated with antibiotics.
But the more common forms of prostatitis are not associated with any known infecting organism. Anti-
biotics are often ineffective in treating the nonbacterial forms of prostatitis.

Proteinuria is the presence of abnormal amounts of protein in the urine. Healthy kidneys take wastes
out of the blood but leave in protein. Protein in the urine does not cause a problem by itself. But it may
be a sign that your kidneys are not working properly.

Urinary incontinence. Uncontrollable loss of urine or involuntary leakage of urine. There are many caus-
es and types of incontinence, and many treatment options. Treatment range from simple exercises to

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surgery. Women are affected by urinary incontinence more often than men. To treat incontinence, an-
ticholinergic drugs oxybutynin is the drug of choice.
Detrusor muscle contraction due to parasympathetic activity (voiding)
Detrusor muscle relaxation and tightening of sphincter is due to anticholinergic activity (storage).
Bladder relaxation is due to beta agonist activity.
Bladder neck/sphincter contraction is due to alpha agonist activity.

Stress
Stress on bladder

Treatment. Vaginal estrogen, Duloxetine

urge
Neurological.
Treatment. Antimuscarinics. (darifen-
acin, fesoterodine, oxybutynin, solifenacin, tolterodine, trospium)
Anticholinergic drugs oxybutynin is the drug of choice.

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Drugs that cause urinary retention includes antihistamine, anticholinergic, TCAs, benzodiazepine, sym-
pathomimetics, levodopa, bromocriptine, and amantadine.

Urinary retention or bladder-emptying problems, is a common urological problem with many possible
causes.

Tips

• Drugs that are used for treatment of urinary incontinence

• Drugs that are avoided in patient with urinary incontinence 
• Enuresis (bed wetting) drug of choice 
• Benign prostatic hyperplasia (BPH) is 
• Benign prostatic hyperplasia symptoms are -->
• Drug of choice to treat benign prostatic hyperplasia 
• Saw palmetto is used for -->

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www.pharmacyprep.com The Eye and Ear

10
The Eye and Ear

10
Questions Alerts!
Common questions in pharmacy exam is to ask!
1) Photoreceptors rods are sensitive for dim light and cones cells sensitivity to daylight and colors.
2) Cornea is upper layer of eye is rate determine step in ophthalmic drops.
4) Eye disorders like conjunctivitis (red or pink eye), blepharitis, and sty (hordeolum), Age related macular
degeneration, Cataract, and glaucoma.

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• Cornea. In the front of the eyeball is a transparent opening known as the cornea.
• Pupil. After light passes through the cornea, a portion of it passes through an opening known as the
pupil.
• Iris. Pupil opening can be adjusted by the dilation of the iris.
• Ciliary muscles. The lens is attached to the ciliary muscles.
• Retina. The inner surface of the eye is known as the retina.
• Macula. Small central area of retina.
• Optic nerve. The network of nerve cells is bundled together to form the optic nerve on the very back
of the eyeball.
• Optic disk. The nerve cells is bundled at very back of eyeball, is also known as blind spot. Rods and
cones are NOT present on the optic disk, therefore blind spot.
• Myopia. If the incoming light from a far away object focuses before it gets to the back of the eye,
that eye’s refractive error is called “myopia” (nearsightedness).
• Hyperopia. If incoming light from something far away has not focused by the time it reaches the
back of the eye, that eye’s refractive error is “hyperopia” (farsightedness).

The retina contains two types of photoreceptors, rods and cones. These rods are responsible for
night vision, our most sensitive motion detection, and our peripheral vision.

• The rods are more numerous, some 120 million, and are more sensitive than the cones. However,
they are not sensitive to color.
• The 6 to 7 million cones provide the eye's color sensitivity and they are much more concentrated in
the central yellow spot known as the macula.
• The image forms in eye at retina. Ophthalmic drug rate limiting step is cornea.

Beta carotene ----> Retinol (vitamin A) ---> 11-Cis retinal---> opsin

RODS CONE
Rhod”opsin” (retinal) Iod”opsin”
Rhodopsin is rod cells pig- Iodopsin is retinal cone cells re-
mentation. Responsible for sponsible for day light vision color
dim light vision. vision
More sensitive Less sensitive
Higher in number Less in number
Rods. Light on the retina converts 11-cis retinal to all trans retinal. The retinal is a vitamin A is essential
for the regeneration of 11-cis retinal. Deficiency of vitamin A causes night blindness.

Carotenoids

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retinol (vitamin A)

Glaucoma: Due to angle closure increasing intra ocular pressure (IOP) cause glaucoma. This is due to;
• Increase aqueous humor production cause increase IOP.
• Decrease aqueous humor secretion from shlemn canal.

Aqueous humor is secreted from celiary tissue (celiary gland).

Treatment of glaucoma:
• Beta blockers (Timolol). They decrease IOP by inhibiting formation of aqueous humor.
• Prostaglandin analogues. ("prost"). Lower IOP by increase outflow of aqueous humor through
uvescleral pathway.
• Topical CA inhibitors (Acetazolamide, Dorzalomide) is diuretics. Decrease IOP by inhibiting enzyme
that involved in formation of aqueous humor.
• Cholinergic agonist (Pilocarpine, carbachol). Directly stimulate muscarinic receptors to contract cili-
ary muscle and increase trabecular outflow.

Age related macular disorder (AMD): It is due to gradual deterioration of macular in central vision. It is
two types
• Dry: this is characterized by drusen (white to yellow spots in the central retina). May or may not
cause vision loss.
• Wet: caused by presence of choroidal neovascular membrane (CNM). This is common cause of se-
vere vision loss.

Cataract: When the eye lens becomes cloudy, and this obstruct the vision is referred as cataract.
Cataract surgery postoperative care. Antibiotics, Dilators and anti-inflammatory drugs.
Antibiotics. Fluroquinolones 7-10 d (basifloxacin, ciprofloxacin, gatifloxacin, moxifloxacin and ofloxacin).
Aminoglycosides 7-10 d. Gentamicin, neomycin, tobramycin
Dilators and cycloplegic. Cyclopentolate, phenylephrine, tropicamide
Anti-inflammatory 3-4 wks. Dexamethasone, prednisolone, diclofenac, and ketorolac.

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Ear: Anatomy ear categorized into outer ear (otitis externa), middle ear (otitis media) and inner ear.

Otitis externa (outer ear): consist of external auditory canal.

Acute bacterial externa
Eczematous otitis externa. Drainage resulting from mild otitis externa may be self treated. (Ear pain
associated with ear drainage, the patient should be referred to a physician)
Otitis media with perforation of the tympanic membrane or drainage from the middle ear, the patient
should be referred to a physician.

Dental anatomy and physiology

• There are 20 primary teeth and 28 to 32 permanent teeth. The last 4 is being wisdom teeth.
• In adult, there are 16 teeth in maxilla and 16 in the jaw.
• Wisdom teeth may or may not grow in.
• Incisors 8 , canine 4, premolar 8, molar 8 ,wisdom(third molar) 4=32.
• Baby teeth start to grow during intrauterine first trimester (8 weeks).
• Teeth are made of enamel, dentin, and cement.
• Dentin composes most of the root.
• Crown is covered by the enamel.
• The root embedded inside the maxilla and jaw bones has a bulb canal.
• The bulb canal contains blood supply and nerve terminals.
• The root teeth may be single in number or multiple.
• Gingival or gums consist of mucosal tissue lies over the alveolar bone.
• Oral hygiene is practice of keeping mouth and teeth clean, to prevent bad breath, and dental prob-
lems.
• Plaque is yellow sticky films that form on the teeth and gums.
• Bacteria in plaque release acid that harm the enamel.
• Brushing and flossing daily the teeth will prevent tartar forming.
• Fluorides are a primary protector against dental cavities.
• Fluorides make teeth surface more resistant to acids.
• Drinking water contains enough fluorides.
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• Sugar free gum increases salivation and help to clean teeth surface.
• Good food items for teeth; green tea, milk and yogurt, cheese, apples, onion.
• Smoking and chewing tobacco causes multiple dental diseases.
• Bulimia nervosa and repeated vomiting causes significant damage to enamel.
• Bad dental hygiene show direct link to systemic diseases;
• Cardiovascular disease.
• Bacterial pneumonia.
• Low birth weight.
• Complication of diabetes.
• Osteoporosis.

S. viridans is present in deep of teeth and also causes cavities.

Prophylaxis of endocarditis prior dental surgeries.
Amoxicillin 2 g 1hr before procedure or 2 hr after procedure, amoxicillin/Clavulanate. If patient
is allergic penicillin give cephalexin, clindamycin, and macrolides.

Tips
• Blind spot is 
• Age related macular degeneration cause due to
• Which photoreceptors are responsible for color vision?
• Which photoreceptors are responsible for night vision?
• Glaucoma occurs due to 
• Drugs that are used to treat glaucoma are 

Select True/False Statements

• The retina contains two types of photoreceptors, rods and cones. (True/False)
• These rods are responsible for night vision, our most sensitive motion detection, and our peripheral
vision. (True/False)
• The rods are more numerous, some 120 million, and are more sensitive than the cones. However,
they are NOT sensitive to color. (True/False)
• The 6 to 7 million cones provide the eye's color sensitivity and they are much more concentrated in
the central yellow spot known as the macula. (True/False)
• Cones are sensitive to color vision(True/False)

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Pharmacyprep.com Blood and Anemia

11
Blood and Anemia
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Blood cells such as platelets, red blood cells, and white blood cells
• Hemostasis
• Morphological changes of anemia. Iron deficient microcytic anemia and megaloblastic
anemia.
• Elemental iron supplements (ferrous fumerate > dried ferrous sulfate > ferrous
sulfate>ferrous gluconate).
• Iron supplement drug interactions, thyroid hormone, tetracycline and quinolones,
cholestyramine.
• Vitamin B12 and Folic acid supplements

This chapter reviews blood cells and functions. Types of anemia and their morphological changes.
Terminology
• Agranulocytosis. Decrease in number of neutrophil
• Neutropenia. Decrease in neutrophil
• Neutrophilia. Increase in neutrophil
• Esinophilia. Increase in esinophil
• Thrombocytopenia. Reduced platelets to less than 150 x 109/L
• Parasthesias. Abnormal tingling sensation as described as tingling & needles.
• Hemocromotasis. Excessive iron

• Function of blood include transportation of gases, nutrients, hormones, metabolic wastes

regulates body temperature, pH, electrolyte balance, fluid volume protects, prevents blood loss
(clotting), and prevents infection (WBC and antibodies).

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Blood

55% Fluid 45% Cells

Water containing salts Erythrocytes (RBC)= 5-6 mil/mL (44%)

Proteins Leukocytes + Platelets = (1%)
Antibodies
Hormones
Electrolytes
Fats and lipids
Sugar (carbohydrates) Erythrocytes Leukocytes Platelets
Mineral
Vitamins

Blood constitute 55% fluid and 45% cells.

Blood proteins
• Blood proteins (albumin, glycoprotein, and fibrinogen).

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• Albumin is the most common blood proteins (55%) in blood. Which is carrier of, buffer,
osmotic pressure, transport lipids, fatty acids and acidic drugs.
Globulins carry ions, hormones, and steroids and bind base drugs.
Fibrinogen changes to fibrin, helps in blood clotting.

Electrolytes. The Electrolytes present in blood are Na+, K+, Ca2+, Mg2+, Cl- and CO3
• Extracellular ion Na+, Cl- and Ca2+
• The most common extra cellular cation is sodium (Na).
• The most common extra cellular anion is chloride (Cl).
• Intracellular ions K+, Mg2+ and phosphate.
• Antibodies (Immunoglobulin) IgG, IgM, IgE, IgA, and IgD.

Erythrocytes (Red blood cells)

• RBC is composed of globin (protein), iron (metal), phospholipid (lipids), potassium phosphate
(salt), hemoglobin (contain porphyrin ring system) bind loosely to oxygen and carbon dioxide.
In the overdose of carbon monoxide, the hemoglobin binds with carbon monoxide.
RBC synthesis. Pre-erythrocyte is the first step in the synthesis of RBC series.
• The normal value of the RBC in adult men would be 4.7 million.
• Erythrocytes are originated in sequence of cells Hemocytoblast Megaloblast Erythroblast
(normoblast) --> Reticulocytes Erythrocytes
• Erythropoietin, a glycoprotein is a key hormone for the production of RBC. In the absence of
erythropoietin. Hypoxia is unable to stimulate the production of RBC. The kidney is a
principal organ for the synthesis of erythropoietin, therefore, kidney failure would result in
severe anemia.

RBC destruction. Life span of RBC is 120 days (4 months). RBCs are destroyed in the spleen (spleen also
referred to as "grave yard" of RBC).

Hemoglobin (Hgb). Blood protein-containing iron metal, carries oxygen in blood.

• Hemoglobin content 14.5 g/100 ml. Carries oxygen in blood. Hemoglobin consists of
porphyrin ring. Oxygen binds with porphyrin ring. Porphyrin ring present in haemoglobin is
tetramer.
• The metabolic degradation of hemoglobin takes place principally in the reticuloendothelial
system (endoplasmic reticulum).
• The non-protein portion of hemoglobin is a "ferrous" complex of proto porphyrin.
• The protein portion of hemoglobin is globin.
• Glycine is an aminoacid is precursor of hemoglobin.
• Myoglobin. protein present in tissues, which is essential for oxygen transport in tissues.
Carries oxygen in tissue. The porphyrin ring present in myoglobin is monomer.
• Methemoglobin. Nitrite ions react with hemoglobin and produce methemoglobin, which has
a low affinity for oxygen and a high affinity for cyanide ions. This forms iron CN complex, it is
referred as cyanomethemoglobin.

Hemoglobin Myoglobin Cytochrome oxidase

Transport oxygen in blood Transport oxygen in tissue Catalyzes phase I
metabolism
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Porphyrin tetramer Porphyrin monomer Porphyrin

Has affinity and binds with Has affinity and binds with Has affinity and binds with
O 2 , CO, CO 2 and CN O 2 , CO, CO 2 and CN O 2 , CO, CO 2 and CN
2+ 2+
Ferrous ion (Fe ) Ferrous ion (Fe ) Ferrous ion (Fe2+)
Death due to cyanide poisoning results from cyanide binding to hemoglobin, myoglobin and inhibiting
cytochrome oxidase.
Glycine is precursor of -CH 2 - in porphyrin ring.

Carboxyhemoglobin. Carbon monoxide bound hemoglobin.

Methemoglobinemia. Abnormal state of hemoglobin contains oxidized iron as Ferric Fe3+

Platelets (Thrombocytes). Platelets are referred to as thrombocytes. Platelets help in the process of
blood clotting. Platelets lack nuclei and platelets are produced in bone marrow.
• Platelet life span is 7 to 10 days. Range in blood 150,000 to 300,000 mm3.
• Deficiency of platelets is referred as thrombocytopenia.

Leukocytes (WBC)
• Leukocytes produced in bone marrow like RBC’s. Leukocytes consist of clearly defined nuclei.
• About 30% are lymphocytes and about 60% are neutrophils and 8% are monocytes.
• Normal range of WBC’s (white count) in blood is 4000 to 11000/mm3 (4000 to 11000/ cmm).
• Neutrophils. About 60% of white blood cells are neutrophils. Responsible for immune defence
phagocytosis.
• Monocytes. About 8% of white blood cells are monocytes.
• B-lymphocytes and T lymphocytes are primary cell of specific immune response.
• Basophils. Responsible for inflammatory response.
• Eosinophils. Defence against parasites.
• Monocytes. Immune defence (precursor of tissue macrophage) also called big eaters.
• B-lymphocytes. Antibody production (precursor of plasma cells).
• T-lymphocytes. Cellular immune response.

Granulocytes are Neutrophils, eosinophils, and basophils, cells that stain.

• Neutrophils gives stain with acidic or basic dyes
• Eosinophils gives stain with acidic dye
• Basophils gives stain with basic dye

Agranulocytes
Cells that do not stain are agranulocytes. There are 2 types of cells lymphocytes and
monocytes.

Rh Factor. Agglutinogens in human RBCs are known as the Rh factor blood with this factor is
described as Rh +ve (90% of population). Blood without this factor is described as Rh (-)
negative. In Rh-negative mother, Rh-positive antigens may transfer from Rh-positive fetuses
to the mother via placenta. This may lead to production of Rh-positive antibodies in the
mother’s blood. These same antibodies may transfer back from the mother’s blood into fetus
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via the placenta, and produce antigen antibody reactions. This leads to lysis of red blood cells
in the fetus, and miscarriage. Rho gram prevents the formation of anti-Rh antibodies in a
mother who bears Rh positive fetus.

Blood Groups
Surface of RBC's have antigen
A RBC has A antigen, plasma has B antibodies
B has B antigen, A antibodies
AB has A and B antigens, no antibodies.
O (universal donor) has no antigens, has antibodies against A and B, transfusion reaction
can lead to kidney failure.
Rh- women who have + babies get a Rhogam shot.

DONOR
O A B AB
AB � � � �
B � �
A � �
O �
Qualities of Blood
• Temperature. 38oC (100.4oF), warfarin (anticoagulant) added in blood storage
Viscosity: 5xH 2 O sticky, cohesive, and resistant to flow pH 7.35 to 7.45
volume: 4 to 6 litres (7% body weight in kg) (2.2 lb/kg).
• Transport O 2 and CO 2 2% of cells in whole blood males: 40-54 (androgens stimulate
production) females: 37-47 (estrogens inhibit production).
• Hemoglobin (Hb): binds transports O 2 and CO 2 (280 million/RBC) Hemoglobin - Fe+2
males: 14 to 18 g/100ml; females: 12 to 16 g/dl, fetal hemoglobin has a higher affinity
for O 2 .

Anemia
Anemia has categorized based on morphological changes of RBC.

Mean cell volume (MCV). The MCV detects changes in cell size. Decrease in (↓) MCV indicates
a microcytic cell anemia, which is due to iron deficiency. Increase in (↑) MCV indicates
macrocytic anemia (megaloblastic anemia), which is due to deficiency of vitamin B 12 and folic
acid.

Mean cell hemoglobin concentration (MCHC). Weight of hemoglobin in average red blood
cell. In microcytic anemia decrease in (↓) MCHC. This is not significant in determining
megaloblastic anemia.

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Serum ferritin. Iron stores are measured by serum ferritin. The concentration of ferritin is
proportional to iron stores.

Total iron binding capacity (TIBC). Increased in microcytic anemia.

Anemia is characterized as deficiency of red blood cells and this can occurs in three forms.

Morphological changes in anemia

Microcytic Macrocytic Normocytic
(Hypochromic) (Megaloblastic) (Normochromic)
(Deficiency of Fe) (Deficiency vit. B 12 (Sickle cell anemia,
& folic acid) thalassemia)
MCV ↓ ↑ No change
MCHC ↓ No change No change
Serum ferritin ↓
TIBC ↑
Cyanocobalamine ↓

Microcytic (hypochromic) anaemia. Symptoms fatigue or dyspnea on exertion may occur

during pregnancy and in infants. Mainly occurs due to iron deficiency. This is could be due to.
• Low mean cell volume (MCV)
• Impaired heme (protein) synthesis
• Deficiency of serum iron
• Increased total iron binding capacity (TIBC)
• Decreased serum ferritin

Monitoring
• Iron storage is measured by serum ferritin (The concentration of ferritin is proportional to
iron stores).
• Response to oral and parenteral iron occurs at the same rate in normal circumstances.
• Good reticulocyte response indicates active red cell production.

Iron supplements
• Food decrease iron absorption thus iron given on empty stomach.
• The most common side effect of iron supplement is constipation. Take with food to decrease GI
side effects like nausea and epigastric pain. However absorption is better on empty stomach. Iron
↓ absorption by food and antacids, Ca, Mg, Al, levodopa, methyldopa, tetracycline, NaHCO 3 ,
separate admin by 2 hr. Separate thyroxin & quinolones.
• Separate antacids from iron supplement, because antacids decrease absorption of iron.
• Antidote for iron overdose is deferoxamine.
• Enteric coated and time released iron preparation is intended to reduce SEs but may be ineffective
because of failure to release iron in the gastric environment.
• The usual target dose is 105-120 mg/day elemental iron in tid divided.

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Ferrous fumerate 33% (300 mg tab contain 100 mg elemental Fe)

Ferrous sulphate 20% (300 mg contain 60 mg elemental Fe)
Ferrous succinate 19% (300 mg contain 60 mg elemental Fe)
Ferrous gluconate 12% (300 mg contain 35 mg elemental Fe)
Proferrin is a heme iron polypeptide. It is the same form of iron found in red meat. 11 mg elemental
Fe.
Polysaccharide-iron complex (150 mg Fe/150 mg) polysaccharide iron complex.
Vitamin C (ascorbic acid) enhances non-heme iron absorption. Whereas polyphenols, and naphtates
found in tea and coffee can inhibit non-heme iron absorption.
Parenteral iron. is reserved for patients with malabsorption or true intolerance to oral iron therapy.

Food rich in heme iron is liver, lean red meats, seafood (oysters, clams, salmon, sardine, shrimp).
To begin iron store replenish may take 6 to 9 mo and can be monitored by measuring serum ferritin.

Transferrin. Free Fe2+ circulates binds transferring and transports it from small intestine to its storage
sites in the liver and from the liver to the bone marrow for the synthesis of hemoglobin.
Ferritin. Iron storage protein.

Megaloblastic Anemia (macrocytic anemia) (MCV >100 fL)

• The main source of vitamin B 12 is meat and dairy product.
• Deficiency of vitamin B 12 or folate due to decreased of DNA synthesis. Megaloblastic anemia (large
abnormal form or precursors to RBC). Impaired DNA synthesis usually due to folate or vitamin B 12
deficiency.
• Mean cell volume is increased.
• Major causes of megaloblastic anemia include folate or vitamin B 12 deficiency this is due to,
chemotherapy and alcoholism and seniors.
• Drugs that cause megaloblastic anemia are acyclovir, alcohol, antiepileptics (carbamazepine,
valproic acid), methotrexate (dose dependent), nitrofurantoin, oral contraceptives, proguanil,
sulfasalazine, trimethoprim (usually due to worsening of pre existing folate deficiency).

Vitamin B 12 deficiency
• Pernicious anemia is a type of autoimmune disorder. This occurs due to deficiency of intrinsic
factor. The intrinsic factor helps in absorption of vitamin B 12 in stomach/ileum.
• Treatment. Parenteral vitamin B 12 supplement. Oral vitamin B 12 supplements are NOT effective in
pernicious anemia due to deficiency of intrinsic factor.
• Schilling Test. To detect pernicious anemia that caused by deficiency of vitamin B 12 . Urinary
excretion test is used to diagnose deficiency of vitamin B 12 caused by decreased vitamin B 12
absorption (lack of intrinsic factor cause pernicious anemia).

Vitamin B 12 available as oral, im/sc 100 mcg daily for 1 wk or 200 mcg weekly sc/im until Hb
normalized. The daily requirement of cyanocobalamine or hydroxycobalamine 6-9 mcg.

Vitamin B 12 . Only nutrient need gastric secretion (intrinsic factor) to be absorbed from GIT.
Vitamin B 12 deficiency cause enlargement of bone marrow, RBCs, WBCs and platelets. It effects all
proliferating cells.

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Folate Deficiency. The most often occurs in chronic alcoholics, pregnancy and drug induced folic acid
deficiency by drugs such as phenytoin, sulfonamides, methotrexate, dapsone, and oral contraceptives.
Intestinal malabsorption caused by Giardia lamblia infection.

Folic acid (folate) supplements. The daily requirement is 200 mcg. For therapy 1 mg, 5 mg is used.
In pregnancy prophylaxis folic acids 1 mg supplements should begin 1 month before conception. Folic
acid supplements in pregnancy 5 mg daily po x 10-12 wks with history of neural tubule (NTD) defect
reduce the risk of neural tubule defect. Certain medical conditions like type 1 DM, therapy with
valproic acid, carbamazepine, BMI >35 kg/m2, and malabsorption disorder.
Folinic acid (Lucovarin) is synthetic form of folate. The folate available in natural product.

Normocytic (Normochromic)
• In normocytic anemia MCV is normal.
• Due to acute hemorrhagic or RBC hemolysis due to immune or non-immune mediated.
• Examples of normocytic anemia includes hemolytic anemia, sickle cell anemia, and thalassemia.

Hemolytic anemia
Sickle cell anemia disease is an inherited disorder caused by a defect in the gene for hemoglobin.
Sickle cell anemia and thalassemia are hemolytic anemia associated with abnormal hemoglobins. Due
to poor solubility of such abnormal hemoglobins in a reduced state, semicrystalline bodies are formed
inside of RBC. These crystalline bodies are pointed and elongated inside of the cell, and rupture the
red blood cells.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency hemolytic anemia. The enzyme G6PD

necessary to maintain the reduce glutathione level (GSH) in red blood cells. This enzyme is necessary
to prevent the hemolysis. The deficiency of this enzyme may cause severe hemolytic anemia in
patients with the use of certain oxidant drugs such as primaquine, sulfonamide, nitrofurantoin,
nalidixic acid, probenecid, chloroquine, and dimercaprol. Glutathione is an antioxidant, which prevents
the oxidation of hemoglobin to methemoglobin.

The Coombs test: The coombs test is used to distinguish immune mechanism or glucose 6-phospho
dehydrogenase (G6PD) deficiency anemia. In autoimmune hemolytic anemia, coombs test is positive.
Example of drugs that cause false positive coombs test penicillin's, cephalosporin's and methyldopa.
Aplastic anemia (Total or partial destruction of the bone marrow). Reduced red blood cell and white
blood cell and platelets (thrombocytopenia) counts is decreased. Aplastic anemia is due to inadequate
production or release of myeloid stem cells.

Drugs that cause cell aplasia. Azathioprine, phenytoin, isoniazid, penicillamine, chlorpropamide,
chloramphenicol, erythropoietin, cephalosporin's, penicillin's, tetracycline's, insulin. Methotrexate,
isoniazid, quinidine, quinine, rifampicin, sulphonylureas, methyldopa, mefenamic acid, drugs with
oxidant effect on cell membrane (particularly in G6PD deficiency).

Agranulocytosis
Agranulocytosis is profound reduction of blood cells such as neutrophil, this can cause symptoms like
fever, mouth, throat ulcers and this can lead to prostration and death. Recovery usually 2 to 3 weeks
after the drug is withdrawn. Repeat exposure to causative drug is not recommended due to
sensitization.

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Drugs that can cause agranulocytosis. Antibiotics (penicillin's, cephalosporin's, cotrimoxazole,

chloramphenicol, sulphonamides), antidepressants (imipramine, clomipramine, desipramine,
mianserin), antiepileptics (carbamazepine, phenytoin), anti-inflammatory (gold, penicillamine,
lefunomide, sulfasalazine, NSAIDs), antipsychotics (chlorpromazine, thioridazine, clozapine),
antithyroid drugs (carbimazole, propylthiouracil), captopril, procainamide, and ticlopidine.

Thrombocytopenia (reduced platelets to less than 150 x 109/L). May present as easy bleeding, bruising
or purpura. Prolong bleeding time but INR remains normal. Usually occurs 7 to 10 days after drug
administered.

Stimulation of erythropoiesis: The most nutritional deficient anemia (iron, vit.B 12 and FA), have
elevated levels of endogenous erythropoietins.
Pharmacologic stimulation of RBC production using erythropoiesis stimulating agents such as Epoeitin
alpha (Eprex), and Darbepoetin alpha (Aranesp). Used in chronic renal failure, cancer chemotherapy,
HIV, hepatitis C patient receiving ribavarin.

Tips
1. Vit C& E 2. Anemia associated 3. Parietal cells in
chronic renal disease stomach
4. Vit B12 5. Intrinsic factor 6. Skin cell cancer
7. Neurotubule defect 8. thrombocytopenia 9. pernicious anemia
10 megaloblastic anemia 11 iron 12 proximal convoluted tubule
(PCT)
13 Methotrexate 14 Sulfa drugs 15 OCP
16 Phenytoin 17 Ferrous gluconate 18 Breathlessness
when lying down
19 Microcytic anemia 20 Sickle cell anemia 21 Folic acid
22 Empty stomach 23 constipation 24 ferrous gluconate
25 diarrhea 26 melena 27 vomiting
28 bronze disease, excessive 29 Deferoxamine 30 Penicillin's
absorption and storage of
iron
31 Primaquin 32 Use straw

• Anemia due to deficiency of iron ( )

• Vitamin supplements recommended in elderly ( )
• Intrinsic factors secreted from.. ( )
• Deficiency of intrinsic factors cause.. ( )
• Megaloblastic anemia is due to ( )
• Oprelvekin (interleukin 11) is approved for ( )
• Epoietin alpha are used to ( )
• Deficiency of folic acid supplements in pregnancy can cause ( )
• What is the meaning of melanoma? ( )
• Drug that gives folic acid deficiency ( )
• Vitamin that decrease oxidative degradation ( )
• Anemia in pregnancy is due to ( )
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• The most abundant metal in the body ( )

• Characteristic of both vitamin B 12 and folic acid deficiency ( )
• Which component is required for vitamin B 12 absorption ( )
• What is orthopnea? ( )
• What iron salts have higher GI absorption? ( )
• A patient G6PD deficiency, sulfa drug can cause… ( )
• Moon shaped RBC are seen in.. ( )
• The highest elemental iron present in…( )
• A patient taking methotrexate for cancer treatment, to treat bucal ulcers give…( )
• How do you take iron supplement? ( )
• Common side effect of iron supplement ( )
• Overdose symptoms of iron ( )
• Iron supplement antidote ( )
• Liquid iron is taken by using.. ( )
• What type of anemia can cause G6PD deficiency? ( )
• Drugs that induce hemolytic anemia? ( )
• What is hemochromatosis? ( )
• Excessive bleeding like menorrhea cause the type of anemia --> ( )

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12
Biochemistry
This chapter reviews basic and essentials of biochemistry topics such as, intermediary metabolism,
carbohydrates, lipids, amino acids, proteins, enzyme kinetics and porphyrins.

Question Alerts!
Common questions in pharmacy exam is to ask!
• Primary metabolism of glucose (glycolysis, glycogenesis, gluconeogenesis,
glycogenolysis).
• Proteins, and aminoacids. Examples of non essential and essential amino acids (PVT
TIM HALL)
• Example of essential fatty acids (Omega 3, 6 and 9).
• Fatty acid oxidation, formation of ketone bodies.

Catabolism. This pathway convert pyruvate (glycolysis), acetyl Co-A (fatty acid degradation), and amino
acid to carbon dioxide and water with release of energy. This cycle is strictly oxygen dependent
(aerobic).

Catabolism examples includes glycogenolysis and glycolysis.

Anabolism. This pathway forms amino acid such as aspartate and glutamate from cycle intermediates
also the porphyrin ring of the heme (hemoglobin, myoglobin and cytochrome) is formed from
intermediates cycle.
Anabolism examples includes Glycogenesis and gluconeogenesis

Fermentation. The formation of ethanol and lactate from glucose are examples of fermentation.

Carbohydrates
Classification
• Monosaccharide's (C 6 H 12 O 6 ) Examples glucose, Fructose.
• Disaccharides (C 12 H 24 O 12 ) Examples. Sucrose, lactose, and maltose
• Polysaccharides. More than two monosaccharide's. Examples. starch, cellulose
• Oligosaccharides. 2 to10 monomers.

Carbohydrate digestion and absorption: Dietary carbohydrate is digested in the mouth and intestine
and absorbed from the small intestine.

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Disaccharides (e.g. sucrose, lactose), oligosaccharides (e.g. dextrins), and polysaccharides (e.g. starch)
are cleaved into monosaccharide's (e.g. glucose, fructose).

Carbohydrate metabolism. Glycogenesis, Glycogenolysis, Glycolysis, Gluconeogenesis.

Glycogenesis (glycogen synthesis). Glycogen (glycogenesis is synthesis of glycogen from glucose. This
glycogen is stored in liver and muscle.)

Glycogenolysis (glycogen breakdown). Glucose (glycogenolysis is break down of glycogen to glucose).

Glycolysis. Glucose  CO 2 + H 2 O
Glycolysis is breakdown of glucose to water and carbon dioxide. Glycolysis occurs in the cytosol and
mitochondria in most organs of the body.

Cystosolic process
aerobic
Glucose Pyruvate

anaerobic
Lactate

Mitochondrial Process
Pyruvate Oxidative phosphorylation CO 2 + H 2 O

Under anaerobic conditions (absence of O 2 ). Glycolysis involves the conversion of glucose to lactate
(lactic acid). This can occurs in cells without mitochondria.

Under aerobic conditions (presence of O 2 ). Glycolysis involves the conversion of glucose to pyruvate
(pyruvic acid), this occurs in mitochondria.

Citric acid cycle (Krebs cycle). This citric acid cycle pathway is also known as the Krebs cycle, which
serves both breakdown and synthetic purposes, and occurs in mitochondrial compartment.

Under aerobic conditions pyruvate enters mitochondria, citric acid (Krebs cycle), where it is completely
oxidized to CO 2 +H 2 O, if the supply of O 2 is insufficient as in actively contracting muscles, pyruvate is
converted to lactate.

Mature RBC lack mitochondria, hence there is no Krebs cycle activity. In bacteria use glyoxylate cycle in
place of Krebs cycle.

The glyoxylate cycle, centers on the conversion of acetyl-CoA to succinate for the synthesis of
carbohydrates. In microorganisms, the glyoxylate cycle allows cells to utilize simple carbon compounds
as a carbon source when complex sources such as glucose are not available. The glyoxylate cycle is
absent in animals.

The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose
monophosphate shunt) For most organisms, it takes place in the cytosol. It is a process that generates
NADPH and pentoses (5-carbon surgars). There are two distinct phases in the pathway. The first is the
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oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-
carbon sugars. This pathway is an alternative to glycolysis. While it does involve oxidation of glucose,
its primary role is anabolic rather than catabolic.

Gluconeogenesis
Gluconeogenesis is the synthesis of glucose from non carbohydrate sources.
This process, which occurs primarily in the liver and kidney is the synthesis of glucose from small
noncarbohydrate precursors such as lactate and alanine.

Pyruvate
(Pyruvic Acid)
aerobic

CO2 + H2O
anaerobic
Lactic
(Citric Acid Cycle)
GLYCOLYSIS

Glycogenolysis
GLUCOSE GLYCOGEN
Glycogenesis

Gluconeogenesis

FAT & PROTEIN

Amino Acids:
The amino acids from proteins are precursor of compounds and energy source like converted to acetyl
CoA. Amino acids degradation eliminated -NH 2 - group and this converts to NH 3 and this may be toxic.
Ammonia eliminates through conversion of urea in animals. The NH 2 group is removed by
transamination and oxidative deamination to urea.

Urea cycle:
Urea is formed from NH 3 and amino (NH 2 ) group of Asp bicarbonate (HCO 3 ) in urea cycle in liver. Five
enzymes involved in urea cycle, two enzyme are in mitochondria and three enzyme involved in cytosol,
thereby the urea cycle partially occurs in mitochondria and partially in cytosol. Ammonia (NH 3 ) is
produced in all tissue, but the urea cycle is only carried out in liver. Thus, NH 3 must be transported to
liver with non-toxic form. NH 3 is converted to glutamine (Gln) which is not toxic.

20 amino acids are converted to 7 common intermediates. Those are:

Alanine, Cysteine, Glycine, Serine, Pyruvate glucogenic and ketogenic
and Threonine are degraded to intermediate
Pyruvate
α-ketoglutarate Succinyl-CoA. Glucogenic intermediate (Form
Fumarate. Oxaloacetate. glucose)
Acetyl-CoA. Acetoacetate Ketogenic intermediates (Form
ketone bodies)

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Ketogenesis or fatty acids oxidation.

It occurs when there is a high rate of fatty acid oxidation in the liver.
Three types of substances betahydroxy butyric acid (80%), acetoacetic acid (20%) and acetone (trace
amounts). These three substances are collectively known as the ketone bodies (also called acetone
bodies or acetone). Enzymes responsible for ketone bodies formation are associated with
mitochondria.

Adipose tissue Blood Liver

Lipolysis Beta
oxidiation
Triglycerides → Free Fatty Acids → FFA → Acyl CoA → AcetylCoA→
Ketone bodies
FFA= Free fatty acids

Amino acid biosynthesis products. Amino acids are not only makes proteins and also precursor of
severs products such as neurotransmitters (dopamine, nor epinephrine and epinephrine), hormones,
and porphyrines.
• Phenylalanine  Tyrosine  levodopa  Dopamine NorepinephrineEpinephrine.
• Tyrosine  Thyroxine (thyroid hormone).
• Tyrosine  Catalization by tyrosinase give phenyl 3-4 quinone than polymerization gives Melanin
(black skin pigment).
• Tryptophan  5-hydroxy tryptophan  5-hydroxy tryptamine (5HT or serotonin).
• Tryptophan  Niacin
• Histidine histidine decarboxylase produce histamine (allergic response)
• Arginine  Nitric oxide (NO) vasodilator
• Arginine  Urea
• Arginine  Creatinine
• Glutamate  catalization by glutamate decarboxylase produce Gamma amino butyric acid (GABA
neurotransmitter).

Hemoglobin. The hemoglobin is protein consist of globulin + Heme (Porphyrin + Fe3+)

Porphyrines: Amino acids are precursor of prophyrines, and these if are component of heme
biosynthesis in mitochondria and cytosol. Porphyrins are derived from succinyl-CoA and glycine.

Glycine  Porphyrine ring  Heme

There are several genetic defects in heme biosynthesis.
• Uroporphyrinogen III cosynthase deficiency, congenital erythropoietic porphyria.
• Red urine, reddish teeth, photosensitive skin, and increased hair growth.
• Ferrochelatase deficiency = erythropoietic porphyria.

Essential and non-essential amino acids

Essential amino acids "PVT TIM HALL" Non essential amino acids
Arginine, Histidine, Isoleucine, Leucine, Alanine, asparagin, Cysteine, Glutamate,
Lysine, Methionine, Phenylalanine, Glutamine, Glycine, Proline, Serine and
Threonine, Tryptophan, and Valine Tyrosine
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Arginine although it is produced but most degrade to urea.

Essential amino acids (EAAs) are the components of proteins that make them essential in the diet, of
the 20 amino acids in proteins, 10 are essential i.e. required in the diet because they cannot be
synthesized in the body. All humans require eight EAAs. Infants require histidine.
Only essential amino acids taken through diet because they are not synthesized in body in sufficient
amounts. Essential amino acids are “PVT TIMHALL“ phenylalanine, valine, tryptophan, threonine,
isoleucine, methionine, histidine (in infants), arginine (in infants), leucine and lysine.

ACID Base properties of amino acids. At all physiological pH all amino acids have both negative and
positive charge.
When pH = pKa, there is 50% ionized and 50% unionized.
Amino acids can act either as an acid or base and are defined as amphoteric or ampholytes.
Zwitter Ion: Amino acids are ionisable +ve ions as amines, -ve ions as acid. (no net charge)
pKa values indicate the pH at which the group (acid or amine) is 50% dissociated
All amino acids have two titration curves.

H 3 N(+)-CH 2 -COO(-)

Isoelectric Point. (pl) The pH at which there is no net charge on the structure.
• At a pH> pl the structure has net negative charge
• At a pH < pl the structure has net positive charge.
• Every structure has one isoelectric point but can be many pKa values.

Proteins
Proteins composed of amino acids. proteins are
formed by condensation of amino acid.
Structural role within the cell and also within
the connective tissue and skeleton of the whole
organism.

Primary structure is linear sequence of amino

acids.

each position occupied by one of 20 amino

acids and linked by peptide bonds

Secondary structure occurs with hydrogen

bonds forming between the carboxyl portion of
amino acids and the amino group of another.
Alpha helix = coiling into a helix

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Beta pleated sheet = a folded sheet as polypeptide folds back on itself.

Weak hydrogen bonds between amino and carboxyl groups and different amino acids form at regular
intervals, creating a regular structure. (Not from interactions between variable R-groups).
Not all of a polypeptide forms secondary structure in most proteins.

Tertiary structure. Three dimensional structure formed by

disulfide bonds.
• Interactions between variable R-groups forming.
• hydrophobic interactions between nonpolar amino acids
• hydrogen bonds between polar amino acids
• ionic bonds between ionic amino acids
• covalent bonds between sulfur containing amino acids.
producing the three-dimensional folded structure of most
proteins.

Quaternary structure. Separate polypeptide chains that assemble together .

aggregations of polypeptides form interactions between more than one polypeptide.

There are 20 amino acids commonly found in proteins, they are linked together by peptide bonds.
Protein is generally classified into three different categories. Simple protein, Conjugated protein and
derived protein.

Conjugated protein: Conjugated proteins are further classified on the nature of their prosthetic
groups

polypeptides + non-proteinaceous Example

Polypeptides Metals (chromoprotein) Iron in hemoglobin, colored group
Metalloprotein
Polypeptides Vitamins Enzyme cofactors
Polypeptides Nucleic acids Ribosomes
Polypeptides Carbohydrates Glycoproteins, mucins
Polypeptides Lipids Lipoproteins, lecithin,
Polypeptides Phosphoric acid Casein ovovitellin

Simple protein are naturally occurring proteins, which upon hydrolysis yield only alpha-amino acids
such as albumins, globulins, prolamines, glutelins, and albuminoids.

Derived proteins. They are formed from primary or conjugated proteins by the actions of the acid,
alkali, heat, water, enzyme or alcohol. They generally differ in physical and chemical properties from
the protein they are derived from. They are subdivided into primary derived protein (denatured
protein) or secondary derived protein.

Denaturation of proteins. A protein denaturation results in the unfolding and disorganization of the
protein structure, which does not occurs by hydrolysis.
Denaturising agents include: heat, organic solvents, mechanical mixing, strong acids or base,
detergents and ions of heavy metals such as lead or mercury. Denatured proteins are insoluble and
precipitate. Denaturation process is often irreversible.

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Globular and Fibrous proteins: Globular hemeproteins. A hemeproteins are groups of specialized
proteins that contain heme as tightly bound prosthetic groups. The most common heme proteins in
human are haemoglobin and myglobin. These proteins bind oxygen reversible. These proteins have
high affinity to carbon monoxide.

Hemoglobin complex of porphyrin ring and ferrous ion (Fe2+). Transport oxygen in blood only. Carbon
dioxides and carbon monoxide also binds with haemoglobin reversible.

Myoglobin. complex of porphyrin ring and ferrous ion (Fe2+). Transport oxygen in tissues.
Myoglobin present in heart and skeletal muscles.

Hemoglobinopathies. Example of hemoglobinopathies. Sickle cells anemia, haemoglobin C disease

(HbC) and the thalassemia syndrome.

Cell Membrane
• Composed of lipid bylayer with proteins embedded within the membrane
• Lipid bilayer- Phospholipids contain hydrophilic head (outer portions of membrane) and
Hydrophobic chains (inner portions of membrane).
• Membrane proteins functions are either transport mechanisms or as receptors.
• The extrinsic proteins bound to outer and inner portions of membrane, easily removed.
• Intrinsic protein strongly bound in the membrane, cannot easily removed. May extend
completely through the membrane.

Enzymes: Protein catalysts substance that alter the rate of a chemical reaction without itself being
permanently changed into another compound.

Fats and Lipids: Fatty Acid Synthesis. Palmitate is an end product. Associated with hexose
monophosphate (HMP) Shunt.

Lipids can be divided into five classes according to their chemical structure.
Glycolipids: Also known as cerebrosides. They are isolated from the brain. Upon hydrolysis, they yield
fatty acid, galactose and sphingosine. They are also known as galactolipids due to the presence of
galactose, such as phrenosin, and kerasin.

Sphingolipids: contains sphingosine formed from palmitoyl CoA and serine. Sphingosine forms
ceramide backbone when joined to fatty acids. The addition of sugars, sialic acid or choline phosphate
forms compounds such as cerebrosides, gangliosides or sphingomyelin found in nerve tissues and
membrane.

Phospholipids: Also known as phosphatides. They are esters that consist of fatty acid, phosphoric acids
and nitrogenous compounds, such as lecithin. These are important part of membrane.

Sterols (steroids): The sterols are alcohols structurally related to steroids. They are obtained from
plants and animals such as cholesterol and ergosterol. Steroid structures have 3 cyclohexane rings and
1 cyclopentane ring. Steroids are converted to compounds such as bile acids, vitamin D and steroidal
hormones. They are not broken down completely.

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Waxes. Waxes are defined as high molecular weight esters. They consist of monohydric alcohol and
high molecular weight of fatty acids.

Fixed oils and fats: These are esters of glycerol and fatty acids, such as olive oil. Fixed oils, such as
hard, which are solid at room temperature, are known as fat.
Lipid metabolism. Catabolism triglycerides stored in fat cells are hydrolyzed by hormone, sensitive
liposes into 3 fatty acids and glycerol.
• Fatty acids- are broken down by B-oxidation to Acetyl CoA (2Carbon Units), which enter the Kreb
cycle to complete oxidation to CO 2 + H 2 O with release of considerable energy, too rapid
breakdown of fatty acids leads to ketone bodies (Ketogenesis) as in diabetes Mellitus.
• Glycerol enters glycolysis and is oxidizes to pyruvate and via the Krebs cycle to CO 2 + H 2 O.
• Steroids may be converted to other compounds such as bile acids, vitamin D or steroidal
hormones, they are not broken down completely.

Anabolism: Biosynthesis forms fatty acids, steroids and other terpene-related metabolites.
Fatty acids are formed in the cytoplasm and unsaturation occurs in the mitochondria or endoplasmic
reticulum. Human cannot make Linoleic acid.
Terpende compounds- are derived from Acetyl CoA via mevalonate and include: Cholesterol and other
steroids, Fat-soluble vitamins (A,D,E and K) and Bile acids.

Sphigolipids- contains sphinegenine formed from palmitoyl CoA and serine. Sphingenine forms
ceramide backbone when joined to fatty acids. The addition of sugars, sialic acid or choline phosphate
forms compounds such as cerebrosides, gangliosides, or sphigomyelin found in nerve tissues and
membranes.
Phosphatidyl compounds- such as phosphatidyl choline (Lecithin), phosphatidyl serine or ethandamine
are also important parts of membranes.

Biosynthesis of lipids, regulation by insulin, glucagon, and atherosclerosis:

Cholesterol production is regulated by intracellular cholesterol concentration and by the hormones
glucagon and insulin. The rate-limiting step in the pathway to cholesterol is the conversion of (3-
hydroxy-(3)-methylglutaryl-CoA (HMG-CoA) into mevalonate, and the enzyme that catalyzes this
reaction. HMG-CoA reductase is a complex regulatory enzyme whose activity is modulated over a 100-
fold range. It is allosterically inhibited by as yet unidentified derivatives of cholesterol and of the key
intermediate mevalonate. HMG-CoA reductase is also hormonally regulated. The enzyme exists in
phosphorylated (inactive) and dephosphorylated (active) forms. Glucagon stimulates phosphorylation
(inactivation), and insulin promotes dephosphorylation, activating the enzyme and favoring
cholesterol synthesis.

HMG-CoA reductase
AcetylCoA --> B-hydroxy, B-methyl, glutaryl CoA --> --> --> Mevalonate --> Cholesterol

When the sum of the cholesterol synthesized and obtained in the diet exceeds the amount required
for the synthesis of membranes, bile salts, and steroids, pathological accumulations of cholesterol in
blood vessels (atherosclerotic plaques) resulting in obstruction of blood vessels (atherosclerosis).

Essential trace elements

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Trace element Complication associated with deficiencies

Copper Wilson’s disease (excess), leucopenia, neutropenia (deficiency), Minks’ (defect of
Cu+).
Penicillamine is used for treatment of Wilson’s disease.
Copper present in: Cytochrome oxidase
Iron The most abundant metal in body.
Deficiency of iron microcytic anemia, and hypochromic anemia
Hemochromatosis (excess of iron).
Enzyme or proteins contain iron: Hemoglobin, myoglobin, Cytochrome oxidase,
myeloperoxidase.
Zinc Children: poor growth, impaired sexual development (deficiency)
Adults: dermatitis (alcoholics).
Selenium Selenium deficiency can cause cardiomyopathy.
Chromium Impaired glucose tolerance
Molybdenum Present in xanthine oxidase enzyme which catalyzes conversion of purine to uric
acid
Iodine Deficiency of iodine may cause goiter disease

Tips
1. linolenic (Omega 3) 2. linoleic (omega 6) 3. Arachidonic
4. Arginin 5. Oxidized hemoglobin 6 HMG Co- Reductase
7. Methylated hemoglobin 8. Prostaglandin 9 Ferrous
10 Hemoglobin 11 Myoglobin 12 Cytochrome oxidase
13 Excessive phenylalanine in the 14 Tryptophan
urine
• Glycolysis occurs in?
• Glycolysis; Glucose→( )
• Glycogenesis; Glucose→( )
• Glycogenolysis; Glycogen→( )
• Gluconeogenesis: fats & proteins→( )
• Krebs cycle occurs in 
• End product of anaerobic glycolysis 
• End product of aerobic glycolysis 
• End product of amino acid (proteins) synthesis 
• Nitric oxide (NO) is a derivative of what amino acid? ( )
• Phenylketonuria (PKU) is? ( )
• Carbon monoxide has affinity to? ( )
• Carboxyhemoglobin is? ( )
• Methemoglobin is? ( )
• Iron in hemoglobin is normally what state? ( )
• Cholesterol synthesis rate limiting step is catalyzed by… ( )
• Essential fatty acids ( )
• Ecosanoids synthesis are dependent on? ( )
• The most basic amino acid ( )
• Energy storage form in body is?
• Starch is composed of?
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• Lecithins
• Sphingolipids are
• End product of purine cycle 
• All amino acids have two titration curve is due to Zwitter ion
• Isoelectric point (pl)
• At pH>pl the structure has net negative charge
• At pH<pl the structure has net positive charge

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13
Nutrition
Questions Alerts!
Common questions in pharmacy exam is to ask!
Vitamin A, D, E, K and Vitamin B deficiency symptoms
Active vitamin D3 is hormone
Essential fatty acids (omega 3 and omega 6 and omega 9)

This chapter review the important feature of the vitamins is that they generally cannot be synthesized
by mammalian cells and, therefore, must be supplied in the diet.

Canada's Food Guide, Eating well with Canada Food Guide provides evidence base information on
nutrient standards and the prevention of chronic diseases.
• Carbohydrate 55%
• Proteins 30%
• Fats <5%
• Fibre 30 g/day (vegetables, cereals etc)
• Minerals/vitamins
• Water 8 to 10 glass/day
• Salt <2 g/day

Infants nutrition.
Compendium of Therapeutic Minor Ailments (CTMA)
Motherrisk. Provides evidence-based information and guidance about safety or risk to the developing
fetus or infant, of maternal exposure to drugs, chemicals, diseases, radiation and environmental
agents.

if mother cannot breast feed to infant 3 mo. What is closest nutrition recommended?

Infants nutrition
• Formula milk (cow milk-based formula, lactose free cow milk based formula, soy protein isolate
based formula, hydrolyzed protein formula, amino acid based formula, pre-thickened formulas).
• Iron fortified formula milk (birth to 6 months)
• Vitamin D drops 400 IU/day, and not exceed 1000 IU/day (only in children who are on complete or
partial breast feeding (human milk).
• Cow milk-based formula for higher protein content.

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• Most formula milk resemble casein and whey content resemble to human milk.
• The carbohydrate sources of cow milk is lactose.
• Soy protein isolate-based formula. Free of cow milk proteins and lactose. Soy formula contain soy
isoflavones, a phytoestrogen which had been linked to reduced reproductive function.

Nutrition Allergens
• Gluten is present in wheat, rye, oat, soy, cereal.
• Milk  lactose or proteins allergy. Vitamins
• Peanut  peanut butter, oil, chocolates
• Tartrazine  Yellow coloring agent

Water soluble Fat soluble

The vitamins are of Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic Acid Vitamin A
two distinct types. (B5), Pyridoxal, Pyridoxamine, Pyridoxime (B6), Biotin, Vitamin D
Cobalamin (B12) Vitamin E
Folic acid, Ascorbic Acid (C) Vitamin K

Fat soluble vitamins absorption depends on.

• The presence of fat substance in GIT
• Hepatic function
• Bile content

Thiamine (Vitamin B 1 )
Derived from a substituted pyrimidine and thiazole, which are coupled by a methylene bridge. It is
rapidly converted to its active form thiamine pyrophosphate (TPP), and thiamine
diphosphotransferase.

Dietary requirements. If the carbohydrate content of the diet is excessive, then thiamine intake should
be required.
Deficiency. Severely reduced capacity of cells to generate energy.
• Beriberi (result from a diet of carbohydrate rich and thiamine deficiency).
• Wernicke-Korsaskoff syndrome (thiamine related disease mostly found in chronic alcoholics due to
their poor dietary lifestyle).
• Deficient in chronic alcoholic thereby take vitamin B 1 supplement.

Riboflavin (Vitamin B 2 )
• It is a precursor for coenzyme flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).
The enzyme that requires FMN or FAD as cofactor are termed flavoproteins.
• Riboflavin decomposes when exposed to visible light. This characteristics can lead to riboflavin
deficiencies in newborns treated for hyperblirubinemia by phototherapy.
Source. Eggs, milk, meat, and cereals.
Dietary requirements. 1.2 to 1.7 mg/day for normal adults.
Deficiency. It is often seen in chronic alcoholics due to their poor dietetic habits.
Sign and symptoms. Glossitis, seborrhea, angular stomatitis, cheilosis and photophobia.

Niacin (Vitamin B 3 )

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• Both nicotinic acid and nicotinamide can serve as the dietary source of vitamin B 3
• Niacin is required for the synthesis of the active forms of vitamin B 3 , nicotinamide adenine
dinucleotide (NAD+), and nicotinamide adenine dinucleotide phosphate (NADP+).
• Both NAD+ and NADP+ function as cofactors for numerous dehydrogenases. E.g. lactate and malate
dehydrogenases.
• Niacin is NOT a true vitamin in the strictest definition since it can be derived from amino acid
tryptophan.

Dietary requirements. Nicotinic acid (but not nicotinamide) when administered in pharmacological
doses of 2 to 4 g/day lowers plasma cholesterol levels and has been shown to be useful therapeutic for
hypercholesterolemia.
• Nicotinic acid therapy is not recommended for diabetics or persons who suffer from gout.
• NAD and NADP are active substances of vitamin B 3 .
• Daily requirement is min 6 mg to 45 mg (adult) min 4 mg (children).

Protein diet restriction like renal disease may cause deficiency of tryptophan. In chronic kidney disease
(CKD) protein-controlled diet (0.8-1g/kg/day) is recommended.

Deficiency. Diet deficiency in niacin (as well as tryptophan) leads to glossitis of the tongue, dermatitis,
weight loss, diarrhea, depression and dementia.
• Severe symptoms. Depression, dermatitis and diarrhea, are associated with the condition known
as PELLAGRA.
• Several physiological conditions e.g. Hartnup disease and malignant carcinoid syndrome.
• In Hartnup disease tryptophan absorption is impaired and in malignant carcinoid syndrome
tryptophan metabolism is altered resulting in excess serotonin synthesis.
• Isoniazid therapy to treat tuberculosis may lead to niacin deficiency.

Pantothenic acid (Vitamin B 5 )

• It is formed from β-alanine and pantoic acid.
• Source. Whole grain cereals, legumes, and meat.
• Deficiency. Extremely rare for it is readily available food sources.

Vitamin B 6 (Pyridoxine, Pyridoxal, and Pyridoxamine)

Biologically active form of vitamin B 6 , and pyridoxal phosphate.
Dietary requirements. During pregnancy and lactation the requirement for vitamin B 6 increases
approximately 0.6 mg/day. Therefore vitamin B 6 used for nausea & vomiting in pregnancy.
Drugs (↓) pyridoxal isoniazid for tuberculosis, and penicillamine (for rheumatoid arthritis and
cystinurias).
Diclectin (vitamin B 6 + doxylamine) is the drug of choice for the treatment of nausea & vomiting in
pregnancy (morning sickness).
Avoid vitamin B 6 with levodopa because, vitamin B 6 increases the peripheral conversion of levodopa
to dopamine thereby it gives nausea and vomiting.

Biotin
Biotin is the cofactor required by enzymes that are involved in carboxylation reactions e.g. acetyl CoA
carboxylase and pyruvate carboxylase.
Source. Found in numerous foods and also is synthesized by intestinal bacteria.
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Deficiency. Excessive consumption of raw eggs due to affinity of egg white protein, AVIDIN, for biotin
preventing intestinal absorption of the biotin.
Drugs (↓). Antibiotics (long therapy).

Cyanocobalamin (Vitamin B 12 )
• Vitamin B 12 composed of a complex tetrapyrrol ring structure (corrin ring) and a cobalt ion in the
center.
• It must be hydrolyzed from protein in order to be active. Hydrolysis occurs in the stomach, and
carried to the ileum where it is absorbed.
• B 12 as cofactor during these reactions. Catabolism of fatty acids with an odd number of carbon
atoms and the amino acids valine, isoleucine and threonine.
• Following absorption the vitamin is transported to the liver in the blood bound to transcobalamin
II.
Source. Liver, meat and dairy product.

Deficiency. Pernicious anemia is a megaloblastic anemia resulting from vitamin B 12 deficiency that
develops as a result of lack of intrinsic factor in the stomach leading to malabsorption of the vitamin
B 12 . For treatment of pernicious anemia use vitamin B 12 parenteral (IM or SC), however do not use oral
supplements.
• Vitamin B 12 malabsorption has been reported with aminosalicylic acid, slow-release potassium
iodide, colchicine, trifluoperazine, ethanol, metformin and oral contraceptives.
• All persons over 50 and elderly should get vitamin B 12 supplements of approximately 2 mcg daily.
• Elderly are achlorhydric, thereby have decreased vitamin B 12 absorption.

Oral absorption is decreased by anticonvulsants, colchicine, metformin, neomycine and

omeprazole.

Folic Acid
• A conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid
(PABA) that forms pteroic acid.
• Animal cannot synthesize PABA or attach glutamate residues to pteroic acid, thus requiring folate
intake in the diet.
• Source. Yeast, leafy vegetables, and animal liver.
• Dietary requirements. An increase in the daily intake of folate during pregnancy is needed, and
doubled by the third trimester of pregnancy.
• Deficiency. Folic acid deficiency in pregnancy can cause neural tubule defect.
• Drugs (↓). Anticonvulsants (Carbamazepine, phenytoin), oral contraceptives, methotrexate, 5-
flurouracil, sulfonamides, trimethoprin, sulfasalazine and dapsone.
• Folinic acid (Lucovarin) is synthetic form of folate.

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H2N N N
O COOH
N N N
N H Glutamyl moity
Pteridyl group
COOH
p-amino benzyl
group (PABA)

Folic acid

Ascorbic acid (Vitamin C):

Ascorbic acid is derived from glucose via the uronic acid pathway. Ascorbic acid is a good water-
soluble antioxidant. An acidifying agent used to treat overdose of base drugs.
Vitamin C required for maintenance of normal connective tissue as well as wound healing.
Hydroxylation of proline residues in collagen is the most important reaction that requires as cofactor.
Source: Citrus fruits, tomatoes, strawberries, broccoli etc.
Deficiency: Cause scurvy. Vitamin C is deficient in smokers, thereby vitamin C supplements.
Cause of vitamin C deficiency is poor diet and increased requirements, especially during severe stress
or trauma (vitamin C is readily absorbed).
Symptoms: Easily bruised skin, muscle fatigue, soft swollen gums, decreases wound healing and
hemorrhaging, osteoporosis, and anemia.

Vitamin A: With 3 active molecules. Beta carotene  retinol  retinal  retinoic acid.
Beta carotene is a precursor of vitamin A.
Rhodopsin is active form of vitamin A in vision. (11-cist retinal to 11-trans retinal)
B-carotene consist of 2 molecules of retinal linked at their aldehyde ends, also referred as provitamin
A. Very effective as antioxidant.
Overdose of vitamin A can cause toxicity. Excessive accumulation of vitamin A in the liver can lead to
toxicity, which manifest as bone pain, hepatosplenomegaly, nausea and diarrhea.

Deficiency: Xerophthalmia. Night blindness (11 cis retinoic acid) in rodhapsin pigment .
Early symptoms. Follicular hyperkeratinosis, increased susceptibility to infection, cancer, and anemia
equivalent to iron deficient anemia.
Prolonged lack of vitamin A leads to deterioration of the eye tissue through progressive keratinization
of the cornea, known as xerophthalmia. Recommended vitamin A dose 2500 IU (over dose can cause
toxicity).
Isotretinoin (Accutane) is 13-cis retinoic acid and this is oral only
Tretinoin (Retin-A) is 13-trans retinoic acid and this is topical (cream, gel and lotion) ("TTT").

Vitamin D: It is a steroid hormone. Active form is 1, 25-dihydroxycholecalciferol (Vitamin D 3 ) is derived

from ergo sterol and from 7-dehydrocholesterol (produced in the skin). In the skin 7-
dehydrocholesterol is converted to cholecalciferol and Ergocalciferol (D 2 ) is formed by UV irradiation
or ergosterol.

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Source: One liter milk fluid/day 400 IU vitamin D 3 . Person with risk for osteoporosis and taking
bisphosphonates should take 800 to 1200 IU vitamin D 3 /day. Found fish liver oil and eggs. Also
produced from skin.

Deficiency: Rickets in children and osteomalacia in adult. Rickets is characterized by improper

mineralization during development of the bones resulting in soft bones. Osteomalacia is characterized
by demineralization of previously formed bone leading to increased softness and susceptibility to
fracture. Chronic renal failure can cause deficiency of vitamin D 3 . Newborn (infant) on breast-feeding
should get vitamin D drops.

Drug (↓): Vitamin D supplement 400-800 IU daily. Excessive intake >1000 IU can lead to hypercalcemia
and then cause nephrolithisis. >75000 IU associated with osteoporosis bone resorption.

Diet
7-Dehydrocholesterol
Cholecalciferol Skin (ultraviolet)
2+
↓ [ Ca ] Liver
↑ PTH 25-OH-cholecalciferol (vit. D 2 ) Storage from of vitamin D
↓ [ phosphate]
(+) Kidney

1, 25-(OH) 2 -cholecalciferol 24, 25-(OH) 2 -cholecalciferol

(Active vit. D 3 ) (Inactive)

α-Tocopherol (vitamin E): Act as a natural antioxidant by scavenging free radicals and molecular
oxygen. Storage site of vitamin E is in adipose tissue (fatty tissues). Alpha tocopherol is the strongest
antioxidant among all tocopherols.
Deficiency: Increased intake of vitamin E is recommended in premature infants fed formulas that are
low in vitamin as well as in persons consuming a diet high in poly saturated fatty acids. Increase in red
blood cell fragility.

Vitamin K
Vitamin K 1 (Phylloquinone) is derived from green vegetables. Vitamin K 2 (Menaquinone) is produced
by intestinal bacteria. Vitamin K 3 is a synthetic menadione. When vitamin K 3 is administered. It will be
alkylated to one of the vitamin K 2 forms of menaquinone.It maintains normal levels of blood clotting
protein factors 2, 7, 9, 10, and protein C, and protein S.
Deficiency: Hemorrhagic syndrome (for infants).
Vitamin K is antidote of warfarin.

Essential fatty acids: Essential fatty acids (EFAs) are required in amounts equalling 6 to 10% of fat
intake (equivalent to 5 to 10 g/day).
15 12 9 1
COOH

Alpha-Linolenic Acid (omega-3)

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• They include -6 (n-6) fatty acids are linoleic acid (cis-9, 12-octadecadienoic acid) and arachidonic
acid (cis-5, 8,11,14-eicosatetraenoic acid) and -3 (n-3) fatty acids are linolenic acid (cis-9, 12, 15-
octadecatrienoic acid), cis-5, 8,11,14,17-eicosapentaenoic acid (EPA), and cis-4,7,10,13,16,19-
docosahexaenoic acid (DHA).
• EFAs must be provided by the diet. Vegetable oils provide linoleic acid and linolenic acid, and
marine fish oils provide eicosapentaenoic acid and docosahexaenoic acid. However, some EFAs
can be made from others. For example, the body can make arachidonic acid from linoleic acid, and
eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) acid can be partially synthesized from
linolenic acid, although fish oil is a more efficient source.

Fats (worst to best)

Trans fats > Saturated > Cholesterol > Monounsaturated > polyunsaturated (Omega).

Tips
1. Vitamin D 2 Vit B 12 3 Trans 1, 3 retinoic acid (Vit A)
4. Vitamin D3 5 ileum 6 folic acid
7. neurotubule defect 8 Vitamin A 9 1,25 dihydrocholecalciferol
Vit D 3
10 25 hydroxycholecalciferol
Vitamin D2 in liver

• What vitamin is found only in animal products? ( )

• The most common vitamin deficiency in United States and Canada ( )
• Active form of vitamin D is? ( )
• Storage form vitamin D is? ( )
• Supplement of folic acid in early pregnancy reduces? ( )
• Sun exposed skin forms the type of vitamin D is? ( )
• Retin A is topical used for wrinkles and acne is isomer of? ( )
• Vitamin A, D, E, K absorption takes place in what part of gastrointestinal tract? ( )
• All B-complex vitamin washouts from body except? ( )
• what vitamin is essential for the synthesis of nitrogenous bases in DNA and RNA? ( )
• People who do not eat from animal sources have deficiency of? ( )
• what vitamin overdose causes toxicity? ( )
• Chronic alcoholics have deficiency of? ( )
• Chronic renal disease patient should receive vitamin  ( )

Select True/False Statement

• Deficiencies in newborns treated for hyperbilirubinemia by photo therapy; Riboflavin
• Niacin is not a true vitamin. (True/False)
• Niacin; derived from the amino acid tryptophan. (True/False)
• Pellagra is due to deficiency of vitamin B 3 (niacin) (True/False)
• Pernicious anemia is due to vitamin B 12 deficiency. (True/False)
• Pteridine ring structure is present in folic acid (True/False)
• Scurvy is due to deficiency in vitamin C. (True/False)
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• β-carotenoids is precursor of vitamin A. (True/False)

• Vitamin D deficiency in children is rickets and in adults is osteomalacia.. (True/False)
• Vitamin D supplements are recommended in newborn that are on breast-feeding. (True/False)
• Folic acid supplements are now recommended for pregnant women to prevent neural tube
defects (spina bifida) in their children. (True/False)
• Omega 6 is Lenoleic acid. (True/False)
• Omega 3 is Lenolenic acid  act like aspirin  Antiplatelets. (True/False)
• Lenolenic acid mainly present in fish and walnut. (True/False)
• Vitamin E toxicity  More than 1100 units (average capsule is 400 units)  Prevent the synthesis
vitamin K coagulant factors (act as anticoagulant). (True/False)
• Severe Vitamin B 1 thiamine deficiency; Beriberi and Wernicke-Korsaskoff syndrome. (True/False)

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14
Microbiology
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Endotoxin (pyrogen) of gram negative and exotoxins gives positive organism
• Infective organism of common infections like pneumonia, traveler's diarrhea, toxic shock
syndrome, endocarditis, cellulites, meningitis, syphilis, athletes foot and warts.
• Herpes virus: HSV1, HSV2, VZV, Epstein bar, and CMV
• Hepatitis: Hepatitis A, B, C
• Influenza A and B
• HIV transmission
Fungal infections: Candidiasis (yeast), Athletes foot

Bacterial Structure
• Bacteria. Contain cell membrane and cell organs
• Bacterial nucleus: Not surrounded by cell membrane
• Bacterial ribosome are 30S, 50S, and 70S.
• Cell membrane consist of cytochrome and lipids and enzymes.
• Mesosomes convoluted invagination of mitochondria.
• Plasmid (bacterial resistant) is closed circular extra chromosomal DNA.
• Endospore = Metabolically inactive cell. Contain calcium dipicolinate (resistant to sever
environmental conditions).
• External layer = Capsule (resistant to phagocytosis)
• Cell wall = Portion external to cell membrane, osmotic protection.
• Peptidoglycan = Present in cell membrane of Gram –ve & +ve
• Mucopeptide = (protein + carbohydrate) is a peptidoglycan
• Techoic acid = Water-soluble polymer. Present in gram +ve only
• Periplasmic space = Found in gram +ve cell, between cell membrane and outer cell membrane
contains proteins.
• Outer membrane = Present in Gram –ve, phospholipid layer, embedded proteins/porins.
• Lipopolysaccharide present in Gram –ve, consist of lipid A, also known as endotoxin.
• Glycocalyx present in external layer, Slime layer, and adhesive.
• Appendages: Flagella, Pili/Fimbriae, ordinary pili or sex pili.
• Bacterial growth curve lag increase in individual size (many nutrient)
• Exponential or log is increase in population.
• Stationary division. Death (accumulate toxin, decrease in nutrient).
• Obligate aerobe. Generate H 2 O 2 , act as bactericidal.
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• Superoxide dismutase. Enzyme to neutralizes peroxide like hydrogen peroxide (H 2 O 2 ).

• Obligate anaerobe has no superoxide dismutase.
• Facultative anaerobe. Most pathogenic bacteria, can shift from fermentative to respiratory
metabolism.
• Aerotolerant anaerobes. Similar to facultative, remains fermentative.
• Capnophilic anaerobes. Require CO 2 example bacteroid fragilis (gram –ve anaerobe)
Oxygen requirement
• Obligate aerobe. Generate H 2 O 2 , it is bactericidal. Super oxide dismutase enzyme neutralizes
H2O2.
• Obligate anaerobe. No super oxide dismutase, killed by O 2 .
• Facultative anaerobe: Most pathogenic bacteria can shift from fermentative to respiratory
metabolism.
• Aerotolerant anaerobe. Similar to facultative to remains fermentative.
• Bacterial shapes. Round (coccus), rod like (bacillus), and spiral (spirochete).

• Virus
 No cell membrane and consist of DNA or RNA and proteins.
 Some viruses have single strand of DNA.
• Fungi
 Cell membrane contain ergosterol layer.
• Protozoa
 Protozoa are unicellular or single cell organisms and classified based on flagellates.
• Atypical bacteria
 Mycoplasma. Have no cell wall
 Rickettsia. Can be transmitted by ticks, mites etc.
 Chlamydia. Lack ATP synthesis.
• Mycobacterium
 Cell membrane contain mycolic acid layer.
 Acid-fast test detect mycobacteria.

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Gram +ve Gram –ve

Stain blue or purple Stain red or rose pink
Techoic acid Lipopolysaccharide (LPS) in outer membrane
Peptidoglycan layer is thick Peptidoglycan layer is thin
Exotoxin is a metabolic product Endotoxin is a metabolic product
Exotoxin is thermolabile (heat sensitive) Endotoxin is more toxic than exotoxin, destroyed at
destroyed at a temperature over 60 oC higher temperatures.
Exotoxin is a high molecular weight Endotoxin a complex structure made up of
protein. phospholipid, polysaccharides and protein.

GRAM +ve and aerobic bacteria GRAM –ve and aerobic bacteria
Gram + ve cocci Gram –ve cocci
Streptococcus (in short Strep.) NISSERIA
S. pyogenes (Group A) N. gonorrhea
S. agalactiae (Group B) N. meningitis
S. bovis (Group D) Moraxella catarhalis
S. pneumoniae Gram –ve bacilli (rods)
S. viridans Escherichia coli (E. coli)
Staphylococcus (in short Staph.) Klebsiella pneumonia
S. aureus (Coagulase +ve) Enterobacter spp.
S. saprophyticus Shigella
S. epidermidis Proteus mirabilis
Enterococcus Salmonella
Gram +ve bacilli S. typhi
Cyanobacteria diphtheriae S. enteritidis
Listeria monocytogenes
Bacillus cereus

GRAM +VE and Anaerobic bacteria Vibrio cholerae

Clostridium Pseudomonas aeruginosa
C. perfringens Pasteurella multocida
C. tetani H. influenza
C. difficile H. duceryl
C. botulinum Legionella pneumophila
Yersinia
Y. enterococolitica
Y. pestis
GRAM –VE and Anaerobic bacteria
Fusobacterium
Bacteroides
B. fragilis

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Have thick, ergosterol containing cell

Fungi walls and grow in humans as budding
yeast cells and slender tubes (hyphae).
Nystatin
Thrush, mucocutaneous infection,
Candida albicans (yeast) Clotrimazole
vulvovaginitis
Miconazole
Clotrimazole
Tinea pedis Athlete’s foot
Tolnaftate (topical)
Sporotrichosis or granulomas Abscesses (puss)
Skin, nail and hair
Dermatophytes Ringworm infections, sometimes
acquired from animals.
Allergic reactions, opportunistic Ubiquitous airborne
Aspergillus sp.
infections filamentous fungus
Present in soil and
Cryptococcus neoformans Meningitis in immunocompromised
pigeon droppings
Protozoa
Malaria. Four sp. infect man via biting Chloroquine, Mefloquine
Plasmodia sp
female anaphlex mosquito. Primaquine, Doxycycline
Low grade gastrointestinal disease:
Giardia lamblia Metronidazole
giardiasis
Entamoeba histolytica Amoebic dysentery (are infective when Metronidazole
and Giardia lamblia (intestinal swallowed, travelers diarrhea). Severe, Ciprofloxacin
protozoa) may invade and spread to the liver Cotrimoxazole
Infections causative organisms

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Bacteria
Gram +ve Cocci
Found on the skin and in the nose
Boils, and Septicemia
Staphylococcus aureus
Food poisoning Penicillin G and Penicillin V
Catalase and coagulase positive
Wound infections
Toxic shock syndrome (TSS)
Tonsillitis, Cellulites, scarlet fever, Clarithromycin
Beta-hemolytic streptococci e.g.
Septicemia may cause immune- Erythromycin
Strep pyogenes (Group A Strep:
mediated disease (e.g. rheumatic Azithromycin
GAS)
fever). Penicillin G, cloxacillin
Amoxicillin
Alpha-hemolytic Pneumonia (CAP), Otitis media, Penicillin G
Streptococcus pneumonia Meningitis, Sinusitis, Pharyngitis Clarithromycin
Azithromycin
Alpha-hemolytic Endocarditis,
Amoxicillin, Penicillin G, Clindamycin
Streptococci viridans Dental caries
Instrument contamination.
S. epidermidis
Catheter infections, UTI
Gram +ve bacilli
Erythromycin or penicillin's (to eliminate
Diphtheria (disease due to toxin
Corynebacterium diphtheria carrier state)
production)
Tetracycline
Clostridia sp.
Cl. tetani Tetanus,
Cl. perfringens Gas gangrene
Metronidazole, or vancomycin
Cl. botulinum Botulism
Cl. difficile Pseudomembranous colitis
Gram -ve cocci
Penicillin G
Meningococcal meningitis +/- shock
Ceftriaxone,
Neisseria meningitides commensal of upper respiratory
cefuroxime Na
tract
Rifampin
Cefixime
Ceftrioxone
Gonorrhea (STIs). Always Ciprofloxacin
Neisseria gonorrhea Levofloxacin
pathogenic.
Oflaxacin

Chlamydia trachomatis Chalmydia Azithromycin

Gram-ve bacilli
Uncomplicated UTI. sulfa drugs
(cotrimoxazole), Nitrofurantoin,
Urinary tract infections (90%),
E. coli Trimethoprin, fluroquinolones (cipro,
Traveler's diarrhea
Proteus sp. norfloxacin, oflaxcin)
Wound infection, sepsis. Normal
Klebsiella sp E. coli (diarrhea). Ciprofloxacin, and
inhabitants of the gut.
Levofloxacin,

Enteric fever (typhoid), food

poisoning
S. typhi Chloramphenicol (typhoid)
Most sp. are animal pathogens (e.g.
Salmonella sp Ciprofloxacin
eggs etc). S. typhi infects man only,
causes typhoid.
Dysentery (bloody diarrhea or
Shigella sp. Ciprofloxacin
shigellosis).
Aminoglycosides +/-
Nosocomial (hospital acquired) and
Ampicillin,
Pseudomonas aeruginosa opportunist infections (most rd
Ceftazidime (3 )
common S. aureus)
Clarithromycin,
Pneumonia, meningitis, Otitis media Azithromycin
Haemophilus influenza
Ampicillin, amoxicillin
Tetracycline

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Bacteria
Gram +ve Cocci
Found on the skin and in the nose
Boils, and Septicaemiae
Staphylococcus aureus
Food poisoning Penicillin G and Penicillin V
Catalase and coagulase positive
Wound infections
Toxic shock syndrome (TSS)
Clarithromycin
Tonsillitis, Cellulites, scarlet fever,
Beta-hemolytic streptococci e.g. Strep Erythromycin
Septicaemiae may cause immune-mediated disease
pyogenes (Group A Strep: GAS) Azithromycin
(e.g. rheumatic fever)
Penicillin G
Amoxicillin
Pneumonia (CAP), Otitis media,
Alpha-hemolytic Penicillin G
Meningitis
Streptococcus pneumoniae Clarithromycin
acute otitis media
Azithromycin
Alpha-hemolytic Endocarditis,
Amoxicillin, Penicillin G
Streptococci viridans Dental caries
Instrument contamination. Catheter infections
S. epidermidis
UTI
Gram +ve bacilli
Erythromycin or penicillin's (to
Corynebacterium diphtheriae Diphtheria (disease due to toxin production) eliminate carrier state)
Tetracycline
Clostridia sp.
Cl. tetani Tetanus,
Cl. perfringens Gas gangrene Metronidazole, or vancomycin
Cl. botulinum Botulism
Cl. difficile Pseudomembranous colitis
Gram -ve cocci
Meningococcal meningitis +/- shock commensal of
Neisseria meningitides Penicillin G
upper respiratory tract

nd rd
Gonorrhea (STIs) Cephalosporin's 2 and 3
Neisseria gonorrheae
Always pathogenic generations or Ciprofloxacin
Gram-ve bacilli
Urinary tract infections (90%),
E. coli E. coli (UTI); sulfa drugs
Traveler's diarrhea
Proteus sp. (cotrimoxazole)
Wound infection, sepsis. Normal inhabitants of the
Klebsiella sp E. coli (diarrhea); Ciprofloxacin
gut.
Enteric fever (typhoid), food poisoning
S. typhi Chloramphenicol (typhoid)
Most sp. are animal pathogens (e.g. eggs etc). S. typhi
Salmonella sp Ciprofloxacin
infects man only, causes typhoid
Shigella sp. Dysentery (bloody diarrhea or shigellosis) Ciprofloxacin
Amino glycosides Ampicillin,
Nosocomial (hospital acquired) and opportunist rd
Pseudomonas aeruginosa Ceftazidime (3 )
infections (most common S. aureus)
Clarithromycin,
Pneumonia, meningitis, Otitis media Azithromycin
Haemophilus influenzae
Ampicillin, amoxicillin
Tetracycline
Acid-fast bacilli
Isoniazid
Tuberculosis Rifampicin
Mycobacterium tuberculosis The most common cause of infectious death world- Streptomycin
wide Ethambutol
Pyrazinamide

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Have thick, ergosterol containing cell

Fungi walls and grow in humans as budding
yeast cells and slender tubes (hyphae).
Nystatin
Thrush, mucocutaneous infection, Clotrimazole
Candida albicans (yeast) vulvovaginitis Miconazole
Fluconazole
Clotrimazole
Athlete’s foot Tolnaftate (topical)
Tinea pedis

Sporotrichosis or granulomas Abscesses (puss)

Skin, nail and hair infections, sometimes acquired from
Dermatophytes Ringworm
animals.
Allergic reactions, opportunistic
Aspergillus sp. Ubiquitous airborne filamentous fungus
infections
Cryptococcus neoformans Meningitis in immunocompromised Present in soil and pigeon droppings
Protozoa
Malaria. Four sp. infect man via biting Chloroquine, Mefloquine
Plasmodia sp
female anopheles mosquito. Primaquine, Doxycycline
Low grade gastrointestinal disease:
Giardia lamblia Metronidazole
giardiasis.
Amoebic dysentery (are infective
Entamoeba histolytica Metronidazole
when swallowed, travelers diarrhea).
and Giardia lamblia (intestinal Ciprofloxacin
Severe, may invade and spread to the
protozoa) Cotrimoxazole
liver.
Viruses
DNA viruses
Adenoviruses Conjunctivitis, Sore throat
HSV1 and HSV2 can cause oral and
Acyclovir
Herpes viruses genital lesions. HSV1 causes cold sores
Famciclovir
Herpes simplex virus and Keratoconjunctivitis.
Foscarnet
Herpes zoster VZV can cause (Varicella: chickenpox,
Ganciclovir
Cytomegalovirus (CMV) zoster: Shingles), glandular fever,
Epstein-Bar (EB virus) Roseola infantum (sixth disease)
Hepatitis B Transmitted via blood and
Hepadnavirus. Hepatitis B Interferon alpha
body fluids and sexual contact.
Slapped cheek disease, (fifth disease,
Parvovirus: parvovirus B Can cause aplastic crises
erythema infectious).
HPV vaccine. Implicated in cancer of the cervix.
Papovaviruses: papillomavirus, Warts, cervical cancer,
Vaccine Gardasil. Quadrivalent human papillomavirus (types
Polyomavirus Hemorrhagic cystitis.
6, 11, 16, 18) recombinant vaccine.
Poxviruses Molluscum contagiosum, smallpox
RNA viruses

Orthomyxoviruses: Amantadine, Ribavirin, Rimantadine (influenza A)

Influenza A and B Influenza (flu) Neuroaminidase inhibitors. Oseltamavir (A and B)
Zanamavir (A and B).
Flaviviruses. Yellow fever, Yellow fever, chronic hepatitis
Hepatitis C
Paramyxoviruses: parainfluenza, Respiratory infections: Croup
May be severe in infants
RSV, Measles Mumps Measles, mumps
Picornaviruses: Enteroviruses (e.g. Meningitis, Common cold
poliovirus), rhinoviruses, Hepatitis (rhinoviruses) Rhino has runny nose
A Hepatitis
Reoviruses: rotavirus Gastroenteritis
Retroviruses: HIV-1, 2 AIDS, T-cell leukemia, NRTI, NNRTI
HTLV I, II Spastic paraparesis Protease inhibitors
Rhabdoviruses: rabies Rabies Zoonotic infection
Togaviruses: Rubella, German measles (Rubella),
Alpha viruses Encephalitis

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Acid-fast bacilli
Isoniazid
Tuberculosis Rifampicin
Mycobacterium
The most common cause of infectious death world- Streptomycin
tuberculosis
wide Ethambutol
Pyrazinamide
Dapsone
Mycobacterium leprae Leprosy
Rifampicin
Spirochetes
Syphilis (STIs) (genital ulcers or chancres), single
large ulcer, painless.
Penetrate through broken skin or mucus membrane Penicillin G
Treponema pallidum
usually through sexual contact. Doxycycline
Genital herpes ulcers are often multiple, small and
painful.
Lyme disease.
Borrelia burgdorferi Tick born infection causing, rash, arthralgia and Tetracycline
neurological signs. (bull eye rash).

Acute otitis externa. The most common etiology of acute otitis externa is bacterial infection. The
microorganism P. aeruginosa (20-60%) and S. aureus 10-70%. Antibiotics aminoglycosides are active
against both bacteria.

Tips
Viruses
DNA viruses
Adenoviruses Conjunctivitis, Sore throat
HSV-1 and HSV-2 can cause oral and
Herpes viruses genital lesions. HSV-1 causes cold Acyclovir
Herpes simplex virus sores and Keratoconjunctivitis. Famciclovir
Herpes zoster VZV can cause (Varicella: Foscarnet
Cytomegalovirus (CMV) chickenpox, zoster: Shingles), Ganciclovir
Epstein-Bar (EB virus) glandular fever,
Roseola infantum (sixth disease)
Hepatitis B Transmitted via blood
Hepadnavirus: Hepatitis B Interferon alpha
and body fluids and sexual contact.
Slapped cheek disease, (fifth
Parvovirus: parvovirus B19 Can cause aplastic crises
disease, erythema infectious)
Papovaviruses: papillomavirus, Warts, cervical cancer,
Implicated in cancer of the cervix. Vaccine Gardasil
Polyomavirus Hemorrhagic cystitis.
Poxviruses Molluscum contagiosum, smallpox
RNA viruses
Neuroaminidase inhibitors: Oseltamavir (A and B)
Orthomyxoviruses:
Influenza (flu) Zanamavir (A and B)
Influenza A and B
Amantadine, Ribavirin, Rimantadine (influenza A)
Yellow fever, chronic hepatitis
Flaviviruses: Yellow fever, Hepatitis C
Paramyxoviruses. parainfluenza, RSV, Respiratory infections: Croup
May be severe in infants
Measles Mumps Measles, mumps
Meningitis, Common cold
Picornaviruses. Enteroviruses (e.g.
(rhinoviruses) Rhino has runny nose
poliovirus), rhinoviruses, Hepatitis A
Hepatitis
Reoviruses. rotavirus Gastroenteritis
Retroviruses. HIV-1, 2 AIDS, T-cell leukemia, NRTI, NNRTI
HTLV I, II Spastic paraparesis Protease inhibitors
Rhabdoviruses. rabies Rabies Zoonotic infection
Togaviruses. Rubella, German measles (Rubella),
Alpha viruses Encephalitis

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Find answers for the tips from the following table:

1. S. pneumonia 2. Chlamydia trachomatis 3. Pseudomonas aeruginosa
4. S. aureus 5. Treponema pallidum 6. Corynebacterium
7. E.coli 8. H. pylori 9. Borrelia burgdorferi
10. Haemophilus 11 M. catarhalis 12. Group B Strep
influenza
13. Herpes simplex 14. Cytomegalovirus 15. Rubella
virus
16. Herpes zoster 17 Influenza A& B 18. N. meningitis
19. Eptein barr 20 Shigella 21. Compylobacter jejuni

• E. coli is classified as? 

• Beta hemolytic bacteria example is? 
• Toxic shock syndrome is caused by? 
• Lyme disease is caused? 
• Techoic acid is present in? 
• Encephalitis is? 
• Chlamydia neonatrum (C. trachomatis) is? 
• Non gonococcal infections that cause UTI are?
• Diphtheria is caused by? 
• Syphilis is caused by? 
• Antrax is caused by? 
• What bacteria catalase degrades H 2 O 2 ? 
• Examples of live attenuated vaccines?
• Example of killed vaccine -->
• Viral diarrhea is caused by 
• The most common cause of community acquired pneumonia ( )
• The most common cause of subacute endocarditis ( )
• The causative organism of syphilis ( )
• The causative organism of lyme disease ( )
• Tick born infection (lyme disease)
• The causative organism of bacterial diarrhea ( )
• The causative organism of otitis externa ( )
• The most common pathogen isolated from middle ear ( )
• Infection when aspiration of ear is performed. ( )
• The most common cause of bacterial meningitis ( )
• The most common cause of encephalitis ( )
• Example of gram +ve bacilli ( )
• The causative organism of sinusitis ( )
• The causative organism of nosocomial (hospital) infections ( )
• A types of herpes virus include,( )
• Causative organism of shingles ( )
• Causative organism of seasonal flu ( )

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15
Cell and Molecular Biology
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Cell and cell organs
• Nucleic acids DNA and RNA bases, nucleotide (phosphate, sugar and base).
• Complimentary base pair (A-T and C-G).
• Transcription (DNA to mRNA) and translation (mRNA to rRNA) in protein synthesis.
• Sequence of protein synthesis DNA --> mRNA --> tRNA --> rRNA --> protein synthesis.
• DNA recombination methods and role of plasmid. What is cDNA?
• What is gene therapy? Antisense technology
• Cloning?

This chapter reviews basics of chromosomes, gene, nucleic acids, DNA structure and functions, replication,
Mutations and recombination. RNA structure and functions, transcription from DNA and translation to
synthesize proteins. Also review topics such as recent development of gene cloning and genetic engineering.

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Prokaryotic Eukaryotic
Primitive nucleus (no nuclear membrane) Have nucleus
Large single DNA molecule Animal: no cell wall but cell membrane
Contain cell wall (rigid): covalently bonded short No chloroplast
chains of amino acids. Yes mitochondria
Cell wall contain murein (polysaccharide chain) Plant yes cell wall
NoChloroplast Yes chloroplast
No mitochondria (cell membrane)
Present in bacteria Present in: Animal, plant, fungi, parasites, algae, and
protozoa
Bacteria are reproduced by type of cell division called
binary fission.

Cell organs compose of a number of tissues, and each tissue composes of cells of the same type. The
individual cell is the minimal self-reproducing unit in all-living species. It performs two types of
functions, such as performs chemical reactions necessary to maintain our life. The second is passes the
information for maintaining life to the next generation.

Since the cell is the vehicle for transmission of the genetic information in all living species, it needs to
store the genetic information in the form of double-stranded DNA.

The cell replicates its information by separating the paired DNA strands and using each as a template
for polymerization to make a new DNA strand with a complementary sequence of nucleotides. The
same strategy is used to transcribe portions of the information from DNA into molecules of the closely
related polymer, RNA. The RNA is the intermediate between DNA and protein and it guides the
synthesis of protein molecules by the complex machinery of translation, i.e. the ribosome. The
resultant proteins are the main catalysts for almost all the chemical reactions in the cell. In addition to
catalyst, proteins are performing also building block, transportation, signalling etc.

Cell Organs
Endoplasmic reticulum (ER). It is a series of membranes extending throughout the cytoplasm of
eukaryotic cells. Cytochrome P450 present in endoplasmic reticulum.
• Rough endoplasmic reticulum helps in protein synthesis.
• Smooth endoplasmic reticulum helps in lipid synthesis, this does not contain ribosome.

Golgi body (golgi apparatus). Series of flattened sacs. Synthesize the cell’s proteins and lipids.
Lysosomes. Drop like sac of enzymes in the cytoplasm. Help digestion within cells.

Mitochondria. (power house of the cell). It releases energy in the form of ATP.

Chloroplast (chlorophyll). It is normally present in green plants. Its principal function is to absorb
energy from the sun.

Vacuoles
• They are big, fluid like structures, and may occupy more than 75% of the plant cells.
• Store nutrients as well as toxic wastes.

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• Flagella. It exists as single and it helps bacteria to move.

• Cilia. It exists as numerous and it helps bacteria to move.

Centrosomes: Microtubule does cell division or formation spindle apparatus during cell division.

Peroxisomes: contains enzymes that produces and decomposes hydrogen peroxides.

Chromosome, Gene and Genome

• Genome. The genome of an organism is its complete set of DNA. All the genetic information in an
organism is referred collectively as a “genome”.

Fig 16.2

Chromosome.
The 3 billion bases of the human genome are not all in one continuous strand of DNA. Rather the
human genome is divided into 23 separate pairs of DNA, called chromosomes. Chromosomes are
structures within the cell nucleus that carries genes. A chromosome contains a continuous molecule of
DNA which is wrapped around histones. Human has 22 pairs of autosomes and 1 pair of sex
chromosome, hence make up to 23 pairs of chromosomes. Autosomes are non-sex determining
chromosomes, while sex chromosomes are X and Y chromosome. Male will have XY sex chromosomes,

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whereas female will carry XX sex chromosomes. The collection of chromosomes in an individual is
called karyotype. For example, the typical male karyotype has 22 pairs of autosomes, one X and one Y
chromosome.

Gene Expression
A gene is a DNA sequence that encodes a protein or an RNA molecule. Each chromosome contains
many genes, i.e. the basic physical and functional units of heredity. Each gene exist in the particular
position of particular chromosome. In human genome, it is expected that there are 30,000 to 35,000
genes. In prokaryotic genome, one gene is corresponding to one protein. Whereas, in eukaryotic
genome, one gene can corresponds to more than one protein because of the process called as
“alternative splicing”.

Nucleotide structure. Consist of 3 units that is base, sugar and phosphate

Nucleic acid (DNA and RNA). Nucleotides are the building blocks of all nucleic acid molecules (such as
DNA and RNA). These structural units consist of three essential components, i.e.
• A pentose sugar deoxyribose (in DNA) and ribose (in RNA).
• Phosphate (bound to the 5’ carbon)
• Base (bound to the 1’ carbon), nitrogenous base. For the structure of nucleotides (in DNA),

Forms of Nucleotides
• Nucleotides can have 1, 2, or 3 phosphate groups. Monophosphate nucleotides
• have only 1 phosphate, which are the building blocks of DNA. Diphosphate
• nucleotides have 2 phosphate groups and triphosphate nucleotides have 3 phosphate
• groups, which are used to transport energy in the cell.

There are two chemically different nucleic acids deoxyribosenucleic acid (DNA) and Ribonucleic acid
(RNA).

Nitrogen Bases

Pure As Gold Purine Bases Pyrimidine

Adenine (A) Cytosine (C) CUT Py

Guanine (G) Uracil (U)
Thymine (T)
DNA RNA
Adenine (A) Adenine (A)
Cytosine (C) Cytosine (C)
Guanine (G) Guanine (G)
Thymine (T) Uracil (U)
Double stranded Single stranded
2-Deoxyribose Ribose
Pairs of purine with pyrimidines formed by hydrogen bonds. When strands base pair, they are said to
be complementary.
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• A pairs with T (2 hydrogen bonds)

• G pairs with C (3 hydrogen bonds)
• A pairs with U (DNA-RNA hybrid)

• Purine can form 2 hydrogen bonds

• Pyrimidine can form 1 hydrogen bond.

Mutations. If complimentary pair incorrectly compliments other than A to T and G to C can result into
mutations. There are 3 possible mutations like purine to purine, pyrimidine to pyrimidine and purine
to pyrimidine.

Deoxyribonucleic acid (DNA). The molecule that carries the genetic information for most living
systems. DNA is present in chromosomes of eukaryotic organisms, mitochondria, chloroplast of plants.
Prokaryotes are single-celled organisms with no nuclei (e.g. bacteria). They have no distinct nuclear
compartment to house their DNA and therefore the DNA swims within
the cells. Eukaryotes, on the other hand, are organisms whose cells contain a nucleus surrounded by
cytoplasm which is contained within a plasma membrane. The DNA locates within the nucleus.
Eukaryotes are organisms with single or multiple cells, for example, plant and animal.

Prokaryotic organism, which does not have nucleus but contain single chromosome. The DNA is
present in single chromosome of prokaryotic organism.

Structure of DNA. Double helix a term often used to describe the configuration of the DNA molecule.
The helix consists of two spiralling strands of nucleotides (a sugar, phosphate and base) joined
crosswise by specific paring of the bases and 3,5-phosphodiester bonds.

Some viruses contain single stranded DNA.

There are proteins associated with DNA present in eukaryotic nucleus, these proteins referred as
nucleoproteins. In prokaryotic this protein present in DNA complex present in neucleoid
The DNA molecule consists of four bases Adenine (A), Cytosine (C), Guanine (G), Thymine (T)
A sugar-phosphate backbone, arranged in two connected strands to form a double helix.

Complementary DNA (cDNA). DNA synthesized from a messenger RNA rather than from a DNA
template. This type of DNA is used for cloning or as a DNA probes for locating specific genes in DNA
hybridization studies.

Ribonucleic acid (RNA). Nucleotide structure for RNA. Similar to the nucleotide of DNA, the nucleotide
for RNA also has Phosphate and Base. The only difference is that the nucleotide here has Ribose Sugar,
instead of deoxyribose in the DNA nucleotide. The ribose has an extra OH group at 2’, which is
different from the H group at the same place of deoxyribose. That’s why we call these two different
things “ribonucleic Acid” and “deoxyribonucleic acid” one is with the OH group, which contains the
“O” molecule, yet the other one without.

RNA Polymerases. Theses enzyme helps in synthesis of rRNA, tRNA and mRNA.

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There are 3 types of types of RNA based on their functions.

• Ribosomal RNA (rRNA). normally synthesize ribosome 80% of total RNA. The rRNA is present in
ribosome in cell.

• Transfer RNA (tRNA). 15% of total RNA. Each tRNA amino acid carries the specific amino acid to
the site of protein synthesis. Each tRNA molecule contain anticodon that generally recognizes all
the codons on mRNA.

• Messenger RNA (mRNA). 5% of total RNA. mRNA carries the genetic information from DNA to
cytosol for protein synthesis.

Codon
• The codon are present in the messenger RNA (mRNA), they are Adenine (A), Guanine (G), Cytosine
(C), Uracil (U). These four nucleotide bases produce three base codons. There are 64 different
combinations of these bases. Sixty one of 64 codons normally produce 20 common amino acids.
However, there are 3 codons UAG, UGA and UAA, do not produce amino acids.
• The following codon do not code for amino acids, they are known as stop, nonsense or
termination codons. When one of the codons appears the synthesis of peptide chain is stopped.

Gene transcription and translation process

Translation
Occurs in the cytoplasm Post-translational Modification
at the ribosome and (including glycosylation,
involves mRNA and tRNA phosphorylation, and
Transcription
sulfatation.

Protein Protein

DNA --------------------- mRNA  tRNA  rRNA  Protein synthesis

Step 1. Transcription  DNA 

Important concept!
mRNA
1) What step comes first in protein synthesis?
Step 2. Translation  mRNA  2) Anticodon is present on? tRNA
tRNA. 3) Making mRNA from DNA is called? Transcription
4) Making DNA from mRNA is? Reverse Transcription
Transcription. This is first step in cell (retrovirus)
protein synthesis, during this 5. Antisense therapeutic agents target mRNA
process information from DNA
copied to mRNA.

Translation. This is second step in cell protein synthesis. The protein synthesis occurs in
ribosome’s. During translation information from mRNA is brought to ribosome’s by tRNA. This
will determine the sequence of amino acids and protein synthesis.
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Reverse transcription: This begins when the viral particles (retrovirus) enters the cytoplasm of target
cell. Reverse transcriptase is an enzyme used to generate complementary DNA (cDNA) from an RNA
template.

Introns and exons: The coding region of an eukaryote’s gene is different from that of a prokaryote. For
Eukaryotes, each gene contains introns and exons. Intron is a segment of gene situated between
exons. It is not responsible for the coding of protein. So the introns will be ultimately spliced out of the
mRNA. And exon is a nucleotide sequence in DNA that carries the code for the final mRNA molecule
and thus defines the amino acid sequence during protein synthesis. The process of removing the
introns for the mRNA sequence is called RNA splicing. This process is done with the help of
spliceosomes. Though the Introns seem “useless”, it is quite
amazing that in eukaryotes, each gene can have many introns, and each intron may have thousands of
bases. Introns in eukaryotic genes normally satisfies the GT-AG rule, that is intron begins with GT and
ends with AG. Introns can be very long.

Plasmid is extrachromosomal substance of DNA. Plasmids are often used for DNA recombination and
cloning.

Restriction Endonuclease Enzymes. Restriction enzymes or restriction endonuclease is a class of

bacterial enzymes. They are DNA cutting enzymes, which recognize certain point, called restriction
site, in the double-stranded DNA with a specific pattern and break the phosphodiester bonds between
the nucleotides. Such process is called digestion. Naturally, restriction enzymes are found and isolated
from various bacterial species, which are used to break foreign DNA to avoid infection or disable the
function of the foreign DNA.

Restrictive endonuclease or restriction enzyme: Enzyme that breaks DNA in a specific site in the
interior of molecule. There are two types of restrictive enzymes lyase and lygase. The lyase split the
DNA on specific site. Lygase is the joining of DNA on specific site.

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Cloning. Given a piece of DNA X, the process of duplicating it into many pieces is called
cloning. The basic steps involve:

1) Insert X into a plasmid vector with antibiotic-resistance gene and a recombinant DNA molecule is
formed. Plasmids and DNA fragments must have compatible RE ends for ligation by T4 DNA ligase. A
linear product of DNA and the linearized plasmid is firstly formed, followed by the joining of the
opposite ends to form a circular product.

rDNA. or recombinant DNA molecules formed by lab methods of genetic recombination (molecular
cloning).

2) Insert the recombinant into the host cell (usually, E. coli). This makes use of a chemical based
transformed method, where the bacterial cells are made “competent” to take up foreign DNA by
treating with calcium ions. After the recombinant DNA molecules are mixed with the bacteria cells, a
brief heat shock is applied to facilitate uptake of DNA.

3) Grow the host cells in the presence of antibiotic. Note that only cells with antibiotic resistance gene
can grow. Note that when we duplicate the host cell, X is also duplicated.

4) Select those cells contain both the antibiotic-resistance genes and the foreign DNA X. Some cells
only contains plasmid vector but without the foreign DNA due to unsuccessful ligation in step 1. The
cells with foreign DNA X can be correctly selected by the complementation of beta-galactosidase, in
which the correct colony will show blue color.

5) Kill them and extract X.

Genetic Diseases. Hemophilia, sickle cell anemia, cystic fibrosis.

Gene therapy: Gene therapy cures genetic diseases such as cystic fibrosis, sickle cell anemia, and
hemophilia, in which defected genes are identified and altered or by altering gene expression to

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prevent or cure genetic diseases and cancers, ADA deficiency (adenosine diaminase deficiency), this
cause autosomal recessive metabolic disorder that cause immunodeficiency.

Apoptosis: In normal component of cell regulation, the suppressor gene (tumor suppressor gene),
arrest replication of a cell with damaged DNA until the DNA is repaired. Failure to repair DNA and
resume normal function will result in programmed cell death, is referred as apoptosis. In Gene therapy
tumor suppressor genes are inserted into tumor lines to stimulate apoptosis killing the tumor cells.

Genetic diseases. Hemophilia

• Hemophilia. This is a genetic disease often associated with X chromosome only. Thus men can
hemophilic or no hemophilic, however there is no carrier in men.
• Hemophilia causes slow blood clot formation.
• There are two types of hemophilia, that is type A and B.
• Hemophilia type A is due to deficiency of clotting factor 8 (antihemophilic factor).
• Hemophilia type B is due to deficiency of clotting factor 9 (Christmas factor).

Tips
Select answers from the following table
1. plasmid 2. lygase 3. lyase
4. gene 5. transcription 6. nucleotides
7. Uracil 8. adenine 9. guanine
10 hemophilia 11 genome 12 Intron
13 A DNA sequence of specific organism.
• What are the building blocks of all nucleic acid molecules are? ( )
• Examples of Purine bases ( )
• Examples of Pyrimidine bases ( )
• Base found only in RNA ( )
• All the genetic information in an organism is referred collectively as…( )
• DNA sequence that encodes a protein or an RNA molecule is a ( )
• This is the first step in cell protein synthesis ( )
• A segment of gene situated between exons is ( )
• Split the DNA on specific site ( )
• Joining the DNA on specific site ( )
• Small circular, extra chromosomal DNA molecule called….( )
• This is a genetic disease often associated with X chromosome only. ( )
• What is plasmid, except?
• What is genome?  Genome (DNA library), complete genetic information of one species.

Select True/False Statements

• Prokaryotes  Have cell membrane. (True/False)
• Eukaryotic  animal cell have no cell wall (True/False)
• Nucleotide  base + sugar + phosphate (True/False)

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• DNA bases  A, C, G and T (True/False)

• RNA bases  A, C, G and U (True/False)
• Complimentary bases  A-T, G-C or A-U (True/False)
• Transcription is  DNA to mRNA (True/False)
• Translation is  mRNA to tRNA (True/False)
• cDNA is  complementary DNA that produced from mRNA (True/False)
• Anticodons are present on  tRNA (True/False)
• The Largest type of RNA? r-RNA (80%) (True/False)
• The Smallest type of RNA? m-RNA (5%) (True/False)
• Single strand DNA is present in? Some virus (True/False)
• RNA polymerase I make? m-RNA (True/False)
• Haploid  single chromosome (True/False)
• Daploid  double chromosome (True/False)
• DNA transferase catalyzes the transfer of various groups such as phosphate and
• amino groups. (True/False)
• DNA hydrolase’s = hydrolyses various substances. (True/False)
• DNA lyase = catalyzes the removal of various functional groups other than the process of
hydrolysis. (True/False)
• DNA isomerase’s = catalyzes various isomerisation's (True/False)
• Reverse transcriptase found in some viruses, they are referred as retrovirus, is an RNA dependent
DNA polymerase. This enzyme requires an RNA template to direct the synthesis of new DNA.
Retrovirus : Virus that contain reverse transcriptase enzyme. Example. HIV utilizes this enzyme to
replicate their RNA genome. (True/False)
• Hapten is a low molecular weight compounds that act as immunogens after chemically complexing
to a larger molecule or cell surface. (True/False)

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16
Pharmacogenetics
Pharmacogenetics search for genetic variations that lead to individual differences in drug response.
e.g. examining the influence of carvedilol a beta blocker gene on blood pressure.

Pharmacogenomics refers to entire spectrum of genes like e.g. study examines the interactions
between CYP 450 and beta 1 , beta 2 , and alpha 1 receptors effects on gene that beta blocker effects.

The pharmacogenomics is integration of pharmacology and genetics. The study of pharmacogenomics

allows to design and develop drugs that are customized to each person’s genetic mark up. The
pharmacogenomics also utilized to study cytochrome enzymes that are responsible for drug
interactions.

Human genome. Mapping the entire sequence of human gene. The human genome contains
approximately three billion nucleotides bases, which code for approximately 20,000 to 25, 000
protein-coding genes. Most nucleotides base pairs are identical from person to person, with only 0.1%
contributing to individual differences. A gene is a series of codons that specifies a particular protein.

Genetic variations. A genetic variation occur as either rare defects or polymorphism. Polymorphism
are defined as variations that occur at a frequency of at least 1% in the human population. Example
the gene encoding cytochrome CYP450 enzymes CYP2A6, 2C9, 2C19, 2D6 and 3A4 are polymorphic.

Single nucleotide polymorphism (SNP) occurs when one base pair of nucleotide replaces another. A
single base differences that exist between individual. This is the most common genetic variation in
DNA.

To perform pharmacogenetics, the first step is detailed analysis of patient list of single nucleotide
polymorphism.

Defective splicing. In which an internal polypeptide segment is abnormally removed, and the ends of
the remaining polypeptide are joined.

New drugs that are developed based on pharmacogenetics is Gleevec (ST1-571) inhibitor of
translocation created enzymes used to treat leukemia.

Individual variability in drug therapy.

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The required daily dose of warfarin for inhibition of thrombosis and embolism in many disease
conditions varies up to 20-30 fold from patient to patient. Therefore frequent blood coagulation
testing in patient receiving warfarin therapy is mandated to achieve safe and effective
anticoagulation's.

The clinical use of statins to treat high cholesterol is large and dose dependant variations in drug
efficacy and drug safety. Study suggest the genetic polymorphism of HMG coreductase and drug
transporter which regulates hepatic uptake or efflux of statins and statin metabolites contributes to
the variability efficacy and the side effects of cholesterol lowering drugs.

Tips
• What is pharmacogenetics 
• Pharmacogenetics 
• The study which allows to design and develop drugs that are customized to each person’s
genetic mark up ( )

References. Made especially for you: pharmacogenomics and pharmacy practice, CPJ. Jan
2008 vol. 141, No.1

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17
Immunology and
Immunizations
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Immune cells response (B cell (Humoral immune response) and T cells (Cell mediated
immune response)
• Immunoglobulin's (IgE asthma and anaphylactic reaction)
• Mechanism of inflammation (bacterial infections neutrophil and viral infections
lymphocytes).
• Mechanism and Types of hypersensitive reactions (poison ivy, Hoshimoto, Montaux test,
anaphylactic reactions).
• Autoimmune diseases (type 1 DM, RA, SLE)

THE ORGANS OF THE IMMUNE SYSTEM

The organs of the immune system are stationed throughout the body. They are known as
lymphoid organs because they are concerned with the growth, development, and deployment of
lymphocytes, white blood cells (WBC) that are key operatives of the immune system.

LYMPH NODE. Lymph nodes are small, bean-shaped structures that are laced throughout the
body along the lymphatic routes. Lymph nodes contain specialized compartments where immune
cells congregate, and where they can encounter antigens.

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CELLS OF THE IMMUNE SYSTEM

Stem Cells

MYELOBLASTS Lymphoblasts Monoblasts Proerythroblasts Megakaryoblasts

Basophils Monocytes
Erythrocytes Megakaryocytes
Neutrophils (Red blood cells)
PLATELETS

Eosinophils Lymphocytes

B Cells T Cells

Cytotoxic T Suppressor T
Plasma
Cell Cell
Cells
Helper T Cell
B lymphocytes and T lymphocytes are primary cell of specific immune response.
Antibody or immunoglobulin (Ig)
Humoral immune response (B cells immunity)
Acquired immunity (immunity that is NOT inherited) is humoral immunity associated with
antibody production.

Cells involved in the immune system. White blood cells (WBC) or leukocytes are two types,
polymorphonuclear leukocytes (granulocytes) and mononuclear leukocytes without granules in
their cytoplasm. The polymorphonuclear leukocytes (granulocytes) Neutrophils, Eosinophils and
Basophils

• Normal range of white blood cells are 4000 to 11000/cmm

• Lymphocytes. About 30% of white blood cells are lymphocytes.
• Neutrophils: About 60% of white blood cells are neutrophil.
• Monocytes: About 8% of white blood cells are monocytes

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The mononuclear leukocytes without granules in their cytoplasm are Monocyte and Lymphocyte
(T-lymphocyte. Helper T-cell, Cytotoxic T-cells and Suppressor T-cells), B-lymphocytes and
natural killer cells.

Neutrophil
• Most abundant WBC.
• Not only phagocytes but also granulocytes
• Uses its prepackaged chemicals to degrade the microbes it ingest
• ↑ in number of neutrophil indicates bacterial infection.

Eosinophils
• Play a role in defending against parasitic worms. They secrete their granule contents onto
worms, which helps kill them.
• ↑ in eosinophils indicates parasite infection.

Basophils
• Smallest circulating granulocytes.
• Discharge the contents of their granules, releasing a variety of mediators such as histamine,
serotonin, prostaglandins, and leukotriene, which leads to inflammation and other symptoms
associated with and infections.

Erythrocytes. O 2 and CO 2 transport

Neutrophil: Immune defense (phagocytosis)
Eosinophil: Defense against parasites
Basophil: Inflammatory response (asthma)
Monocyte: Immune defenses (precursor of tissue macrophage)
B-lymphocyte: Antibody production (precursor of plasma cell)
T-lymphocyte: Cellular immune response
Platelet: Blood clotting
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LYMPHOCYTES. The LYMPHOCYTES are a type of white blood cells found in the blood and many
other parts of the body. TYPES OF LYMPHOCYTES INCLUDE B cells, T cells, Natural killer cells

B CELLS: B CELLS have thousands of identical antibodies in their membranes that allows them to
bind chemically to a small group of chemically related antigen.

VIRGIN B CELLS: never respond to an antigen since they release into the circulation from bone
marrow. Their membrane antibodies are of the immunoglobulin M and D (Ig M and Ig D).

MEMORY B CELLS: are derived from cell division form another B cell that has responded to an
antigen, Their membrane antibodies are Ig A, Ig E, Ig G

B CELLS (B lymphocytes) mature into plasma cell that secrete antibodies (immunoglobulins), the
proteins that recognize and attach to foreign substances known as antigens. Each type of B cell
makes one specific antibody, which recognizes one specific antigen.

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Classes of ANTIBODIES (Immunoglobulins, Ig). Antibodies respond to antigens by latching on to,

or binding with, the antigens. Specific antibodies match specific antigens, fitting together much
the way a key fits a lock.

Ig A 10%, Ig A1 and Ig A2, present in saliva, tears, urine, and external body fluids.
Ig D Less than 1%, Functions not well understood.
Ig E 1% located on the cell surface of blood basophils and on connective tissue mast cells to
trigger the secretion of inflammatory mediators from these cells in the presence of specific
antigen. IgE mediates allergic reactions (asthma).
Esinophils and basophils have IgE antibodies receptor.
Serum half is 2 to 3 days. When this bound mast cells, the serum half-life could be several
months. Ig E levels increased in allergic reactions.
Ig G 70%, most common (abundant) of all Ig’s found in all body fluids. This is secreted at the end
of primary immune response and during memory responses. IgG 1 to IgG 4 , and can cross
placenta.
IgM 20% IgM is the most potent activator of all immunoglobulins.
IgM1 to IgM2. First immunoglobulin produced in body.

Structure of immunoglobulin's

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Ig A
Ig A is secreted during memory response, this accounts for 10% of serum immunoglobulins. It is
secreted across mucosal surfaces into gastrointestinal, respiratory, lachrymal, mammary, and
genitourinary secretions. Where this protects mucosa from colonization of pathogen (Bacteria)
and other microorganisms.
SERUM HALF LIFE IS ~ 5 DAYS.
Subclass: IgA1 and IgA2
Ig G
Ig G is the predominant immunoglobulin, (~ 70%). This is secreted at the end of primary immune
response and during memory responses. It diffuses from blood into other extra cellular fluids,
particularly in inflamed vasculatures, and it crosses the placenta to enter the fetal circulation.
SERUM HALF LIFE IS 25-35 DAYS.
Subclass: IgG1 – IgG4
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Ig E
This accounts for ~ 1%.
This binds to Ig E receptors located on the cell surface of blood basophils and on connective tissue
mast cells to trigger the secretion of inflammatory mediators from these cells in the presence of
specific antigen. IgE mediates allergic reactions (asthma).
SERUM HALF IS 2 to 3 DAYS. When this bound mast cells, the serum half life could be several
months.
Ig M
It does not leave the blood in significant amount because of it PENTAMERIC STRUCTURE (molecular
size 900,000 daltons). This accounts for ~ 20%. Serum halflife 9 to 11 days.
IgM is the most potent activator of all immunoglobulins.
Subclass: IgM1 and IgM2

Ig D
Accounts for less than 1%. Has no known function.

T CELLS
T cells contribute to the immune defenses in two major ways. Some help regulate the complex
workings of the immune system, while others are cytotoxic and directly contact infected cells and
destroy them. Chief among the regulatory t cells are "helper/inducer" t cells. They are needed to
activate many immune cells, including b cells and other t cells. Another subset of regulatory t cells
acts to turn off or suppress immune cells.

Cytotoxic t cells help rid the body of cells that have been infected by viruses as well as cells that
have been transformed by cancer. They are also responsible for the rejection of tissue and organ
grafts.

THYMUS GLAND: T cell do not enter the circulation directly from bone marrow. But first enter the
thymus gland to mature. Most developing T cells die in thymus gland.
VIRGIN T CELLS: Release from thymus to circulation are virgin T cells.
MEMORY T CELLS: Originate through cell division and responses of other T cells.

T Cell receptors (T antigen receptors)

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T Cell have two membrane proteins (alpha and beta or gamma or delta). These proteins define
specificity of each T Cell and several other membrane proteins know as CD 3 complex occurs in
cell mediate immune response.

T cells. Helper T Cells, Cytotoxic T Cells, and Suppressor T Cells

The helper T cells. Glycoprotein's. The most T cells can be classified by the presence of
membrane glycoprotein's. The helper T cells (T H cells) CD 4 and Cytotoxic T cells (CTL) or T C Cells
CD 8 .

The helper T cells (T H cells). These can be divided two type T H 1 and T H 2.
These cells produce lymphokines are small proteins that act on other cells in autocrine, paracrine,
and endocrine manner.

T H 1 Activate other cells, inhibit antibody production by inhibiting the formation of T H 2.

T H 2 Activate B cells to divide and produce antibody.

Natural Killer Cells

At least two types of lymphocytes are killer cells; cytotoxic T cells and natural killer cells. Can
increase the number of red blood cells and reduce the need for red blood cell transfusions in
patients receiving chemotherapy; and Oprelvekin can reduce the need for platelet transfusions in
patients receiving chemotherapy.
MONOCYTES are white blood cells that can swallow and digest microscopic organisms and
particles in a process known as phagocytosis. Monocytes can also travel into tissue and become
MACROPHAGES, or "big eaters."

CELLS IN THE IMMUNE SYSTEM SECRETE TWO TYPES OF PROTEINS. ANTIBODIES

and CYTOKINES

CYTOKINES (Lymphokines). Soluble protein molecules released by participating and interacting

cells in the adaptive immune system.
Substances produced by some immune system cells to communicate with other cells.

Therapeutic cytokines
Types of cytokines (Lymphokines) includes.
• Interferons
• Interleukins
• Colony stimulating factors (CSF).

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Interferon. The interferons are the family of cytokines proteins, important in the immune
response. Interferon Proteins that are secreted by cells when they become infected with virus.
Bind to nearby infected cells and prevent viral infection. This increased resistance of cells to viral
infection and slows the spread of disease.

There are three major types of interferon.

Interferon’s inhibit viral infections and may have anticancer properties. Interferon's are indicated
in hepatitis infections.

• Alpha (leukocyte) interferon is used for treatment of chronic hepatitis. (peginterferon alpha
2a) chronic hepatitis B.
• Contraindications of interferon. autoimmune disease (SLE, RA), severe depression, or
psychosis, neutropenia, thrombocytopenia and cardiac arrhythmias.
• Interferon Beta (fibroblast) is used for treatment of multiple sclerosis.
• Gamma (immune)

Interleukin (Class I cytokine receptors IL-2, IL-3, IL-7, IL-11, IL-13, IL-15)
A type of lymphokine that regulates the growth and development of white blood cells. The
interleukins also called lymphokines. Twelve interleukins (IL-1 through IL-12) have been identified
to date.

Interleukin-3 (hematopoietic growth factor), Oprelvekin (interleukin-11) is a polypeptide growth

factor obtained by recombinant DNA technology. Increases platelet production via stimulation of
hematopoietic stem cells.
Therapeutic use. Chemotherapy related thrombocytopenia.
Side effects. Fluid retention, peripheral edema and dyspnea.

Colony Stimulating factors

Colony-stimulating factors (CSFs) also called hematopoietic growth factors. Usually do not
directly affect tumor cells rather, they encourage bone marrow stem cells to divide and develop
into white blood cells, platelets, and red blood cells. Bone marrow is critical to the body's
immune system because it is the source of all blood cells.

The CSFs stimulation of the immune system may benefit patients undergoing cancer treatment.
Some examples of CSFs and their use in cancer therapy erythropoietin, epoetin alpha, and
epoetin beta. Darbepoetin (chemotherapy induced anemia occurs within weeks to months).
Therapeutic use. Treatment of anemia resulting from chronic renal failure.
Side effects. Increase BP, thus monitor blood pressure.

Granulocyte Colony Stimulating Factors.

Produced by recombinant DNA technology. Filgrastim, Pegfilgrastim and Sargramostim. These
are glycoproteins produced via recombinant DNA technology.
Filgrastim sc 5 mcg/kg QD for 7-10 days given after 24 h of chemotherapy. (chemotherapy
induced neutropenia can occur within days to weeks).

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Therapeutic use. Treatment of chronic and chemotherapy induced neutropenia.

Sargramostim is approved for myeloid reconstitution (in bone marrow transplantation).
Side effects. Skin allergies, respiratory allergies, and cardiovascular allergies.
Filgrastim and pegfilgrastim are contraindicated for patient with
allergic to E. coli derived proteins.

MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) proteins

Recognize peptide epitopes (fragment of antigens), combined with chemical and MHC proteins to
produce two major classes of MHC proteins.
Class 1 proteins: Present on all surfaces of body cells.
Class II proteins: Present on specific antigen presenting cell (APC’s).
Lymphokines are part of larger network of regulatory cytokines. This network includes secretion
of other cell types in addition to those lymphocytes.

Hypersensitivity Reactions. Excess, inappropriate and prolonged immune responses that cause
damage to normal tissue.
Causes Symptoms
IgE mediated type I hypersensitivity reaction Inflammation of upper and lower
Respiratory allergies grass, animal fur, carpet respiratory tract (asthma), GI and
mites. skin.
GI allergies. Dairy products, shellfish, and Atopic dermatitis, pruritis, rhinitis,
peanut. asthma, and food allergies.
Type I

Skin allergies, topical drugs (procaine). Urticaria, eczema.

Intravenous allergiesinsect venoms. Approximately 50% of patient with
IgE mediated type I. Anaphylactic reactions. It asthma secret IgE.
is treated by epinephrine. (Penicillin's, bee
stings, latex, pea nut).
Cytotoxic/anti-body mediated hypersensitivity Hemolytic anemia and
Type II

Transfusion mismatches, hemolytic anemia, thrombocytopenia are more

Rh disease, specific autoimmune diseases common.
Hashimoto thyroiditis, and myasthenia gravis. Hyper acute graft rejection
Antigen-antibody (IgG/IgM) complex Lympoadenopathy, fever, and rash-
Non specific autoimmune disorders such as first symptoms.
Type III

systemic lupus erythematous, rheumatoid More serious. glomerulonephritis,

arthritis. Hepatitis infections, local respiratory vasculitis and lupus, arthralgia and
form of fungal reactions. Penicillin and arthritis.
sulfonamides.
Delayed type reactions mediated by cell (T Symptoms of type IV. Contact
cells). dermatitis. microvesicle formation,
Type IV

Prolong action of protozoa. Mycobacterium spongiosis.

Tuberculin test and poison ivy. Tuberculin (Monteux test) reaction
gives erythema.

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Immunodeficiency's and Immunopathology

Primary. Either hereditary or congenital and at least one basic element to the immune system
does not function properly or is absent
X-linkedaggamaglobinemia (hypogammaglobulinemia). Inherited deficiency in antibody
production in which T cell function is relatively normal but B-cells do not fully mature
Symptoms. Pneumonia, sinusitis, meningitis and septicemia
SCIDS. Heterogenous group of inherited disorders with deficiencies of T cells, B cells and serum
Ig. Infections with opportunistic organisms occur in the 1st few postnatal and survival for longer
than one year is rare without successful bone marrow transplantation.

Secondary Immunodeficiency. invoke decreased immunologic responsiveness

AIDS. Acquired deficiency syndrome is a serious and most fatal condition in which the immune
system breaks down and does not respond normally to infection.
Diagnosis of HIV infection (Positive HIV ELISA antibody test confirmed by western blot). Base line
assessment including CD 4 and viral load.

CD 4 <500 cell/microL consider initiating antiretroviral therapy.

HIV is retrovirus. The retrovirus stores it genetic information in RNA rather than DNA. when virus
enter target cells. The RNA produce cDNA and this incorporate with host DNA and this reverse
pattern of human cell which does DNA to RNA.

How is HIV transmitted?

• Sexual transmission (contraceptives like condoms can prevent).
• Transfusion of infected blood and blood products.
• Maternal transmission (breast feeding).
• HIV contaminated instruments.

Tests that are used to diagnose HIV infection.

• ELISA (Enzyme linked immunosorbent assay).
• Western blot
• Polymerase chain reaction (PCR assays)
Stages of HIV reproduction
Stage 1. HIV enters a CD cell (helper T cell)
Stage 2. HIV is a retrovirus that its genetic information is stored on single stranded RNA instead of
double stranded DNA found in most organisms. To replicate, HIV uses an enzyme known as
reverse transcriptase to convert its RNA into DNA.
Stage 3. HIV DNA enters the nucleus of the CD 4 cell and inserts itself into the cell’s DNA then
instructs the cell to make many copies of the original virus.
Stage 4. With the help of the protease enzyme, new virus particles are assembled. These newly
formed viruses have the cell ready to infect other CD 4 cells.
Step 5. Shortly after HIV infection, the CD 4 cell count falls sharply in the early stages of HIV
infection because the virus targets and destroys CD 4 cells. When the body starts to cope with the
infection, the CD 4 cell count rises again. In the advance stage, the rate at which the virus
reproduces or rate at which the virus reproduces or “replicates” surpasses the rate of CD 4 cell
turnover, making the body more susceptible to a variety of AIDS-defining illnesses such as

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Pneumocystis carinii pneumonia (PCP), as the viral load rapidly increases unchecked and the CD 4
cell counts decline these illnesses that signal late stage infection eventually lead to death.

Common opportunistic infections.

1. Tuberculosis, both pulmonary as well as extra pulmonary. This is the one the commonest
presentations. Atypical mycobacteria such as Mycobacterium avium complex (MAC) may also
cause infection.
2. Oral candidiasis
3. Esophageal candidiasis
4. Herpes zoster
5. Diarrhea, which may be due to a variety of pathogens
• Protozoal – amoeba, Giardia, isospora belli, cryptosporidium
• Helmints – strongyloids
• Viral – cytomegalovirus
6. Bacterial pneumonia and Pneumocystis carinii pneumonia
7. Toxoplasma encephalitis
8. Cytomegalovirus renitis
Cancers such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma are also seen in these patients

CD 4 cells /microL (µL) Type of opportunistic infections

350 M. tuberculosis
275 Kaposis sarcoma
200 Non-Hodgkins lymphoma
100 P. carinii jerovici (pneumonia)
50 Cytomegalovirus and M. avium intracellular

Autoimmune Disease. When the immune system mistakes self-tissues for non-self and mounts an
inappropriate attack, the result is an autoimmune disease. There are many different autoimmune
diseases.

Organ specific autoimmune disorders Non organ specific

autoimmune disorder.
• Rheumatic fever Sjogren syndrome,
• Antithyroid autoimmunities Systemic lupus erythromatus.
• Myxedema (hypo)
• Hashimoto thyroiditis (hypothyroidism)
• Graves disease (hyperthyroidism)
• Myasthenia gravis (weakening of muscles)
• Autoimmune pernicious anemia
• Goodpasture’s syndrome
• Autoimmune hemolytic anemia, thrombocytopenia,
neutropenia, lymphopenia
• Insulin dependent diabetes mellitus (IDDM)-type1
• Multiple sclerosis

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Systemic lupus erythromatus. Drugs that provoke lupus like syndrome (HIPPP MCQ).
Procainamide, hydralazine, quinidine, methyldopa, isoniazid, phenytoin and chlorpromazine,
penicillamine.
Treatment. Mild diseases, low fever, arthritis by NSAIDs severe symptoms by oral methyl
prednisone.

Immunizations

Immunization is the means of providing specific protection against common and damaging
pathogens.

Natural Immunity. Occurs when the person is exposed to a live pathogen, develops the disease,
and becomes immune as a result of the primary immune response.

Artificial Immunity.
• Can be induced by vaccine, a substance that contains the antigen. A vaccine stimulates a
primary response against the antigen without causing symptoms of the disease.
• Injection of antibody containing serum or immune globulin, from another person or
animal or the injection of monoclonal antibodies.
• The use of pooled adult human immune globulin (IG) to prevent infections in people with
certain immunodeficiency diseases
• Hepatitis B immunoglobulin (HBIG) to prevent hepatitis B in those not actively immunized
with hepatitis B vaccine.

ACTIVE Immunity
• Antigen enters the body and the body responds by making its own antibodies and B-
memory cells.
• Longer lives

PASSIVE IMMUNITY
• Antibodies made in another person or animal enter the body
• Short-lived

There are two categories of immunizations

Active Passive
Slow acting, is used for prophylaxis Fast acting. Short duration of action. Require
Long duration of action. booster dose. Administered im or iv, or sc.
Example. Flu shot takes 2 wk to be Example. Hepatitis B immune globulins (HBIG).
effective and taken annually. Prophylaxis and therapy.
Pneumococcal vaccine takes 2 wks to be Vericella zoaster immune globulins (VZIG).
effective. High-risk patient can take Rh o (D) immune globulin (RhoGAM) prophylaxis for
every 5 to 10 years. Rh +ve fetus by Rh –ve mother receives RhoGAM).
Tetanus vaccine effective for 10 years. Prophylaxis given during pregnancy and after labor
(delivery).

Biological used as active immunity. Bacterial vaccine, Bacterial antigen and Toxoids
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Live (attenuated) organism. MMR vaccine (measles, mumps, rubella), and Trivalent oral polio
vaccine (TOPV).

Killed (inactivated) organism. Inactivated poliomyelitis vaccine (IPV), Rabies vaccine, Influenza
vaccine, Hepatitis B.

There are two methods of vaccines preparations

Live (attenuated) vaccine Killed (inactive) vaccines
Measles, Mumps, Rubella Influenza A and B, Salk Polio (injected).
Chicken pox (varicella) Pertusis, Plague, Hepatitis A and B,
Sabine polio (oral), typhoid (oral), Rabies, Typhoid (injected), and cholera.
Tuberculosis (BCG), yellow fever, small
pox.
Live vaccines are contraindicated in Killed vaccine are can be given in pregnancy and
pregnancy and HIV patients. Avoid with immunocompromised.
biological response modifiers (Infliximab,
anakinra, Adalimumab).
Live vaccines are made from live viruses Inactivated vaccines consist of whole microbes
and bacteria. that have been killed by heat or chemicals.
Vaccines with fragments of microorganisms
• immunization for meningococcal meningitis
• Pneumococcal pneumonia
• Haemophilus influenza type B (Hib) or secreted toxins (detoxified)

Toxoid. Diphtheria and tetanus component of the DtaP and Toxoid vaccines.
• Toxoids are detoxified toxins.
• Antigens
• Available precipitated or adsorbed form of Al(OH) 3 , AlPO 4
• Need booster dose q10 yrs (tetanus)

Flu vaccine. Influenza A&B vaccine (seasonal flu).

• Given annual
• Flu season in Canada is Oct to April
• Flu immunization season is Oct to mid-Nov
• High risk group, seniors (>65 yo), asthma, COPD, CVD, diabetics, children >6 mo to 2 yo,
healthcare workers, and pregnancy.
CIs. Children <6 mo, egg allergies, and with flu symptoms.
All flu vaccine are killed vaccine, except Flu Mist.

Hepatitis vaccine
Hepatitis A & B (Twinrex) >1 yo can use. Give 3 doses,
Fast track 0, 7d, 21d or normally 0, 1mo and 6 mo.
Hepatitis A. >1 yo, 2 doses 0, 6 to 12 mo
Hepatitis B. 3 dose, can be used children age 0,1, 6 mo
• Hepatitis A and B have vaccine.
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• Hepatitis A is given anyone over 1 year age

• Hepatitis A transmits by food or oral fecal
• Hepatitis B & C are chronic, transmit by sexual contact, blood transfusion, and drugs abuse
(needle sharing).
• Hepatitis B vaccine protects Hepatitis D.

Travellers diarrhea vaccine

• Dukoral oral vaccine (oral powder) for E. coli and Vibrio cholera.
• Adult and children >2y. Give 2 dose po. Administered within 7-42 d after 1st dose. and at
least 1 wk before reaching destination.
• Booster 1 dose Q 3 mo if the risk is continuous.
• Taken orally an empty stomach, 1h before or 1h after eating or drinking.
• Effective after one week of 2nd dose.

Drug induced lupus like syndrome

Drugs such as procainamide, chlorpromazine, and quinidine cause the production of antinuclear
antibodies against the histone dimer H2A-H2B. Hydralazine forms antinuclear antibodies to H1
and the H3-H4 complex. Drugs that cause drug induced lupus like syndrome usually take months
to years before the associated symptoms occur, whereas flares of SLE due to drugs may occur
within hours to days.

Tips
• Monocytes are white blood cells that can swallow and digest microscopic organisms
and particles in a process known as --> phagocytosis
• Hashimoto is type of hypersensitivity? Type 2
• Graves disease is? hyperthyroid
• Type 1 DM is? Autoimmune
• Lupus (SLE) caused by “HIPPP MCQ”?(hydralazine, INH, Phenytoin, procainamide,
penicillamine, methyldopa, chlorpromazine and quinidine.)
• Mechanism of Systemic Lupus Erythromatus? Antigen antibody complex.
• What does NOT transmit HIV? mosquito
• What is approximate life of HIV patient? 2-3 y
• When does HiV patient’s tuberculosis and PCP (pneumonia) prophylaxis should be
initiated? CD 4 count 300 and 100.
• If patient get in contact with HIV. What cells are the first response to HIV? CD 4
lymphocytes (helper T cells).

Mnemonics.
Hypersensitive reaction is "ACID"
Type 1 - Allergic (<30 min)
Type 2 - Cytotoxic (5-12 hrs)
Type 3 - Immune complex deposition (3-8 hrs)
Type 4 - Delayed (24-48 hrs)

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www.pharmacyprep.com Biotechnology

18
Biotechnology
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Biotechnology methods for manufacturing pharmaceuticals
• Examples of biological medicines produced by monoclonal antibodies (MAB).
• Chimeric antibodies or Human Antimouse Antibody (HAMA). Examples infliximab,
rituximab and trastuzumab

This chapter is focused on pharmaceutical products that are developed using recent biotechnological
methods and their storage conditions, and role of pharmacist.

Clotting Factors. Recombinant antihemophilic factor (rAHF). Indicated for treatment of classical
hemophilia A. The dry concentrate of rAHF should be stored between 2 to 8o C and protect from
freezing.
• Hemophilia is a genetic disease. It is categorized as hemophilia A and B.
• Hemophilia A is due to deficiency of clotting factor 8.
• Hemophilia B is due to deficiency of clotting factor 9 (Christmas factor).

Cytokines. Cytokines functions as the messengers of the immune system. They are secreted by cells of
immune system in response to stimulations.

Colony stimulating factors (CSF). Glycoprotein cytokines that promote proliferation, differentiation and
activation of immune cells.

Granulocyte CSF (Filgrastim). This drug stimulates the production of neutrophil within bone marrow. It
is approved for chemotherapy related neutropenia. It does not contain preservatives it should be
stored between 2 to 8 °C. It is not frozen.

Granulocyte Macrophage CSF (GM-CSF Sargramostim). This drug is indicated for acceleration of bone
marrow for patient with Non Hodgins lymphoma, acute lymphoblastic leukemia.

Erythropoietins
Erythropoietins are sialic acid containing proteins secreted by kidney in response to hypoxemia and
transported to the bone marrow through the plasma. It resembles an endocrine hormone more any
other cytokines.

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Erythropoietins enhance erythropoiesis by stimulating the formation of proerythroblasts and release

of reticulocytes from bone marrow. Erytopoietins are indicated in anemia, associated with cancer
chemotherapy. It is also used to chronic renal disease associated anemia.

Epoietin alpha. once week. It is approved for anemia related to cancer chemotherapy, chronic dialysis,
and HIV therapy.

Darbopoietin alpha: every 3 week.

Human growth hormone (hGH)

• The pituitary gland secretes human growth hormones (hGH), which stimulates an individual
growth.
• Systemic growth hormone. Humatrope, protropin, and somatrem.

Interferon’s
• Interferon’s inhibits viral multiplications, thus indicated for viral infections.
• Interferon's are classified into two types, type I interferon’s (alpha and beta), which share the
same molecular receptors, and type II (gamma or immune), which has different receptors.
• Interferon beta 1b-Betaseron, Interferon-beta 1b (IFNB) is effective in the treatment of relapsing
remitting types of multiple sclerosis.
• Interferon alpha 1a is used in the treatment of hepatitis viral infections.

Interleukins. synthesized by monocytes, macrophages, and lymphocytes. Interleukins are soluble

messengers between leukocytes.
• IL-1 Intensify the production of collagen, prostaglandin and antibodies.
• IL-2 Fusion protein
• IL-3 Hematopoietic growth factor
• IL 11 Operlaveukin. Indicated for thrombocytopenia associated with cancer chemotherapy. A type
of lymphokines that regulates the growth and development of platelets.

Hybridoma technology (Biologics)

Monoclonal antibodies. Monoclonal antibodies are ultra sensitive, hybrid, immune system derived
proteins designed to recognise a specific antibodies.

Human antimouse antibody (HAMA) monoclonal antibody also known as chimeric antibodies.
Chimeric antibodies (antibodies with mixture of mouse and human component) are produced by
Human AntiMouse Antibody (HAMA) technology.

Example of drugs produced by 5 chimeric antibodies. Rituximab, abciximab, infliximab, cetuximab,

basiliximab.

Example of drugs produced by murine antibody. Muromonab (Orthoclone OKT3), capromab

Example of drug produced by 12 Humanized antibody (Human monoclonal antibodies from transgenic
mice). Trastuzumab, omalizumab, daclizumab.

Example of drug produced by 4 human antibody. Adalimumab

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Example of drug produced by 4 immunoadhesin (protein). Etanercept, abatacept.

TNF alpha inh. Adalimumab, Certolizumab, etanercept, golimumab, infliximab.

B cell depletor. Rituximab
T cell co-stimulation inh. Abatacept
Interleukin-1 inh. Anakinra
Interleukin-6 inh. Toclizumab

Home work

Type of MAB Drugs examples Therapeutic use

Chemeric Infliximab RA and Crohn's disease
Murine
Humanized
Human
Mice

Muromonab (Orthoclone OKT 3 ). Indicated in acute graft rejection in renal, cardiac and hepatic
transplant patients.

Omalizumab. Binds free IgE, reduces binding to mediator releasing cells (mast cells, basophil).

Recombinant tissue.
The fibrinolytic system enzyme. This enzymes are activated in response to the presence of an
intracellular thrombus or clot.
Tissue plasminogen activators (t-PA). (Alteplase, tenecteplase, reteplase) These are substances
produced in small quantities by the inner lining of blood vessels and by the muscular wall of uterus.
Tissue plasminogen activator prevents abnormal blood clotting by converting plasminogen, a
component of blood, the enzyme plasmin. The plasmin is breakdowns to fibrin, the main constituent
of blood clot.

Recombinant alteplase (Activase). This drug is indicated in management of acute myocardial

infarction.

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VIIa
Blood
IX X
Xa X
Prothrombin (II) Thrombin IIa

Thrombolytics:
Streptokinase XII
Urokinase
Alteplase
Fibrinogen

Catalyzation

Plasminogen Plasmin Fibrin (Soluble)

XIIa

Fibrin degradation product Fibrin (insoluble)

Site of injury

Tumor Necrosis Factor (TNF). It is produced mainly by activated mononuclear phagocytes, have both
beneficial and potentially harmful effects, mediating cytotoxic and inflammatory reactions. Two anti-
TNF alpha monoclonal antibodies are approved for the treatment of rheumatoid arthritis and Crohn's
disease.

Infliximab (Remicade). It is chimeric IgG antibody directed against TNF alpha (selectively binds with
alpha). It is approved for Crohn's disease and for the treatment of rheumatoid arthritis. Administered
iv. 3 mg/kg, at 0, 2, and 6 weeks and then every 8 weeks after. Infliximab should be administered with
methotrexate to prevent the formation of antibodies to infliximab.

Etanercept binds with both TNF alpha and beta. The greater risk of etanercept therapy is immuno
suppression and subsequent serious infections.

Antisense drugs (Antisense Oligonucleotide therapy). Non coding base pairs (stop codons) of
messenger RNA.
Antisense oligonucleotides are single strand of DNA or RNA that are complementary to chosen
sequence. The antisense RNA protein translation of certain "messenger RNA" by binding to them. The
antisense DNA is used to target a specific complementary RNA.

Antisense drugs inhibit gene expression by oligonucleotide.

Tips
Find answer from the table:
1 Infliximab 2. Etanercept 3 Megakaryoblast
4 Hemophilia A 5. Muromonab-CD 3 6 Erythropoietin's
Orthoclone OKT 3
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7 Filgastrim 8. Epoetin alpha

• Indicated for anemia, associated with cancer chemotherapy; also used for chronic renal disease
associated anemia ( )
• What is approved for anemia related to cancer chemotherapy, chronic dialysis and AZT therapy (
)
• What is the treatment of neutropenia associated to chemotherapy ( )
• Precursor of platelets ( )
• What drug binds with both TNF alpha and beta ( )
• What drug is used to treat acute graft rejection in renal, cardiac and hepatic transplant patients (
)
• What it is approved for Crohn’s disease and the treatment of rheumatoid arthritis ( )
• Due to deficiency of clotting factor 8 cause ( )
• Infliximab is indicated for?
• Infliximab is given as?
• What drugs attacks CD 4 + T cells? 
• Muromonab (Orthoclone OKT 3 ) is used to treat?
• 1) Infliximab mechanism?
• 2) Infliximab therapeutic use?
• 3) Infliximab storage conditions?

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www.Pharmacyprep.com Toxicology

19
Toxicology
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Overdose symptoms of benzodiazepines, opioids, acetaminophen, tricyclic antidepressants
and iron supplements.
• Antidotes of overdoses of benzodiazepines, barbiturates, opioids, acetaminophen, ASA,
tricyclic antidepressants, warfarin, heparin, LMWH and iron supplements.

This chapter focuses in methods of treatment associated with overdose of drugs and overdose
symptoms, chemicals toxicity. Drugs and chemicals that commonly cause toxicities, and the role of the
pharmacist. Antidotes and treatment are presented for specific drug toxicities.

General management of toxicity

• Supportive care (ABCs)
• Gathering information of toxicity
• Evaluating toxic symptoms and refer to doctor or emergencies
• Documentation

Poison prevention strategy: Child proof containers, Constant vigilance, Labelling

• Formulation

GI Decontamination procedures
Decontamination consists of removal of any unabsorbed poison from the patient’s body.
Commonly used methods include gastric lavage or gastric gabage, emesis, ipecac, adsorbent agent
charcoal.

Gastric lavage or gastric gabage. This procedure can be used:

• Good for patient if unconscious
• Depression
• Seizures
• Coma and convulsion

Contraindicated in patients who have ingested Acids, Alkali, Hydrocarbons, Risk of GI perforation

Emesis (vomiting): This method is used to evacuate GI tract.

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Emesis procedure is contraindicated in

• Children less than 6 month
• Strong acid and base
• Depression
• Unconsciousness
• Seizures
• Coma and convulsion
• Extremely rapid onset of action
• Emesis following ingestion
• Sharp objects
• Hydrocarbons, petroleum products

Ipecac induced emesis and gastric lavage primarily removes substances from the stomach and their
efficacy is affected by time and quantity of ingestions. These procedures are more effective if they are
implemented within 1 hour of ingestion.

Syrup of Ipecac is administered within 60 min toxic dose ingestion (later has no benefit)
• Onset of emesis 30 min. Effect could last 2 hours.
• 3 episodes of emesis in 60 min

Dose of Ipecac for adults and children

For emesis adult 15 to 30 ml po with 1 to 2 glass of water
For emesis child 10 to 15 ml po with 1 to 2 glass of water
For expectoration adult 1 to 2 ml po
For expectoration child 0.25 to 0.5 ml po

Decontamination
Activated Charcoal
• This method is preferable method of decontamination.
• Higher the surface area of charcoal higher the adsorption.
• Heating charcoal increase adsorption.

Adsorbent agent. Charcoal is good for drug and chemicals. NOT for (because not adsorbed) methanol,
ethanol, iron, cyanide, ethylene glycol, mercury, organic solvents, potassium, strong acids and bases.
Do not use if patient is vomiting.

Dosage. Adults 25 to 100 g. Children 1 to 12 years 25 to 50 g, 0 to 1 years. 1 g/kg

Charcoal available as colloidal dispersion form.

Bowel Irrigation Method. Osmotic solution of polyethylene glycol (PEG) is used (1-2 liter /hr orally).

Enhancement of elimination. Enhancement of elimination is possible for a number of toxins, including

manipulation of urine pH to accelerate renal excretion of weak acids and bases.

Diuresis. Promotes elimination acids and bases. This can be alkaline and acid diuresis.

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Alkaline Diuresis. Promotes the ionization of weak acids therefore prevents re-absorption by the
kidney, facilitate excretion of weak acids. Example salicylic acids, ASA, phenobarbital, and
barbiturates.
• Dosage of NaHCO 3 (sodium bicarbonate) 50 to 100 mEq
• pH 7.3 to 8.5 (urine)
• Urine output 5 to 7 ml/kg/hr

NaHCO 3 side effects. Metabolic alkalosis, hypernatremia, hyperosmolarity, and fluid overload.

Acid Diuresis. Used to promote elimination of weak bases. Example amphetamines, phencyclidines,
quinidine derivative, and alkaloid drugs.
Dosage. Ascorbic acid 500 mg to 1 g and ammonium chloride 4 g every 2 hours serum electrolyte and
pH should be monitored.

Important characteristics of the toxicology of arsenic, iron, lead and mercury

Metal From Entering Route of Target Organs for Treatment
Body Absorption Toxicity
Lead Inorganic lead Gastrointestinal Hematopoietic Dimercaprol, Edentate (EDTA),
oxides and salts tract, respiratory, system, CNS, kidneys penicillamine, succimer.
skin (minor)
Tetraethyl lead Skin (major), GIT CNS Seizure control, supportive
Arsenic Inorganic arsenic All mucosal Capillaries, GI tract, Dimercaprol succimer,
salts surfaces hematopoietic system penicillamine
Arsine gas Inhalation Erythrocytes Supportive
Mercury Elemental Inhalation CNS, kidney Dimercaprol
Inorganic salts GI tract Kidneys, GI tract Penicillamine, dimercaprol
Organic GI tract CNS Supportive
Iron Ferrous sulfate GI tract GI tract, CNS, blood Deferoxamine (chelation)

Toxic features of specific agents

Agent Toxic Features
Acetaminophen Mild anorexia, nausea, vomiting, delayed jaundice, hepatic and renal failure
Max dose 4 g/day. Max dose 2 g/day for chronic alcoholic, and hepatic disease
Antidote is acetylcysteine, should be administered within 8 hours of overdose.
Antifreeze (ethylene Toxic oxidized product of ethylene glycol is oxalic acid.
glycol) Renal failure, crystals in urine, anion and osmolar gap, initial CNS excitation. eye
examination normal.
Botulism Dysphagia, dysarthria, ptosis, ophthalmoplegia, muscle weakness. Incubation
period 12 to 36 hours.
Carbon monoxide Coma, metabolic acidosis, retinal hemorrhages
Cyanide Bitter almond odor, seizures, coma, and abnormal ECG.
Gasoline Distinctive odor, coughing, pulmonary infiltrates on x-ray.
Iron Bloody diarrhea, coma, radiopaque material in gut (seen on x-ray), high leukocyte
count, and hyperglycemia.
Lead Abdominal pain, hypertension, seizures, muscle weakness, metallic taste,
anorexia, encephalopathy, delayed motor neuropathy, changes in renal and
reproductive function. Gray mouth.
LSD Hallucinations, dilated pupils, and hypertension
Mercury Acute renal failure, tremor, salivation, gingivitis, colitis, Erethism (fits of crying,

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irrational behaviour), nephritic syndrome.

Methanol Rapid respiration, visual symptoms, osmolar gap, severe metabolic acidosis.
Methanol toxicity gives blindness due to formic acid.
Mushrooms Severe nausea and vomiting 8 hours after ingestion; delayed hepatic and renal
(Amanita phalloides failure
type)
Paraquat Oropharyngeal burning, headache, vomiting, delayed pulmonary fibrosis, and
death
Phencyclidine (PCP) Coma with eyes open, horizontal and vertical nystagmus, hyperacusis, myoclonic
jerks, violent behaviour
Plants Nightshade Hallucinations, mydriasis, seizures (these plants contain atropine-like alkaloids)
family, jimsonweed
Oleander and Digitalis poisoning
foxglove
Predatory bean Delayed severe gastrointestinal distress, seizures, hemolytic anemia, death
(rosary pea)

Specific antidotes
Antidote Overdoses
Acetylcysteine best given within 8 to 10 hours after overdose of acetaminophen.
Antivenin Snakes, black widow spiders
Atropine Cholinesterase inhibitors, organophosphates, carbamates.
Bicarbonate, sodium Membrane-depressant cardiotoxic drugs, e.g. Quinidine, TCA and ASA
Deferoxamine Iron salts
Digoxin-specific Fab Digoxin and related cardiac glycosides
antibodies (Digifab)
Esmolol Caffeine, theophylline, metaproterenol
Ethanol Methanol, and ethylene glycol
Flumazenil Benzodiazepines, zolpidem
Glucagon Insulin, beta-blockers
EDTA Lead
Dimercaprol Lead, gold, arsenic, and mercury
Hydroxocobalamine Cyanide
Penicillamine Copper, lead, arsenic, gold and Wilson’s disease
Naloxone Opioid analgesics (blocks mu receptors)
Oxygen Carbon monoxide
Physostigmine Atropine (muscarinic antagonist), not tricyclics
Pralidoxime Organophosphate cholinesterase inhibitors
Sodium thiosulfite Cyanide (Nitroprusside)
Protamine sulfate Heparin/LMWH
Vitamin K (Phytanodione) Warfarin

Dabigatran idarucizumab

Fomepizol (alcohol Methanol, ethanol, and ethylene glycol

dehydrogenase enzyme
inhibitors)

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Tips
Find answers from the table:
1. Flumazenil 2 N-acetylcysteine 3 Glucagon
4. Latanoprost 5 NaHCO 3 6 Amiodarone
7. Myopathies 8 elevated CK MM 9 Rhabdomyolysis
10 Hydrochloroquine
• Insulin antagonist is? ( )
• Benzodiazepine antagonist is? ( )
• Salicylates overdose may be treated by? ( )
• Acetaminophen antagonist is? ( )
• Naloxone is antidote against overdose of ( )
• Vitamin K is antidote against overdose of ( )
• Protamine sulfate is antidote against overdose of ( )
• Aminophylline is an antidote against overdose of ( )
• Glucagon is used in emergencies to treat symptoms of ( )
• Which glaucoma medication causes iris pigmentation? ( )
• Latanoprost side effect  ( )
• Which antiarrhythmic drug cause pulmonary toxicity? ( )
• Amiodarone ( )
• Which antimalarial drug causes retinopathy side effect? ( )

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20
Pharmacokinetics
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Absorption, Distribution, Metabolism and Elimination (ADME)
• Volume of distribution
• Renal or hepatic elimination
• Steady state concentrations

Pharmacokinetics describes the absorption, distribution, metabolism, and excretion of drugs in

patients receiving a drug therapy.

A Absorption
D Distribution
M Metabolism
E Elimination

Distribution: Volume of distribution is a hypothetical volume of body fluid that would be required to
contain the entire drug administered so that the concentration will be the same as that found in the
blood. High distribution (blood flow) is in liver, kidney and brain. Skeletal muscle, Adipose tissue has
the slowest blood flow.
V d = A b (amount of drug in the body)/C (concentration of drug in plasma)
To calculate volume of distribution To calculate initial plasma drug concentration
Vd = D / C p
Cp = D/ V d
To calculate dose: D = C p x V d To calculate loading dose: D L = C ss x V d
D L = loading dose
To calculate renal clearance CL R = Kx V d

Factors affecting drug distribution

Rate of distribution Extent of distribution
(speed of distribution) (amount of distribution)
Membrane (capillary) Lipid Solubility (chemical
permeability. structure)
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Blood (flow) perfusion pH - pKa (ionization)

Plasma protein binding
Intracellular binding

The factors affect drug excretion into breast milk:

• Drug that have higher protein binding have less excretion into breast milk.
• The breast milk is more acidic than plasma. So basic drugs have more excretion into breast milk.
• Lipid soluble drug have higher excretion into breast milk.

Plasma Protein Binding: The Plasma proteins refer to the proteins present in the plasma binding to
drugs. There are two major types of proteins in the plasma, these are albumin and glycoprotein's.

Drug undergoes protein binding with three types of proteins. Acid drugs, albumin (55% major
proteins), albumin has strong affinity to for anionic drugs (weak acids) and hydrophobic drugs.
Base drugs binds to alpha acid glycoprotein's, and lipoproteins. Vitamins, steroid etc binds globulins.

Extensive plasma protein binding will cause more drugs to stay in the central blood compartment.
Therefore drugs that bind strongly to plasma protein tend to have lower volumes of distribution. Drugs
that have high plasma protein binding, less volume of distribution and vice versa.

Tissue Binding. Generally, high degree of tissue binding implies large V d , e.g. digoxin.

% protein binding = (Total - Unbound) x 100

Total

Drug Absorption Free drug Protein Bound

in blood Drug

Drug effect at Phenytoin 90%

site of action Vancomycin 30%
Warfarin 97%
Plasma proteins concentration that changes with some conditions
Conditions Albumin Alpha 1 acid glycoprotein
Renal Failure ↓ (hypoalbuminemia) ↑
Hepatic Failure ↓ ↑
Arthritis - ↑
Burns ↓ -
Pregnancy ↓ -
Stress/Trauma ↓ ↑

Elimination. Removal of drug from the body may occur via a number of routes. The most important
routes of elimination are kidney into urine. Other routes of elimination are bile, intestine, lung or milk
in nursing mothers. Second most important organ for elimination is liver.

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Drug Elimination

Metabolism

Bile (hepatic or Liver)

Drug
in
Excretion Urine (renal or kidney)
Body

Sweat
Breast milk
Exhaled air
The rate of elimination (disappearance of the active molecule from the blood stream or body)
determines the duration of action for most drugs.
K = elimination rate constant represents the fraction of drug eliminated per unit time.

Renal Clearance. Drugs metabolites or unchanged drugs excreted in urine.

Total clearance (CL T ) = CL R + CL NR
CL T = total clearance
CL R = renal clearance
CL NR = non renal clearance (hepatic)
Renal clearance. CL R = CL T -CL NR

CL T = F x D /AUC, where F= bioavailability, D= dose rate, AUC Area under the curve
CL T = V d x K el
where V d = volume of distribution and K el is the elimination rate constant
t 1/2 = 0.693 /K el
K el = 0.693/t 1/2
CL T = V d x (0.693/t 1/2 )

Factors that affect renal clearance: As clearance is decreased half-life increases, changes in Vd cause
proportional changes in half-life. Half life = 0.693 x Vd/ClT
Steady-State Drug Plasma Concentration C ss = 1/(K el x V d ) x (FxD)/T

Hepatic Clearance: The volume of drug containing plasma that is cleared by liver per unit time.
Measured indirectly as difference between total body clearance and renal clearance.
Cl H = Cl T - Cl R
Cl H = Hepatic clearance
Or Cl H = Q ER
Q = product of blood flow
ER = [C a -C v ]/Ca
C a = arterial plasma drug concentration liver
C v = venous plasma drug concentration in liver
Values for ER range from 0 to 1, if the ER is 0 then no drug removed by liver, if 0.8 then 80% of
incoming drug is removed by the plasma profuse in liver.

Hepatic clearance depends on blood flow to the liver is approximately 1.5 L/min. Exercise, disease or
drugs may alter blood flow.

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Intrinsic clearance (Cl int ). The ability of the liver to remove the drug independent of the blood flow
(mixed-functions oxidase enzymes biotransform drugs). Intrinsic clearance primarily occurs because of
ability of metabolizing enzymes (mixed function oxidase) as they metabolize the drugs they enter in
liver.

Steady state concentrations C ss Plasma concentration at steady state (C ss ). Under the steady state
conditions. The fraction of drug absorbed equals to the fraction of drug eliminated in the body.

Cmax SS
Plasma drug

200

Cav
concentration (mcg/ml)

180

160 CminSS

140
ϑ

The time to reach C ss

• The concentration of drug rises from zero to C ss by first order process.
• To reach 90% of the final steady state concentration takes 3.3 half lives.
• The sole determinant of the rate that a drug reached C ss is the half-life or K el and rate is influenced
by only those factors that effects half-life.
• C ss time does NOT influenced by rate of infusion. C ss concentration rises with infusion.
Clearance
• CL = rate of elimination/C
• CL = Vd x k el where V d = volume of distribution and k el is the elimination rate constant
• CL = Vd x (0.693/t 1/2 ) where 0.693 = ln 2 and t 1/2 is the drug elimination half-life note that plasma
clearance CL P include renal (CL R ) and metabolic (CL M ) components
• t1/2 = 0.693 Vd/Clt

Dosage Regimens: The number of doses to be given per day is usually determined by the half-life of
the drug and the difference between the minimum therapeutic and toxic concentrations.
QAlerts!
1) Rate in = Rate out means rate of absorption is equal to rate of eliminations.
2) How many half lives? takes to reach steady state concentration? 5-7 half life

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ko
Css = ko = rate of infusion
CL
CL = total body clearance
DL = loading dose
DL = Css x Vd
DM = maintenance dose
Vd = volume of distribution
DM = Css x CL x τ
τ = dosing intervals

Relationship between pharmacokinetic factors and eliminations. The relationship between steady
state plasma concentration and volume of distribution can be obtained by;

C ss = R/(V d xK)
R = rate of infusion
K = elimination constant
V d = volume of distribution

The relationship between loading dose and volume of distribution:

D L = C ss x V d
D L = loading dose
The relationship between body clearance and average plasma concentration:
C av = F x D o / CL T x t

t = dosing interval, C av = average plasma conc, CL T = total clearance

The relationship between AUC and volume of distribution can be obtained by intravenous F is = 1

The relation between steady state plasma concentration and volume of distribution can be obtained
by: C ss = R/V d x K
R = rate of infusion
K = elimination constant
V d = volume of distribution
QAlerts!
Over 95% of the drug lost or eliminated in 5 half lives. Which is typically considered to be the
completion of process.

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Rate of infusion of drug is equal to the # of half life % remained % eliminated

drug’s elimination from body at Css. 1 50 50
ko 2 25 75
Css = 3 12.5 87.5
VdK
4 6.25 93.75
K o or R = rate of infusion 5 3.125 96.8
6 1.5 98.4
Plateau Principle
7 0.78 99.2
• Time to reach steady state
depends only upon the t 1/2 of the drug and is independent of the size of the dose and the
frequency of dosing. The zig-zag and graph represents the same data. It takes >7 t 1/2 to reach
mathematical 99.2%steady state.
• Steady state is reached when either rate in = rate out or when the values associated with a dosing
interval are the same in the succeeding interval.

Therapeutic Drug monitoring:

• Drugs in renal failure; Aminoglycosides, cyclosporine A
• Drugs with saturable kinetics (non linear kinetic); Phenytoin and salicylates
• Drugs with linear kinetics; Theophylline, digoxin and procainamide

Aminoglycosides: The normal half life is 2-3 hours. In renal disease patient the half life can extend to
30-60 hrs.
• Aminoglycosides given at intervals that are much longer than one half-life.
• Phenobarbital intervals that are smaller than one half-life are slowly cleared from body, therefore
their peak concentration are relatively smaller.

Phenytoin: Linear kinetic means when the dose of drug is increased we expect that concentration at
steady state will increase proportionately i.e. if the dose rate is increased or decreased say two fold
the plasma concentration will also increase/decrease two folds. However for non linear kinetics
changes in dose rate can cause more or less changes in plasma concentration. This can cause
problems in dose adjustment.
Css = (F x dose rate)/Clearance
F= bioavailability.

Theophylline: Theophylline is a narrow therapeutic index drug, which require drug serum level
monitoring to correlate with both therapeutic and toxic effects.
10-20 mg/L needed to produce bronchodilatation with minimum side effects.
>20 mg/L is toxic dose can produce higher side effects.
>35 mg/L increase incidence of seizure and cardiac arrhythmias.
The clearance of theophylline is affected by many variable which makes necessary careful individual
dosage, age, smoking, CHF and drug interactions.

QAlerts!

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If volume of distribution increases (drug displacement from protein binding, heart failure, cadiogenic
shock). How this effect on half-life? Half-life increases because it is directly proportional to Vd.
• What if clearance decreased (renal diseases, hepatic cirrhosis)? Half life increase
• What if metabolism decreases? Half-life increases.
• What if dose is increase, how the half-life effects? dose does not affect half life.

Formulas
1st order Half life
C = C o x 10 –kt/2.303 t 1/2 = 0.693/k
–kt/2.303
Log C = log C o t 1/2 = C o /2k
-kt
C = Co x e
–kt
ln C = ln C o
Shelf life Clearance
t 90 = 0.105/k Cl t = Amount absorbed/AUC
t 90 = 0.1C o/2k Cl t = FD/AUC
C ss = R o /KV d
C = R o /KV d (1-e-kt)
Distribution: Vd = A o /C o

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21
Rates and Orders of Reactions
Questions Alerts!
Common questions in pharmacy exam is to ask!
• First order elimination
• Half life calculations

Rate: Speed (velocity)

Order: The way in which concentration affects rate.
Reaction orders. There is four orders of reactions are described below. Zero order reactions, 1st order
reactions, 2nd order reactions, 3rd order reactions, and pseudo order reactions.

Zero order reactions:

Independent of concentration
Time dependent
-dc/dt = Ko
Slope -ko
Example. Photochemical degradations

Zero order constant expressed in units of concentration e.g. milligrams per millilitre per hour. or
gram/L/hour.
Linear equation = C = -K o t +C o
K o is slope of the line = zero order constant (conc/time)
C o is initial concentration
T = time
C = drug concentration
Slope of the line is not equal to the rate constant because it includes minus sign.
The negative indicates that slope is decreasing. Rate of elimination is independent of the amount of
drug to be eliminated. The zero order elimination rate constant is K o and has the units of
amount/time. A constant amount of drug is eliminated per unit of time.
Most drugs do not follow zero order processes. In zero-order equations, a constant amount is
removed for each unit of time. This kinetics fit the following equation.

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Zero order elimination alcohol, toxic doses of Aspirin, and high doses of phenytoin, amino glycosides.
A constant fraction of drug is eliminated
4 hr 4 hr 4 hr 4 hr
80 mg  70 mg  60 mg  50 mg  40 mg

Units of drug

time
The serum level curve observed from a drug elimination by a zero order process. X axis is Time/hr and
Y axis is Cp mg/L.
Slope = -k

Zero order process application include administration of a drug as an intravenous infusion and
controlled release dosage forms and trans dermal patches.

First order reactions: Rate of reaction is proportional to the first power of concentration.

Concentration and time dependent: Log C o /C = K t /2.303

Where
C o = concentration at t o
K = rate constant
A plot of log scale on Y axis of concentration (Cp mg/L)against time/hr produces a straight line with a
slope. The slope of straight line correlated to Kel,
Slope –k/2.303
Half-life 0.693/k

A constant fraction (percent) of drug is eliminate half of the starting amount of drug is a constant and
is known as the half-life t 1/2 .
4 hr 4 hr 4 hr 4 hr
80 mg  40 mg  20 mg  10 mg  5 mg
First order rate constant DC/dt = -kC time-1 (1/hr or hr-1)
k = first order rate constant
C = C o e-kt
ln C = -kt + ln C o
log C = - kt/2.303 +log C o
Comparison or zero and first orders process
Zero order First Order
Slope -k -kt/2.303
Rate -dx/dt Rate remains constant Rate changes over time
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Rate Ko unit mgh-1 K unit h-1

Formula C = C o e-kt
ln C = -kt + ln C o

Zero Order First Order

k 0 = amt./time k= time-1
toxicity, saturation all common situations

units of drug
Units of drug

time
time

Semi log plot Semi log plot

Units of
drug

time time

t1/2
t1/2

dose dose

Half-life (t 1/2 ): A half-life is time required to decrease the amount of drug in body by 1/2
during elimination (or during a constant infusion). Plasma t ½ is the time it takes for the plasma
drug concentration to fall to half its initial value.

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0.693
t1/2 =
k

No. Of half-lives 1 2 3 3.3 5 7

Concentration 50% 75% 87.5% 90% 96% 99.9%

Second order equation: Rate of reaction proportional to the each of the two reactant
concentration and time.
Dx/dt = k (a-x) (b-x)
where
a = concentration of reactant A at time t
b = concentration of reactant B at time t
dx/dt = rate of reaction
x= number of moles of reactant A and B at time t
k = reaction constant
If concentration of reactant A and B are equal:
dx/dt = k(a-x)(a-x)
dx/dt = k(a-x)2
Second order t 1/2 = 1/ka
When there is concentration of A and B not equal, secondary order equation will be:
k = 2.303/t(a-b) = log b(a-x)/a(b-x)
Examples of second order. Saponification of esters
CH 3 COOC 2 H 5 + OH-  (double arrows) CH 3 COO- + C 2 H 5 OH

Third order reaction: Rate of reaction is proportional to concentration of each of the three
reactions
Dx / dt = k (a-x) (b-x) (c-x)
When a = b = c
Dx/dt = k (a-x)3

Pseudo order: Rate of reaction is proportional to the concentration of only one reactant, in
two-reactant reaction, if a reactant present in high concentrations.
Example. Saponification of esters in presence of high concentration of bases (OH-) or acids
CH 3 COOC 2 H 5 + OH- (excess)  (double arrows) CH 3 COO- + C 2 H 5 OH.

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Tips
What is the plasma t ½ of a drug? The time it takes for the plasma drug concentration to fall to half its
initial value.

Zero order reactions

• Independent of concentration
• Time dependent
• -dc/dt = Ko
• Slope -ko
• Example: Photochemical degradations
Zero order constant expressed in units of concentration eg. milligrams per millilitre per hour. Or
gram/L/ hour
• Linear equation = C = -K o t +C o
• K o is slope of the line = zero order constant (conc./time)
• C o is initial concentration
• T = time
• C = drug concentration

First order reactions: Rate of reaction is proportional to the first power of concentration.
Concentration and time dependent
Log C o /C = K t /2.303
Where
C o = concentration at t o
K = rate constant

A plot of log of concentration against time produces a straight line with a slope: Slope –k/2.303
C = C o e-kt
ln C = -kt + ln C o
log C = - kt/2.303 +log C o
Half-life (t 1/2 )
0.693
t1/2 =
k
Blood or plasma considered in equilibrium with total volume of distribution: t 1/2 = ( 0.693 X V d ) / CL

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22
Pharmacodynamics
Questions Alerts!
Common questions in pharmacy exam is to ask!
Competitive or non competitive agonist and antagonist rates!

Pharmacodynamics is the relationship between the concentration of a drug and the response obtained
in a patient.
Concepts!
• Drug/Receptor Interactions (Fig 27.1) Affinity, Efficacy and Potency
• Affinity. Measure of ability of drug to bind to
receptor.
• Efficacy. Measure of how well the drug/receptor complex produces a physiological response.
• Potency. is comparative measure. It compares the amounts of two drugs necessary to produce
the same size effect in the body. Example. Rosuvastatin 10 mg and atorvastatin 20 mg
• Agonist has affinity and efficacy.
• Antagonist has affinity and zero efficacy.
• Partial agonist is the only class of drug that can be used either as an antagonist or as an agonist.
• When only partial agonist present, it will give the response until its ceiling effect.
• When a full agonist is already present in the body, administration of partial agonist reduce the
effect full agonist, thus act as antagonist.
• Physiological antagonism.
• two drugs act on different receptor; cancelling effect.
• Neutralizing antagonism/chemical antagonism
• does not need receptor
• chemicals act on the body (e.g. antacids, digoxin).

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Drug A & B have equal efficacy. Drug A & B efficacy is not comparable.
Drug A has more affinity than drug B Drug A has more affinity than drug B

Fig 27.1
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Competitive antagonist. Curve shifts to the RIGHT, and the shift is parallel.
Non competitive antagonist. Curve shifts to the RIGHT, but the shift is nonparallel E max

Competitive (equilibrium) Non competitive (irreversible)

competitive inhibitors are molecules that bind to Non competitive inhibitors are molecules that bind
the same site as the substrate preventing the to some other site on the enzyme reducing its
substrate from binding as they do so but are not catalytic power
changed by the enzyme.
Parallel rightward shift of agonist dose response Flattening of dose response curve
curve shift.
Intensity of response depends on concentration of Response depends on only on the concentration of
both agonist and antagonist. antagonist
The same maximal response is attained by Maximal response is suppressed
increasing the dose of agonist

Reversible enzyme inhibitors. This can be categorized into competitive and non-competitive.
Competitive (Reversible) Drug competes with the substrate for binding to the enzyme at active site,
this binding is mutually exclusive. Inhibition can be reversed in the presence of saturating substrate,
since in this case all enzyme active sites will be occupied by substrate.

Non-competitive (irreversible)  It is independent binding, both substrate and drug bind to the
enzyme at different site. This cannot be reversed by increasing concentration substrate.

Type of drug interactions; Mathematical model

Addition 1+1 = 2 (same effect)
Synergism 1+1 = 3 (gives greater effect)
Potentiation 0+1 = 2
Antagonism 1+1 = 0

Quantal response:
• ED 50 Effective dose in 50% of test population
• LD 50 Lethal dose in 50% of test population
• TD 50 Toxic dose in 50% of test population
• TI: Therapeutic index, a measure of safety of a drug measure by LD 50 /ED 50 or TD 50 /ED 50 .

Therapeutic Window. The therapeutic window is the useful “opening” between the minimum
therapeutic concentration and the minimum toxic concentration of a drug.
The minimum effective concentration usually trough levels of a drug.
The minimum toxic concentration determines the permissible peak plasma concentration.

Narrow therapeutic index drugs that require routine plasma/serum drug monitoring.
• Therapeutic range of select medications
• Procainamide 4 – 10 mg/L
• Quinidine 2 – 6 mg/L
• Disopyramide 2 – 6 mg/L
• Lidocaine 2 – 5 mg/L
• Valproic acid 50 – 100 mg/L
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• Carbamazepine 4 – 12 mg/L
• Phenobarbital 15 – 40 mg/L
• Lithium 0.4 – 1.5 mEq/L
• Theophylline

Quantal Dose-Response Curve: Guassian (bell-shaped) distribution. and graded Dose-Response Curve
Efficacy = maximum effect
Potency = different doses, same effect

Log Dose-Response Curve:

Efficacy: height of log dose-response curve (E max )
Potency: ED 50

Mechanism Of Drug Action: Interaction with receptors and Interaction with enzymes
Enzyme induction. Barbiturates, phenytoin, other anti-epileptics, rifampicin, antihistamines,
griseofulvin, oral contraceptives.
Enzyme inhibition. Chloramphenicol.

Replenishers. Replace/fill-in endogenous substances or fluids and IV fluids, vitamin supplements, and
hormone replacement therapy.
Diagnostic agents. functional macromolecular component of a cell with a specific stereo chemical
configuration with which a ligand interacts in a lock-and-key fashion
• Regulatory proteins
• Structural proteins
• Enzymes
• Transport proteins

Enzyme Kinetics (Enzyme Inhibitors). Enzymes are catalyst. In biochemical reactions, reactants are
commonly known as substrates (S), enzymes (E), ES = Enzyme and substrate complex, P = product

In the following reaction: E + S <---> ES <---> ES* <---> EP <---> E + P

Enzyme substrate (ES) complex, Enzyme product complex (EP) and The transition state (ES*)

Enzyme inhibition classified in two categories, reversible enzyme inhibition (competitive) and
irreversible enzyme inhibition (Non competitive)

The Michaelis-Menten equation. By

using Michaelis-Menten equation, rate
and order of enzyme reaction can be
determined. V 1 = V max [S] /{K m +[S]}
The reaction rate [v 1 ], maximum
reaction rate (V max ), substrate
concentration [S] and the Michaelis-
Menten constant (K m ).

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The Michaelis-Menten equation first order, when the substrate concentration is much smaller than
Km.

The Michaelis-Menten equation describes how the rate of the reaction (v) depends on the
concentration of both the enzyme [E] and substrate [S].
The only way to increase V max is by increasing [E] enzyme concentration.

The Michaelis-Menten equation has the same form as the equation for a rectangular hyperbola
graphical analysis of reaction rate (v) versus substrate concentration [S] produces a hyperbolic rate
plot.

First order
• Substrate concentration is much lower than K m
• K m is lower than V max
• Substrate concentration directly proportional to rate of reaction.

Zero order
• Substrate concentration is same as K m
K m = V max
• Substrate concentration do not effect rate

Km
• K m is the measure of the affinity of the enzyme for it substrate.
• K m is the intrinsic property of the enzyme substrate system and cannot be altered by changing
enzyme and substrate concentration.
• K m lower than V max indicates first order reaction.
• K m and V max approximately same at zero order reaction.
• 1st order rate linear relation with substrate concentration [S]

V max
• V max depends on [E] and [s] concentration in 1st order equation.
• V max is the maximum rate possible to achieve with given amount of enzyme.

Tips
1 physiological 2 potency of drug 3 efficacy of drug
antagonism
4 dose-response curve 5 synergistic effects 6 non-competitive inhibitor
7 competitive inhibitor 8 partial agonist 9 EC 50
• Effects that are greater than additive ( )
• The effect whereby two drugs acting on the same tissue or organ through independent receptors
may result in opposite effects? ( )
• A graphic representation of a quantitative response between the amount of drug given and the
response of the drug ( )
• The amount of drug necessary to produce an effect. The concentration or dose of the drug
required producing 50% of the drugs maximum effect. ( )
• The maximal response produced by a drug ( )
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• The drug concentration required producing 50% of the maximum response ( )

• An agonist, which at even higher concentrations, gives less than 100% response ( )
• A drug which compete reversibly with agonists for the same receptor site and produces no
response ( )
• It is called an irreversible antagonist that binds to the receptor site or another site which inhibits
the response to the agonist (True/false)

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23
Medicinal Chemistry
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Functional groups. Geometric (cis & trans) isomerism, optical isomerism, calculating optical
isomers 2n.
• Active chemical rings in drugs structures dihydropyridine, indole, and piperidine, pyridine,
thiazolidine, dihydrothiazine, and pteridine.

Basics of Organic Chemistry

Organic chemistry is the study of substances that contain carbon, hydrogen, oxygen, nitrogen, sulphur
etc. However carbon is the essential element in organic chemicals.
Atomic number of carbon is 6. Valence of carbon is 4. Carbon can form only 4 bonds (not less or more
than 4). Carbon can form chains and rings and can bind to the functional groups.
Carbon can form covalent bonds (sharing of electron between two elements).
Electronic configurations of carbon are 1S 2 2S 2 Sp 2 .

Hybridization:
SP 3 = Alkanes = 107 = Tetrahedral
SP 2 = Alkenes = 120 = Trigonal
SP = Alkynes = 180 = Linear

Functional groups:
Alcohol (-OH) or hydroxyl group.
• Water soluble or aqueous soluble.
• More tertiary alcohol have more lipid soluble.
• Primary alcohol. Primary alcohol oxidation produces an aldehyde.
• Secondary alcohol. Secondary alcohol oxidation produce ketone.
• Tertiary alcohol. Does not undergo oxidation.

Alcohols
OH OH OH

H H R1 R2 R1 R3
H H R2
Primary (1o) Secondary (2o) Tertiary (3o)

Amines (-NH 2 ): Amines are base

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• Categorized as primary, secondary and tertiary.

• Tertiary amines are more basic than secondary.
• Base strength of amines tertiary amine>secondary>primary>aromatic.
Amines: R1
NH2 R1 NH R2 N
R1 R2 R3

Primary (1o) Secondary (2o) Tertiary (3o)

Amine are water soluble. The primary amine more water soluble than secondary and tertiary (due to
increase in Alkyl chain). Primary>secondary>Tertiary.

• Amines undergo (phase 2 metabolism) glucuronidation, sulfate conjugation and methylation.

• Primary amines also undergo oxidative deamination (MAO enzymes).
• Primary & Secondary undergo acetylation.
• Secondary & tertiary amines undergo N-dealkylation.
• Tertiary undergoes N-oxidation.
• Phenolic amines susceptible to N-oxidation on the shelf.

Carboxylic acid (COOH): Pharmaceuticals that contain carboxylic acid group are acidic.

Esters (COOCH 3 ): Pharmaceutical that contain ester functional group, are acid or base sensitive, due to
hydrolysis.
Hydrolysis of ester produce  acid + alcohol.
Example. Penicillin G and acid sensitive beta lactam antibiotics, undergoes hydrolysis when taken
orally.

Amide (CONH 2 ): Amides undergo hydrolysis, however amides hydrolysis are slower than ester
hydrolysis. Amides upon hydrolysis produce acid + amine. Amides bonds are commonly exist in
proteins.

Stability of compounds

Benzene Cyclohexane Boat Tautomerism Chair

Conformation Conformation

Which is more stable

60 72 90 60

Tautomerism More Stable More stbale More Strain

Planar
Less strain Less Strain

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Isomerism: Compounds that have the same molecular formula but different chemical structures are
isomers or isomeric.

Optical isomerism: The optical isomers contain at least one asymmetric or chiral carbon atom.
Asymmetric centre or chiral centre, a carbon atom attached to four different groups. Using number
stereogenic centre or chiral centres or asymmetric carbon, one can predict the number optical isomers
possible in the structure. To calculate possible of optical isomers with given chiral centres use formula
2n where n = number of chiral centres.
Enantiomer are mirror image with one asymmetric center and non superimposable.

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if 3 chiral groups in structure. How many optical isomers are possible? 2n

CH3 CH3
C H H C
H3C CH3
OH HO

D (+) or L (-) or recemic (dL) or (±)

Same physical and chemical properties except in rotation of plane polarized light. Enantiomers can
have large differences in potency, receptor fit, biologic activity, transport and metabolism.
Levorphanol Dextrophanol
L(-) D(+)
Narcotic analgesic and antitussive Only antitussive

Diastereoisomers. Two asymmetric carbon atoms. They are super imposable and are not mirror
images.
Diastereomers

H NH CH3 OHNH-CH3
C C CH3 C C CH3
HH
OH H

Geometrical isomers (Cis and Trans isomers). To form trans isomers, it is essential to have double
bond. Examples of geometrical isomers include 2-butene, and diethyl stilbesterol (synthetic
estrogens) and several other drugs.

Structure Activity Relationship (SAR)

Lead structure. Chemical substance with therapeutic use.
Pharmacophore. The pharmacophore of drug molecule is that portion of the molecule containing the
essential organic functional group that directly interact with receptor active site thereby it shows
biological activity of interest.

Analog. Molecule with same skeletal structure with different functional groups attached.
Some examples of analogs H 1 -antihistamines (O-missing).

Homolog. Difference of –CH 2 - in identical molecules. Example. phenothiazines (antipsychotic), a

chlorpromazine is a dopamine antagonist and used as antipsychotic drug and tricyclic antidepressants.

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S S

N Cl N Cl
CH2CH2N(CH3)2 CH2CH2CH2N(CH3)2

Phenothiazines chlorpromazine

Bioisosters. The functional groups or atoms that impact similar physical and chemical properties on a
molecule. Example methyl, ethyl, bromine, and chlorine.

S O

N Cl N Cl
CH2CH2C(CH3)3 CH2CH2C(CH3)3

Some examples of bioisosters phenothiazines, and diethyl stilbesterol (synthetic estrogens).

Important concept!
Fundamental pharmacophores for drugs used to treat disease.

Pyridine ring Nicotinic acid is vitamin B 3 . This metabolizes to

Nicotinic Acid nicotinamide.
Nicotinamide
Nicotine N

Isoniazid Pyridine
Dihydropyridine ring Dihydropyridine are molecules based upon pyridine
Amlodipine that have been semi-saturated with two
Nifedipine substituent's replacing one double bond
Felodipine N Particularly well known in pharmacology as L-type
Nicaradipine H calcium channel blockers.

Dihydropyridine

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Piperidine ring Present in numerous natural alkaloids such as

Morphine piperidine and quinine, and is the main active
Codeine chemical agent in black pepper and relatives, hence
Heroin N the name. Piperidine is also a structural element of
Meperidine H many pharmaceutical drugs such as raloxifene,
Thioridazine minoxidil, thioridazine and mesoridazine.
Haloperidol Piperidine
Risperidone
Muscarinic blockers
Atropine
Ipratropium
Bromotropin
Scopolamine
Pyrrolidine ring is a cyclic amine
Muscarinic blockers H Pyrrolidine is found naturally in the leaves of
Atropine N tobacco and carrot. Pyrrolidine ring is the central
Ipratropium structure of the amino acids proline and
Bromotropin hydroxyproline.
Scopolamine Pyrrolidine

Imidazoline ring Imidazoline is a nitrogen containing heterocycle

Clonidine N NH derived from imidazole.

Imidazoline
Isoxazole: Sulfonamide Isoxazole is an azole with an oxygen atom to the
nitrogen. Isoxazole also form the basis for the COX-2
N inhibitor.
O

Isoxazole
β-Lactams H Penicillin nucleus. Beta lactam is the square at the
Penicillin’s
R N S centre.
Cephalosporin N Cephalosporin's  Beta lactam
O
O
O OH

Beta Lactam
Amino penicillin's NH2 Beta lactam antibiotics
Amoxicillin
Ampicillin CH
R
HO

Amino Penicillin's
Pyrazole Pyrazoles are used for their analgesic, anti-
COX II inhibitors H inflammatory, antipyretic, anti-arhythmic,
N tranquilizing, muscle relaxing, psychoanaleptic,
N
anticonvulsant, Monoamineoxidase inhibiting,
antidiabetic and antibacterial activities.
Pyrazole
Indole is an aromatic heterocyclic compound
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Indole ring Indole is solid at room temperature. It occurs

Serotonin naturally in human feces and has an intense fecal
(Neurotransmitters, N odor. At very low concentrations, however, it has a
present in CNS). H flowery smell, and is a constituent of many flower
Triptans Indole scents (such as orange blossoms) and perfumes. It
also occurs in coal tar.

Quinolone Quinoline or benzopyridine, is a heterocyclic

Quinine, hydroxyl quinine aromatic organic compound
and quinidine It is toxic: short-term exposure to the vapour causes
irritation of the nose, eyes, and throat as well as
N
H dizziness and nausea. Longer-term effects are
uncertain, but quinoline has been linked to liver
Quinoline damage
Sulfhydril group Captopril is an ACE I consist of sulfhydril group that
Captopril O gives rash and metallic taste. Sulfhydril group is
HS - H2C active groups binds with enzyme.
N
CH3
CO2H
Captopril
GABA derivatives Gabapentin was initially synthesized to mimic the
Gabapentin, Pregabalin, H2N COOH chemical structure of the neurotransmitter gamma
Vigabatrin aminobutyric acid (GABA), but is not believed to act
on the same brain receptors. Its exact mechanism of
action is unknown, but its therapeutic action on
neuropathic pain is thought to involve voltage gated
GABA Group N-type calcium ion channels.

Imidazole
Histamine, histidine and N
azole antifungals
N
H

Tips
Essential functional groups in the Structure activity of drugs
1 Amlodipine, Felodipine, 2. Muscarinic blockers, 3. nicotinic acid,
Nifedipine, Nicardipine Atropine, Ipratropium, nicotinamide,
Bromotropine, nicotine,
Scopolamine isoniazid
4 Penicillins, Cephalosporin 5. Pteridyl ring 6. Morphine, Codeine,
7. Clonidine 8. Ranitidine 9. Sulfonamide
10 histamine, histidine & 11 Indole ring 12 quinolone ring
azole antifungals, ARB’s
13 combination of piperidine & 14 3 rings of cyclohexane and 1 COX II
pyrrolidine ring cyclopentane 15 inhibitors

• Pyridine ring ( )

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• Dihydropyridine ring ( )
• Piperidine ring ( )
• Pyrrolidine ring ( )
• Imidazoline ring ( )
• Isoxazole ( )
• Beta lactam ( )
• Amino penicillins ( )
• Pyrazole ( )
• Steroids ( )
• Folic acid ( )
• Imidazole ( )
• Imidazole ring ( )
• Serotonin ( )
• Quasi ring ( )
• Vitamin K ( )
• Ciprofloxacin ( )
• Quinidine & Quinine ( )
• Isomers ( )
• example of geometrical isomers ( )

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24
Medicinal Chemistry and Pharmacology of
Autonomic Nervous System

Questions Alerts!
Common questions in pharmacy exam is to ask!
• Biosynthesis of catecholamine's (Tyrosine --> Levodopa --> dopamine --> norepinephrine --
> epinephrine).
• Structure activity relationship of direct acting acetylcholine agonist.
• Structure activity relationship of atropine and muscarinic blockers.
• Pharmacology and structure activity relationship of sympathomimetics like
pseudoephedrine, ephedrine, and crystal meth.
• Pharmacological actions of sympathetic receptors alpha1&2 and beta 1&2.
Parasympathetic receptors like muscarinic and nicotinic.

Nervous System

Central Nervous System (CNS) Peripheral Nervous System (PNS)

Spinal cord and brain

Autonomic Nervous System (ANS) Sensory somatic nervous System

12 pairs of cranial nerves
31 pairs of spinal nerves

Cholinergic Adrenergic

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Functions of ANS
• The autonomic nervous system (ANS) controls involuntary body functions.
• The ANS is composed of two divisions:
• Sympathetic (adregenic) system
• Parasympathetic (cholinergic) system.

Types of Neurons in ANS

• Efferent neurons (motor neurons)  deliver message from brain to organs
• Afferent neurons  Collects message from organs
to the brain
• Efferent neurons divided into the
• Sympathetic (adrenergic) nervous system
• Parasympathetic (cholinergic) nervous system

ANS is responsible for regulation of

• Internal metabolic activity
• Myocardium
• Smooth muscle of the viscera
• Glandular activity
• Hormonal activity
• Ensure that the body operates in optimum range

Sympathetic (adrenergic) Parasympathetic (cholinergic)

Originate in the thoracic and lumbar region Originate in sacral and cranial region
Post ganglionic nerve fibre very long Post ganglionic nerve fibre very short
Preganglionic nerve fibre very short Preganglionic nerve fibre very long
Ganglia is near spinal cord Ganglia is near innervated organs
Neurotransmitters Neurotransmitters. ACh
Norepinephrine (NE)
Epinephrine (epi)
Dopamine (D)
ACh
Receptors: Receptors
Norepinephrine (NE) α 1 ,α 2 , β 1 (Not on β 2 ) AChM 1 , M 2 , M 3 , M 4 and M5, N1 and
Epinephrine (epi) α 1 , α 2 , β 1 , β 2 N2
DopamineD 1 > β > α
ACh  N 1

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α1 α2
Vasoconstrictor in peripheral Centrally in brain inhibitory

B1 B2

Drug receptors
Generally pharmacological receptors can be categorized into 4 types
• Seven trans membrane proteins
• Ion channels
• Transcriptional regulators
• 1-Transmembrane proteins

Seven trans membrane proteins

The G protein coupled receptors are the largest types of pharmacological receptors, which almost 200
human receptors are known to date.

The G proteins coupled receptors are the major therapeutic significance with well-established
therapeutics studies.

Examples of G proteins coupled receptors as therapeutic targets are Acetylcholine, muscarinic,

norepinephrine, beta receptors, angiotensin AT 1 , dopamine, Serotonin, histamines, and opioids.

• Glutamic acid (glutamate) excitatory NMDA receptor. Example. Memantine

• GABA inhibitory. Example Benzodiazepine, barbiturates, and antiseizure drugs.
• Dopamine inhibitory. G protein linked cAMP. Antiparkinson drugs and antipsychotics.
• Norepinephrine excitatory, antidepressants, and antianxiety.
• Serotonin excitatory and inhibitory. Antidepressant and antianxiety.
• Opioids peptide inhibitory neurotransmitters Enkephalins, and endorphins.

Ion channels. There are two types of ion channels

• Voltage gated. Na+ channel, Ca2+ channel, K+ channel
• Transmitter gated. neurotransmitter interact with specific receptors

Transcription regulators. There are over 150 receptors of this family, which acts as transcriptional
receptors. This is second major class of receptors, which include steroid hormones including estrogens,
androgens, the glucocorticoids such as corticosteroids, vitamin D, retinoic acid, and thyroxin.

One transmembrane proteins. These receptors include several growth factors such as tumor necrosis
factor, serine/threonin kinase, neurotropins, and cytokines.
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Most neurotransmitters interact primarily with postsynaptic receptors, but some receptors are located
on presynaptic neurons, providing fine control of neurotransmitter release.

Receptors in autonomic nervous system

Cholinergic receptors are classified as nicotinic N 1 (in the adrenal medulla and autonomic ganglia) or
N 2 (in skeletal muscle) or muscarinic M 1 (in the autonomic nervous system, striatum, cortex, and
hippocampus) or M 2 (in the autonomic nervous system, heart, intestinal smooth muscle, hindbrain,
and cerebellum).

Neurotransmitters Chemical structures Characteristics

Acetylcholine (ACh) CH3 Is a neurotransmitter of peripheral
N O
CH3 nervous system neuromuscular junction,
H3C
CH3
parasympathetic system, visceral motor
O nuclei in the brain stem, and basal nucleus
Acetylcholine (ACh)
of Meynert.
Epinephrine OH
H
Uses α1 , α 2 or β 1 , β 2 , β 3 adrenergic
N CH3
receptors, which are G-protein linked
receptors. Plays insignificant role in CNS
HO
Epinephrine
and is found in the adrenal medulla.
OH

OH
Uses α1 , α 2 or β 1 , β 2 , β 3 adrenergic
Norepinephrine NH2 receptors, which are G-protein linked
receptors is the transmitter of post
HO ganglianic sympathetic neurons and CNS
OH
Norepinephrine
(locus ceruleus), plays role in anxiety
states, panic, attacks, depression
Dopamine NH2 Uses D 1 and D 2 dopamine receptor, which
are G-protein-linked reception is depleted
HO Dopamine
in Parkinson disease and is increased in
schizophrenia.
OH

Serotonin (5- NH2

Uses 5HT receptor, which is a transmitter-
hydroxy- HO gated ion channel that is permeable to Na+
tryptamine. 5HT) and K+ ions is neurotransmitter of the
N raphe nuclei of the brainstem whose
H
neurons project to widespread areas of
5-HT
the CNS.
γ-Aminobutyric COOH Uses the GABA receptor, which is a
acid (GABA) H2N transmitter-gated ion channel that
-
Gama-Aminobutyric Acid (GABA) permeable to Cl ions. Uses the GABA
receptor, which is G-protein-linked
receptor is a major inhibitory
neurotransmitter in the CNS.

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Glycine COOH Uses the glycine receptor, which is

H2N H transmitter-gated ion channel that is
permeable to Cl- ion is the major inhibitory
H neurotransmitter in the spinal cord.
Glycine
Glutamate COOH Uses the N-methyl-D-aparate (NMDA),
H2N kainite, or quisqualate. A receptors, all of
COOH which are transmitter gated ion channels
H that are permeable to Na+, K+ and Ca2+
Glutamate ions.

Adrenergic receptors are classified as 1 (postsynaptic in the sympathetic system), 2 (presynaptic in

the sympathetic system and postsynaptic in the brain), 1 (in the heart), or 2 (in other sympathetically
innervated structures).

Dopaminergic receptors are classified as D 1 , D 2 , D 3 , D 4 , and D 5 . The D 3 and D 4 play a role in thought
control (limit negative symptoms of schizophrenic processes), whereas D 2 receptor activation controls
the extra pyramidal system.
GABA receptors are classified as GABA A (activating chloride channels) and GABA B (potentiating cAMP
formation). The GABA A receptor consists of several distinct polypeptides and is the site of action for
several neuroactive drugs, including benzodiazepines, newer anticonvulsants (e.g. lamotrigine),
barbiturates, picrotoxin, and muscimol.

Serotonergic (5HT) receptors (with at least 15 subtypes) are classified as 5HT 1 (with four subtypes),
5HT 2 , and 5HT 3 . 5HT 1A receptors, which occur presynaptically in the raphe nucleus (inhibiting
presynaptic uptake of 5HT) and postsynaptically in the hippocampus, modulate adenylate cyclase.
5HT 2 receptors, located in the fourth layer of the cortex, are involved in phosphoinositide hydrolysis.
5HT 3 receptors occur presynaptically in the nucleus tractus solitarius.

Glutamate receptors are classified as inotropic NMDA (N-methyl-D-aspartate) receptors, which bind
NMDA, glycine, zinc, Mg2+, and phencyclidine (PCP, also known as angel dust) and affect the influx of
Na+, K+, Ca2+ and non-NMDA receptors, which bind quisqualate and kainate. Non-NMDA channels are
permeable to Na+ and K+ but not to Ca2+. These excitatory receptors mediate important toxic effects by
increasing calcium, free radicals, and proteinase. In neurons, synthesis of nitric oxide (NO) involving
NO synthase increases in response to glutamate.

Opioid receptors and neurotransmitters are peptide type. Endorphin-enkephalin (opioid) receptors are
classified as µ 1 and µ 2 (affecting sensor motor integration and analgesia), 1 and 2 (affecting motor
integration, cognitive function, and analgesia), and 1 , 2 , and 3 (affecting water balance regulation,
analgesia, and food intake).

Home work
µ 1 and µ 2 1 and 2 1, 2, and 3
Morphine
Fentanyl
Methadone

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Effector Organ Sympathetic Parasympathetic

Adipose ↑ Lipolysis (β 3 )
Metabolise fatty acids
Arterioles
Skin and mucosa Constriction (α 1 ) Some relaxation (M)
Skeletal Muscle Usually relaxation (β 2, M) Some relaxation (M)
Bladder
Detrusor Relaxation (β 2 ) Contraction (M 3 )
Sphincter Contraction (α 1 ) Relaxation (M)
Eye
Radial Muscle, Mydriasis (contraction, α 1 ) -
iris - Miosis (M)
Sphincter muscle, Accommodation Contraction for near vision (M)
iris (Relaxation, β 2 )
Ciliary muscle
Heart
Sinoatrial node ↑Heart rate ↓ Heart rate (M 2 )
Atrioventricular (β 1 )Chronotropic ↓ Conduction (M)
node ↑ Conduction ↓ Contractility (M)
Atria (β 1 )Dromotropic ?
Ventricles ↑ Contractility
(β 1 )Inotropic
?
Kidney Renin secretion (β 1 ) -
Lacrimal glands - ↑ Tear secretion (M)
Liver Glycogen breakdown (β 2 ) Glycogen synthesis (M)
Lung (bronchial Relaxation (β 2 ) Contraction (M 2 )
muscle)
Male sex organs Ejaculation (α 2 ) Erection (M)
Nasopharyngeal - Mucus secretion
glands
Pancreas ↑ Insulin secretion (β 2 ) ↑ Fluid secretion (M)
Salivary Glands Viscous secretion (α 1 ) Marked water secretion (M)
Stomach & intestine
Motility Decrease (β 2 )  Peristalisis Increase (M)
Sphincters Contraction (α 1 )Spincter Relaxation (M)
Secretion - Stimulation (M)

Sweat glands ↑ Secretion (M) ↑ Secretion (M)

Uterus ↑ Contraction (α 1 ) -
Relaxes detrusor muscles
Relaxation (β 2 )
Veins (systemic) ↑ Dilation (β 2 ) -
Spleen Contraction (α 1 ) -
Heroin
Meperidine
Naloxone

Sigma receptors, currently classified as non opioid and mostly localized in the hippocampus, bind
drugs.

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Autonomic Innervations and Primary Effects

Receptor type shown in parentheses (α alpha, β beta, M=cholinergic-muscarinic). Note that
preganglionic synapses for both systems are cholinergic-nicotinic.
indicate absence of direct innervations. However, receptors are present and may be stimulated by
agonists.

Classification of adrenergic agonist (Sympathomimetics)

Sympathomimetics (agonist)

Catecholamines Noncatecholamines
* Dopamine * Albuterol (Salbutamol)
* Epinephrine * Terbutaline
* Isoproterenol * Salmeterol
* Norepinephrine * Metaproterenol
* Amphetamine
* Ephedrine
* Methylphenidate
Catechol amine type of neurotransmitters
NH2 Tyrosine
HO COOH

Tyrosine hydroxylase

HO NH2
L-dopa
HO COOH
dopa decarboxylase

NH2
Dopamine
HO
OH
dopamine b-hydroxylase

OH
NH2
Norepinephrine
HO
OH
phenylehtanolamine-N-methyltransferase
(S-Adenosyl Methionine - SAM)

OH H
N CH3

HO Epinephrine
OH

Note. phenylethanolamine

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Alpha2 agonist
H
N
R HN Imidazoline ring

Clonidine

CH3
OHCH3 OH
HO NH2
HO NH2
COOH
Decarboxylation

Methyl dopa - a prodrug Methyl Norepinephrine

Sympathetic antagonists

Beta Blockers Alpha Blockers

O
CH3
CH3O N NC
O CH2CHCH2NHCH N O
CH3
N
CH3O
NH2
Propanolol Prazosin

All alpha blockers contain 4-amino-6-7-dimethoxyquinazoline ring system attached to piperazine ring.
Reduction of furan ring of prazosin to the tetrahydrofuran ring of terazosin increases the duration of
action by altering rate of metabolism. Terazosin, doxazosin, tamsulosin have long half life and duration
of and that allows once daily dosing. Tamsulosin & Terazosin, alfazosin used for BPH.

Lipophylicity of beta blockers.

The lipophylic BBs primarily cleared by liver (Propranolol, pindolol, and metoprolol) hepatic
elimination). Hydrophilic (atenolol and Nadolol) are renally cleared.

Propranolol can penetrate into CNS thus can be used for anxiety and CNS SEs insomnia, depression,
and vivid dreams present only in propranolol.

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Cardioselective beta selective blockers are 4-substituted aryloxypropranolamine.

Labetalol and Carvedilol. Alpha 1 , beta 1 , and beta 2

Timolol, betaxolol, metoprolol block B 2 receptors in ciliary muscles. The ciliary muscles (gland)
produce aqueous humor.

Cholinergic

Cholinergic Agonist Muscarinic Antagonist

Direct cholinergic agonist Indirect cholinergic Tertiary amines Quaternary amine

agonist Atropine Ipratropium
Scopolamine Tiotropium
Acetylcholine agonist anticholinesterase Benztropine Glycopyrrolate
Trihexyphenidyl

Choline ester Pilocarpine

Bethanachol
Carbachol Reversible Reversible Organophosphate
Methanacol Quaternary alcohols Carbamate (Irreversible cholinesterase inh)
Donepezil Physostigmine Echothiophate, Malathion
Neostigmine Parathion
Rivastigmine Sarin
Pyridostigmine

Cholinesterase
Acetylcholine -------------> Acetyl + Choline

Structure activity of direct acting cholinergic drugs

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CH3
O CH3
H3C-N
Acetylcholine CH3 O
CH3
O CH3
Methanocholine H3C-N
CH3 CH3 O

Methyl group
CH3
O NH2
H3C-N
Carbacholine CH3 O
Carbamate group

CH3
O NH2
H3C-N
CH3 CH3 O
Bethanacholine Carbamate group

Methyl group

Indirect acting sympathomimetics amine. Example. Hydroxyamphetamine, ephedrine or

pseudoephedrine, methyl amphetamine, and tyramine.
Indirect acting sympathomimetics amines may have one, two, or no hydroxyl groups. The less the
hydroxyl group the higher the lipophylic and the greater the absorption and greater duration of
activity after oral administration. Alkyl substitution at the alpha carbon next to amino group reduces
the destruction of phenol and phenyl compounds and increases lipophylic characters meth crystal
structure.

OH H OH H H
NH2 CH3 N CH3 N CH3 N CH3

CH3 NH2 CH3 CH3 CH3

Amphetamine Dextroamphetamine Ephedrine

Pseudoephedrine Methamphetamine
A B C D E

Structure activity of anti-cholinergic drugs

Muscarinic antagonist

Tertiary amines Quaternary amine

Atropine Ipratropium
Scopolamine Tiotropium
Benztropine Glycopyrrolate
Trihexyphenidyl

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Quasi ring is present in muscarinic antagonist. It is combination of piperidine + pyrrolidine. Longer the
chain on nitrogen of quasi ring, lower antimuscarinic activity.

Tips
1. Methanol 2. Carbachol 3. Bethanechol
4. One methyl group 5. Alpha 1 6. Alpha 2
7. Beta 1 8. Beta 2 9. Scopolamine
10 phenylethanolamine N-methyl transferase 11 Quasi ring 12 Piperidine & pyrrolidine ring
13 Competitive muscarinic blockers, it act on
vestibular system and the CNS.
• Epinephrine act on? ( )
• Norepinephrine act on? ( )
• Enzyme that catalyzes norepinephrine to epinephrine ( )
• Muscarinic drugs essential group for anticholinergic action is? ( )
• Muscarinic blockers structure contain? ( )
• Acetylcholine, methanchol, carbachol and bethanechol differs in? ( )
• competitive muscarinic blocker, that act on vestibular system and the CNS ( )
• Choose 3 examples of direct acting acetylcholine agonist? ( )
• Scopolamine mechanism is  ( )
• Methanachol is structurally similar to acetylcholine, however differs in 
• Write three examples direct acting acetylcholine agonist? ( )
• Organophosphate antidote is? ( )
• Atropine overdose is treated by ( ) can get into brain
• Myasthenia gravis is treated by ( )

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25
Medicinal Chemistry and Pharmacology of
Histamines, Serotonin, Prostaglandin and Non-
Steroidal Anti-inflammatory Drugs

Questions Alerts!
Common questions in pharmacy exam is to ask!
• Chemical structure of diphenhydramine (lipid soluble) as sedative.
• Serotonin synthesis from tryptophan --> 5-hydroxy tryptophan -->Serotonin
• Serotonin pharmacological actions of agonist (triptans) and antagonist of 5HT3
(ondansetron).
• Structure activity of prostaglandin analogues PGE1 (misoprostol) and PGF2α (latanoprost).
• Pharmacology of leukotriene receptor antagonist montelukast and zafirlukast.
• Acetaminophen structure and metabolism that explains hepatotoxicity.
• Glutathione chemical structure.
• Acetylsalicylic acid pharmacological actions Antiplatelets, Antipyretic, Analgesic and Anti-
inflammatory actions.

Autocoids (local hormones). Chemical mediators that the body releases as a response to pathogens or
noxious substances. Produced in the body and has profound pharmacological effects.

Autocoids or chemical mediators

Endogenous type
Amine types
Ecosonides

Histamines Prostaglandins
Serotonin
Prostacyclin
Thromboxane
Leukotrienes
Bradykinin
Amines. No real clinical application in the treatment of diseases however antihistamines are of great
importance. Amine types of autocoids include histamines and serotonin.

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Endogenous Peptides
• Site of production for endogenous peptides are GIT, kidneys, lungs, pancreas and uterus.
• Physiological actions of endogenous peptides are.
• Prostaglandin’s. Pain sensation, development of inflammation
• Thromboxane. Aggregation of platelets
• Prostacyclin. Inhibition of platelet aggregation
• Leukotrienes. Inflammation, chemotactic properties (pull substances to them)

Histamines. The histamine is produced from mast cells. Histamines act on three receptors, of these H1,
H2 receptors are excitatory and H3 receptors.

Physiological functions of H 1 receptor typical

• Allergic and anaphylactic response to histamines.
• Gives bronchoconstriction, and vasodilatation.
• Increase capillary permeability.
• Spasmodic contractions of gastrointestinal smooth muscle.

H COOH H Important Concept!

N N Structure activity relation of
NH2 NH2
antihistamines
N N Ethanol amine lipid soluble and
-CO2 have tertiary amine cause
Histadine Histamine
-CH 2 - in histadine sedation
Chemistry of H 1 antihistamine. Usually lipid soluble, and similar
in terms of absorption and distribution.
• Good absorption after oral administration distribution with peak plasma concentration of 1 to 2
hours.
• Allows some to go to the blood-brain-barrier especially structural resemblance to histamine.
H 1 antihistamine chemical classification
• Ethylene diamines. Pyrilamine, and triplennamine
• Alkylamines. Brompheniramine, chlorpheniramine, and acrivastine.
• Ethanolamines. Diphenhydramine,
dimenhydrinate, and doxylamine. Identify structures!
• Piperazines. Meclizine, cyclizine, Diphenhydramine chemical structure!
hydroxyzine, and cetrizine. Tertiary amine is present
• Phenothiazine. Promethazine Lipid soluble
• Dibenzocycloheptenes. Has C-O-C, C-N bonds
Cycloheptadienes. Has aromatic rings (hydrophobic)
• Pthalazinone. Azelastine.
Piperidine. Terfenadine, astemizole, levocabastine, loratadine, and fexofenadine.

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Tertiary amine

CH3
O CH2CH2 N CH N N CH3
CH3

Diphenhydramine Cyclizine

Mechanism. Competitive antagonist of histamine receptors. H 1 receptors are located in the brain,
heart, bronchi, GI tract and vascular smooth muscle. Mast cells and basophiles are principle histamine
containing cells.

H1 Antihistamine

1st Generation (PM) 2nd Generation (AM) 3rd Generation

Ethanol amines. Piperazine derivatives Piperadine Derivatives
Diphenhydramine Cetrizine (Reactine) Desloratadine (Aerius)
Dimenhydrinate Piperidine Derivatives
Doxylamine Fexofenadine (Allegra)
Alkyl amines Loratadine (Claritin)
Chlorpheniramine
Piperidine Derivatives Once daily dose
Azatadine, Cyproheptadine
Piperizines
Meclizine, Cyclizine
hydroxyzine

Side effects. Sedation, dizziness, nausea, constipation, diarrhea, loss of appetite and anticholinergic.

Metabolism of antihistamines. Some examples of metabolites of antihistamine, that are used as drugs.
• Loratadine metabolizes to desloratadine.
• Hydroxyzine metabolizes to Cetrizine
• Terfinadine metabolizes to Fexofenadine.
O
H3C
H3C
OH
CH3 CH3
CH3
HO N
HO N
OH
OH

Terfinadine Fexofenadine

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N N
N COOCH2CH3 NH

Cl Cl
Loratadine Desloratadine

Histamine H1-receptor blockers

Particularly Particularly Particularly All H1- antihistamines

Diphenhydramine, promethazine cyproheptadine
promethazine

Anti Alpha Dopamine Serotonin Histamine H1 Histamine H2

Cholinergic Adrenergic receptor receptor receptor receptor
(muscarinic) receptor

Pharmacology H1-antihistamines
H 1 antihistamine pharmacological actions (drugs action) takes place by blocking blocks H 1 -histamine
receptor effect. This results in beneficial effect on, Allergic symptoms, seasonal rhinitis, conjunctivitis,
rhino viral infections (common cold) and urticaria.
H 1 -antihistamine therapeutic uses. Antihistamine may bring relief to cold symptoms, runny nose, red
and itchy eyes. Allergic rhinitis symptoms such as nasal allergies. Antihistamine sedative properties are
utilized to treat temporary relief of insomnia. Antihistamines are effective to treat nausea and
vomiting.

Used for
• Allergies 2nd gen
• Runny nose Diphenhydramine
• Insomnia  Diphenhydramine
• Nausea and (motion sickness)  Dimenhydrinate, doxylamine.
• Motion sickness  Dimenhydrinate, Meclazine & scopolamine, Promethazine.

Side effects.
Anticholinergic. Dry mouth, constipation, tachycardia, and difficulty voiding urine.
CNS. Dizziness, drowsiness, performance impairment (memory, work performance, visual motor
coordination).
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GI. Constipation
Contraindications with mainly first generation anti histamines. Narrow angle glaucoma, bladder neck
obstruction, hyperthyroidism, cardiovascular disease, and benign prostate hyperplasia.

Comparison of 1st and 2nd generation of H 1 antagonist

First generation Second generation
Higher sedation and anticholinergic Less sedation due to less lipid soluble and do not
Tertiary amine (cause sedation) penetrate the BBB.
Lipids soluble, and can cross blood brain barrier NO anticholinergic effect
More central anticholinergic side effect Drug interaction
Anti-serotonin Terfenadine/astemizole. Cardiac arrhythmias
Anti-bradykinin characterized by prolong QT interval (torse de
Usually QID pointes).
Grapefruit juice (apple, orange) reduces oral
bioavailability of fexofenadine.
Dimenhydrinate, Meclizine, cyclizine and Cetrizine have high fatigue and somnolence
promethazine are useful for the prophylaxis of (10%).
motion sickness and vertigo. Loratadine have low fatigue and somnolence.
Promethazine is the most potent antihistamine,
and limits its use due to sedation.

Pregnancy. Bromopheniramine can cause teratogenicity. All 1st gen and 2nd generation antihistamine
are used in pregnancy except bromopheniramine due to its teratogenicity. 1st generation commonly
used due to its wide experience.

In children (less sedative) antihistamines such as loratidine or use sodium chromoglycate. First
generation impairs academic and learning abilities in children. Most antihistamine and nasal cromolyn
considered safe in children over 2 years of age. There is limited information about fexofenadine in
under 12-year-old age.

Topical antihistamines. Olopatadine (Pantanol), Levocabastine (Livostin), Emedastine (Emadine),

Azelastine (Astelin), and Kitotifen (Zaditor).
Topical applications of H 1 receptor antagonist to the eye relieves itching, congestion of conjunctiva
and erythema. The density of mast cells are high conjunctiva and tear film.

H 2 receptor antagonist (H 2 RA) present on parietal cell, and help to produce HCl secretions. H 2
receptors mediated functions. H 2 receptors responses to histamine such as increased secretion of
gastric acid increase pepsin and intrinsic factor (Castle’s factor).

Ach Histamine Gastrin

Atropine Ranitidine

Muscarinic receptor H 2 receptor

IP 3 C a 2+ cAMP ?

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H+ secretion
PPIs

Classification of H 2 antagonist (H 2 RA). Ranitidine, Cimetidine, Famotidine and Nizatidine (drug names
end with "tidine").

H2 antagonist chemistry
Cimetidine, an H2-receptor antagonist

CH3 N CN
CH2SCH2CH2 NH C NHCH3
HN N
H 2 antagonist pharmacology. H 2 receptor antagonist competitively blocks H 2 receptors thus blocking
the effect of histamines on gastric secretions.

H 2 antagonist therapeutic use. To treat heartburn, dyspepsia GERD, GI ulcers, Stress-induced gastritis.

H 2 antagonist side effects. Cimetidine can cause gynecomastia. Mild diarrhea, or constipation,
headache, myalgia, confusion, hallucination, and excitement.

Administration: all H 2 RA are available oral and cimetidine, famotidine and ranitidine are also
parenteral . Oral have rapid absorption.

Serotonin (5-Hydroxy tryptamine 5HT)

Serotonin neurotransmitters involved in vasoconstriction, vasodilation, regulation of body
temperature, sleep, depression and hormonal regulations.

Tryptophan (amino acid)  5-hydroxy tryptophan  Serotonin (neurotransmitter).

Tryptophan is precursor of serotonin and tryptophan taken up in neuron and converted to serotonin.
Conversion of tryptophan to serotonin takes place in two reaction, first hydroxylation and
decarboxylation catalyzed by tryptophan hydroxylase and L-amino acid decarboxylase respectively.
Serotonin contain indole ring.

NH2
NH2
HO HO CH2CH2NH2
COOH COOH
N
H N N
Hydroxylase H Decarboxylase H
Tryptophan Hydroxy tryptophan Serotonin (5HT)

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HO CH2CH2NH2 Niacin

N Tryptophan Serotonin
Indole ring H

Serotonin (5HT) Melatonin

MAO
Serotonin---------------> 5-hydroxy indole acetic acid

Serotonin targets
Serotonin receptors
Serotonin reuptake
Break down of serotonin by MAO.

Physiological functions of serotonin receptors. Serotonin group has several subtypes of receptors:
5HT 1 , 5HT 2 , and 5HT 3 Deficiency of 5HT 1 , 5HT 2 and 5HT 3 gives anxiety, depression, aggression,
impulsive and appetite.
• 5HT 1D ; Auto receptors inhibit presynaptic activity in both serotoninergic and adrenergic neurons in
the CNS.
• 5HT 2 . Vasoconstriction, and platelet aggregation
• 5HT 3 . Excessive of 5HT 3 gives nausea, vomiting
• 5HT 4 . Release of acetylcholine in the enteric region

Subtype Clinical significance Drug Clinical Use

5HT 1a CNS Buspirone 5HT 1a agonist Antianxiety,
antidepressant, antiaggressive,
antiemetic.
5HT 1b/1d CNS, vasoconstriction Triptan Migraine attacks
5HT 1c CNS
5HT 2 Platelets, smooth muscles. Ergotamine Antimigraine (acute)
CNS (-ve schizophrenic Cyproheptadine
symptom).
5HT 3 CNS, gastrointestinal Ondansetron Antiemetic in chemotherapy
5HT 4 CNS, gastrointestinal

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Serotonin

5HT1a 5HT1b/1d 5HT2 5HT3 5HT4

Agonist Non selective Agonist

Agonist Antagonist
Buspirone Ergotamine (DHE) are Cisapride
Triptans Ondansetron
5HT2 agonist.
Sumatriptan Alosetron
Cyproheptadine affects
Rizatriptan Fabesetron
both 5HT2 and 5HT1
Zolmitriptan Ramosetron
Trazadone is 5HT2
Naratriptan agonist

Antagonist of 5HT2a
atypical antipsychotic
olanzapine
clozapine
risperidone
Quetiapine

5HT 1 receptor class of drugs

5HT 1B/1D receptor agonist
Mechanism. Contraction of arterial smooth muscles, especially in carotid and cranial circulations.
Triptans (all are indole derivatives). Sumatriptan, Rizatriptan, Naratriptan, Zolmitriptan, Almotriptan,
and Frovatriptan.

CH3 CH3
NSO2CH2 CH2CH2N
H CH3
N
H
Indole ring
Sumatriptan

5HT 1D/1B receptor agonist therapeutic uses. Triptans are used to treat migraine headache attacks.
5HT 1D/1B receptors pharmacological actions cause constriction.
5HT 1D receptor agonist side effects. Feeling of warmth, dizziness, tightness or heaviness in the chest,
rarely patient may experience chest pain.

5HT 4 agonist
Cisapride (a benzamide), and tagaseride (indole derivative). Ergotamine serotonin partial agonist.
Ergot alkaloids have agonist and antagonist properties.

Ergot alkaloids and derivatives with antagonist/partial agonist activity include ergonovine,
dihydroergotamine (DHE), methysergide and bromocriptine.
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Cl
O
H2N C NH N CH2CH2CH2O F

OCH3 CH3O

Cisapride

5HT 3 receptor antagonist. Ondansetron (indole derivatives) and Granisetron (benzimidazole

derivative).
O
CH2 N N

N
CH3

Indole ring Ondansetron

5HT 3 receptor antagonist pharmacology act on 5HT 3 mixed receptors and can effect on nausea and
vomiting.
5HT 3 receptor therapeutic use ondansetron and granisetron are used to treat chemotherapy induced
or vagal stimulation and surgery nausea and vomiting.
5HT 3 receptor antagonist side effects. Ondansetron side effects. Constipation, headache, dizziness and
granisetron diarrhea.

Prostaglandins, throboxanes, prostacyclins and leukotrienes are synthesized from arachidonic acid.
These four substances are naturally occurring 20-carbon cyclopentanofatty acids derivative.

Ecosonides
Ecosonides are metabolites of arachidonic acid (a fatty acid). Examples of ecosonides are
prostaglandin analogs, thromboxanes, and prostacyclins. Arachidonic acid is derived from linoleic acid
or taken from diet and esterified to phospholipids (phosphatidylethanolamine). Site of production of
endogenous peptides are GIT, kidney, pancreases and uterus.

Arachidonic acid is derived from dietary linoleic acid (2 double bonds) or is ingested from the diet and
esterified to phospholipids.

Prostaglandin
Prostaglandin has been classified based presence and absence of keto or hydroxyl groups at 9 and 11.
Subscripts relate to the number of double bond present in aliphatic chains.
O
9 COOH

HO 11

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Corticosteroids Leukotrienes

Lipoxygenase

Membrane phospholoipids Arachidonic acid

Cyclooxygenase
NSAID, ASA, COX-II

Phospholipase A2
Prostaglandins G

Hydroperoxidase

Prostacyclin (PGI2) Thromboxane A2

PGH2
Platelet aggregation Paltelet aggregation
Vascular tone Vascular tone
Bronchial tone Dipyridamole
PGE2 & PGF2
Uterine tone
Uterine tone
Vascular tone
Bronchial tone

PHYSIOLOGICAL FUNCTIONS. Platelet aggregation, relaxes bronchial and GI smooth muscles, relax
smooth muscles, and inhibit gastric acid secretion, pain, edema, and inflammation.

Prostaglandin analogs

PGE1 PGE2 PGF2α PGI2 TxA2

Pyrogen elevate Bronchoconstriction Increase Platelets

Protects gastric Decrease platelets
PGE2 contraction contraction of aggregation
mucosa aggregation
of uterus uterus

Misoprostol Dinoprostone Epoprostenol Thromboxane A2

Alprostadil Bronchial & Latano"prost" Dipyridamol
Blood vessels
Bronchial & smooth muscle Bronchial & inhibits platelet
dilatation
smooth muscle dilatation smooth muscle aggregation
Inhibit aggregation
dilatation constriction of platelets

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PGE analogs
PGE 1 analogs classification. Misoprostol, and alprostadil.
PGE 1 analogs medicinal chemistry. Misoprostol is chemically belongs to Economides.
O
COOCH3
CH3
CH3
HO PGE1
Misoprostol structure. Consist of 2-OH and one double bond.

PGE 1 analogs pharmacology. PGE 1 and PGH 1 can be used to produce relatively local vasodilatation.

PGE 1 analogs therapeutic uses.

• Misoprostol is used for prevention of NSAID induced GI ulcers.
• Combination products. Naproxen + misoprostol, and diclophenac + misoprostol.
• Misoprostol vaginal use is for cervical priming before endometrial procedures.
• Alprostadil. In adults it useful for the treatment of impotence due to erectile dysfunction.
• Alprostadil is used for temporary maintenance of a patent ductus arteriosus when awaiting
corrective surgery for congenital heart defects.

PGE 1 analogs side effects

• Misoprostol. Abortificient side effect. The common side effects is diarrhea.

PGE 2 analogs classification

• Dinoprostone derivatives. Dinoprostone
PGE 2 analogs therapeutic uses. Dinoprostone are used for their abortificient effects and to induce
cervical ripening in pregnancy.

PGF 2α analogs classification. LATANOPROST (XALATAN), TRAVOPROST (TRAVATAN), BIMATOPROST

(LUMIGAN), UNOPROSTONE (RESCULA) and Carboprost (Hemabate).

PGF 2α analogs pharmacology. Lowers IOP by increasing uvescleral (aqueous humor) outflow.
PGF 2α analogs therapeutic uses.
• Latanoprost (Xalatan) 0.005% ophthalmic solution. Used topically to lower intra ocular pressure
in OAG, combination products latanoprost + timolol indicated for open and close angle glaucoma.
• Travoprost (Travatan). Topical ophthalmic drug
• Bimatoprost (Lumigan). Topical ophthalmic drug
• Unoprostone (Rescula). Topical ophthalmic drug
• Carboprost (Hemabate). Abortificient (withdrawn).

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PGF 2α analogs side effects. Eye pigmentation, lengthening and thickening eyelashes.
PGI analogs. Epoprostenol (Prostcyclin)
PGI analogs (prostacylcin) chemistry

PGI analogs (prostacylcin) pharmacology

PGI analogs (prostacylcin) therapeutic use. Epoprostenol. Used in the treatment of emergency
pulmonary hypertension. It produces antiplatelets action.

Thromboxanes (TxA2).
• Increase platelet aggregation and potent vasoconstrictors.
• Dipyridamol blocks thromboxane thus produce antiplatelet action.

Leukotrienes

Leukotrienes are produced from arachidonic acid; this reaction is catalyzed by 5-lipoxygenase enzyme,
which oxidize polyunsaturated fatty acids possessing two cis double bonds separated by a methylene
group to produce lipid hydroperoxide. Plays important role in numerous physiological functions.
• Slow reacting substance of anaphylaxis.
• Heart. Negative inotropic, and smooth muscles chemotaxis.
• GI tract. Neutrophil chemotaxis.
• Pulmonary (major). Bronchoconstriction, increase permeability, and increase mucus secretion.
• Blood. Chemotactic agent for neutrophil, eosinophils, and modify lymphocyte proliferation and
differentiation.
Leukotriene antagonists chemistry. Zafirlukast and montelukast have peptidomimetic structure and
inhibit LTC 4 and LTD 4 receptors.

Leukotrienes antagonists therapeutic uses.

Zafirlukast. For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age
and older. Take empty stomach to enhance it absorption.

Montelukast. Can be used in children over 2 year age, montelukast may be taken without regard of
food. Available as chewable tablet (once daily in the evening) and granules. Administer granules
directly into mouth or mix with teaspoon of cold or room temperature applesauce, carrot, rice or ice
cream. Do not take Aspirin or NSAIDs while on this medication.
Leukotriene inhibitors are drug of choice for the treatment of Aspirin induced asthma and
maintenance.
Side effects. GI upset, abdominal pain, diarrhea, liver dysfunction, and headache.
Drug interactions. Terfenadine significantly reduces the plasma concentration of zafirlukast.

Non Steroidal Anti-inflammatory Drugs (NSAIDS)

Salicylates derivatives
Acetyl salicylic acid (ASA) Antiplatelets, antipyretic, analgesic and anti-inflammatory
Salicylic acid
Methyl salicylates Wintergreen oil-topical agent, counter irritant
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Salsalate, sodium thiosalicylate Injectable

Choline salicylate Oral liquid
5-Aminosalicylic acid Crohn's disease and ulcerative colitis
(Mesalamine)
Olsalazine
Sulphasalazine Ulcerative colitis and Crohn's disease
Diflunisal Diflurophenyl derivative of salicylic acid

Pyrazolone derivatives
Sulfinpyrazone
Phenylbutazone
Propionic acid derivatives The order of gastric ulcerogenic activity.
Sulindac>naproxen >ASA, indomethacin, ketoprofen, ibuprofen
Ibuprofen
Ketoprofen
Naproxen
Carprofen
Fenoprofen
Acetic acid derivatives
Indomethacin High renal side effects, have high anti-inflammatory
Diclofenac Voltaren
Ketorolac Toradol. NSAID used for acute pain.
Sulindac Clinoril
Etodolac
Anthranilic acid derivatives
Mefenamic acid
Meclofenate
Oxicams derivatives
Piroxicam Feldene
Meloxicam
Pyrazole derivatives.
COXII inhibitors
Celecoxib Celebrex

Only Lumerocoxib has no sulfa allergy, where all other Cox II inhibitors have sulfa allergy.
Chemistry of Salicylates derivatives

F OH
COOH OH

F COOH
O
CH3 COOCH3
O

Diflunisal (Dolobid) Methyl salicylate (Wintergreen oil)

Acetyl Salicylate

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Acetyl salicylic acid (ASA)

• Pharmacological actions. ASA exhibits analgesics, antipyretics, anti-inflammatory and antiplatelet
actions. ASA irreversibly inactivates both COX 1 & COX 2 , where as all other NSAIDs inactive
reversible COX 1 &COX 2 .

Analgesic action
• Prostaglandin PGE 2 thought to sensitize the nerve endings to the action of bradykinin, histamines
and other chemical mediators, thus inflammatory process may cause analgesic action. Decrease of
PGE 2 synthesis represses the sensation of pain. ASA analgesic dose 325 mg every 4 to 6 h.

Antipyretic action
• Prostaglandin PGE 2 stimulation occurs when pyrogen an endogenous fever producing agents such
as cytokines is released from the white blood cells that are activated by infection, hypersensitivity,
malignancy or inflammation. Salicylates lower temperature by decreasing PGE 2 synthesis. ASA
antipyretics dose 325 to 650 mg q 4 to 6 h PRN.
• Reye syndrome. Children with flu and viral infection should avoid using ASA, because it may cause
Reye’s syndrome.

Antiplatelets action
• Irreversible platelet inhibition and inhibition of Cox-I & Cox-II action gives antiplatelets action.
Antiplatelets 60 to 80 mg.

Anti-inflammatory action
• Cox-I, Cox-II and prostaglandin inhibition. The anti inflammatory dose of ASA 650 mg
Mechanism of action of ASA.
COOH
O OCH3
ASA
O

Cyclooxygenenase Active
O
COX I & II
O C CH3
Cyclooxygenase (inactive)

COOH
OH

Problems associated with NSAID and acetyl salicylic acid.

• Respiratory depression. Toxicity respiratory alkalosis and metabolic acidosis (increase CO2 and
decrease pH).
• GI effects. due to inhibition of prostaglandin PGEs. Prostacyclin PGI 2 inhibit gastric secretion. The
most common side effects of salicylate are GI disturbances like nausea, vomiting, epigastric
discomfort, peptic ulcers (dyspepsia, heart burn).
• PGE 2 and PGF 2α stimulates synthesis of protective mucosa in stomach and small intestine.
• Indomethacin has the highest incidence of (35 to 50%) of GI ulcers.

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• Renal problems. PGE 2 and PGI 2 are responsible for renal blood flow. It can cause acute renal
failure.

Reye's syndrome is an acute syndrome that may follow influenza and chicken pox infections in
children. It is characterized by symptoms of sudden vomiting, violent headache, and unusual behavior.
The Reye's syndrome is associated with only ASA.

Sulfasalazine chemistry
• Contains azo bond. Sulfasalazine contains a sulfonamide group, may cause allergy patients with
sulfa allergy.
• In metabolism undergoes azo reduction (phase I). Metabolism produces 5-amino salicylic acid.
Sulfasalazine, olsalazine, balsalazine are metabolized in the colon by gut flora to yield 5ASA. Avoid
in ASA allergic patients.
• Sulfasalazine therapeutic use drug of choice for ulcerative colitis.
• Sulfasalazine side effects: can cause megaloblastic anemia, and infertility (in men).

NH2 CO2H

Azo bond OH
5-aminosalicylic acid
O N (Mesalamine)
S
COOH N OH
N Azoreductase +
O N
N S
HO at Gut N
OH
Sulfasalazine NH2
Sulfapyridine

Azoreduction in colon
Diflunisal
• Diflurophenyl derivative of salicylic acid.
• No salicylate toxicities (does not produce salicylic acid)
• No antipyretic action

Propionic acid derivatives. Ibuprofen, Ketoprofen, Naproxen, Carprofen and Fenoprofen.

Propionic acid

H3C
CH COOH

Ibuprofen

Acetic acid derivatives. Indomethacin, Diclofenac , Ketorolac , Sulindac and Etodolac.

Acetic acid
H3CO COOH
CH3
N
O
Indomethacin

Cl
Acidic acid derivative therapeutic uses
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• Indomethacin is used for acute gout attacks treatment, more CNS effect, aplastic anemia and
contraindicated in elderly
• Diclofenac (Voltaren) ophthalmic drops
• Ketorolac (Toradol) short-term use only
• Sulindac (Clinoril) safest in renal failure

Anthranilic acid (fenamates) derivatives

• Mefenamic and Meclofenate acid

Anthralnic acid

H3C CH3
NH

COOH
Mefenamic acid
Mefenamic acid is associated with severe diarrhea and associated with inflammation of bowel.

Anthranilic acid (fenamates) derivatives therapeutic use:

Preferred in dysmenorrhea TC, 4th Ed. Page 758

Oxicams derivatives
Piroxicam (feldene), Meloxicam (Mobic) and Tenoxicam.
OH
CONH
N N
S CH3
O2
Piroxicam
Oxicams derivatives side effects
• Piroxicam (Feldene) Its mean half life is 50 hours, thus this can be used once daily dose, more
bleeding, contraindicated in elderly.

p-Aminophenol derivatives. Acetaminophen chemistry.

Acetaminophen is an active metabolite of phenacetin or acetanilide.

Phenacetin or acetanilide Acetaminophen
H3COCHN

Dealkylation
CH3CONH OCH2CH3

OH
Phenacetin Acetaminophen
Acetanalide--> Hydroxylation--> acetaminophen
Acetaminophen pharmacology. Acetaminophen has antipyretic and analgesic action.

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• Inhibits central prostaglandin synthesis in CNS. Less effective in blocking peripheral prostaglandin
synthesis, acetaminophen has no anti-inflammatory activity and does not effect on platelet
function.
• Antipyretic action dose is 325 to 650 mg q 4 to 6 h PRN.
• Acetaminophen does NOT have Rye syndrome and may safely be able to be used in patient (child)
with varicella or an influenza type viral infection.
• Can be used in ASA or NSAID allergic patients. Can be used in children because no Rye syndrome.
Advantages are stable in liquid thus available in various solutions.

Acetaminophen side effects.

• Skin rash, hemolytic anemia (long term phenacetin use) renal dysfunction and tubular necrosis
hepatotoxicity if it used more than 4 g/day. With excessive alcohol max dose 2 g/day.

Acetaminophen metabolism. Acetaminophen undergoes phase I metabolism and glucuronidation,

sulphate conjugation, and glutathione conjugation. Toxic intermediate of phase I metabolism is N-
benzoquinoneimine, which is catalyzed by glutathione conjugation leading meracaptopurine.

Acetaminophen Metabolism

O
CH3 C NH OH

Acetaminophen
f er a se UDP-GT
tr ans
S ulfo
Glucoronidation
Sulfate conjugation
Cytochrome CYP 450

N-benzoquinoneimine

Glutathione conjugation

Mercaptopurine

HS
O
H
HOOC N COOH
N
H
NH2 O
Glutatione
Glutathione is consist of glutamic acid, cysteine, and glycine
Antidote of acetaminophen is N-acetylcysteine (CH 3 CONH-CH-(COOH)CH 2 SH)
NAPB. N-acetyl p-benzoquinoneimine.
UDP-GT. Uridinyl diphosphate glucuronidase transferase.
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Cyclooxygenase inhibitors
• COX-I functions
• Daily synthesis of prostaglandin that contribute to normal homeostatic (arrest of bleeding).
• Protection of the gastric mucosa through prostaglandin
• Hemostasis through the synthesis of thromboxane.

COX-II functions
• Expressed only in response of inflammation of injury. E.g. Celecoxib (Celebrex), Veldecoxib
(Bextra).

Pyrazole derivatives
• COX 2 inhibitors. Celecoxib (Celebrex), and veldecoxib (Bextra).
• Side effects: Arrhythmias, GI upset, diarrhea, back pain, respiratory problems, and nephrotoxicity.
Celebrex contain sulfa group, therefore celecoxib has sulfa allergy.
• Celecoxib and veldecoxib have sulfonamide functional group.

Celecoxib (cerebrex)
SO2NH2
F3C N
N

CH3

Opioid Analgesics

Chemical classification of opioids

Benzomorphan derivatives
Pentazocine hydrochloride
Pentazocine lactate
Diphenylpropylamine derivatives
Propoxyphene hydrochloride
Propoxyphene napsylate

Morphinan Derivatives
Butorphanol tartrate
Nalbuphine hydrochloride

Natural opium alkaloids

Codeine phosphate
Hydromorphone hydrochloride
Morphine hydrochloride
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Morphine sulfate
Oxycodone hydrochloride
Oxymorphone hydrochloride

Phenylethylamine Derivatives
Methadone
Phenyl piperidine Derivatives
Alfentanil hydrochloride
Fentanyl citrate
Meperidine hydrochloride (pethidine)
Sufentanil citrate
Loperamide

CH3 Acetyl groups CH3

CH3
9 N N
N
1

O O
CH3O O OH O
HO 3 O 6 OH H3C C O O C CH3
Morphine Codeine Heroin

CH3 CH3
N CH3 H3C CH2 O
N H3C
N CH2CH2 C O C CH2CH3
N
HO CH3
H3C O
HO O O CH3O O O

Hydromorphone Oxycodone Methadone Propoxyphene

CH2CH CH2 CH3

Allyl group CH2CH C CH2
N CH3
N N
HO CH3 HO
CH3
HO O O HO HO
Pentazocine Butorphanol
Naloxone

Morphine structure activity

• Reactive metabolite of morphine is morphine 6-glucuronide

• Phenolic hydroxyl is important for activity. Analgesic activity is depends on p-phenyl-N-
alkylpiperidine moiety (4-phenylpiperidine). Piperidine ring is chair-form conformation and
perpendicular aromatic ring. It has tertiary amine group (methyl).
• Codeine, heroin, morphine, meperidine, hydromorphone is structurally same class and have cross
allergy. Hydrocodone is derivatives of codeine, hydromorphone is derivative of morphine.
• Methadone is chemical structure of propoxyphene.
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• Meperidine is piperidine analgesics, meperidine metabolizes to toxic metabolite normeperidine

this can cause seizures.
• Partial agonist/antagonist characteristics replacement of methyl moiety on the nitrogen atom with
larger substituent's.
• Allyl substitution is present in naloxone. This allyl group is associated with opioid antagonist
action.
• Substitutions at the C 3 and C 6 morphine hydroxyl group’s pharmacokinetic properties altered.
• Methyl substitution at C 3 reduces first-pass hepatic metabolism by glucuronide conjugation as a
consequence codeine and oxycodone have a higher oral, parenteral potency.
• Acetylation of both morphine hydroxyls gives heroin (more rapid access across the blood-brain
barrier compared morphine) in the brain heroin is rapidly hydrolysed to monoacetylmorphine and
morphine.
• Opioids as analgesics activity is due to p-phenyl n-methyl piperidine.
Pentazocine-kappa agonist, given with naloxone to prevent abuse.
Buprenorphine a mixed analgesic, more potent than morphine but less efficacy.
Butrophenol. A kappa agonist, mu antagonist more potent but less efficacy than morphine
and not orally active.

Opioids as antidiarrheal drugs

• Loperamide (Imodium). Has low abuse potential. Used as antidiarrheal. Maximum dose 16
mg/day.
• Diphenoxylate + Atropine: Lomotil

Opioids as antitussives drugs:

• Codeine is used extensively as cough suppressants.
• Hydro codeine bitartrate is 3 times more effective as antitussive.
• Dextromethorphan HBr is the (+) isomer of the 3-methoxy form of the synthetic opioids
levorphanol.

Tips
1. PGF2a analog 2. Ecosonide PGE1 analog 3. Tryptophan
4. histadine 5. LTC 4 and LTD 4 6. N-acetyl-p-
benzoquinoneimine
7. Mercapturic acid 8. proton pump inhibitor 9. Pyroxicam
10. Misoprostol 11. Tertiary amine 12. Lipid soluble
13. Crosses BBB 14. GI bleeding 15. Renal diseases
16. 5HT3 antagonist 17. 5HT1B/1D agonist 18. peptide opioid
neurotransmitter
19. Diacetyl morphine 20. cysteine 21. glycine
22. glutamic acid 23. pinpoint pupil 24. respiratory depression
25. constipation 26. Type 1 PG analog 27. steroid sparing agents
28. analgesic 29. antidiarrheal 30. antitussive

• Histamine precursor is? ( )

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• Serotonin precursor of? ( )

• Misoprostol is? ( )
1st generation antihistamines often cause sedation, this is due to? ( )
• Ondansetron is classified as? ( )
• Triptans is classified as? ( )
• Latanoprost is classified as? ( )
• Montelukast and zafirlukast act on? ( )
• Endorphins are? ( )
• Acetaminophen hepatotoxicity is due to? ( )
• Glutathione conjugation produce? ( )
• The most common side effects associated with NSAIDs ( )
• What NSAID has highest GI bleeding? ( )
• Drug of choice to treat NSAID induced GI ulcer ( )
• Drug of choice to prevent NSAID induced GI ulcer? ( )
• Glutathione consist of? ( )
• Ibuprofen, indomethacin, mefenamic acid are? ( )
• Leukotriene antagonist also referred as? ( )
• Opioids can be used as? ( )
• Heroin structure ( )
• Morphine overdose symptoms; ( )
• Gluathione ( ) is a tripeptide that contain unusual tripeptide linkage between
aminoacids of L-Glutamaic acid, L-Cysteine and Glycine

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26
Medicinal Chemistry and
Pharmacology of
Cardiovascular Drugs

Questions Alerts!
Common questions in pharmacy exam is to ask!
• Mechanism of diuretics and site of actions. Hydrochlorothiazide chemical structure.
• Structure activity relation ACEi. and captopril structure
• Structure activity relation ARBs.
• Statins or HMG Co-A reductase inh. and structure activity relation
• Calcium channel blocker (CCBs) structure activity relationship

Thiazide Loop diuretics K+ Sparing CA inhibitors Osmotic

Chlorthalidone Ethacrynate Na Amiloride Acetazolamide Mannitol
Hydrochlorothiazide Ethacrynic acid Spironolactone Urea
Indapamide Furosemide Triamterene
Metolazone (K+ STAys)

Distal convoluted Ascending loop Collect duct Proximal tubule Proximal

tubule tubule
Hyper GLUC OH DANG HyperKalemia
Loops loose Ca
Metabolic alkalosis Metabolic alkalosis Metabolic Metabolic
acidosis and acidosis
intracellular
alkalosis

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Diuretics
In general, the opposite findings of serum electrolytes are seen in urine
Type of Site of Ca Mg Na K Uric Blood Lipids Metabolic Disturbances
diuretic action acid sugar
Thiazide Distal ↑ ↓ ↓ ↓ ↑ ↑ ↑ Hypokalemic metabolic alkalosis
convuluted
tubule
Loop Loop of ↓ ↓ ↓ ↓ ↑ ↑ _ Hypokalemic metabolic alkalosis
henle
K- Early _ ↑ ↓ ↑ ↑ _ _ Hyperchloremic metabolic
sparing Collecting acidosis (↑CO 2 )
duct Intracellular alkalosis
CAI Proximal _ _ _ ↓ ↑ ↑ _ Heperchloremic metabolic
tubule acidosis
Osmotic Glomerular ↑
Thiazide diuretics. Chlorthalidone, hydrochlorothiazide, indapamide hemihydrate, and metolazone.

Thiazide diuretics chemistry. Benzene ring with sulfonamide in position 7, and halogen or trifluoro
methyl group in position 6. The electron withdrawing group at position 6 is necessary. Saturation of 3,
4 double bond (increases potency with hydrochlorothiazide).
Methyl group at position 2, or lipophylic substituents at position 3, enhance the potency and prolong
the activity. Replacement of sulfonyl in position 1 by a carbonyl group prolongs the activity.
H No Doble bond
Cl N on position 3 - 4 Cl N

NH NH
Essential NH2SO2 S NH2SO2 S
O2 O2

Hydrochlorothiazide Chlorothiazide

Cl
O N CH3

NH2SO2 NH
Cl S
N CH3 O2

Indapamide (Lozol) Diazoxide (Hyperstat)

Thiazide diuretics pharmacology

• Thiazide act on distal tubule of nephron and ↑ H 2 O, Na, Cl, K, excretions (↓ levels in body),
hyperuricemia and retain calcium (Ca). long term use of thiazides can cause hypokalemia and
hypomagnesemia thus K and Mg supplement may require.
• May cause alkaline urinary pH by effecting on carbonic anhydrase.
• Metabolic alkalosis (Hypochloremic alkalosis).

Thiazide diuretics therapeutic uses

• Thiazides are the drug of choice for uncomplicated hypertension.
• Especially useful in elderly and African populations and with chronic renal diseases.
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• Not effective in patient renal clearance less than 50 ml/min.

• Not preferable in diabetic and hyperlipidemic patient.

Thiazides diuretics side effects (Hyper GLUC)

• Hypokalemia, hypomagnesia, hyponatremia, hypercalcemia, hyperuricemia, hyperglycemia,
metabolic alkalosis, photosensitivity rashes, acute pancreatitis, libido, difficulty with erection and
ejaculation (long term).

Loop Diuretics. Furosemide, ethacrynate sodium, and ethacrynic acid. Also known as high ceiling
diuretics. i.e. produce a peak diuresis much greater than other diuretics.

Loop Diuretics chemistry. Anthranilic acid derivatives with sulphonamide substituent, or aryloxyacetic
acids without sulphonamide substituent.
Cl Cl
Cl NH CH2
O O
O CH2COOH
NH2SO2 COOH R

Furosemide (Lasix) Ethacrynic acid (Edricin)

Loop diuretics pharmacology

• Increase H 2 O, Na, Cl, K, Ca excretion (decrease levels in body) and increase Ca2+ ion excretion
(Loops Lose Calcium).
• No change in urinary pH. Metabolic alkalosis (hypochloremic alkalosis)
• Act in the thick ascending loop of henle and inhibit the sodium/potassium dichloride co-transport
system. Potent agent can excrete up to 25% of filtered Na+. No ions come into the cell therefore
the sodium pump and Na/Cl symport do not work.

Loop diuretics therapeutic use

• Furosemide is the drug of choice in renal disease (CrCl is less than 50 ml/min), acute pulmonary
edema, and hypercalcemia.

Loop diuretics side effects: OH DANG

Ototoxicity
Hypokalemia
Dehydration
Allergy (sulfa), except ethacrinic acid
Nephritis (intestinal)
Gout arthritis
Sequence of ototoxicity (ethacrynic acid > furosemide > bumetanide)
Ototoxicity.
Ethacrinic acid ototoxicity is irreversible (permanent hearing loss). Renal disease increase risk of
ototoxicity.
Furosemide ototoxicity is reversible sensoryneural hearing loss, i.e. discontinuing drug can be normal.
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Carbonic anhydrase inhibitors: Acetazolamide (Diamox)

Carbonic anhydrase inhibitor chemistry
Acetazolamide. Aromatic or heterocyclic sulfonamides with a thiadiazole ring. The sulfamoyl group is
essential for CA inhibitory activity.

O N N
Acetazolamide
CH3 C NH S SO2NH2

Structure activity of Dorzolamide (sulfa allergy)

Carbonic anhydrase inhibitor pharmacology. Increase water, sodium, potassium and bicarbonate
excretion. Cause alkaline urinary pH, and gives metabolic acidosis.

Carbonic anhydrase inhibitor therapeutics

Used in treatment of glaucoma (not chronically). Acute mountain sickness (respiratory alkalosis) also
high altitude sickness (mountain sickness). Because of the alkaline diuresis it produces, acetazolamide
has been used for the treatment of overdoses of acidic drugs.

Carbonic anhydrase side effects

• Because of the alkaline Electrolytes  Hyperchloremic metabolic acidosis (loss of HCO 3 -),
hypokalemia
• Formation of renal stones (phosphaturia & hypercalciuria).
• CNS  depression, drowsiness, sedation, fatigue, and disorientation.
• GI  Nausea, Vomiting, and Constipation
• Blood related  Bone marrow depression, thrombocytopenia (reduction of number of platelets in
blood), hemolytic anemia, leucopenia (reduction in number of WBC), agranulocytosis (acute
deficiency of neutrophils). Sulfa drugs antibiotics type allergies.

Osmotic diuretics. Mannitol (Osmitrol), and Urea

Osmotic diuretics chemistry

• Water-soluble with low renal threshold, and highly polar.
• They limit tubular reabsorption of water.
• Promote diuresis.
• Increase in urinary pH
• Mannitol (monosaccharide a carbohydrate

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H H OHOH
HOCH2 C C C C CH2OH Mannitol (Osmitrol)
OHOHH H

O
NH2 C NH2 Urea (Ureaphil)
Osmotic diuretics pharmacology
• This drugs limit tubular reabsorption of water and promote diuresis.
• Increase excretion of H 2 O, Na, Cl and HCO 3 (decrease levels in body), increase alkaline urinary
pHIncrease excretion of HCO 3

Osmotic diuretics therapeutic use

• This drugs limit tubular reabsorption of water and promote diuresis.
• Mannitol used in treatment of shock, to treat drug overdose and to decrease intracranial or
intraocular pressure.
• Prophylaxis of acute renal failure.

Osmotic diuretics side effects. Pulmonary edema, dehydration and contraindicated in CHF, and anuria
(renal failure).

Potassium sparing diuretics

• Spirolactone, amiloride hydrochloride, and triamterene

Potassium sparing diuretics chemistry

• Spiranolactone binds at the receptors at the late distal tubule and collecting tubules thus prevents
the reabsorption of Na+ and Cl- ions.
• Pteridine or pyrazine derivatives or steroid analogue antagonist of aldosterone.
• Triamterene, amiloride contain pteridine or pyrazine derivatives.
• Spironolactone. Contain sterol structure + lactones.

CH2 CO
H3C CH2
O NH2
H3C N
N

H2N N N NH2
O SCCH3
O
spironolactone(Aldactone) triamterene(Dyrenium)

Spironolactone metabolized to main active metabolite canrenone by first pass metabolism.

Eplerenone is a new aldosterone antagonist. Metabolized by CYP450.

Potassium sparing diuretics pharmacology

• Act in the early collecting duct to inhibit the electrogenic reabsorption of Na+ by blocking the Na
channels and hence the exchange of sodium for potassium.
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• After administration: ↑ Na+, Cl- elimination, ↓K+, Ca2+ (amiloride).

• Increase Na, H 2 O, HCO 3 excretion (decrease levels in body), decrease K+, H+ excretion.
• Alkaline urinary pH, and increase excretion of HCO 3 .
• Potassium sparing diuretics gives the intracellular alkalosis.

Potassium sparing diuretics therapeutic use

• Amiloride, spironolactone and triamterene act as competitive antagonists of aldosterone in the
kidney. Because they are weak diuretics when given alone, they are often used in combination
with hydrochlorothiazide.
• Spironolactone is the drug of choice for the treatment of ascites.
• Spironolactone is antiandrogenic and has been used to treat hirsutisms in doses of 200 mg/day.
• Amiloride used in nephrogenic diabetic insipidus
• Spironolactone is the drug of choice for the treatment of ascites.

Potassium sparing diuretics side effects

• A side effect may be hyperkalemia, an increase in potassium levels, so that potassium
supplements are usually not taken with these drugs. If they are needed, the dose of potassium is
frequently administered three times a week instead of daily.
• Side effects of spironolactone include endocrine  Gynecomastia, menstrual irregularities,
Electrolytes  Hyperkalemia, irregularities, CNS  mental confusion

Vasodilators

Vasodilators cause the smooth muscle in blood vessels to relax. Relaxed or dilated blood vessels allow
more blood to flow through, causing a reduction in blood pressure by decreasing peripheral
resistance. As vasodilators work, the blood vessels become dilated causing a drop in pressure because
there is less blood volume to fill the vessel. The body can compensate for this by retaining enough fluid
to fill the blood vessel sufficiently to raise the blood pressure again.
Hydralazine and minoxidil are direct vasodilators not usually used a sole therapy for high blood
pressure, as their effect is usually short-lived when administered alone. Minoxidil is available in
tablets and also as a topical lotion (Rogaine) for treatment of male-pattern baldness).

NH2
HN
hydrazine group
NH (Basic)
NH

Hydralazine

ACE Inhibitors
Captopril, benazepril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, and
trandolapril.
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O
HS - H2C
N
CH3
CO2H

ACE Inhibitors chemistry Captopril

Sulfhydril containing inhibitors.. Captopril

Dicarboxylate containing inhibitors.. all ACEi
Phosphonate containing inhibitors.. Fosinopril

Captopril and fosinopril are acidic drugs while all other are amphoteric.

The carboxylic attached to N-ring is common structural feature in all ACEi.

The sulfhydryl group of captopril is proved to responsible for excellent activity of captopril, and this
also responsible of its two most common side effects skin rashes and taste disturbances (example
metallic taste and loss of taste). The sulfhydryl group also present in another drug penicillamine, which
attributes to its metallic taste.

O O-CH2-CH3
O Esterase O OH
NH O
N HN N
CH3 CH3
HO2C

Bioactivation of Enalapril
Captopril and FOSinopril are acidic drugs while all other ACE inhibitors are amphoteric.
ACE Inhibitors that are NOT prodrug captopril and FOSinopril.
All ACEi are once daily used, except captopril (2-3 times) daily

Angiotensinogen Sympathetic action

(alpha globulin in blood)
Vasodilation
Renin
(kidney)

BP
Angiotensin I Angiotensin II

Bradykinin
ACE I
Na & H2O levels

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ACE Inhibitors pharmacology

• ↓ sympathetic output
• Increase vasodilatation of smooth muscles
• ↑ levels of bradykinin causes dry cough
• By reducing circulating angiotensin II levels ACEi ↓ the secretion of aldosterone, resulting ↓
retention of Na and H 2 O retention leads to decrease in cardiac output (CO).
• ↓ in preload and after load
• Dilation of venous blood vessels leads to decrease in cardiac preload by ↑ venous capacitance.
• Arterial dilator reduces systemic arteriolar resistance and ↓ after load.
• Lower blood pressure by reducing peripheral vascular resistance with reflex increasing cardiac
output rate.
• Little change in HR, or GFR.

ACE Inhibitors therapeutic use

• ACE inhibitors are used to treat uncomplicated hypertension and pre-hypertensive patient.
However, if Angiotensin is not the contributing factor for the hypertension, the chances of ACE
inhibitors working are diminished.
• These drugs represent a major advance in hypertensive treatment and have most displaced
digoxin as the drug of choice in congestive heart failure. 1st line treatment for: Heart failure.
• ACE inhibitors also tend to protect the kidneys of diabetics from developing renal failure when
used in the early stages of diabetic nephropathy. Diabetes nephropathy, post MI.
• LVH (Left ventricular heart failure).
• Prior CVA/TIA (Cardiovascular Attacks/ Transient Ischemic attacks) & in renal disease.

ACE Inhibitors side effects

• Profound low pressure (hypotension), taste abnormalities, dry cough (5 to 15%), blood cell
abnormalities, and kidney problems such as proteinuria (presence of protein in urine). They are
contraindicated in pregnancy. A persistent dry cough may necessitate discontinuing the drug.
ACE inhibitors increase the risk of hyperkalemia. Allergic reactions angioedema (rare). Reversible
neutropenia and fatigue.

Angiotensin Receptor Blockers (ARBs)

Losartan, telmisartan, valsartan, irbesartan, and candesartan.
ARBs are analogs of imidiazole ring group (imidazole-5-acetic acid).

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N
Cl
Imidazole ring (essential) N

Tetrazole ring OH

N N
N
N
H

Losartan

Angiotensin receptor blockers, block the effects of angiotensin II, a naturally occurring substance that
causes blood vessels to narrow (constrict). When these drugs are administered, blood vessels dilate,
thereby lowering blood pressure and decreasing the workload of the heart. These drugs appear to
have the same benefits as ACEi, without or less producing the common side effect of a dry cough.

Pharmacological actions
• Angiotensin binds to its own receptors are found on vascular muscle and in the adrenals.
• Stimulation leads to vasoconstriction and release of aldosterone in the adrenal gland.
• It blocks aldosterone secretion.

Side effects
Less dry cough (cough associated with ACEi does appear with these drugs), Bradykinin causes
vasodilation of arterioles and venules results ↓ TPR, less dry cough. Dizziness, hypotension/syncope,
renal dysfunction (reversible renal failure), hyperkalemia and angioedema.
Contraindications. Pregnancy (renal fetal toxicity), and bilateral renal artery stenosis (stenosis;
abnormal narrowing of passage or opening, such blood vessels or heart valve.
Pharmacokinetics. Losartan may increase the effects of potassium supplements, potassium-sparing
diuretics, and cyclosporine, leading to raise of potassium in the blood.

Antihyperlipidemic Drugs
Classification of antihyperlipidemic drugs
Fibrates Bezafibrate BEZALIP
Fenofibrate LIPIDIL
Gemfibrozil LOPID
Clofibrate
3-Hydroxy-3- Atorvastatin calcium LIPITOR
Methylgluteryl Fluvastatin sodium LESCOL
(HMG)-CoA Lovastatin MEVACOR
Reductase
Pravastatin sodium PRAVACHOL

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Inhibitors Rosuvastatin CRESTOR

Simvastatin ZOCOR

Niacin Niacin
Derivatives
Resins (Bile Acid Cholestyramine resin QUESTRAN
Sequestrants) Colestipol hydrochloride COLES
Antihyperlipidemic drug chemistry. Categorized into non-absorbable agents and absorbable agents.

Nonabsorbable agents. Resins (Polystyrene resins). Anion-exchange resins bind with the enzymes in
intestine and prevent the synthesis of cholesterol. It decrease LDL 15 to 30%, increase HDL 3 to 10%,
however no change or increase in TG (disadvantage).

Pharmacological actions
GIT Blood Adipose tissue

Ezetimibe inhibit Statins inhibit Fibrates ↓

intestinal absorption HMG-CoA Triglycerides
of Cholesterol reductase

Cholester VLDL
ol
Acetyl-CoA

IDL Fatty acids

Cholesterol
Bile acids
LDL Triglycerides
Bile acids
Bile
acids

Niacin inhibit
breakdown of
Resins bind to BAs and excrete
cholesterol to LDL
in stools thus ↓ BAs absorption
into liver

Cholestyramine chloride

• A basic anion-exchange resin made of trimethylbenzylammonium groups in a large copolymer of

styrene and divinylbenzene.
• Act on small intestine.
• Available as powder only
• Mixed with juice, water or non carbonated beverages

Colestipol hydrochloride
• A copolymer of diethylpentamine and epichlorodrin
• Available as granules or tablets (1 g)
• Do not crush, chew or cut and should be taken with plenty of water.
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• Hygroscopics
• Water insoluble
• Do not absorb orally
• Do not metabolized and excreted in feces

All resins do not change triglycerides or may increase TG. Avoid in cholelithiasis or complete biliary
obstruction due to impaired secretion of bile acids caused by these conditions.
All oral medication should be administered 1 hour before and 4 to 6 hour after resins.
Absorbable agents
• Niacin.Nicotinic acid (Niacin or vitamin B 3 )
• Fibrates. Clofibrate and Fenofibrate (aryloxyisobutyric acid derivatives)
• Probucol (sulfur containing bis-phenol)
• Statins. Lovastatin (3-hydroxy-3methylglutaryl-coenzyme A)
• Fatty fish oil. Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA)

Nicotinic acid
Administered orally, it converted in body to nicotinamide, NAD+ and NADP+. The later two are
coenzymes essential for biochemical oxidation, reduction reactions. Participation in tissue respiration
oxidation, reduction reactions, which decreases hepatic LDL and VLDL production. At high doses
lowers LDL, VLDL and raises HDL. Strongly inhibits lipolysis in adipose tissues. Inhibits tubular secretion
of uric acid, causes gout or hyperuricemia.

COOH

N
Niacin

In Liver
Adipose tissue Fatty acids Triacylglycerol VLDL LDL
Triglycerides
The most common side effect and often dose limiting is cutaneous vasodilatation that gives flushing
and pruritus. Taking ASA 325 mg and take with food can manage the flushing.
Hepatic dysfunction (elevate LDH, AST, and ALT) is another serious side effect of niacin at higher doses
and avoids alcohol. GI side effects such as nausea, vomiting, and diarrhea can be minimized be taking
with meals.

Statins
Blocks the action of enzyme HMG CoA reductase, this enzyme needed for the synthesis of cholesterol,
mainly in the liver. Decrease LDL receptors (18 to 55%), and lower cholesterol synthesis (cholesterol
pills).

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HMG-CoA reductase  Mevalonic acid

Statins Structure Activity Relationship. HMG-CoA reductase inhibitors are statins are chemical
component is a prodrug lactone ring, and activates to 3,5 dihydroxy acid. The 3,5-
dihydroxycarboxylate is essential for inhibiting HMG Co reductase action. Lovastatin and simvastatins
are prodrugs have lactone structure, it require in vivo hydrolysis. Statins may increase blood
transaminase (ALT & AST) and creatinine kinase (CK-MM) activity associated with myopathy, especially
when combined with fibrates or cyclosporine. Lovastatin and simvastatin are prodrugs. It has lactone
structure and it becomes active liver.
Lactone ring
O
CH3
O
CH3CH2CH-C-O
OH
CH3

H3C

Lovastatin
HMG-CoA Reductase Inhibitors Pharmacokinetics
Statin
Atorvastatin Fluvastatin Lovastatin Pravastatin Rosuvastatin Simvastatin
Metabolizing CYP3A4 CYP2C9 CYP3A4 Not Known CYP2C9 CYP3A4
Enzyme (s)
Grapefruit juice Avoid Avoid Avoid
Take At night At night At night
Food With or without With or after With or after With or With or without With or
without without
FLS = Take at bed time (night). ALS = Avoid grapefruit juice (because grape fruit juice inhibit CYP 3A4),
FL = Take with Food. HMG = 3-hydroxy, 3-methyl glutaric acid.

• Lovastatin should be always administered with food to increase bioavailability, otherwise it can
decrease 30%-50 bioavailability.
• Atorvastatin can be taken anytime of the day, because has long half-life.
• The best agent for renal disease patient is atorvastatin, because it has minimal renal elimination,
thus do not require dose adjustments.

Fibrates
Clofibrate and fenofibrate (aryloxyisobutyric acid derivatives). Decrease TG levels, increase HDL levels
(moderately), decrease LDL levels inhibit cholesterol synthesis.

Peroxisome proliferator activated receptor alpha agonist

Fenofibrate has uricosuric effect thus this can be used to treat hyperuricemia.

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Antianginal agents
Chemistry of Nitrates
• Nitrates. Nitroglycerin and isosorbide nitrates are organic esters of nitric acid.
• Nitrites. Amyl nitrites are organic esters of nitrous acid.
• Inorganic nitrate. Nitroprusside Sodium

Pharmacology of nitrates
• Nitrites and nitrates. Directly relax vascular smooth muscle by formation of free radical nitric
oxide. Nitric oxide (NO) activates guanylyl cyclase to increase synthesis of cGMP within smooth
muscle.
• Vascular effects. Peripheral pooling of the blood, reduced preload decreased systemic vascular
resistance, reduced after load. Reduce myocardial oxygen demand, redistribution of coronary
flow.
Nitrates Vascular smooth muscle
↑ Nitrites ↑ Nitric oxide (NO) relaxation

Nitrates therapeutic use. Relieve acute anginal attacks, as prophylaxis, for long-term management of
recurrent angina pectoris.
Nitrates side effects
• Nitroglycerin (sublingual). Headache (usually resolves if patient persists with therapy),
hypotension, tachycardia, flushing, and edema.
• Nitrate tolerance. Nitroglycerin transdermal patches associated with nitrate tolerance, to minimize
the tolerance “nitrate free period” is used. Patients should have a 10 to 12 h nitrate-free period
each day to prevent tolerance.
• Nitroglycerine (transdermal) patch may cause contact dermatitis at site of patch.
• Nitrate drug interactions. Avoid concomitant use of PDE 5 inhibitors such sildenafil, verdanefil, and
tadanafil within use of 5 days, because can cause severe hypotension.
• Nitroglycerin SL spray and tablets
• Stored at room temp
• Stored original tightly closed container
• It is hygroscopic, keep tightly closed

Calcium Channel Blockers

Calcium channel blockers can be characterized in two types non-dihydropyridine and hydropyridines.
Dihydropyridine (DHP) Non-Dihydropyridines (NDHP)
Phenylalkylamine Benzothiazepines
Nifedipine, Amlodipine, Verapamil hydrochloride Diltiazem hydrochloride
Nicardipine, Felodipine
↓ Vascular resistance ↓ Myocardial oxygen demand Have both cardiac depress and
thus vasodilatation and and reverse coronary vasospasm vasodilator.
hypotension may lead to reflex Bradycardia Bradycardia
tachycardia.

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Dihydropyridine type calcium channel blockers.

R1 CYP 3A4 inhibitors.

CO2R2 4 3 CO2R2
Erythro &clarithromycin
Cimetidine
5 2
Grape fruit juice
CH3 6 N
H
1 CH3 Gemfibrozil
Verapamil
General structure of 1,4 dihydropyridines Amiodarone
Azole antifungals
1,4-dihydropyridine ring Pyridine ring
Protease inh.
H3C
H
N CH3
H3C N CH3
Cyclosporine

H3CO2C CYP3A4 H3CO2C CO2CH3

CO2CH3
NO2
NO2

Oxidized analog
Nifedipine
(inactive)
(active)

Calcium blockers pharmacology. These agents are used to treat hypertension and are effective in
treating angina as well. All muscles, including the smooth muscle of the blood vessels, require calcium
inorder to contract. If the CCB block the entrance of the calcium into the muscle, the muscle will not
contract. This will allow the muscle to relax and subsequently reduce the blood pressure. Other
therapeutic uses angina, migraine, and antiarrhythmic.

Non-dihydropyridine

Verapamil is similar to beta-blockers in effect, verapamil can cause bradycardia. The effect on Heart is
graded from higher to lower: verapamil > diltiazem > nifedipine.
Verapamil avoid using in CHF (cause –ve inotropic effect) and constipation.

Dihydropyridine
Dihydropyridine are similar to Nitrate in effect. Act on peripherally by decrease afterload (good for
vasospastic angina) or decrease total peripheral resistance. Dihydropyridine can cause reflex
tachycardia in response to hypotension caused by decreased in total peripheral resistance.
Dihydropyridines relax and dilating arteries. The sequence of effect on vascular smooth muscles is
high to low nifedipine > diltiazem > verapamil.

Calcium channel blockers therapeutic uses

Calcium channel blockers are used to treat hypertension and are effective in treating angina as well.
All muscles, including the smooth muscle of the blood vessels, require calcium in order to contract. If
the calcium-channel blocking agents block the entrance of calcium into the muscle, the muscle will not
contract. This will allow the muscle to relax and subsequently reduce the blood pressure. Other
therapeutic uses: angina, migraine, and antiarrhythmic.

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Non-dihydropyridine side effects

Flushing, profound low blood pressure, swelling of legs and feet, constipation and stomach upset. If
edema (swelling) of the legs and feet occur, a diuretic may be added to the regimen.

Dihydropyridine side effects. Blood pressure will fall too low and sometimes causes reflex tachycardia.
The other side effects include, flushing, headache, dizziness, orthostatic hypotension, and edema.

Anticoagulants
Anticoagulants classification
Heparin Catalyzes the inhibition of Heparin sodium
thrombin
Low molecular weight Dalteparin sodium (Fragmin)
Heparin (LMWH) Enoxaparin sodium (Lovenox)
Nadroparin calcium (Fraxiparine)
Tinzaparin sodium (innohep)
Heparinoids
Warfarin sodium Vitamin K Antagonists

New anticoagulants

Dabigatran Direct thrombin (factor II) oral

inhibitor
Rivaroxaban, apixaban Direct factor Xa inhibitor oral
Fondaparinux Indirect factor Xa inhibitor SC

Anticoagulants chemistry
Heparin Large, highly acidic mucopolysaccharide made up of sulfated D-glucosamine and
D-glucuronic acid molecules
LMWH Low-molecular weight heparin fragments (1-10 kDA), enoxaparin, dalteparin,
tinzaparin, and ardeparin, are being produced through controlled
depolymerization of Heparin
Danaparoid A low-molecular weight heparinoids that are glycosaminoglycans extracted from
porcine mucosa.
Lepirudin A recombinant DNA-derives 65 amino acid polypeptide (nearly identical to
hirudin).
Coumarin Warfarin, and dicumarol chemically related to vitamin K, are water-insoluble,
derivatives weakly acidic 4-hydroxycoumarin lactones.
Phenindione are indanedione derivatives.

Warfarin is racemic structure. The S-isomer is 3-5 times more potent than the R-isomer. The S-isomer
is a substrate of CYP 2C9 and inducers or inhibitors of this enzyme have the most effect on the INR.
Warfarin has a narrow range for efficacy and toxicity and inducers or inhibitors of either isoform can
be significant. CYP 450 drug interactions with warfarin are the most common cause of an INR increase
or decrease.

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Onset of action. Anticoagulation effects 2-3 days. The delay is due to factor V turnover if 5 hours and
factor 2 (thrombin) is 2-3 days.

O
OH

O O
Coumarin ring

Structural formula of coumadin derivative oral anticoagulants (Warfarin) .

Anticoagulant pharmacology
• LMWH. These agents are not interchangeable with heparin in their actions and use. Because these
highly acidic. These administered parenteral as sodium salt. Because poorly absorbed from GI
tract.
• Heparin: Enhances the serum protease antithrombin III results in inactivation of factors 2a, 9a,
10a, 11a, 12a, and 13a. Maximum effect occurs within minutes. Heparin stops the expansion of
thrombi by preventing fibrin formation. Antidote of heparin is Protamine sulfate: Works by acid
base neutralization. Heparin act In vitro and In vivo. It has faster onset of action
• Warfarin: Inhibits the hepatic synthesis of vitamin K dependent factors 2, 7, 9 and 10. Warfarin
antidote is Vitamin K. This agent act only in vivo (in liver). Onset of action is slower (8 to10h).
Warfarin is contraindicated in pregnancy.

Anticoagulant therapeutic use

• LMWH: Used in prevention of deep vein thrombosis (DVT) or pulmonary embolism (PE).
• Heparin: Major antithrombotic drug for DVT and pulmonary embolism. To prevent postoperative
venous thrombosis in-patient undergoing surgery.
• Warfarin: used to prevent blood clots, mainly in areas where blood flow is slowest, particularly in
the leg and pelvic veins.

Anticoagulant side effects

• LMWH: Hypersensitivity reaction (chills, fever, urticaria etc), Bleeding, Heparin induce
Thrombocytopenia (HIT), Osteoporosis.
• Heparin: Hypersensitivity reaction (chills, fever, urticaria etc), Bleeding and heparin induce
Thrombocytopenia (HIT).
• Warfarin: Bleeding; hair loss; Skin necrosis (rare), blue fingers and toes (uncommon) this also
referred as purple toe syndrome

Add table of comparison of anticoagulant

Cardiac glycosides
Digoxin is the most widely used cardiac glycoside increase myocardial contractility ad efficiency,
improve systemic circulations, improve renal perfusion and reduce edema

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Cardiac glycosides Chemistry

• Consist of one or more sugars (glycine portion) and a steroidal nucleus (aglycone or genin portion)
bonded through an ether (glycosilic) linkage. Have an unsaturated lactose substituent (cyclic ester)
on the genin portion.

• Digoxin has an additional hydroxyl group at position 12. Duration of action is inversely
proportional to the number of hydroxyl groups, which increase polarity.

DIGOXIN O O
OH
CH3
CH3H
CH3 OH H3C H OH
OH O O O
O O O H
OH OH OH
O O
CH3
CH3H
CH3 OH H3C
O O H OH
OH O
O O O H
OH CH3 OH

DIGITOXIN

Cardiac glycosides Pharmacology

• Cardiac glycoside at therapeutic doses produce. Positive inotropic effect (+ve inotropic). negative
chronotropic effect (-ve chronotropic), and increased vagal tone of the sinoatrial (SA) node
(vegomimetic).

Digoxin mechanisms of action

Electrolyte ‘ rearrangement ’ Increased Vagal tone

(Mechanism) (Mechanism)

↑ Ca i

↑ Inotropic Tachyarrhythmias Brady arrhythmias ↓ Heart Rate

(Desired) (Side effect) (Side effect) (Desired)
• Inhibit the membrane bound Na+/K+ activated ATPase increase intracellular sodium concentration,
reduce calcium transport form cell, and facilitate calcium entry via voltage gated membrane
channel.

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Cardiac glycosides Therapeutic use

• Cardiac glycoside at therapeutic doses produce: Myocardial contractility and efficiency, improve
systemic circulation, improve renal perfusion and reduce edema thereby it indicated in treatment
of:
• Congestive heart failure, atrial fibrillation, atrial flutter, paroxysmal atrial tachycardia

Contraindications:
Digoxin is contraindicated in ventricular arrhythmias

Thrombolytic Drugs

Streptokinase Anistreptase (Aminase) Urokinase

t-pa
(Strepto protein from Prodrug of streptokinase (Abbokinase)
(tissue type
Group C-B-hemplytic plasminogen activator)
steptococci bacteria
Directly degrade Alteplase (activase)
fibrin and Reteplase (Retevase)
fibrinogen very high affinity to
plasminogen, bound to
thrombus
Thrombolytic chemistry
Alteplase, Recombinant DNA-derived plasminogen activators (t-PA) with 527 and 355
reteplase, and amino acids.
Tenecteplase
Streptokinase Nonenzymatic 47-kDa. Derived from β-hemolytic streptococci cultures.
Anistreplase APSAC is a complex of human lys-plasminogen and streptokinase with an
anisoyl group blocking the catalytic site.
Urokinase A two chain serine protease obtained form human kidney cell culture.

Thrombolytic pharmacology
• Facilitate conversion of plasminogen to plasmin that subsequently hydrolyzes fibrin to dissolve
clots.

Thrombolytic therapeutic use

• Acute MI (STEMI), stroke and acute massive pulmonary embolism (PE), and deep vein thrombosis
(DVT).

Thrombolytic side effects

• Hypersensitivity reactions, Internal GI bleeding, retroperitoneal bleeding, superficial bleeding at
catheter injection site. nausea and vomiting.

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Antiarrhythmic agents
Antiarrhythmic drugs are classified as follows:
• Class IA: Procainamide, quinidine, disopyramide
• Class IB: Phenytoin, lidocaine, mexiletin, tocainide
• Class IC: Propafenone, Flecainide, Moricizine
• Class II: All the beta-blockers
• Class III: Sotalol, Bretylium, Amiodarone, dronedarone
• Class IV: All the calcium channel blockers

Antiarrhythmic drugs Chemistry

Cinchona alkaloids, natural products (Example: quinidine, it is an optical isomer of quinine)
Amides type of local anesthetics (Example: procainamide, flecainide, disopyramide)
Xylyl derivatives (Lidocaine, xylocaine), Mexilitine.
Quaternary ammonium salts (bretylium)
Diiodobenzyl oxyethylamines (amiodarone)
β−blockers (nadolol, propranolol, esmolol)
Non-dihydropyridine type calcium antagonist (diltiazem, verapamil)
Hydantoins (phenytoin)

Amiodarone chemical structure

Antiarrhythmic drugs pharmacology

Class Ia: Quinidine (Biquin durules), and Procainamide (Procaine SR), Disopyramide (Norpace CR): Slow
the phase 0 (slow entry of Sodium ion), Prolonged re-polarization, Prolonged effective refractory
period
Class Ib: Lidocaine, Tocainamide, and Mexiletine: Minimal effect on Phase 0 Slow phase –III
repolarization (decrease K pump out).
Class Ic: Encainide (Enkaid), Propafenone (Rhythmol), and Flecainide (Tambocor); Very effective on
slowing phase 0 depolarization, Little effect on repolarization.
Class II: Beta blockers: Propranolol, Atenolol, and Timolol: Competitively block catecholamine induced
stimulation of Beta receptor thereby suppressing phase IV depolarization
Class III K+ channel blockers: Amiodarone, Bretylium, Sotalol: Prolong Phase III repolarization (Prolong
QT interval)Torose de pointes
Class IV Ca2+ channel blockers: Verapamil, Diltiazem, Nifedipine: Shortens action potential
Digoxin: affects vagotonic response (vegomimetic) thereby increasing AV nodal refractoriness. It is
contraindicated in ventricular fibrillation. Ventricular tachycardia may result from digitalis toxicities

Antiarrhythmic drugs therapeutic use

Class Ia: Quinidine (Biquin durules), Procainamide (Procaine SR), Disopyramide (Norpace CR): indicated
to treat SVT, VT.
Class Ib: Lidocaine, Tocainamide, and Mexiletine: indicated in the treatment of VT, VA
Class Ic: Encainide (Enkaid), Propafenone (Rhythmol), and Flecainide (Tambocor); Indicated in the
treatment of VA

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Class II: Beta blockers: Propranolol, Atenolol, and Timolol: Indicated to treat AT, SVT, VT, VA
Class III K+ channel blockers: Amiodarone, Bretylium, Sotalol: Prolong Phase III repolarization
(Prolonged QT interval)Torose de pointes.
Class IV Ca2+ channel blockers: Verapamil, Diltiazem, Nifedipine: Indicated in the treatment of SVA, VA
Digoxin: Effects vagotonic response (vegomimetic) thereby increases AV nodal refractoriness. It is
contraindicated in ventricular fibrillation. Ventricular tachycardia may result from digitalis toxicities.

Antiarrhythmic drugs side effects

Class Ia. Quinidine, procainamide , disopyramide. Torsades de pointes

Amiodarone  blue skin, photosensitivity, photophobia, Respiratory. Pulmonary toxicity which

including interstitial pneumonitis; Respiratory muscle impairment, pigmentation. GI: nausea, anorexia,
constipation, hepatitis and cirrhosis, hypothyroidism, hyperthyroidism.
Blue skin color, corneal deposits, hepatic toxicity, optic neuritis, and erectile dysfunction.
Structure of amiodarone, dronedarone and levothyroxine

Antiplatelet drugs
Antiplatelet Drugs

ASA Dipyridamole Ticlopidine Glycoprotein Prostaglandin

& inhibitors analogs
Clopidogrel

Epoprostenol
Eptifibatide
Tirrofiban
Change chart

ASA , clopidogrel (Plavix), ticlopidine (Ticlid), dipyridamole

dipiperdino-dinitro pyrimidine and theonopyridine.
ADP inhibitors. Ticlopidine and clopidogrel, prasugrel

Fab fragments of human monoclonal antibody to the glycoproteine (GPIIb/IIIa) receptors (Abciximab,
tirofiban, eptifibatide).
Antiplatelet drugs pharmacology
ASA Inhibits platelet cyclooxygenase production of thromboxane A 2 , thus
preventing platelet aggregation or clumping.
ASA act as antiplatelet action at dose 60 to 80 mg
Ticlopidine & Interfere ADP-induced membrane-mediated platelet-fibrinogen
Clopidogrel binding.
Fab fragments Monoclonal antibodies act against the glycoprotein IIb/IIIa-receptor
thus prevent platelet-platelet aggregation.
GPIIb/IIIa-receptor Reversible antagonist of fibrinogen, von Willebrand’s factor
antagonist

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Antiplatelet drugs therapeutic use

• Platelets of the elements of blood cells, tend to clump together. The antiplatelet drugs interfere
with the coagulation by inhibiting platelet aggregation. Heart attacks and strokes occur when a
blood clot that forms in a narrowed portion of an artery blood flow and cuts off the supply of
oxygen and nutrients to the tissue that lies beyond the site of the clot.

Antiplatelet drugs side effects

• ASA: Bleeding (epistaxis to major GI bleeds), Serious GI bleeding less common with lower doses
(80-325mg/day)
• Clopidogrel. Bleeding, diarrhea, rash, and thrombocytopenia.
• Ticlopidine . Neutropenia, bleeding, diarrhea, rash, thrombocytopenia (2.5%) that is generally
reversible with drug discontinuation. Monitor neutrophils every 2 wk for 1st 3 months

Antianemic agents
Iron preparations. Consist of complex ferric hydroxide and low-molecular weight dextrans.
Cyanocobalamin (Vitamin B 12 ). A nucleotide macromolecule with corrin ring containing a trivalent
cobalt atom. Cyanide with the cobalt atom, as benzimidazole. Benzimidazole is bonded to ribosol
phosphate.

Folic acid. Pteridine nucleus is bonded to nitrogen of p-amino benzoic acid, and p-amino benzoic acid
is bonded to glutamic acid through an amide linkage.

H2N N N
O COOH
N N N
N Glutamyl moity
H
Pteridyl group
COOH
p-amino benzyl
group (PABA)

. Folic acid

Erothropoetins
• Erythropoetins are glycoprotein produced through recombinant DNA technology. Epoetin is same
with natural erythropoietin.
• Therapeutic use of erythropoietins such as Epoetin and Darbepoetin are anemia. associated with
cancer chemotherapy and renal disease. Oprelvekin therapeutic use is thrombocytopenia.

Filgrastim. It is glycoprotein produced through recombinant DNA technology.

Therapeutic. neutropenia associated with cancer chemotherapy.
Oprelvekin (IL-11). A recombinant DNA produced non glycosylated polypeptide growth factor.

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Tips
Find answers from the table
1. Nitroglycerin 2. ALS 3. APR
4. Fluvastatin and Lovastatin 5. Contain sulfhydryl 6. CYP3A4
group
7. increase HDL 8. decrease LDL 9. decrease TG
10. act on distal collecting 11 intracellular alkalosis 12 Sulfonamide and
tubules halogen at position 6 & 7
13 angina 14 MI 15 CHF
16 Nitrates
• Spironolactone ( )
• Hydrochlorothiazide ( ), essential functional group ( )
• Dihydropyridine are used for the treatment of? ( )
• Essential functional group that are present in thiazide diuretics? ( )
• What diuretics cause intracellular alkalosis? ( )
• Nitric oxide (NO) is a neurotransmitter that acts on? ( )
• Drugs that cause venous pooling? ( )
• Nitroglycerin is classified as? ( )
• Fibrates? ( )
• Statins that should be avoided with grapefruit juice ( )
• Statins that should be taken with meals ( )
• Statins that can be taken anytime of the day ( )
• Dihydropyridine oxidized to pyridine by enzyme? ( )
• Drug that contain sulfhydryl group ( )

Write the examples of drug that affects systolic and diastolic blood pressure.
• Norepinephrine 
• Epinephrine 
• Dopamine 
• Dobutamine, isoproterenol 
• Reserpine 
• Phenylephrine
• Non selective Beta blocker

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27
Medicinal Chemistry and Pharmacology of Psychiatric
and Neurological Disorder Agent

Questions Alerts!
Common questions in pharmacy exam are to ask!
• Phenothiazine structures activity relation. Benzazepine (clozapine, olanzapine, quetiapine)
structure activity.
• Pharmacological actions of SSRIs and dual acting antidepressants and serotonin syndrome,
Structure activity of TCAs.
• Structure activity antipsychotic drugs.
• Structure of activity antiepileptics carbamazepine, phenytoin, gabapentin
• Structure activity and classification of benzodiazepine and half-lives.
• Conversion to levodopa to dopamine. Selegiline and rasegiline, tolcapone
• Structure activity of CNS stimulants (pseudoephedrine formation to meth amphitamine.

Classification of Antidepressants

Monoamine Oxidase Amine reuptake α2 receptor blockers

(MAO) Inhibitors inhibitors drugs Mirtazapine

Irreversible MAOI
Phenelzine Non-selective 5HT only
Tranylcypromine 5HT, NE, D Selective serotonin
Reversible MAOi (RIMA) reuptake inhibitors (SSRI’s)
Moclobemide Fluoxetine, Fluvoxamine
Paroxetine, Sertraline
Citalopram, Escitalopram
5HT, NE
Tertiary amine type Dual action
(5HT > NE) SNRI
Amitriptyline Venlafaxine
Imipramine Duloxetine
Secondary amine type Desvenlafaxine
(5HT = NE) NDRI
Desipramine Bupropion
Nortriptyline
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Abbreviations. 5HT = 5hydroxy tryptamine (Serotonin), NE = Norepinephrine; SNRI = Serotonin

Norepinephrine Reuptake Inhibitors, NDRI = Norepinephrine Dopamine Reuptake Inhibitor; RIMAs =
reversible inhibitors of monoamine oxidase. TCA = Tricyclic

Antidepressants
Classes of antidepressant drugs include: tricyclic compounds (TCAs), monoamine oxidase inhibitors
(MAOIs), selective serotonin re-uptake inhibitors (SSRIs) and reversible inhibitors of monoamine
oxidase (RIMAs).

Monoamine oxidase inhibitors (MAOis) chemistry

Irreversible MAO inhibitors. Phenelzine, Tranylcypromine
Selegiline and Rasagiline (MAO-B selective) used for the treatment of Parkinson's disease.

Reversible MAO inhibitor type A (RIMA). Moclobemide

Monoamine oxidase inhibitors (MAOis) pharmacology
These drugs inhibit the destruction of these brain chemicals, which leads to increased concentrations
of these neurotransmitters, which may account for their antidepressant activity.

Monoamine oxidase inhibitors (MAOIs) therapeutics

The monoamine oxidase inhibitors (MAOis) were the first class of compounds used to treat
depression. They are also used as anti-anxiety and narcolepsy. Selegiline is used for the treatment of
Parkinson’s disease.

Monoamine oxidase inhibitors (MAOIs) side effects

• Patients, taking these drugs, must monitor their diet for tyramine, an amino acid present in many
foods that are fermented, aged or smoked e.g. cheese. There are a number of foods containing
tyramine and such` drugs must be avoided. Monoamine oxidase is an enzyme, which inactivates
the neurotransmitters, epinephrine, nor epinephrine and dopamine. CVS affects  Orthostatic
Hypotension, Tachycardia, Arrhythmias, Stroke.
• CNS effects  Sleep disturbances, CNS stimulations. Weight Gain, Sexual Dysfunction
• Anticholinergic less than TCAs.

Tricyclic antidepressants (TCA) chemistry

Secondary amine type. Dibenzocycloheptadine (Example Nortriptyline) and dibenzapines (Example

Desipramine).
Tertiary amine type. Dibenzocycloheptadine (Example Amitriptyline and Dibenzapines (Example
Imipramine).

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Dibenzocyclohepatadiene Derivatives

Tertiary Amine type Secondary Amine type of TCA

CHCH2CH2N(CH3)2 CHCH2CH2NHCH3

Amitriptyline Nortriptyline

Dibenzapine Derivatives

N N
CH2CH2CH2N(CH3)2 CH2CH2CH2NHCH3

Imipramine (tofranil) Desipramine (Norpramin)

Tricyclic antidepressants (TCA) pharmacology

These drugs inhibit reuptake of NE and 5HT at receptor site, which leads to increased concentrations
of these neurotransmitters, which may account for their antidepressant activity.

Tricyclic antidepressants (TCA) therapeutic use

• These drugs are used for the treatment of major depression. Clomipramine is the drug of choice
for anxiety disorder (OCD). Amitriptyline also used in migraine prophylaxis and treatment of
Neuropathic pain. Imipramine was used to treat enuresis in children (Bedwetting)

Tricyclic antidepressants (TCA) side effects

• CVD effects: Orthostatic Hypotension, Tachycardia (AV blockade); CNS Confusion/Delirium.
Weight Gain, Sexual Dysfunction, and Bone marrow depression
• Anticholinergic side effects (Constipation, Blurred vision, Urinary retention, Dry mouth).

Selective Serotonin Reuptake Inhibitors Chemistry

NHCH3
F3C O O Cl
N
N CH2CH2CH2 N N N
N

Fluoxetine (Prozac) Trazodone (Desyrel)

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Selective Serotonin Reuptake Inhibitors pharmacology

The SSRIs are selective in blocking the reabsorption of serotonin by nerve cells by acting at the 5-HT
receptors, and therefore, increasing the amount of serotonin available in the brain.

Selective Serotonin Reuptake Inhibitors therapeutic use

This class of antidepressants has fewer side effects than MAOI’s or TCA’s. They are also used for
bulimia, obsessive-compulsive disorder and panic attacks.

Selective Serotonin Reuptake Inhibitors side effects

GI. Nausea (most common), headache, insomnia, nervousness, and fatigue. Sexual dysfunction
(orgasmic delay).

Antipsychotic drugs
Antipsychotics are used to treat schizophrenic individual is out of touch with reality, hallucinates,
hears voices and exhibits bizarre behaviour. These symptoms are only one aspect of schizophrenia.
Other symptoms are social withdrawal, and an inability to communicate or to concentrate.
Typical or 1st generation

Phenothiazine Thioxanthenes Butyrophenones Diphenylbutyrylpiperidine Dibenzoxazepine Dihydroindolone

Chlorpromazine Chlorprothixene Haloperidol Pimozide Loxapine Molindone
Fluphenazine Thiothixene Droperidol
Trifluoperazine
Thioridazine

Phenothiazines. Chlorpromazine, thioridazine, and prochlorperazine,

Must contain nitrogen containing side chain substituents on nitrogen for antipsychotic activity drug.
The ring and nitrogen must be separated by three-carbon chain such as chlorpromazine (Thorazine).

Phenothiazines. Such as thioridazine in which the ring and side chain nitrogen are separated by a two-
carbon chain has only antihistaminic or sedative activity.
Difference of one -CH 2 - in side chain referred as homolog.
Side chain containing piperazine derivatives have the greater potency and highest pharmacological
activity.

Butyrophenones. Haloperidol
S
Butyrophenones are chemically not related to
phenothiazines but have similar activity. Side chain
N X
Haloperidol produces a high incidence of
R
extrapyramidal SEs and less sedative effect than
chlorpromazine and produce less autonomic effect R = CH2CH2CH2N(CH3)2
like mild hypotension at high doses.
Thioxanthines. Thiothixine, chlorprothixine. Lack of ring Phenothiazine skeleton

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nitrogen and side chain is attached through double bond.

Phenothiazines
• Chlorpromazine (aliphatic)
• Thioridazine, mesoridazine (piperidine ring)
• Fluphenazine, perphenazine, prochloperazine
• Trifluoperazine (piperazine rings)

Atypical or 2nd generation. Clozapine, olanzapine, risperidone, paliperidone, quetiapine, ziprasidone,

laursidone and aripiprazole.

Benzazepine derivative
2nd generation antipsychotics such as benzazepine derivative act on less on D 2 , and high on 5HT 2A.
Where as in typical antipsychotic haloperidol binds equally high affinity to D 2 , serotonin and putative
alpha 2 receptors.

Dibenzazepine. Clozapine and quetiapine

Clozapine acts less potent D 2 , more potent 5HT 2A, H 1 , α1&2 , low on M.
Olanzapine acts potent D 2 and 5HT 2A .
Quetiapine acts less potent D 2 , Most effectively binds 5HT 2A , H 1 , α 1&2 , low on M
Risperidone blocks 5HT 2 greater than D 2 receptors.
Paliperidone. Active metabolites of risperidone. This is not metabolized in liver thus have low drug
interactions. Available as PO daily dose (taken in morning due to insomnia SE), and prolong released
injectable suspension.
Ziprasidone. Agonist of 5HT 1A and moderate inhibition of synaptic reuptake of 5HT and NE. Thus
ziprasidone has potential efficacy in –ve symptoms and depression.
Aripiprazole. partial agonist at 5HT 1a and D 2 receptors. Thus has potential efficacy in –ve symptoms
and depression. Available oral single daily dose. Taken with or without food.
• D 2 inhibitory effect effective produce more pharmacological benefit to treat positive symptoms.
• 5HT 2A inhibitory effect effective in producing more pharmacological benefit to treat negative
symptoms.
D2 5HT 2 M1 H1 Alpha 1 Alpha 2 5HT 1A QT pro
Clozapine least high +/- (less) high + +
Olanzapine
Risperidone
Quetiapine least high +/- (less) high
Paliperidone
Ziprasidone yes yes
Aripiprazole yes

Antipsychotic drugs pharmacology

• 1st generation antipsychotic mainly bind to D 2 thereby block dopamine receptors in cortical and
limbic areas of brain. Blockade in dopamine at basal ganglia leads to side effects such as
Parkinson’s (Extra pyramidal side effects).
• 2nd generation antipsychotics bind and inhibit serotonin receptors and dopamine receptors. Some
examples clozapine 5HT 2 , D 1 and D 2 , D 4 , muscarinic, and alpha-adrenergic receptors. Risperidone
blocks 5HT 2 greater than D 2 receptors. Quetiapine, Least effect on dopamine.
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Antipsychotic drugs therapeutic use

The antipsychotic agents are used to treat schizophrenia and other psychoses (major mental
disorders).
1st generation antipsychotics are preferred to treat positive schizophrenia symptoms. 2nd generation
antipsychotics preferably used to treat negative schizophrenia symptoms.

Antipsychotic drugs side effect. Extra pyramidal Symptoms (EPS), Parkinsonism, sexual dysfunction,
anticholinergic side effects, tardive dyskinesia, sedation. The first generation antipsychotics have high
extra pyramidal side effects, and second generation have high weight gain side effects.

CNS stimulants. Methylphenidate, amphetamines

Methylation. Amphetamine --> Methyl amphetamine

Dehydroxylation. Ephedrine or pseudoephedrine --> Methyl amphetamine

OH H OH H H
NH2 CH3 N CH3 N CH3 N CH3

CH3 NH2 CH3 CH3 CH3

Amphetamine Dextroamphetamine Ephedrine

Pseudoephedrine Methamphetamine
A B C D E
(meth amphetamine street name crystals meth, glass, ice)
Benzodiazepines
Neurotransmitters that play important role in sleep or hypnotic actions are GABA, histamine,
acetylcholine, catecholamine and adenosine.

The Serotonin agonist of 5HT1A, 5HT1B, 5-HT2 and 5HT3 receptors cause wakefulness and inhibit
sleep.

Short acting Intermediate Long acting

Benzodiazepine chemistry
acting
Midazolam Alprazolam Diazepam
Triazolam Lorazepam Flurazepam
Oxazepam Clonazepam
Temazepam Chlordiazepoxide 2
N
1
9 1
O 10 D X3
N N
8 2 9
A B 3 A B 4
7 8
N 4 6 N5
6 5 7
1' 1'
6' 6'
2'
C 2' C
5' 5'
3' 3'
4' 4'
5-Phenyl-1,4-benzodiazepine Annelated benzodiazepine
Annelated benzodiazepine. Example. Alprazolam, and triazolam

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The ring B in benzodiazepine is "diazepine"

Dealkylation
• Diazepam and chlordiazepoxide. metabolized to desmethyl diazepam or desmethyl
chlordiazepoxide have long half life (>50 hr).
• Flurazepam metabolized to desalkyl flurazepam.

Oxidation
• Alprazolam and triazolam oxidized to short and intermediate acting.

Rapid conjugation
• Oxazepam and lorazepam metabolite have no intrinsic activity.
• Benzodiazepines such as lorazepam, Oxazepam and temazepam (LOT) have OH group at position 3
easily undergo phase II glucuronidation conjugation, and have short half-life.
• Benzodiazepine without OH group at position 3, must undergo phase I hydroxylation reaction and
then phase II metabolism thus have long half life (long acting).

Benzodiazepine pharmacokinetics
Long acting benzodiazepines include Diazepam (longest half life), flurazepam, clonazepam,
chlordiazepoxide.
Intermediate acting: Alprazolam, Lorazepam, Oxazepam, temazepam and nitrazepam.
Short acting:. Triazolam, midazolam (shortest half life). Short acing benzodiazepine have no phase I
metabolism, or extra hepatic metabolism.

Benzodiazepine pharmacology
Benzodiazepine receptors BZ 1 and BZ 2 are found in brain, benzodiazepines bind to BZ 1 and BZ 2 that
are parallel to GABA receptors.

Benzodiazepine therapeutic use

Benzodiazepine are minor tranquilizers are used to treat insomnia, anxiety and seizure.
Benzodiazepine are used to help panic attacks and insomnia, benzodiazepines should be administered
for short-term use only as they become ineffective and cause memory loss. Continuous R.E.M. sleep
deprivation makes people more irritable and less able to concentrate.

Benzodiazepine side effects: The benzodiazepines in some patients, especially with long-term use,
experience drowsiness; tolerance dependency and withdrawal symptoms can be problematic. Even
with short-term use, some patients experience tolerance and dependency.

Barbiturates

Ultra-short action Short acting Long action

Thiopental Amobarbital Phenobarbital
Secobarbital
Pentobarbital

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Barbiturates chemistry
• 5, 5-disubstituted derivatives of barbituric acid, a saturated diketopyramidine.
• Two side chains in position 5 are essential for sedative hypnotic activity and long acting has a
phenyl and an ethyl group in position 5. Barbiturates have structural similarity with hydantoins
(phenytoin), however, hydantoins have five membered ring structure.
• Primedone is prodrug, and active metabolite is phenobarbital.
R1 R2
O O
O
HN NH N
N CH2CH2CH2CH2 N N
O N
O
General Barbiturate Structure
Buspirone (Buspar)
Barbiturates pharmacology
Barbiturates interfere with Na+ and K+ transport across membrane potentiates GABA A action on Cl-
entry. These drugs do not bind to BZ 1 and BZ 2 benzodiazepine receptors.

Barbiturates Therapeutic Use

They are effective only for a few weeks since they alter the length of time spent in R.E.M. sleep. They
should only be used for short-term therapy as sedative or hypnotics. Tuinal (a combination of
secobarbital and amobarbital), and secobarbital are reportable controlled drugs. Phenobarbital is
used to control seizure disorders, often in combination with primidone and/or phenytoin.

Barbiturates Side effects

Drowsiness the next morning, tolerance, and dependence.
Non benzodiazepine GABA-A agonist
• Act at GABA A receptors and have high affinity than benzodiazepines.
• Short acting
• No rebound effect on withdrawal
• Low physical dependence
Imidazopyridines
• Zopiclone
• Zolpidem (ambien)
• Pyrazolopyridine
• Zeloplon (Sonata)

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Anti-Parkinson’s Drugs
Drugs to treat Parkinson’s disease

Dopamine COMT Dopamine MAO B Anticholinergic

precursor inhibitors agonist inhibitor
Anti-viral drug
Peripheral dopa Entacapone Amantadine
Selegiline
decarboxylase
inhibitor
Benztropine
D2 Selective Ergot alkaloids
Levodopa Carbidopa Pramipexole D1 and D2 Non selective
Ropinirole Bromocriptine
Pergolide
Combination
Sinemet

COMT = Catecholamine O-Methyltransferase Inhibitors: DA= Dopamine

Anti-Parkinson’s drugs chemistry

HO COOH NCH2CH2 OH
NH2
HO
Levodopa Trihexyphenidyl
S

N CH2CH3
N CH3 O CH2CH N
CH2CH3
CH3

Benztropine Ethopropazine
Direct acting dopamine agonist: (Bromocriptine, Pergolide, Pramipexole, and Ropinirole), Direct
acting D 2 agonist. Inhibiting the secretion of the hormone prolactin from pituitary gland.

Dopamine precursors (levodopa): High protein content meals interfere with transport of levodopa
into the CNS. Levodopa should be taken on an empty stomach, typically 45 min before a meal.
Dopamine precursors and decarboxylase inhibitors: Levodopa (L-dopa)/carbidopa is the single most
effective anti-Parkinson drug. It is changed into dopamine in the brain. Antiviral agent with
antiparkinsonian properties (Amantadine). Indicated in drug induced Parkinson’s Disease because
levodopa will reverse the beneficial effect of the drug.

Anti-Parkinson’s drugs therapeutic use

Anti-Parkinson’s drugs side effects

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• Levodopa /carbidopa. Nausea, vomiting, orthostatic hypotension, dyskinesia, hallucinations,

confusion Long term use of levodopa/carbidopa therapy can produce mydriasis & precipitation of
glaucoma, and melanoma.
• Amantadine. anticholinergic side effects, hallucinations, edema of feet & ankles.
• Anticholinergic drugs, avoid in elderly. It aggravates glaucoma, memory impairment
• COMT inhibitors. dyskinesias, nausea, sleep disorders, anorexia, diarrhea, hallucinations.

Direct acting dopamine agonist. (Bromocriptine, Pergolide, Pramipexole, Ropinirole)

nausea, vomiting, orthostatic hypotension, psychosis, pleural fibrosis (chest x ray before initiating
therapy).

Non selective dopamine agonist. Bromocriptine and pergolide are ergot alkaloids that have effects on
partial dopamine (D 1 ) and full on D 2 receptors and other receptors.

Selective (Full) dopamine agonist. Pramipexole, and Ropinirole selective full agonist on D 2 and D 3
receptors. These drugs do not have effect on non-dopamenergic receptors; thereby there are no
peripheral effects associated with these drugs.

Anti-epileptics chemistry
Anti seizure drugs (Antiepileptics, anticonvulsants)
• Phenytoin (Dilantin). Hydantoins
• Carbamazepine . Iminostilbenes
• Valproic acid Dialkylacetate. divalproex and valproic acid are related chemicals. Divalproex is a
mixture of valproic acid and sodium valproate. In the body they are metabolized to separate
compounds, and both exert anticonvulsant effects.
• Primidone. Phenobarbital and primidone are chemically related. Primidone is metabolized to
phenobarbital and another compound in the body, both of which have anticonvulsants properties.
• Ethosuximide (Zarontin). Suxinamides

GABA analogs. Gabapentin, vigabatrin, pregabalin and baclofen (a muscle relaxant).

Gabapentin (structurally similar to GABA neurotransmitter), Lamotrigine. Phenyltriazine derivative.
NH2
O CH3
O CH2CH3 O
HN
HN NH

O
O Gabapentin OH
Phenytoin (Dilantin) Ethosuximide (Zarontin)
NH2
H
H2N COOH O
N
CONH2
GABA Pregabalin OH
Carbamazepine (Tegretol) Gabapentin (Primary amine)

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Anti-epileptics pharmacology
Anticonvulsants are CNS acting drugs that are used to treat seizures. Epilepsy is a disorder of electrical
conduction in the brain and results in loss of consciousness, seizures and convulsions. The electrical
activity causes nerve cells to become hyper-excitable and to discharge uncontrollably. Phenytoin
decreases the sodium content of nerve in the brain and thereby decreases the hyper excitability of the
cells that are involved in initiating seizures.
Carbamazepine blocks Na channels thereby reducing abnormal impulses in brain.

Anti-epileptics side effects

Phenytoin: can cause overgrowth of the gums (gingival hyperplasia) and proper mouth hygiene is
necessary for people taking this drug. Encephalopathy, blood dyscrasias, Nystagmus, Hirsutism. Birth
defects like cleft palate, and Stevens Johnson syndrome.
Phenytoin structure has hydantoins. Thus it give hydantoins syndrome. This can give congenital defect
in children as cleft palate.

Carbamazepine. Rash, ↑ liver enzymes, neutropenia, aplastic anemia

Chronic: drowsiness, vertigo (sensation of dizziness and confused, disoriented state of mind). Aplastic
anemia, Stevens Johnson syndrome (skin hypersensitivity reactions), Acute intoxication: Coma,
hyperirritability, convulsions and respiratory depression.

Topiramate. Cognitive dysfunction, headache, kidney stones, and weight loss.

Clobazam. Tolerance to therapeutic effects, insomnia, depression, dizziness, drowsiness, Light

headedness, ataxia.

Local anaesthetics
Local anaesthetics chemistry. Most local anesthetics are structurally similar to the alkaloid cocaine,
however these structures consist of a hydrophilic amino group through ester or amide functional
groups.

Ester Type. Cocaine, procaine, chloroprocaine, and benzocain.

Short acting due to rapid hydrolysis. Ester type of local anesthetic hydrolysis produces para amino
benzoic acid (PABA).

Amide Type. Lidocaine, dibucaine, prilocaine, mepivacaine, bupivacaine, and etidocaine. Long acting,
and metabolized in liver. Procainamide is long acting amide type local anesthetic than procaine an
ester type, because isosteric replacement of ester oxygen with a nitrogen atom.

Lidocaine (tertiary amine) Procaine (aromatic amine)

CH3 CH2CH3 CH2CH3

O O
N N
N CH2CH3 O CH2CH3
H
H2N
CH3
Ester Type
Amide Type

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Local anesthetics pharmacology

Inhibit sensory nerves that carry stimuli to CNS, block nerve fibre conduction. Blockade is reversible,
must continue administration of the drug for effects to continue.

Local anesthetics therapeutic use

Procainamide  Antiarrhythmic drug (Na+ channel blocker).
Lidocaine is used for  antiarrhythmic drug and amide type local anesthetic.

General anesthetics
Add classification from pharmacology
General anesthetics chemistry

O
Cl
NH
O O NH2CH3 Cl-
O
HN N H2C6H5O7- N+
H CH2CH2
S- Na+
Thiopental Sodium Ketamine Hydrochloride Fentanyl Cytrate
General anesthetics pharmacology
Ketamine. Short acting non-barbiturate anesthetic induces a dissociated state in which the patient
appears awake but is unconscious and does not feel pain.

Propofol. Sedative or hypnotic action, used in induction and maintenance of anesthesia. Fast onset (40
seconds of administration).

Thiopental is rapid acting barbiturates.

General anaesthetics therapeutic use

• Halothane is used in pediatric anaesthesia; it is infrequently used in adults.
• Isoflurane (Forane), enflurane, sevoflurane and desflurane are frequently used in adults.
• Enflurane is used as an inhalation agent for adults, but is not widely used for pediatric cases.
• Isoflurane may be the most widely used inhalation agent.
• Fentanyl is a narcotic, available as transdermal patch. Good analgesic property

General anaesthetics side effects

Ketamine. Causes sedation, immobility, amnesia, and nightmares.
Halothane. is associated with malignant hyperthermia.

Tips
• SSRI onset of action is 
• Fluoxetine washout period 
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• Depression with sexual dysfunction 

• To treat depression in insomnia patient 
• Depression with diabetes 
• Venlafaxine at higher dose act on 
• Higher dose of venlafaxine (225 mg/day) have effect on 
• Patient on antidepressants and shows with dilated pupil, may be due to
• TCA onset of action is 
• A substance found commonly in fermented foods, which can be toxic when MAO inhibitors are,
used
• MAO is classified as 
• Avoid taking cheese with 
• Milk + MAOI 
• St. Johns wort is 
• Selegiline and Rasagiline 
• Venlafaxine is classified as 
• Drug of choice against bipolar disorders and manic depression 
• Lithium toxicity symptoms -->
• CNS-->
• Thiopental 
• Lithium blood levels in adults 
• Serotoninergic syndrome 
• Fast or quick acting benzodiazepine is 
• GABA analogs are 
• Antiseizure drugs that gives Stevenson Johnson syndrome 
• What antiseizure drugs that is also used as weight loss therapy?
• Nystagmus 

Select TRUE OR FALSE Statements______________

• Lithium concentration varies with Na+ ions (T/F)
• Li+ conc. increases with decrease Na+ (T/F)
• Li+ conc. decreases with increase in Na+( T/F)
• ACEI decrease Na+ and increase Li+( T/F)
• NSAID decrease Na+ renal perfusion is less (T/F)
• Thiazide deplete Na+( T/F)
• Fluoxetine (SSRI) increase Li+ toxicity (T/F)
• Renal dysfunction  Li+ increase( T/F)
• Dehydration Li+ increases (T/F)
• Clorgyline (specific for MAO type A) --> T/F

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28
Medicinal Chemistry and
Pharmacology of Endocrine
Drugs
Antidiabetic drug chemistry

Oral diabetic drugs

Hypoglycemic drugs Antihyperglycemics

Increase insulin secretion

Meglitinides
Sulfonylureas Repaglinide
Nateglinide

1st Generation 2nd Generation 3rd Generation

Chlorpropamide Glyburide Glimepiride
Tolazamide Gliclazide Extra pancreatic action
Tolbutamide Glipizide
DPP-4 inhibitors
Sitagliptin, Saxigliptine and linagliptine
Biguanide Thiazolidinedione Inhibitor of dipeptidyl peptidase enzyme (DPP that
Metformin Rosiglitazone enhances the incretin hormone.
Increase insulin sensitivity Pioglitazone DPP-4 inactivates incretin hormone.
Increase glucose uptake in PPAR-γ receptors agonist
GLP-1 (incretin like peptide) enhancers
cell
α-glucosidase inhibitor Incretin analog. GLP-1 receptor agonist.
Decrease gluconeogenesis Acarbose Activates incretin pathway by utilizing DPP-4
Glucosidase breakdown starch resistant analogue GLP-1
and disaccharide into glucose. Liraglutide. Incretin hormone analog
Starch ----> glucose Exenatide
Canagliflozin. SGLT2 inh.
Inhibit reabsorption of glucose in nephron.

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Questions Alerts!
Common questions in pharmacy exam is to ask!
• Structures activity of steroidal hormone such as estrogen (phenolic group), progesterone (ethinyl
group) and testosterones.
• Thyroid hormones thyroxine (T4) and triiodothyronine (T3)
• Structure activity of Adrenal corticoids mineral corticoids and glucocorticoids such as
hydrocortisone (11- position hydroxyl group). Topical glucocorticoids ranking of potency.
• Classification hypoglycemic drugs like 1st & 2nd gen sulfonylureas. The second generation such as
glyburide, gliclazide and glimipride.
• Insulin and incretin hormones functions and analog liraglutide and Exenatide.
• DPP-4 inhibitors such as sitagliptine and saxigliptine.

Oral Hypoglycemic Agents

Generic Name Brand Name Generic Name Brand Name
acarbose Prandase pioglitazone Actos
metformin Glucophage (generics) rosiglitazone Avandia
repaglinide GlucoNorm chlorpropamide Generics, Diabinase
gliclazide Diamicron, Diamicron MR glimepiride Amaryl
(generics)
glyburide Euglucon, Diaβeta (generics)

Antidiabetic drugs pharmacology

Sitagliptine. Prolong the half life of an endogenously produced glucagon like peptide-1 (GLP-1). In DM-
2, the GLP-1 levels are deficient. GLP-1 are inactivated by DPP-4. Thereby DPP-4 inhibitors partially
reduce the inappropriately elevated glucagon post prandially and stimulate glucose dependant insulin
secretion.

Sulfonylureas (Chlorpropamide, Gliclazide, Glimepiride, Glyburide, Tolbutamide). Increased secretion

of insulin by action on β-cells of pancreas. Glyburide may produce a mild diuresis by enhancing renal
free water clearance. Chlorpropamide has antidiuretic activity possibly due to potentiating of
antidiuretic hormone (ADH) in the renal tubules.
First generation. Tolbutamide, Chlorpropamide,
Second generation. Glyburide, Gliclazide. Glyburide all action is due to insulin secretion (most
hypoglycemic).

Third generation. Glimepiride

Glimepiride is quick onset of action and long acting. It has extra pancreatic activity thus has less
hypoglycemia SE. Binds to a different proteins in the putative sulfonylurea receptors. Exerts
hypoglycaemic effect with less secretion of insulin.

Second generation agents have larger R 1 substituent's, because of large substituent's these are more
lipids soluble and more potent compared to first generation. Sulfonylureas areas acidic compounds
attached to aromatic ring.

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O H H
R1 HS N N
R2
O O

General Sulfonylurea srtucture

T 1/2 Duration
Glyburide 1.5 – 3 h Up to 24 h Pancreatic
Gliclazide 2-4 h Up to 24 h
Glimepiride 2-3 h Up to 24 h Extra pancreatic

Meglitinides (Nateglinide, Repaglinide): Increased

secretion of insulin by action on β-cells of pancreas. Important Concept!
Metformin is basic compound. Meglitinides are acidic Acarbose does not decrease
compounds. Rosiglitazone and pioglitazone are acidic glucose absorption.
compounds.

Alpha-glucosidase Inhibitors (Acarbose)

Inhibits alpha glucosidase in intestinal border thus decreasing the absorption of starch and
disaccharides.

Biguanides (Metformin hydrochloride). Increased peripheral utilization of glucose by decreased

gluconeogenesis. Do not cause hypoglycemia in monotherapy.

Thiazolidinediones (Pioglitazone and Rosiglitazone). Decreases insulin resistance in the periphery and
liver. Improves glycemic control while reducing circulating insulin levels.

Orlistat. Blocks the action of stomach and pancreatic enzymes (lipases) that digest fats, so fats and
other fat soluble vitamins ADEK are not absorbed in the body but pass through and excreted in the
feces.

Antidiabetic drug Therapeutic uses

Sulfonylureas (Chlorpropamide, Gliclazide, Glimepiride, Glyburide, Tolbutamide)
Disulfiram like reaction is caused by which type of antidiabetic drugs, when taken with alcohol.

Chlorpropamide has antidiuretic activity possibly due to potentiating of ADH in the renal tubules;
there is some evidence that chlorpropamide may actually stimulate ADH secretion.

Meglitinides (Nateglinide, Repaglinide): Nateglinide used for type 2 diabetes. It is imperative that
there be rigid attention to diet and careful adjustment of dosage. When metformin is combined with
a sulfonylurea, instruct the patient on hypoglycemic reactions and their control. If vomiting occurs,
withdraw drug temporarily, exclude lactic acidosis, then resume dosage cautiously.
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Biguanides (Metformin). Metformin can be of value for the treatment of obese diabetic patients. May
cause hypoglycaemia when combined with sulfonylureas (glyburide).
Metformin: basic compound. Meglitinides; acidic compounds. Rosiglitazone and pioglitazone; acidic
compounds

Alpha-glucosidase Inhibitors (Acarbose). For type II Diabetes Mellitus in combination with other
antidiabetic drugs. In combination oral hypoglycemic therapy, always use agents from different class
of oral hypoglycemics.

Thiazolidinediones (Pioglitazone, Rosiglitazone). These agents depend on the presence of insulin for
its mechanism of action. Contraindicated in patients with serious hepatic impairment, acute heart
failure. Increasing insulin sensitivity in type 2 diabetes. It improves sensitivity to insulin in muscle and
adipose tissue and inhibits hepatic gluconeogenesis.
Agonist of the peroxisome-proliferator activated receptor- γ (PPAR γ). Τhe PPAR γ binds to DNA
activating transcription of wide variety of metabolic regulators (antihyperglycemic).

Rosiglitazone + Metformin. Indicated for use when diet, exercise, and metformin or rosiglitazone
alone do not result in adequate glycemic control. Rosiglitazone+metformin is the combination used in
case of insulin resistance.

Rosiglitazone + Metformin (Avandamet). If acidosis of any kind develops, Avandamet should be

discontinued immediately. The use of rosiglitazone in combination therapy with insulin is not indicated
due to its side effects, therefore, Avandamet is not indicated for use in combination with insulin.
2,4-thiazolidinedione is pharmacophore of glitazones.

Orlistat (Xenical). Reduces fats stores and produce weight loss. It is an intestinal lipase inhibitor.
Antidiabetic drugs Side effects
Sulfonylureas (Chlorpropamide, Gliclazide, Glimepiride, Glyburide, Tolbutamide).
GIT disturbance (metallic taste), hypoglycemia, weight gain, hepatic x renal insufficiency. (Jaundice),
tachycardia, headache, rash, increased ADH.

Structure activity of biguanide (metformin)

Biguanides (Metformin hydrochloride)
• GI. Diarrhea, nausea, vomiting, abdominal bloating, flatulence, and anorexia(weight loss) are the
most common reactions to metformin and are approximately 30% more frequent in patients.
Occasionally, temporary dose reduction may be helpful.
• Decreased vitamin B 12 (cyanocobalamine) absorption thus can cause megaloblastic anemia.
• Unpleasant or metallic taste, which usually resolves spontaneously.
• A rare and serious side effect is lactic acidosis.

Alpha-glucosidase Inhibitors (Acarbose). GI. Flatulence, diarrhea, abdominal pain, cramps, nausea.

Thiazolidinediones (Pioglitazone, Rosiglitazone). Weight gain, fluid retention, and hemodilution,

varying effects on lipids, increase HDL, increase LDL, pioglitazone decrease TG. As a consequence of
their improved insulin sensitivity, these patients may be at risk of pregnancy if adequate contraception
is not used.
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Orlistat. Stethorrhea (oily leakage), and abdominal discomfort.

Canagliflazin (Invokana)
Increase glucose excretion in urine. Act as Sodium-glucose transport protein 2 (SGLT 2 )
inhibitor.

Ketoacidosis. Mainly Type 1DM

Acetyl CoA (produced in liver) --> acetoacetic acid Beta-hydroxybutyric acid

Acetone

Thyroid disorders
Thyroid gland secretes levothyroxine, liothyronine or triiodothyronine and calcitonin
Medicinal chemistry of thyroid disorders
Drugs Used In Thyroid Disease

Hypothyroids Hyperthyroids

Thyroxine (T4)
Synthroid Triidothyronine (T3)
Eltroxin

Thioamides: Iodide 131 Ipodate

I
Methimazole Lugol solution:
Propylthiouracil (KI+I)

Important Concept!
1) levothyroxine (T4) have 4 iodines and Levothyronine have 3 iodine.
2) Deiodination reaction is catalyzes T4 to T3 by deiodinase enzyme which takes place in peripheral
tissues and liver.
3) Lugol's solution is 10% KI + 5% I, is taken as oral drops. It can stain.
4) Drugs that affects thyroid functions? Warfarin, heparin, lithium, amiodarone.
5) Amiodarone structure is similar to thyroxine. Thus amiodarone interferes with peripheral conversion
of T4 to T3. Where as dronedarone has NO iodines.

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Deionidation

HO HO
I I
I H NH2 H NH2
I COONa I COONa

O O

I I
Sodium Levothyroxine (T4) Sodium Liothyronine (T3)
3,5, 3’, 5’ thyroxine (T 4 ) 3,5,3’ Triiodothyronine (T 3 )

5-monodeiodinase enzymes found in extra thyroidal peripheral tissues catalyzes T 4 to T 3 .

Thyroid hormone pharmacology. Levothyroxine a major hormone of thyroid gland is liothyronine and
thyroid, desiccated.

Thyroid hormones therapeutic use. Levothyroxine , liothyronine, thyroid, desiccated is used for the
treatment of Goiter and thyroid cancer.

Thyroid hormones Side effects. Levothyroxine . Rare side effects such as anxiety, diarrhea, weight
loss, sweating, insomnia, and muscle cramps.

Thyroid hormones drug interactions Important Concept!

1) Overdose symptoms of thyroid hormone
Thyroid hormones increase catabolism of cause hyperthyroid symptoms
vitamin K dependent clotting factors thereby 2) Levothyroxin taken empty stomach.
increase the effect of warfarin. Glycemic 3) Hypothyroidism: Increase serum TSH,
control may decline with initiation of decrease FT4 and TT3
levothyroxine, potentially requirement of
antihyperglycemic agents. Antiepileptic, cholestyramine, and sucralfate may reduce the absorption of
levothyroxine because these agents bind with levothyroxine.

Drug and Food interactions. May decrease absorption of levothyroxine by iron salts, cholestyramine,
colestipol and sucralfate.

Thyroid hormones monitoring

Levothyroxine. Periodic tests of thyroid function, monitor serum TSH levels to adjust initial Dosage
after 6 to 8 weeks then as required or annually adrenal insufficiency may adrenal insufficiency may
have to be increased during pregnancy to maintain TSH in desired range, check TSH each trimester and
4 to 6 wk after any dosage adjustment.

Treatment of hyperthyroidism
Antithyroid drugs Chemistry. Thioamides such as methimazole, and propylthiouracil. The iodides,
Lugol's solution (KI + I) oral drops and radioactive iodine.

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Antithyroid drugs Pharmacology

Antithyroid drugs such as methimazole and propylthiouracil (PTU) act by.
• Decreasing thyroid hormone production
• Decreasing response to thyroid hormone
Antithyroid drugs structure, thiocarbamide (R-(C=S)-NH-R) is essential group for antithyroid activity.

Antithyroid drug mechanism.

• Inhibit the synthesis of T 3 and T 4 by inhibiting the iodination of tyrosine in the thyroglobulin.
(inhibits thyroid peroxidase or TPO).
• Blocks the coupling of the iodo thyroxin.
• Inhibits the conversion of T 4 to T 3 thereby thyroid hormone synthesis is decreased.
• Obvious effects are very slow since it takes 3 to 4 weeks before the hormone levels show a
decrease.
• Do not prevent the uptake of I by the gland (do not effect the extensive amount of hormone
stored in thyroidal thyroglobulin).

Propylthiouracil. Manage the overactive thyroid gland

Iodides.(Lugol's solution)
• Lugol solution is KI+I
• Inhibits the uptake of I 2 by a tyrosine.
• Inhibit hormone release by inhibiting thyroglobulin degradation.
• Decrease the size of the gland, decrease blood supply to the enlarged gland therefore it is used in
preparation for surgery

Radioactive iodine
• Effects of iodide on the thyroid gland.
• Emission of B rays.
• Gets incorporated into the storage facility
• Very effective as it concentrates in the thyroid destroys the gland within a few weeks

Antithyroid drugs side effects

Antithyroid drugs (Methimazole and propylthiouracil). Reduction in white blood cells leading to the
risk of infection, nausea and vomiting, joint pain, headache, rashes and itching, Jaundice, fever.

Iodides: Uncommon, reverses when the drug is discontinued, outbreak of acne

Swollen salivary gland, ulceration of the mucous membranes, conjunctivitis, rhinorrhea, and metallic
taste, bleeding disorder, anaphylactic reaction.

Radioactive iodide: induced genetic damage, leukemia, neoplasia. Cannot be administered to

pregnant and nursing mothers cross placental barrier secreted into the breast milk

Therapeutic uses
• Antithyroid drugs (Methimazole Propylthiouracil)
• Methimazole: used to treat hyperthyroidism
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• Propylthiouracil: used to treat hyperthyroidism

• Iodides: Used in the treatment of thyroid storm
• Radioactive iodine: I131 isomer of iodine is used in the treatment of thyrotoxicosis
Antithyroid drugs Contraindications / Precautions
• Propylthiouracil: Prescribed with caution in pregnant women. There is a risk of goiter and
hypothyroidism in the newborn infant if too high dose is used. Reduce dose to infant and children
• Iodides: Should be avoided in pregnancy as it crosses the placental barrier thus causing fetal
goiter.

Antithyroid drugs Pharmacokinetics

Methimazole: Well-absorbed, Slow excretion, t 1/2 is 6 hours
Propylthiouracil
• Propylthiouracil – rapid absorption after oral administration
• Peak serum levels seen after 1 hour, and t 1/2 is only 2 hours
• Extensive first pass metabolism
• Excreted by the kidneys as glucuronide (inactive)
• Preferred in pregnancy for it does not cross the placental barrier
• Strongly protein bound. Secreted in breast milk less than methimazole
Radioactive iodine: Sodium I131 given orally and well absorbed from the GIT, t 1/2 is 5 days

Medicinal Chemistry Steroid Hormones. The hormones that consist of fused 17-carbon atom ring
system are classified as steroids. Examples of hormones that have steroidal structure. Vitamin D,
adrenocorticoids or corticosteroids, and gonadal hormones or sex hormones (estrogen, progesterone,
and testosterones). Chemically these are derivatives of cyclohepanoperhydrophenanthrene, which
also similar to aromatic phenanthrene ring structure. Steroid skeleton consist of three 6 member
cyclohexane rings and 1 cyclopentane ring.
17
11
1 C D
16
A B 7
3
4 6

Steroid Skeleton
Adrenocorticoids. Derived from C-21 pregnane steroidal nucleus. Cortisone and hydrocortisone.

Adrneocroticosteroids are classified as glucocorticoids and mineral corticoids.

• Glucocorticoides formed and secreted from the middle layer of adrenal cortex.
• 17-β-keto side chain (COCH 2 OH), the 4-ene, and the 3-ketone structures.
• Oxygen atom at C-11 is essential for glucocorticoid activity.
• Double bond between C-1 and C-2 increases glucocorticoid activity without increasing mineral
corticoid activity.
• Fluorination at C-9 increases both mineral corticoid and glucocorticoid activity.
• Fluorination at C-6 increases glucocorticoid activity and less on mineral corticoid activity.

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• Hydroxyl group at C-17 and methyl group at C-16 enhances glucocorticoid activity and abolishes
mineral corticoid activity.
• An acetate ester at C-21 or 16α, 17α-isopropylidenedioxy groups enhances topical absorption.
O O
OH OH
OH OH
O HO

Cortisone Hydrocortisone
O O

Mineral corticoids are aldosterone

• Desoxycorticosterone acetate and fludrocortisone acetate. Formed in the outer layer of the
adrenal cortex, a prototypical mineral corticoid (aldosterone) and middle layer gives cortisones.

O O
OAc OAc
OH
HO HO

Desoxycorticosterone F Fludrocortisone
O O
CH3
Glucocorticoids potency ranking
Topical glucocorticoids potency ranking Inhaled and intranasal corticosteroids
• Very high potency. Betamethasone (0.05%) • Beclomethasone
dipropionate, Clobetasol (0.05) • Budesonide (highly potent nonhalogenated
• High potency. amcinonide, Triamcinolone steroid)
0.5% • Flunisolide
• Medium potency. Betamethasone benzoate • Triamcinolone
(0.025), Triamcinolone 0.025 to 0.1 • Fluticasone
• Low potency. dexamethasone, and • Mometasone (quick onset, more local
hydrocortisone absorption and lowest systemic absorption,
consequently fewest systemic SEs).

Gonadal Hormones
O
OH OH
C CH
Phenolic ring

HO O O

Estrogen Progesterone Testosterone

Although there is a new chiral group at C 7 . It is considered antiestrogen since there is no functional
group at carbon 7.

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Gonadal Hormones

Testes
Ovary

Testosterone
Estrogen Progesterone

Estradiol Norethidrone Testosterone Testosterone

Ethinyl estradiol Norgestrel Anabolic Antagonist
Mestranol (prodrug) Norethynodrel steroids
Norgestimate Finasteride
Desogestrel Dutasteride
Estrogen antagonist Medroxy proge Cyproterone
Tamoxifen acetate
Progesterone antagonist Nonsteroidal
Clomiphene
Estrogen agonist + Mifepristone (RU-486) Flutamide
antagonist (SERM) Bicalutamide
Raloxifine nilutamide

Estrogens
Estrogen chemistry: Ovaries produce 17β estradiol and estrone. These hormone have 18 carbons for
four rings. Three 6 membered rings and one 5 member ring. Estrogen exist as estradiol in body in
equilibrium with oxidized form of estrone and further biochemically modifies water soluble of estriol
that let excrete estrogen. Estrogen A ring is phenolic ring (aromatic), basic nucleus is known as estrane
with methyl group designated as C-18 on position C-13 cyclopentano-perhydrophenanthrene. Ethinyl
estradiol  17 alpha estradiol.

Diethylstilbestrol  Non steroidal synthetic estrogen (stilbene derivatives)

OH OH
O
Phenolic ring OH

HO HO HO

Estradiol Estrone Estriol

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Estrogen Pharmacology
Estrogens are female sex hormones that are used primarily to decrease bone loss and to treat the
symptoms of menopause. Estrogen is used to reduce or prevent osteoporosis in susceptible women.
Estrogens decrease the frequency and severity of hot flashes as well as the dryness in the vagina that
many post-menopausal women experience.
Estrogen therapeutic uses
Estrogen is the component of all brands of oral contraceptive pills. Estradiol and conjugated estrogens
are available in tablet form; estradiol is available in a patch and injection. Conjugated estrogens are
available in a vaginal cream. Estrogen is component of Diane 35 and Alesse oral contraceptive that are
used for the treatment of acne.

Estrogen side effects. Feminization (Breast tenderness), GI: Nausea, stomach upset, depression,
weight gain, CVS: increased blood clotting (Increased risk of thromboembolism diseases), edema,
hypertension, stroke, and MI. The most frequent adverse effect is nausea. Prolonged used of
unopposed estrogens (estrogen given without progesterone) in postmenstrual women increases the
risk of endometrial cancer.

Antiestrogens
The two-drug tamoxifen and clomiphene are categorized as full antiestrogens. Raloxifene is a Selective
estrogen receptor modulator (SERM) has partial antiestrogen and estrogenic actions.
Antiestrogen chemistry. These drugs are non-steroidal antiestrogenic compounds equally effective in
oral or injection forms.

N O N O N O

OH
Cl S
HO

Tamoxifen Raloxifen
(NOLVADEX) Clomiphene (EVISTA)

Tamoxifen and clomiphene are bioisoster.

Antiestrogen pharmacology
Tamoxifen competes for binding to the estrogen receptors thereby inhibits the action of estrogen.

Clomiphene Interferes with negative feedback of estrogen on hypothalamus and pituitary thereby
increases the secretion of gonadotropin releasing hormone (GnRH) and causes stimulation of
ovulation.

Antiestrogen therapeutic use: Tamoxifen is indicated in advanced breast cancer in postmenopausal

women. Clomiphene is used to treat infertility associated with anovulatory cycles.

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Antiestrogen side effects: Tamoxifen: hot flashes, vaginal bleeding, menstrual irregularities, risk of
endometrial cancer, nausea, vomiting Least nauseating anticancer drugs.
Clomiphene: ovarian enlargement, vasomotor flushes, visual disturbances.
Raloxifene Pharmacology : Reduces bone resorption thereby decrease bone turnover. Exhibit
estrogen like (agonist) effect on bones and lipid metabolism. Exhibit estrogen antagonist action on
uterine and breast tissues.
Raloxifene therapeutic use: Used in prevention of osteoporosis.
Raloxifene side effects: Hot flushes

Progesterone
Progesterone chemistry. Progesterone is a C-21 steroid, its basic nucleus is known as pregnane.
Two types of progesterone
• 17-alpha hydroxyprogesterone such as medroxyprogesterone acetate and megestrol acetate.
• 17-alpha ethinylandrogens (more potent). Norethindrone and Norethynodrel are commonly used
in OCs, because potent oral activity, more lipids soluble and less first pass metabolism.

norethindrone spelling correction

Progesterone therapeutic use
Progesterone is used alone for the treatment of amenorrhea, abnormal uterine bleeding, and
endometriosis. Levonorgestrel is progesterone, which is available as a sub-dermal implant for long-
term contraception. Six capsules are implanted on the inside of the upper arm. Contraception begins
within 24 hours and may last up to 5 years. Side effects nausea, depression, liver failure, cancer and
high blood cholesterol. Medroxyprogesterone acetate (Depo-Provera injection) is used to treat
amenorrhea (cessation of menstrual periods) and abnormal uterine bleeding. It is also used as a
contraceptive. As a contraceptive, 150 mg is injected once every three months.
O
(no aromatic ring O
C OC - CH3
and ketone at position 3 O
C

O
O CH3

Progesterone Medroxy Progesyterone Acetate

HO C C-H

Noethindrone
O
Progesterone products
Prometrium (micronized progesterone) 100 mg capsules powder is suspended in peanut oil, glycerine.

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Progesterone side effects

Medroxyprogesterone acetate unexpected or increased flow of breast milk, depression, loss or
changes in speech, coordination, stomach pain, swelling of face, ankles or feet, headaches, mood
changes, and unusual fatigue.

Anti Progestins
Anti Progesterone: Mifepristone (RU – 486)
Anti Progesterone pharmacology
Progestin antagonist with partial agonist activity. Mifepristone also has anti glucocorticoid property.
Causes abortion if administered in early pregnancy (85%) due to interference with progesterone and
decrease in production of human Chorionic Gonadotropin (hCG).

Anti Progesterone therapeutics use

Abortifacient: Administration of mifepristone used as contraceptive given once a month when
progestin levels are high (Prostaglandin E 1 and misoprostol orally after single dose of mifepristone
effectively terminates the gestation.

Androgens
Danazol, Nandrolone, Stanozolol, and Fluoxymesterone
Testosterone. C-19 steroid
Androgenic effect. Testosterone 17-enantahne, resemble estradiol esters that increases duration of
action when given I.M. Agents with 17-methyl groups are orally active
O

OH O C (CH2)5 CH3

O O
Androgen Testosterone enanthate
Testosterone (no ester or ethinyl group)
O
O R
C C
O CH2CH3
H3C

O N H Finasteride (presence of Heterocyclic ring)

O H
Dromostanolone Antiandrogen

Androgen pharmacology
Testosterone is the androgen that leads to the development of male secondary sexual characteristics
and maintains the male reproductive system.
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Androgen therapeutic use

Testosterone is commonly prescribed in the treatment of female breast cancer, androgen deficiency,
and for stimulation of growth, weight gain, and red blood cell production. Commonly known as
"anabolic steroids" because they promote muscle growth. They are also commonly used to help
patients recover from a surgery and cancer treatment that resulted in damage to muscle tissue.
Androgens orally ineffective.

Danazol. Indicated in endometriosis (ectopic growth of the endometrium)

Androgen side effects
• In males. Priapism (continuous erection), impotency, and gynecomastia.
• In females. masculinization, acne, hirsutism, deepening of voice, menstrual irregularities. Contra
indicated in pregnancy.
• Increase LDL, decrease HDL levels, and increase coronary artery disease, fluid retention (edema).

Anti-androgens
Finasteride, Dutasteride, Flutamide, and Cyproterone acetate. Antiandrogen nonsteroidal in nature
(example: Flutamide, bicalutamide, and nilutamide).
O R
OH C

O N H
O H
Antiandrogen
Androgen

Testosterone (no ester or ethinyl group) Finasteride (presence of Heterocyclic ring)

Anti-androgens pharmacology. Inhibit the synthesis of androgen.
• Finasteride. Competitively inhibits 5-alpha reductase this alpha reductase catalyses testosterone
to dihydrotestosterone (DHT). Because prostate growth is dependent on DHT, rather than
testosterone. This drug is used for treatment of BPH, it suppress (shrink) the prostate size.
• Finasteride is effective in 3 to 6 months.

Anti androgens therapeutic. Finasteride is steroid like drug approved for benign prostate hyperplasia
treatment.

Anti-androgen side effects

• Sexual dysfunction. Decrease libido, testicular pain breast tenderness and hirsutism.
• Hypersensitive reactions like rashes, pruritus, swollen face and lips.
• Contraindications. Pregnancy.
• Absorbs from skin avoid contact in pregnancy.

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Tips
• What drug shows it action by acting on cell surface? 
• Insulin has pharmacodynamic effect on 
• Insulin is stored at -->
• Insulin hormone antagonist 
• Glucogan hormone cause
• Diabetic ketoacidosis (DKA) mainly occurs in 
• Sulfonylureas: Chlorpropamide, Gliclazide, glimepiride (Amaryl),glyburide and tobutamide.
• Chlorpropamide + alcohol can cause 
• Meglitinides – Nateglinide, repaglinide
• Biguanides - metformin
• Dose adjustment in renal impairment, SE: lactic acidosis, diarrhea (most), VB 12 ↓
• ONLY oral, NO Wt↑ → good for obese Pt, NO hypoglycaemia on its own
• DI: alcohol (potentiates hypoglycemic effect)
• CI: hepatic impairment, renal impairment, CHF, hypoxemic states Pts
• Metformin + glyburide may cause
• Thiazolidinediones (TZDs) pioglitazone, rosiglitazone and combination rosiglitazone with
glimepiride or metformin.
• Thiazolidinediones SEs: Wt↑(most), fluid retention, ↑ HDL, NO hypoglycaemia on its own
• DIs: gemifibrozil ↑repaglinide concentration thereby avoid combination. CIs: congestive heart
failure. Can use renal impairment patients.
• Alpha-glucosidase Inhibitors: Acarbose, SE: flatulence, diarrhea
• With meal, NO use as monotherapy.
• Incretin hormone or glucagon like peptide-1 (GLP-1) are inactivated by? Dipeptidyl peptidase-4
enzyme (DPP-4s).
• Sitagliptine inhibits? DPP-4
• Sitagliptine SEs: Nasopharyngitis, DI: low potential (NO inhibit CYP P450),
• Take with metformin, with or without food, NO potentiates hypoglycaemia
• Intestinal Lipase Inhibitors – orlistat, SE: Diarrhea, Stethorrhea, abdominal discomfort, and oily
leakage. Take with food; impair absorption of fat-soluble vitamins (A, D, E, K)
• Thyroid Hormones-levothyroxine (Eltroxin, Euthyrox, Synthroid): T4
• Dosage: 1.6 µg/kg/day (adults), 12.5-25 µg/day (pts with coronary artery disease or elderly)
• Example of antithyroid drugs 
• Myxedema is malfunction of 
• Antithyroid Agents - methimazole: MMI (Tapazole), propylthiouracil: PTU (Propyl-Thyracil).
• SE: agranulocytosis, monitor WBC or CBC
• Stop about 5days prior to a thyroid scan, RAIU or treatment with 131I
• Increase in cortisone cause (Hypercorticoids) 
• Decrease in cortisone cause (Hypocorticoids) 
• Glutathione is 
• During ovulation increase of 
• Corpus luteum is stimulated by 
• What steroidal hormone structure have phenolic ring 
• Finaseride is 

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• Vitamin D 3 acts as 
• The effect of vasopressin on kidney 
• Deficiency (absence) of ADH cause 
• Glutathione protects
• The endocrine gland plays important rule in calcium metabolism 
• The major factor that controls Na excretion in kidney )
• The effect of the antidiuretic hormone is to 
• In postmenopausal therapy, which drugs have, risk of endometrial cancer 
• Oral contraceptives completely contraindicated in
• Oxytosin is used 
• Calcium reabsorption of distal convoluted tubule due to
• Testosterone to 5-hydroxy testosterone is catalyzed by? 
• Example of antiandrogenic drug 
• Finasteride mechanism of action 
• Steroid structures are common in hormones, such estrogen, progesterone, and testosterones.
Steroid contain how many cyclohexane and cyclopentane respectively in it skeleton.

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29
Medicinal Chemistry and
Pharmacology of
Respiratory Drugs
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Pharmacology of beta2 agonist
• Side effects of oral steroids like prednisone
• In children asthma use short acting steroids like prednisone and avoid long acting
dexamethasome. Short acting have less side effects on growth suppression.

Asthma
Chronic inflammatory disorder of the airways, ↑ airways responsiveness, causes reversible
obstruction. In asthma esinophils, mast cells and T lymphocytes plays significant role. ↑
sensitivity, and hypersensitivity of airways to specific and non-specific stimuli, such as air, odour,
allergens, and virus etc.

Asthma COPD
Airway (Bronchus) Progressive, partially reversible airway limitation. Increases
frequency and severity of exacerbations. COPD is
preventable and treatable. The cardinal symptoms are SOB
and activity limitation.
Terminal alveoli
Inflammatory disease Emphysema (permanent Chronic bronchitis
enlargement of alveoli)
Esinophilic Neutrophil Neutrophil
Coughing with wheezing during SOB (dyspnea) SOB (dyspnea) + sputum
breath, and SOB.
DOC for acute asthma attacks is DOC bronchodilator Antibiotics are used to
salbutamol, anti-inflammatory ipratropium, tiotropium, manage exacerbations of
Inhaled corticosteroids (ICS). salmeterol, formoterol (LABA). pneumonia. Corticosteroid
Inhaled corticosteroids are PO for less than <2wks.
NOT used.
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Beta 2 Adrenergic Agonist

MOA. beta 2 stimulation causes increase camp in smooth muscle leading to bronchodilation.

Short acting beta 2 agonist (SABA). (only for rescue as needed)

• Inhaled. Salbutamol (Albuterol) 1-2 puff tid-QID maximum 8 puffs
• Terbutaline maximum 6 inhalations/day
• Onset. within 5 min
• Therapeutic use. Relieve bronchoconstriction, the acute symptoms of cough, wheezing and
chest tightness, asthma emergencies and exercise induced asthma.
• SEs. Tremors, nervousness, tachycardia, palpitation, weakness, flushing of face or skin,
nausea and vomiting.
• Regular use can lead to decline in lung function.

Oral beta 2 agonist. The oral beta 2 agonist have more SEs, and less bronchodilation effect than
inhaled preparations.

Long acting beta2 agonist (LABA) (Maintenance or daily). In asthma LABA combined with ICS.
• Inhaled. Formoterol (full B 2 agonist), salmeterol (partial agonist)
• Onset. 14 min and duration up to 24 hours. Regular BID treatment.
• Therapeutic use. Maintenance therapy and EIA. NOT for acute. Used in patients already
taking corticosteroids. Formoterol can be used for acute and maintenance.
SEs. Same as SABA.

Anticholinergic. Ipratropium bromide is used as alternative for patients who are already
susceptible to tremors or tachycardia from B 2 agonist.
Ipratropium 2puffs Q6-8h

Tiotropium DPI (Spiriva, Handihaler, and inhaler) 18 mcg/daily capsule for inhalation. Long
acting anticholinergic taken once daily, it is administered by handihaler.
SEs. Dry mouth, metallic taste, mydriasis, and glaucoma if released into eye.

Corticosteroids
Inhaled corticosteroids (ICS). Benefit ↑ lung function, ↓ airway hyper responsiveness, ↓
symptoms of exacerbations. Max clinical effects in 2 to 4 wks. Fluticasone in few days, given 2 to
4 pf BID.

SEs. Sore mouth and sore throat. oral pharangeal candidiasis (oral thrush), dysphonea
(hoarseness) from vocal cord myopathy and cough. Rinsing mouth and using spacer (aero
chamber) can minimize SEs.
High dosages. Check bone densitometry, patient with glaucoma check IOP.

Oral corticosteroids (Po CST)

• Therapeutic use. Severe asthma with intensive airway inflammation.

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• SEs. Hyperglycemias, osteoporosis, hypothyroidism, hypertension, weight gain, ulcers,

edema, and susceptible to infections.

Leukotriene antagonist. Montelukast and zafirlukast.

The montelukast and zafirlukast have anti-inflammatory action, however LTRAs are not as
effective as low dose inhaled corticosteroids for improving symptoms or exacerbations. It is
considered as ad-on therapy with ICS.
• Therapeutic use. Asthma maintenance (steroid sparing agents), and the drug of choice for
ASA induced and beta blockers induced asthma.
• Montelukast 10 mg QHS po tablets is used in children >2 yr age, available as granules and 4
mg, 5 mg chewable tablets.
• Zafirlukast 20 mg BID po at least 1 h before and 2hr after meals is used in over >12 yr age
and only oral available.

Combinations. ICS + LABA.

Symbicort = budesonide/formoterol
Advair = Fluticasone/salmeterol
Zenhale = mometasone/formoterol

Advantage of combinations. More convenient, enhance adherence, less expensive.

Disadvantage. Loss in dosing flexibility

Chronic Obstructive Pulmonary Diseases

Chronic obstructive pulmonary diseases (COPD) is due to chronic obstruction of airway passage.
COPD is two types. Emphysema (high altitude sickness) and chronic bronchitis.

Emphysema is a disease in which the small air exchange sacs (alveoli) in the lungs become
permanently enlarged and damaged (alveoli walls destroyed) decreasing oxygen absorption and
resulting in shortness of breathe.

Chronic bronchitis is an inflammation of the airways in the lungs that causes lungs to produce
excessive amounts of mucus (phlegm), associated with chronic productive cough. This reduces
the flow of air to the lungs.

Drug used for the treatment of COPD

Anticholinergics. Ipratropium and tiotropium are muscarinic blocker and act as bronchodilator.
• Beta adrenergic agonists
• Corticosteroids
• Theophylline

Community acquired pneumonia (CAP) without risk factors

Pneumonia in COPD patient is treated by amoxicillin, doxycycline, cotrimoxazole, azithromycin,
or clarithromycin.

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COPD with risk factors (FEV 1 <50%, Ischemic heart diseases, use of home O 2 , chronic use of
steroids, antibiotic use <3m, >4 exacerbation/yr. Amoxi/clav, cephalosporin's (1st , 2nd, and 3rd)
or fluroquinolones (levofloxacin and moxifloxacin).

Tips
1. B 2 receptor 2. Cough 3. Wheezing
4. permanent enlargement 5. Salbutamol 6. Emphysema
of alveoli
7. chronic bronchitis 8. emotional stress 9. cold air
10. dust pollen 11. ASA 12. Animal dander
13. mold 14. humid>50% 15. exercise
• Emphysema is characterized as ? ( )
• COPD is? ( )
• asthma symptoms( )
• asthma triggers include? ( )
• The drug of choice to treat allergen induced bronchospasm ( )
• what action of adrenergic agonist action is selected treatment of asthma? ( )
• A young patient having asthma and allergic to air conditioners. What will be the pharmacist
recommend? 
• What is the drug of choice in allergy induced bronchospasm? 
• What action of adrenergic agonist action is selected treatment of asthma? 
• Formoterol is can be best described as
• Theophylline clearance is increased by 

Drugs that cause branchodilation Drugs that cause branchospasm

Examples of beta 2 agonist Beta blockers

(sympathomimetics)  Salbutamol,
salmeterol, formeterol
Examples of mixed alpha & beta 
Examples of muscarinic antagonists

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30
Medicinal Chemistry and
Pharmacology of
Musculoskeletal Drugs
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Osteoarthritis symptoms are pain in weight bearing joints
• Acetaminophen and NSAIDs side effects such as renal, and ulcers
• Rheumatoid arthritis treatment. Methotrexate dose and infliximab
• Acute gout attack therapy. Indomethacin, colchicine and prednisone
• Allopurinol (purines) structure and drug interactions with azathioprine. Allopurinol
associated with skin rash, alternatively use Febuxistat.
• Bisphophonates are pyrophosphates.

Rheumatoid Arthritis

Glucocorticoids NSAIDs
Joint
inflammation
Antigen
Activation of ↑ Prostaglandin Synoviocyte
macrophages proliferation,
Methotrexate Bone and
cartilage
Activation
Induction destruction
IL-2 TNF α of cytotoxic ↑ Cytokines
of T cells
T cells

Production of
Activation of
autoimmune IgRF
B cells
antibodies complex

Osteoarthritis (OA) is a degenerative joint disease caused by a breakdown of the cartilage

between bones.

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Rheumatoid arthritis (RA). Inflammation of joints with frequent acute attacks.

• Rheumatoid arthritis occurs when body’s immune system attacks the tissue lining and
results in the joints causing cartilage to erode.
Causes.
• RA. Autoimmune
• OA. aging of cartilage and trauma
Sex distribution
• RA. More common in females
• OA. Equal in both sex
Symptoms
• RA. Joint stiffness in the morning, painful and swollen joints, weight bearing and non
weight bearing joints. Affects on soft tissue.
• OA. Painful joints, restricted joint movements. Mainly weight bearing joints.
Diagnosis
• RA. Rheumatoid factor, erythrocyte sedimentation rate, x-ray, antinuclear antibody
• OA. X-ray only
Treatment
Rheumatoid arthritis  NSAID’s and DMARD’s
Osteoarthritis  Acetaminophen, NSAID’s

Symptoms Osteoarthritis Rheumatoid arthritis

Stiffness Morning or after inactivity (last 30 min) In the morning (last 1 hour)
Limited affected joints. Does not affect Affects on Soft tissue
Localized soft tissue. Not localized
Pain Worsens with activity or Worsened with prolonged inactivity. (usually
after prolong use, (weight bearing activity) improves with activity).
Generally weight bearing joints (hip, knee, Affects on weight bearing and non weight
ankle) bearing joints
Inflammatio Uncommon Common
n
Risk factor >65 years Autoimmune
Osteoarthritis
A degenerative joint disease caused by a breakdown of the cartilage of the bones. Degradation
of articular cartilage in synovial joints.
Non-prescription
• Acetaminophen is initial drug of choice for symptom relief. Maximum therapeutic dose
should be tried for 2 to 3 weeks.
• Acetaminophen 650 mg 4 to 6 times a day.
• ASA/NSAIDs/Ibuprofen is 2nd line therapy.
• Acetaminophen + caffeine + codeine
• Glucosamine and chondroitin
• Topical counter irritants (Methyl salicylate/Menthol/Capsaicin).

Prescription Medication
• COX-2 inhibitors as effective as NSAIDs but lower incidence of GI side effects.
• Intraarticular corticosteroids (3 to 4 injections year)
• Hyalunon injections only for those who failed other therapies
• Narcotic analgesics
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Rheumatoid arthritis
A chronic systemic, autoimmune inflammatory condition. Symmetric synovitis affecting similar
joints bilaterally.
• It is non-organ specific autoimmune disease.
• Type III hypersensitive reaction
• Blood contain rheumatoid factor
• Stiffness occurs in the morning.
• Large of areas of joints are effects.
• Not associated with frequent of use of joints.
• It effects on weight bearing and non-weight bearing joints.

Pharmacological Choices
Disease modifying anti-rheumatic drugs.
• Methotrexate is the drug of choice rheumatoid arthritis.
• Should be started within 3 months of disease onset (max effect in 3 to 6 months).
• Initial dose of 20 to 25 mg po/wk, do not exceed >25 mg/wk.
• Minor SEs oral ulcers can be reduced by concurrent use of folic acid.
• Should be avoided in patients with hepatitis B and C, renal insufficiency, or lung disease,
serious SEs are cytopenia, and hepatic toxicity.
• Hydroxychloroquine. SEs corneal and retinal deposition.
• Leflunomide. Can be used in combination with methotrexate (CI in pregnancy) or in place of
it for patients who have failed or have contraindications to methotrexate.
• Should be stopped in both males and females at least 3 months before attempting
conception (patient must undergo drug elimination by taking cholestyramine 8 g TID for 11
days.
• Azathioprine a purine analog immunosuppressive agent.
• Cyclosporine
• Minocycline
• Penicillamine
• Gold sodium thiomalate

NSAIDs. The NSAIDs are used in conjunction with DMARDS. The analgesic effect of NSAIDS and
salicylates is prompt but reduction of inflammation can take 2 to 4 wks.

Glucocorticoids. Prednisone/Triamcinolone safest therapy during pregnancy and lactation.

Biological response modifier. Infliximab, etanercept, adalimumab.

Rituximab and trastuzumab, infliximab Produced by human antimouse antibody (HAMA).

Monoclonal antibodies, these antibodies also known as chimeric antibodies.

Infliximab, adalimunab, certolizumab, etanercept, golimumab. Tumor necrosis factor TNF is key
mediator of inflammatory synovitis and bone cartilage destruction.
SEs. TB infections, psoriasis, increased risk of lymphoma, leukemia. Contraindication. SLE, CHF.
• Only available as iv. Store in refrigerator.
• Approved for ulcerative colitis. It is always used with methotrexate.

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• SEs. The most common SEs is headache, fever, chills, fatigue, diarrhea, pharyngitis upper
respiratory tract and UTIs.
Toclizumab. An interleukin (IL-6) inhibitor
Abatacept. A natural inhibitor of Tcell
Rituximab. a chimeric antibody removes memory B-cells.
Anakinra. Blocks interluekin-1 (IL-1)

Gout Arthritis
OH

N
N

H2N N N
H Guanine
Guanine deaminase

NH2 OH
OH
N N
N N N
Adenine Xanthine N
deaminase Oxidase
N N N
H N H HO N
N H
Adenine Hypoxanthine H
Xanthine

Xanthine
Allopurinol Inhibit oxidase

OH

O N N
O O H2N Uricase N
H2N-C-NH2 + HO-C-C-H OH

O N N HO N N
Glyoxylic acid H H
Urea H
Allantoin Uric acid

Formation or uric acid, urea and glyoxylic acid from purines

Gout is a disease in which monosodium urate monohydrate (MSU) crystal deposit in joints, soft
tissues such as cartilage, tendon and bursa or renal tissues such as glomeruli, interstitium
tubules.

Gout is associated with increased body stores of uric acid. Acute attacks involve joint
inflammation caused by precipitation of uric acid crystals.
Hyperuricemia  Urate crystal in joints  inflammatory response

Acute gout arthritis

Abrupt onset of excruciating pain and inflammation of joint during the night or early morning.
Patient cannot tolerate even light pressure such as a bed sheet on the affected joint. Attacks
often resolve spontaneously over 3 to 10 days.

OH3C
NHCOCH3 (C3H7)2N-SO2
OH3C CO2H

OH3C O
CH3O Probenecid
Colchicine
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1st line treatment is indomethacine, if contraindicated then colchicines and if contraindicated

then corticosteroids
Indomethacin
• It is prostaglandin type I NSAID
• It has the highest anti inflammatory action in all NSAIDs
• It has high GI irritation SE
• It do not decrease uric acid

Colchicine
• It produce an anti-inflammatory and analgesic effect
• It not used as analgesic action
• The most common SE is GI irritation
• CI: in severe renal diseases (CrCl <50 ml/min)

Corticosteroids
• Given intraarticular injections for monoarticular pain
• Given oral for polyarticular pain

Antihyperuricemic agents
Allopurinol. Inhibit xanthine oxidase.
• Xanthine oxidase enzyme is metabolizing enzyme of mercaptopurines. This enzyme is
inhibited by allopurinol.
• SEs: The major SEs are dermatological (skin rash, exofoliative lesions), GI (nausea, vomiting,
and diarrhea).
• Can form urate crystal in kidney and take with plenty of fluids.

OH OH

N N
N
Xanthine
N
Oxidase
N N N
HO N
H H
Alloxanthine
Allopurinol (oxypurinol)

Febuxostat is a xanthine oxidase inhibitor. Allopurinol associated with skin rash, alternatively
use Febuxostat.
Structurally different than allopurinol, thus can be used in patient allergic to allopurinol.
Febuxostat is consist of thiazole ring.
Can be used in renal diseases.

Sulfinpyrazone
• Increase uric acid excretion
• SEs. Can form kidney stones
• Drink plenty of fluids

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Probenecid
• Increase uric acid excretion
• SEs. can form kidney stones
• Drink plenty of fluids

Fenofibrate and losartan are used as uricosuric agents and for treatment of hyperuricemia.

Osteoporosis

Calcium homeostasis (serum concentration of ionic calcium)

Three hormones parathyroid, calcitonin and vitamin D control calcium homeostasis.

Osteoblast. Formed in bone marrow, stimulate bone formation.
Osteoclast. Responsible for carrying out the bone resorption or destroying process.

Bisphosphonates. Pyrophosphates (P-O-P group) and bisphosphonate (P-C-P)

Alendronate, residronate, etidronate, pomedronate and zoledronic cid

Tips
1. Anti hyperuricemia drugs 2. GI irritation 3 Allopurinol
4. Sulfinpyrazone 5. Probenecid 6 Alloxanthine or oxypurinol
7. Acetaminophen 8. Renal failure

• Drink plenty of fluids while taking… ( )

• Side effect of colchicine ( )
• Colchicine is contraindicated in? ( )
• What analgesic is not used in gout arthritis? ( )
• Example of drug that decrease uric acid production ( )
• Example of drug that increase uric acid secretion ( )
• What drug is not used for acute gout attack? ( )
• The major metabolite of allopurinol ( )

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 31
Medicinal Chemistry and
Pharmacology of
Antimicrobial Drugs
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Structure activity of penicillin's and cephalosporin's and mechanism of penicillin resistance.
• Quinolones mechanism of action and structure activities.
• Structure activity Tetracycline epimerization gives 4-epitetracyclin.
• Macrolides side effects explain by structure activity.

Antibiotics classifications
Mechanisms Antibacterial
Cell Wall synthesis inhibitors Penicillin's, Cephalosporin's, Vancomycin
Protein Synthesis inhibitors Aminoglycosides, Macrolides, Tetracycline’s, Lincosamide
DNA Synthesis inhibitors Quinolones/Fluoroquinolones, Metronidazole
Folate Inhibitors Sulfonamides, Trimethoprin.
Penicillin's

6-Aminopenicillanic acid

β-lactam ring
H H
H R N N S
R N S
S R R

O N N
N O O R
O
COOH COOR
COOH Dihydrothiazine
C Thiazolidine
D

C = Bond cleavage by beta-lactamases Penicillins Cephalosporins

D=Susceptible to hydrolysis
R = Substitution of R effects in solubility's Salts are given orally, R = benzyl penicillin = Pen G. R = Phenoxymethyl = Pen V

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A chemical drug-drug incompatibility between gentamycin C 2a and beta lactam. Two drugs react
with each other so that N-acylation of C1 of gentamycin by the beta lactam bond takes place,
thus inactivates both antibiotics.

R = Benzyl amine = Amoxicillin and ampicillin (Amino penicillin's)

Protein Synthesis Inhibitors

50 S Antibacterial Agents 30 S Antibacterial Agents

Aminoglycosides Tetracycline's
Macrolides Chloramphenicol
Gentamycin Demeclocycline
Erythromycin Lincosamides
Azithromycin Clindamycin Streptomycin Doxycycline
Clarithromycin Lincomycin Kanamycin Minocycline

TEST CC: T = tetracycline, E = erythromycin S = Sulfadrugs, T = trimethoprin, C = clindamycin C = Chloramphenicol, are bactereostatic.

Macrolides. Erythromycin, clarithromycin and azithromycin.

Mechanism. Protein synthesis inhibitors.
Structure. Large lactones ring of 12 or 14 or 16 atoms are attached to amino sugar (hexose) &
neutral sugar by glycosidic link.

Erythromycin
• Lactone ring + desoamine (amino sugar) + cladinose (neutral sugar).
• Common SEs. Gastric upset is due to conversion of erythromycin to ketal.
• The macrolide are generally unstable to acids, bases & high temperature.

Azithromycin
• Stable to acids, bases & high temp, thus less gastric upset.
• Long half life, greater and longer tissue penetration and covers H. influenza.

Clarithromycin Important Concept!

1) Tetracycline must take empty stomach due to chelation with
• The enhanced lipophylic metal ions (Al, Mg, Ca, Fe).
allows for lower or less 2) Tetracycline epimerized to epi-tetracycline at C4. It is inactive
frequent doses. product.
3) Tetracycline empty stomach. Doxycycline with or after meals.
Erythromycin and tetracycline Minocycline with or without.
cross placenta in appreciable
amounts and also appear in breast milk.
Tetracycline’s. Tetracycline, doxycycline and minocycline.
Chemical instability. Tetracycline a-stereo orientation of the C4 dimethylamino-moiety is
essential for the bioactivity.

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 H N(CH3)2
N(CH3)2 H N(CH3)2
OH
4 OH OH
Base H+ 4
NH2
H+ NH2 Base NH2
OH
O O OH OH
O O O O
Tetracycline
4 Epi- Tetracycline

Epimerization of Tetracyclines

OH OH
OH O O M HO OMO
H

M= di or trivalent metal ion

Metal chelation with the tetracyclines

Phototoxicity. Tetracycline with C7 chlorine, absorb light in the visible region leading to free
radical generation and potentially cause severe erythema to sensitive patient on exposure to
sunlight.

Tetracycline Doxycycline Minocycline

Less SEs. Less SEs High SEs. Has reactive amino acid. Causes
Hepatitis, liver necrosis serum sickness (discoloration of nail, bones,
from iv, avoid in teeth).
pregnancy. Vestibular toxicity (vertigo, ataxia, nausea),
Pediatric (<8y) tooth dizzy, headache
discoloration.
Empty stomach With or after food With/without
but empty better
absorbed
Renal safe
Effective acne Effective acne More effective for acne due to lipid soluble.
Used in RA.
Dis with bi, tri valent Less Dis. More Less DI
photosensitive
Once daily, bioavail 90-100%
Expired tetracycline cause Funconi like syndrome (renal tubular necrosis, diabetes like
symptoms) and extreme cases has been fatal.

Quinolones & Fluoroquinolones

Mechanism of action. DNA gyrase inhibitor (topoisomerase II) and topoisomerase IV
Nalidixic acid (urinary disinfectant)
Fluoroquinolones 1st gen. Nalidixic acid, Norfloxacin
2nd gen. Ciprofloxacin, Oflaxacin
3rd gen. Gatifloxacin, Moxifloxacin, Levofloxacin (respiratory)
4th gen Travofloxacin

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Inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV makes cell inaccessible and
leads to cell death. Different quinolones inhibits different extent of topoisomerase II and IV.
DNA gyrase seems more important in gram –ve. Topoisomerase IV in gram +ve.

Nalidixic acid is primary effective against gram –ve.

Quinolones chelate with polyvalent ions such as Fe, Al, Mg, Ca to form less water-soluble.
complexes and thus lose considerable potency.

Nitrofurantoin
• Used as prophylaxis for UTI in pregnancy.
• Nitrofurontoin inhibits bacterial DNA and RNA.
• Not used in renal diseases, it inhibits kidney stone growth.

Folate antagonist sulfa drugs

Dihydroteroate diphosphate + PABA  dihydroteroic acid  tetrahydrofolic acid  thymidine
 DNA

Oxazolidinones. Linezolid (po, parenteral).

• Mechanism. Binds to bacterial ribosome's to inhibit protein synthesis.
• SEs. Reversible thrombocytopenia.
• DI. It can cause serotonin syndrome with antidepressants.
• Therapeutic use. MRSA infections

Tips
1 Folate antagonist 2 Nalidixic acid 3 Thiazolidine
4 epimerization 5 DNA gyrase & topoisomerase II 6 Antacids
7 Ca (bi and trivalent) 8 Dihydroteroic acid 9 Dihydrothiazine
10 Tetrahydrfolic acid
• The chemical ring present in penicillin's ( )
• The chemical ring present in cephalosporin's ( )
• Tetracycline at 4 position undergoes…( )
• Tetracycline chelate with.. antacids, Ca and Iron ( )
• Sulpha drugs act on? ( )
• Sulpha drugs action prevent formation of? ( )
• Quinolone antibiotic are bactericidal act by inhibiting…( )
• What is an example of urinary tract disinfectant? ( )
1 Amoxicillin 3 Penicillin G and V 5 Tetracycline
2 Cephalexin 4 Cefuroxime 6 Ceftriaxone
7 Erythromycin 8 Clarithromycin 9 Azithromycin
10 Ciprofloxacin 11 Ofloxacin 12 Clindamycin
13 Trimethoprim-sulfamethoxazole 14 Metronidazole 15 Vancomycin
• What drug commonly causes dose-related GI tract disturbances, including nausea, vomiting,
and diarrhea ( )
• raises blood levels of theophylline and potentiates terfenadine in producing ventricular
arrhythmias. ( )
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• have enhanced activity against Haemophilus influenza ( )
• Inhibit the activity of DNA gyrase ( )
• What antibacterial effective in bacterial prostatitis and bacterial diarrhea except that caused
by C. difficile ( )
• What drug act as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism
cycle ( )
• It is used primarily for the treatment of Trichomoniasis, Amebiasis, Giardiasis (14)
• and P.colitis ( )
• Stevens-Johnson Syndrome is a severe form of erythema multiforme ( ) characterized by
bullae on the oral mucosa, pharynx, anogenital region, and conjunctiva; target-like lesions;
and fever
• Antacids containing Mg or aluminum interfere with absorption if taken within 4 h ( )
• Example: NRTI –Nucleoside reverse transcriptase inhibitors. NNRTI-Non nucleoside reverse
transcriptase inhibitors.
• DNA synthesis by reverse transcriptase can be inhibited by AZT (zidovudine). (Anti HIV)

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www.pharmacyprep.com Metabolism

32
Metabolism

Questions Alerts!
Common questions in pharmacy exam is to ask!
• Phase 1 or functional group metabolism, example oxidative deamination reactions.
• Cytochrome CYP450 (major CYP3A4) substrates, inhibitors and inducers.
• Phase II or conjugation metabolism like glucuronidation, glutathione conjugation, and
acetylation.
• Alcohol metabolizing enzymes.

Definitions
• Biotransformation. Biochemical reactions that are catalyzed by enzymes.
• Bioactivations. Metabolic reactions that produce active metabolite.

• After metabolism of drugs. Drugs become more water soluble, excreted faster and toxicity
can increase or decrease.
• Reactive metabolites are breakdown to other active or toxic metabolites.

Biotransformation Bioactivation Reactive metabolites

Cefuroxime auxetil Meperidine
Methyldopa
Enalapril, ramipril
Valacyclovir

Phase 1 Phase II
Functional groups metabolism (OH, NH 2 , COOH, Conjugation metabolism
SH etc)
Oxidation, reduction, hydroxylation, Glucuronidation, glutathione conjugation,
deamination, dealkylations, demethylation, sulfonation, acetylation, and methylation.
oxidative deamination
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Cytochrome oxidations (CYP450),

reductase, aminase and monoamino oxidase

(MAO).

Phase 1 Metabolism
Phase I metabolism (Functional group metabolism or mixed function oxidase metabolism)
Reactions that convert the parent drug into more polar (water-soluble) molecules by introducing a
polar functional group, such as -OH, or-NH 2 , COOH, SH. Phase I metabolism mainly occurs in liver,
kidney, GI tract and other tissues. These reactions are catalyzed by cytochrome (CYP450).
Cytochrome is mainly found in ribosomes, specifically endoplasmic reticulum.

Drugs in phase 1 metabolism undergoes the following reactions oxidation (most common phase 1
reaction), hydroxylation, dealkylation, deamination, reductions, hydrolysis, and de-sulfuration.

Oxidative metabolism
The most common phase I reaction is oxidation. Oxidation metabolism most commonly occurs in liver.
Less in intestine, lungs and kidney catalyzed by CYP450 with different routes 3A4, 2C9, 2C6 and others
oxidizing enzymes. Example substrate, enzyme inducers and enzyme inhibitor.

Alcohol oxidations
• Primary alcohol oxidation  aldehyde  acid.
• Secondary alcohol oxidation  ketone
• Tertiary alcohol  no oxidation
• CH 3 OH (methanol) HCHO (formaldehyde) HCOOH (formic acid)  formic acid is toxic can
cause blindness.
• CH 3 CH 3  CH 3 CH 2 OH (ethanol) CH 3 CHO (acetaldehyde)  CH 3 COOH
• Ethylene glycol  oxaldehyde  oxalic acid (toxic).
• Ethylene glycol is used as antifreeze.

Ethanol

Alcohol dehydrogenase

Nausea and vomiting

Acetaldehyde headache
Hypotension
Thiamine decrease
bioavailability
Acetaldehyde dehydrogenase

Acetic acid

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Methyl group to Carboxylic

acid (Oxidation)
O O O O
H3C S N N C4H9 HOOC S N N C4H9
H H H H
O O

Reduction Reactions
Common metabolic reactions are azoreduction, nitro reduction and carbonyl reductions.
Reduction – Bacteria resident in the GI tract are known to be involved in azo and nitro reductions.
Reactions catalyzed by reductase. Both mechanism of oxidation and reduction is to create a polar
substrate to be excreted.

Azoreduction. As in sulfasalazine and olsalazine. Reducing enzymes called reductase, such as

azoreduction is catalyzed by azoreductase enzyme, which catalyzes reduction reaction. Example of
azo (-N=N-) reduction sulfasalazine undergoes azoreduction in gut (colon) and produces 5-
aminosalicylic acid (5ASA) and sulfpyridine.
NH2 CO2H

Azo bond OH
5-aminosalicylic acid
O N (Mesalamine)
S
COOH N OH
N Azoreductase +
O N
N S
HO at Gut N
OH
Sulfasalazine NH2
Sulfapyridine

Azoreduction in colon
Nitro reduction: Nitro (NO 2 ) group upon reduction produce amine (NH 2 ) group. Drugs that undergo
nitro reductions e.g. nitro reduction takes places in the metabolism of chloramphenicol and
clonazepam. Carboxylic acid upon reduction produces aldehydes and then alcohol.
Carbonyl (ketone or aldehyde) reduction example: acetohexamide.
acetohexamide undergoes carbonyl reductions.

Reduction OH
O
C C

R1 R2 R1 R2
Hydrolysis
Hydrolysis is a metabolic reaction that most commonly occurs in gastrointestinal tract. Hydrolysis is
catalyzed by enzyme called esterases. There are two functional groups commonly undergo hydrolysis
are esters and amides.
Esters (esterases) present in plasma and various tissues.
Esters (hydrolysis) produce  acid + alcohol.
Amide hydrolysis products  acid + amine.
Amide hydrolysis is catalyzed by amidases.

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Fixed oils consist of ester functional groups, metabolized by ester hydrolysis and produce glycerol +
fatty acid.

Ester hydrolysis Hydroxylation

CH3 CH3 NHCOCH3 NHCOCH3

N N

OC2H5 OH + C2H5OH
O O OH
Meperidine Acetanilid Acetaminophen

Deamination. Examples of deamination include amphetamine and dopamine.

Oxidative Deamination
H2 H H2 O
C NH2 C NH3
CH3 CH3
MAO
Serotonin ---------------------------------> 5-hydroxy indole acetic acid (5HIAA)
Oxidative deamination

MAO
Dopamine -----------------------------------> 3,4-dihydroxy phenyl acetic acid (DOPAC)
Oxidative deamination

Aliphatic Hydroxylation
(Phenobarbital, meprobamate) R CH3 R OH

Aromatic hydroxylation
Phynetoin, phenylbutazone R R OH

Olefinic Hydroxylation CH3

R R
(carbamazepine, cyproheptadine) OH

OH OH
Benzylic Hydroxylation
(Tolbutamide, imipramine)
R R R R

Allylic Hydroxylation OH
R R
(Pentazocine, hexobarbital)

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Phase 2 reaction Enzymes Drugs

Glucuronidation Uridenyl Diphosphate Acetaminophen, morphine, diazepam, sulfathiazole, digoxin,
Glucuronyl Transferase and salicylic acid.
(UDP GT)
Acetylation N-acetyl transferase Sulfonamides, isoniazid, clonazepam, and dapsone (Primary
(NH 2 , OH) amines undergo acetylation).
Glutathione Glutathione S- Ethacrynic acid, reactive phase 1 metabolite of acetaminophen
conjugation (glycine transferase (GST) mercapturic acid is produced.
+ Cysteine + glutamic
acid)
Glycine conjugation Acetyl transferase Salicylic acid (75% of salicylic acid is excreted after glycine
(Amino acid conjugation, nicotinic acid (Niacin), deoxycholic acid.
conjugation)
Sulfate conjugation Sulfotransferase Acetaminophen, methyldopa, estrone
Methylation N-Methyltransferase Epinephrine, norepinephrine, dopamine, histamine
Phase 2 reaction Enzymes Drugs
Glucuronidation Uridenyl Diphosphate Acetaminophen, morphine, diazepam, sulfathiazole, digoxin,
Glucuronyl Transferase and salicylic acid.
(UDP GT)
Acetylation N-acetyl transferase Sulfonamides, isoniazid, clonazepam, and dapsone (Primary
(NH 2 , OH) amines undergo acetylation).
Glutathione Glutathione S- Ethacrynic acid, reactive phase 1 metabolite of acetaminophen
conjugation (glycine transferase (GST) mercapturic acid is produced.
+ Cysteine + glutamic
acid)
Glycine conjugation Acetyl transferase Salicylic acid (75% of salicylic acid is excreted after glycine
(Amino acid conjugation, nicotinic acid (Niacin), deoxycholic acid.
conjugation)
Sulfate conjugation Sulfotransferase Acetaminophen, methyldopa, estrone
Methylation N-Methyltransferase Epinephrine, norepinephrine, dopamine, histamine
Dehalogenation. (Halothane, Chloramphenicol)

Cl Cl (-) O
CF3 - C - H CF3 - C
H
Br
Br (-)

Phase 2 Metabolism
Phase 2 metabolism reactions are referred as conjugation reactions, parent drug or its metabolite
with certain natural constituents such as glucuronic acid, glycine, glutamine, sulfate, and glutathione.
There are 6 major conjugation pathways.

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Factors affecting Drug Metabolism

Chemical structure (functional group)
Species differences. Quantitative (presence of enzyme inducers or inhibitor) phase I, qualitative in
phase II reaction
Physiological or disease state. liver disease, CHF, renal disease, Hypo & hyperthyroidism. Also
alteration in albumin production as in elderly.

Genetic factors. Acetylation rate by N-acetyltransferase, which may result in fast acetylators or slow
acetylators (pharmacogenetics).

Nutritional status. Low protein diet decreases oxidative drug metabolism, vitamin C deficiency
decreases oxidative pathways. Vitamin E deficiency retards dealkylation and hydroxylation

Age. Infants, children, elderly. Circadian rhythms, nocturnal plasma levels of theophylline and
diazepam are lower than the diurnal plasma levels. Drug administration route (first by pass) for
oral only, iv, sublingual no first by pass.
Elderly person have less phase I metabolism.

Cytochrome classification. The cytochrome P450s enzymes are located in the endoplasmic reticulum
and are highly concentrated in the liver and small intestine. Additionally, CYP P450s are also found in
the mitochondria membrane. CYP 450s encompass a highly diverse "superfamily" of hemoproteins and
one of their most relevant functions is that of metabolizing drugs in humans.

Cytochrome P450 classified into subtypes.

CYP = Cytochrome, 1 or 2 or 3 number, family
A, B, C, indicate subfamily and 1,2,3 indicate individual genes
CYP1A1 CYP2D6 CYP 3A4
CYP1B2 CYP2C9 CYP 3A5
CYP1C3 CYP2C19
Drug metabolism (secondary). CYP1, CYP 2. CYP3, and CYP4 subtype of enzyme catalyze drugs, or
exogenous chemicals. CYP3A is the most common enzyme that catalyze phase 1 oxidative reactions.

Steroid and bile acid metabolism (primary). CYP7. CYP11, CYP 17, CYP19, CYP21 and CYP27 enzymes
metabolize steroids, and bile acids, is referred to as primary metabolism.
Cytochrome P450s are a large group of monooxygenase enzymes responsible for the metabolism of
toxic hydrocarbons. NADPH is required as a coenzyme and O 2 is used as a substrate.

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Substrate (catalyzing their

Enzyme metabolism) Inhibitor Inducers Examples
CYP3A4 Benzodiazepines Nefazodone Phenobarbital Generally all anticonvulsants
Dihydropyridine CCBs SSRIs Phenytoin are inducers + Rifampin
Carbamazepine Azole antifungals Carbamazepine
Ethynilestradiol Cimetidine Prednisone CYP3A is the most abundant
Statins (ALS) Macrolides (E,C) Toglitazone CYP3A4 is most next CYP3A5
Terfenadine Protease inhibitors Rifampin
Theophylline Verapamil Cisapride and terfenadine can
Protease inhibitors Omeprazole (PPI) St. Johns Wort have cardiotoxic levels with
Triazolam Ritonavir Saquinavir Azoles and Clarithromycin
Amitriptyline
Lidocaine
Cyclosporin
Digoxin
Caffeine
Non-sedative antihistamine

CYP3A4 Grapefruit Flavanoids D-F interaction

CYP3A5 Nifedipine Glucocorticosteroids

Cyclosporine
Steroid hormones (i.e., sex
hormones)

CYP2D6 TCAs SSRIs None a potential D-D interaction as

SSRIs Nefazodone 2 drugs from 1 therapeutic class
Antipsychotics Venlafaxine TCA and SSRI as well as other
Antipsychotics
Beta blockers (Haloperidol) Psychotherapeutics
Narcotics (codeine) Quinidine
Venlafaxine Ritanavir 2nd most CYP Enzyme

Quinolones
CYP1A2 TCAs (ciprofloxacin) Omeprazole
Propranolol Grapefruit Phenobarbital D-F interaction
Warfarin Nefazodone Phenytoin
Theophylline Fluoxetine Rifampin
Acetaminophen Smoking D-C interaction
Charbroiled meats
Carbamazepine

CYP2C9 Phenytoin Azole antifungal Rifampin

Warfarin Metronidazole Carbamazepine Fatal D-D interaction
NSAIDs Ritonavir Phenytoin
Losartan Clopidogrel
Amitriptyline Fluvastatin

CYP2E1 Alcohol D-F interaction

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CYP 2C19 PPI Clopidogrel

They have porphyrin ring so susceptible with CO, O 2 ,CN
CYPs in endoplasmic reticulim in liver and small intestine and also mitochondrial membrane
are monoexygenase Catalizers (oxidizing) need NADPH as co-enz. to use O 2
their naming is CYP # Alphabet # (i.e.CYP3A2) genetic family/genetic subfamily/specific gene
CYP 1,2,3,4, isoforms involved in drugs and xenobiotics.
CYP 7,11,17,19,21,27 involved in steroids and bile acids.
Inhibitors. Sickfaces.comg
Inducer. Crapgps
Substrates. ABCDEFSubstrate

Drug Pathway
CH3
Deamination (followed by oxidation and reduction of the ketone
α formed)
N-oxidation
NHR N-dealkylation
β Hydroxylation of the aromatic ring
Hydroxylation of the β-carbon atom
Conjugation with glucoronic acid of the phenol products from the
ketone formed by deamination.

Amphetamines
Oxidation and complete removal of substituents at carbon 5.
' N-dealkylation at N1 and N3
R5 R5
Desulfuration at carbon 2 (thiobarbiturates)
O 6 4 O
Scission of the barbiturate ring at 1:6 bond to give substituted
5
malonylureas

R1N 2 NR3
1 3

O
Barbiturates
N-dealkylation in the N10 side chain
5 4 N-oxidation in the N10 side chain
6 S Oxidation of the heterocyclic S atom to sulfoxide or sulfone
7 3 Hydroxyaltion of one or both aromatic rings
Conjugation of phenolic metabolites with glucuronic acid or
sulfate
8 10 2 Scission of the N10 side chain
N
9 R 1
Phenothiazines

Acetylation at the N4 amino group

Conjugation with glucoronic acid or sulfate at the N4 amino group
Acetylation or conjugation with glucoronic acid at N1 amino group
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SO2NHR Hydroxylation and conjugation in the heterocyclic ring, R

1
2 6

3 5
4

NH2
Sulfonamides

Tips
Tips practice format 02: Find answers from the table:
1. UDP-gluconyltransferase 2. CYP3A4 3. UDPGT
4. formic acid 5. alcohol dehydrogenase 6. oxidation
7. inhibit metabolism and increase 8. in the liver 9. drug metabolism is impaired
concentration by protein deficiency
10. levels of some cytochrome P450 11. Phenobarbital, Phenytoin, 12. Codeine & Fluoxetine
isoenzymes will vary between Carbamazepine, Rifampin,
individuals St. John’s wort
13. CYP 450 14. Increased metabolism of 15. Acetylation
drugs
16. Benzodiazepines, statins (ALS), 17. Erythromycin, 18. it becomes more inactive,
Digoxin, Sildenafil Clarithromycin, grapefruit more polar, larger and more
juice, Ketoconazole, easily excreted in the bile &
Cimetidine, Protease INH urine)
19. Sulfasalazine 20. Glutathione conjugation 21. CYP 1,2,3 and 4
22. endoplasmic reticulum 23. decreased in elderly 24. Glucuronidation
25. hydrolysis
• where does the majority of drug metabolism take place? ( )
• what is the primary enzyme system involved in drug metabolism? ( )
• what is the significance of induction of drug metabolism ( )
• what is meant by inhibition of drug metabolism and what is its significance? ( )
• what happens to the drug after conjugation? ( )
• what enzyme catalyzes most conjugation reactions? ( )
• how does age affect drug metabolism? ( )
• what type of nutritional factors affect drug metabolism? ( )
• How does genetics affect drug metabolism? ( )
• the most common metabolic reaction in the GI( )
• the most common Phase I metabolic reaction is? ( )
• the most metabolic reaction in human ( )
• the most common cytochrome subtype enzyme is? ( )
• Benzodiazepine are metabolized by? ( )
• Glucoronidation reaction is catalyzed by? ( )
• What enzyme is responsible for drug metabolism? ( )
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• Acetaminophen detoxification mechanism involves, what type of metabolic reaction? ( )

• Azo reduction occurs in? ( )
• Primary amine undergoes what type of metabolism? ( )
• What are the most common CYP 3A4 inhibitors? ( )
• What are the most common CYP 3A4 substrates? ( )
• What are the most common CYP 2D6 substrate and inhibitor? ( )
• What are the most common CYP 3A4 inducer? ( )
• What is not a drug metabolizing enzyme? ( )
• methanol toxicity can lead to blindness due to? ( )

"Pneumonic"
CYP3A4 Substrates. ABCDEF substates Ami, Benz, CBZ, DHP-CCB, Estrogen, terFinadine, Substrates
CYP 3A4 Inhibitors. “NOVACRAMPS”

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33
Biopharmaceutics
Questions Alerts!
Common questions in pharmacy exam are to ask!
• Relative bioavailability and absolute bioavailability.
• Drug interchangeability
• Partition coefficient (octanol/water)
• Factors effecting ionization and unionization like pH, and pKa

This chapter review on the concepts of physicochemical properties of oral drugs and dosage form, and
the effect of route of administration on absorption. Emphasis is on bioavailability and bioequivalence
studies. Biopharmaceutics is the study of the relationship between the physiochemical properties of a
drug to those of dosage form in which contained

Bioavailability: The fraction of unchanged drug reaching the systemic circulation following
administration by any route. The rate and extent of absorption from administered dose can be figured
out by using bioavailability.

Sustained release and

immediate release
formulations of a drug have
different rate of bioavailability
however the same extent.

Absolute bioavailability: Calculated by comparing the bioavailability of the product to that of an IV

bolus dose. Absolute bioavailability is “F’ which is the fraction of drug systematically absorbed from
the dosage form. Always AUC of iv is 100% or 1.
AUC po /AUC iv
Relative bioavailability: Calculated by comparing similar data for the product to another drug product
of the same dose and dosage form.
Relative Bioavailability= (AUC of the dosage form/dose)/( AUC of the reference/dose)

QAlerts!
To determine the AUC? AUC = [F x Dose]/V d x K

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Bioavailability RATE (SPEED): “C MAX ” AND “T MAX ”

Extent (amount): Area under the curve (AUC) or the total amount of an unchanged drug excreted in
urine.
C max peak concentration and T max is time that take to reach C max . Bioequivalent are pharmaceutical
equivalent + rate and extent are equal.

Factors that influence bioavailability: First pass hepatic metabolism, solubility of drug, chemical
stability, and drug formulation.

First pass effect: Extent to which a drug is removed by the liver during its 1st passage in the portal
blood through the liver to the systemic circulation. In simple words it is the amount loss during
metabolism in the liver.

Bioequivalence or bioequivalent drugs. Bioavailability of the active ingredients in the 2 products are
not statistically different under suitable test conditions. Example generic and brand.

Bioequivalence and inter-changeability

Description Examples
Generic Different brand or unbranded product over Ramipril generic and Altace brand.
substitution. the prescribed drug and pharmaceutical
equivalent.
Pharmaceutical Same active drug ingredient, identical Brand to generic
equivalent. strength or concentration, dosage form and Rx. Dimicron MR 30 mg
route of administration and bioequivalent. Pharmacist dispensed
Pharmaceutical equivalent can differ in color, Gliclazide MR 30 mg.
flavor, shape, scoring, configuration, packing,
preservative, expiration time and labelling.

Pharmaceutical Pharmaceutical alternative for the prescribed Tetracycline HCl and tetracycline PO 4 ,
substitutes or drug product. Two products containing same cefuroxime Na and cefuroxime auxetil,
alternates. therapeutic moiety. erythromycin base and erythromycin estolate
or pantoprazole Na and pantoprazole Mg,
metoprolol succinate and tartrate

Therapeutic Two chemical equivalent have same (Extended scope of pharmacy practice
equivalent. therapeutic effects (efficacy and safety). The pharmacist can do therapeutic substitution
same therapeutically active drug, same like prescription adaptation).
therapeutic effect, equal potential for
adverse effects
Therapeutic Products of different active ingredients
alternate. having same therapeutic or clinical response.
e.g. antihistamines.

Home work Examples

Pharmaceutical equivalents
Pharmaceutical alternates
Therapeutic equivalents Amoxicillin suspension/capsules
Therapeutic alternates

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Predicting water solubility: Partition coefficient (P). Refers to the ratio of the concentration of drug in
octanol (lipid) to that of water.

Partition Coefficient (P)= (Drug) lipid /(Drug) aqueous

P = solubility in octanol/solubility in water
P=1
A drug is hydrophobic if partition coefficient is >1
A drug is hydrophilic if partition coefficient is <1

Mechanism of drug absorption: Transport process across membrane

Passive paracellular Carrier

Glycoprotein
Diffusion Diffusion mediated
mediated
(transcellular)
Efflux

Cell membrane (phospholipids layer). Drugs high in lipids move faster in a phospholipid bilayer and this
means that water soluble drugs used carrier proteins for transport.
Types of absorption. Four types of absorptions occur across membrane 1. Passive absorption (passive
diffusion), 2. Active transport, 3. Facilitated diffusion, and 4. Endo/exocytosis.

Passive absorption (diffusion): It is also referred as simple absorption or diffusion. The movement of
drugs across lipid membranes driven down by their concentration gradient. Characteristics
• There is concentration gradient (high  low) is essential for passive absorption
• No energy is needed for passive absorption
• There must be semi permeable membrane
• Fick’s Law can determine rate of diffusion of absorption

Primary Active transport: An energy dependent movement of compounds across membranes against a
electrochemical gradient that is carrier mediated and requires metabolic energy e.g. multi drug
resistant transporters.
Characteristics:
• Active transport also referred as active absorption
• Need energy
• No need of concentration gradient
• Can go against concentration gradient if facilitated by energy.
• Example of active absorption includes: tubular secretion.

Examples of primary active transport ion channels:

• Na+, K+, ATPase (Na+, K+ pump) in cell membrane transport Na+ from intracellular to extracellular
fluid and K+ extracellular to intracellular. Examples of drugs (digoxin) that blocks Na K ATPase.

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• H+, K+, ATPase (proton pump) in gastric parietal cells transports H+ into the lumen of the stomach
against the electrochemical gradient. Drugs that block proton pump: Proton pump inhibitor such
pantoprazole.
• Ca2+ ATPase (Ca2+ pump) in the sarcoplasmic reticulum or cell membrane transport Ca2+ against
electrochemical gradient.

Facilitated diffusion: The carrier-mediated transport of compounds down an electrochemical gradient.

e.g. the cation transporters in the kidney.

Characteristics
• Require carrier (proteins)
• Similar to passive absorption because do not require metabolic energy.
• Examples of facilitated diffusion. Glucose uptake into muscle and adipose cells facilitated by
insulin. If impairs this can lead to diabetes mellitus.

Endo/exocytosis --> Internalization of drug molecules (cell drinking)

Factors that determines the absorption

Oral drug

Disintegration

Dissolution Rate of Dissolution

Noyes-Whitney

Absorption

Ficks Law - Rate of absorption

Factors that affect the rate of absorption

Hasselback &
* pH effect
Handerson
* ionization & unionization

Ranking of various oral dosage (fastest → slowest)

• Solutions (ready for absorption)
• Suspensions (wetted and ready for dissolution)
• Powder [(dispersed + GI fluid → wet) absorbed]
• Capsules (dissolve gelatine cap first → then powder)
• Tablets (disintegrate from tablet to smaller granulate then → powder.
• Sustained release tab (barrier of coating materials).

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The rate of absorption of solid drugs.

Solid drug -->(disintegration) and then (dissolution) --> Drug in solution --> (absorption) in to blood.
Dissolution is the rate-limiting (slowest) step in sequence.
• Disintegration. Breaking down of drug so as to facilitate dissolution. This usually occurs in oral
routes.
• Dissolution. Dissolving substances in the GIT fluids to facilitate absorption of the drug.
• Rate limiting step. It is the time it takes for a drug to dissolve and become available for absorption.

Factor that effect rate of absorption. Degree of ionization, solubility, pH (acidity or alkalinity of the
substance.

Degree of ionization: Drugs will pass thru a membrane at a faster rate if they are unionized. The size of
an ion increases due to dipole-to-dipole attraction especially water. Ionized portion of drug is less
soluble in lipid but more in water.

Solubility
• Extremes of either water or oil solubility is associated with poor absorption.
• Hydrophilic = water soluble (water lover), poorly absorbed. Removed faster from the body.
• Hydrophobic or lipophilic = oil or lipid soluble, or oil and lipid lover.

pH (acidity or alkalinity of the substance)

• Most drugs are weak acid or weak bases. Dissociation of weak acids or bases is directly affected by
pH therefore absorption is directly affected by pH.
• As pH rises (H+ decreases), the amount of weakly acidic drug in the non-ionized state decreases
• As pH falls (H+ increases) the amount of weakly acidic drug in the non-ionized state increases; i.e.
diffusion pressure increases.
• For weak bases the effect is opposite.

NOTE. One changes the pH by 1 unit, the ratio of non-ionized to ionized changes by factor of 10. The
direction of change and ration can be calculated in one’s head when the pH changes are 1 full unit

Henderson-Hasselbalch Equation. Helps to determine pH effect on absorption. (Determining the drug

absorption by pKa). If the pKa of drug and pH of the medium are known, the fraction the molecules in
the ionized state can be predicted by means of the Henderson-Hasselbalch equation. How much of
drug is found on either side of membrane.
For an acid:
pH = pKa + log (Salt)/ (Acid)

pKa = pH – log (Salt)/ (Acid)

For base:
pH = pKa + log (Acid)/ (Salt)
You may also see the above as:
pH = pKw – pKb + log (base)
(salt)
Since pKw = pKa + pKb

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Weak acid RCOOH (Cross membrane)  RCOO + H+

Weak Base R-NH 3  RNH 2 + H+ (cross membrane)

Predicting Percent ionized (To calculate percent of a weak acid or base that is ionized)

Where charge -1 if acid drug or 1 if basic drug

Notes on ionization
• Ionized drugs are water soluble and poor absorption through stomach, blood brain barrier, and
placenta, no reabsorption across membrane and excrete faster.
• Non-ionized (unionized) are lipid soluble and absorbed well in membrane (cell membranes are
composed of lipids), and have higher reabsorption.
• An acid in an acid solution will not ionize (acid + acid = non ionized).
• An acid in a basic solution will ionize (acid + base = ionized).
• A base in a basic solution will not ionize (base + base
= non-ionized).
• A base in an acid solution will ionize (base + acid =
ionized).
• pKa=pH drug exists as 50% ionized and 50%
unionized.
• If pH-pKa = 0, then 50% of drug is ionized and 50% is
unionized.
• If the acid/base ratio is 1:1, then the log of that
number will be zero, and pH = pK a .
• If pH - pKa = 0.5, then the solution is 75% ionized/25% unionized or 75% unionized/25% ionized.
• If pH - pKa >1 then the solution is 99 to 100% ionized or 99 to 100% unionized.
• If pH - pKa >2 then the solution is 100% ionized or unionized.

Surface area (Ficks law of diffusion): Ficks law predicts the rate of movement of molecules across
barrier.
Formula: Rate of diffusion = D x A x (C 1 – C 2 )
L
D = Diffusion coefficient
A = Surface area of solid
C 1 = Concentration near to stagnant layer
C 2 = Concentration of solute to other side
of stagnant layer
L = The length of the stagnant layer

This relationship demonstrates the drug absorption is faster from organs with large surface areas. The
rate of diffusion is directly proportional to the area of the solid, the concentration difference between
the concentration of solute in the stagnant layer at the surface of solid and its concentration on the
farthest side of the stagnant layer and diffusion coefficient. It is inversely proportional to the length of
stagnant layer. The driving force behind the movement of the solute molecules through the stagnant
layer is the difference in concentration of solute at C 1 and its concentration at C 2 .
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Solubility: Defined as the concentration of solute in a saturated solution under specific conditions of
temperature and pressure. It may be viewed as an equilibrium condition in which solute molecules
are leaving the solid (or undissolved phase) at the same extent as solute returning to it.
Saturated solution: Is a state in which solute is at equilibrium with solid phase
Supersaturated Solution: Contains more dissolve solute then it normally would contain at a specific
temperature if there were undissolved solute present. If upon cooling, the excess solute fails to
crystallize from the lower temperature, the solution is supersaturated.
Unsaturated solution: Contains dissolved solute in a concentration below that necessary for complete
saturation

Compendia expressions of approximate

• Very soluble………………………..Less than 1 part
• Freely soluble……………………...1-10 parts
• Soluble…………………………….. 10-30 parts
• Sparingly soluble ………………… 30-100 parts
• Slightly soluble …………………… 100-1,000 parts
• Very slightly soluble ……………… 1,000-10,000 parts

Types of Solvents
Polar solvents: These consist of strongly dipolar molecules having high dielectric constants, e.g.,
water, and methyl alcohol, ethyl alcohol.

Semi polar solvents: These are strongly dipolar molecules, but which do not form hydrogen bonds.
Examples are ketones and certain alcohols. They may induce a degree of polarity in nonpolar solvent
molecules.

Nonpolar solvents: These solvents have a small or no dipolar character. Theses include hydrocarbons,
fixed oils, and mineral oil. They have a low dielectric constant and possess little tendency to reduce
the attractive forces between ions of strong and weak electrolytes.

Factor Affecting solubility and Rate of Solution:

Noyes-Whitney Equation: A thin layer of solvent, which behaves as an integral part of the particle and
is referred to as the diffusion layer, C 1 -C 2 , surrounds a particle of solute dispersed in a solvent
medium. The diffusion layer remains a part of the solute particle regardless of extent of agitation of
the bulk solution. The dissolution rate of the solute is expressed by the Noyes-Whiteney equation:
Dc/dt = KA (C 1 -C 2 )
Where dc/dt is the change in concentration of solute in solution with respect to time.
Effect of Temperature: Solubility of a solid in a liquid is dependent on the temperature. If heat is
absorbed in the solution process, solubility of solute will increase with increase in temperature.

Effect of electrolytes on the solubility of non electrolytes:

Salting out and salting in. The addition of a salt may either increase or decrease the solubility of
nonelectrolyte. When the solubility is decreased, the effect is referred to as “salting out”. When the
solubility is increased, it is known as “salting in”.

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Action potential across cell membrane: Neuronal excitability depends on the influx of ions through
specific channels in membranes.
Membrane depolarization. Excitation = increase Na entry (influx), decrease K exit (efflux)
Membrane repolarization. Inhibition = increase Cl- enter in and increase K+ exit.

Agent Action Results

Botulinus toxin Blocks release of ACh from Total blockade
presynaptic terminals
Curare Competes with ACh for receptors Decrease size of end plate potential : maximal doses
on motor end plate produce paralysis of respiratory muscles and death
Neostigmin anticholinesterase Prolongs and enhances action of ACh at muscle end
plate
Hemicholinium Blocks reuptake of choline into Depletes ACh stores from presynaptic terminal.
presynaptic terminal

Tips
1. Oral 2. rectal 3. in the stomach and intestine but
mainly in the liver
4. first pass metabolism 5. sublingual 6. lungs
7. nasal mucosa 8. intramuscularly 9. intravenous
10 transdermal

• The metabolism of the drug before the drug reaches the general circulation ( )
• Where does the first pass metabolism occur? ( )
• Which route of administration is most likely to subject a drug to a first-pass effect? ( )
• What sites of absorption have low first pass metabolism? ( )
• What factors affect the bioavailability of a drug? ( )
• What is responsible for the different phases of a two-compartment model of drug elimination? ( )
• What is meant by first pass metabolism? 
• Where does the first pass metabolism usually occur? 
• Which routes of administration is most likely to subject a drug to a first-pass effect? 
• What sites of absorption have low first pass metabolism? 

TRUE OR FALSE
• After oral administration of Iron it is absorbed from duodenum by an active transportation (T/F)
• Whenever a drug is more rapidly and more completely absorbed from a solid form, the rate-
limiting factor is the dissolution process (slowest).
• Write sequence of absorption for oral dosage, from higher to lower: solution > suspension > liquid
gel caps > powder>

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34
Physical Pharmacy
Questions Alerts!
Common questions in pharmacy exam is to ask!
• United States Pharmacopeia/National Formulary (USP/NF) standards of alcohol and
temperatures, Compounding Formula
• Colligative properties. Osmotic pressure.
• Arrhenius equation
• Polymorphism
• Critical solution temperature
• Eutectic point

State of the matter

Gases Liquids Solids

• Changes in state. Increase in temperature of a substance increases its heat content, or enthalpy.
• Melting. Solid to liquid state.
• Vaporization. Liquid to gaseous state.
• Volatile liquids used as inhalation anesthetics e.g. ether, halothane, and methoxyflurane.
• Also used in vasodilatation in acute angina e.g. amile nitrite.
• Sublimation. Solid heated directly to gaseous or vapor state without passing through the liquid
state e.g. camphor and iodine. Examples of process like lyophylization.
• Deposition. The reverse process to the sublimation i.e. direct transition from the vapor state to the
solid state. Example colloidal silicon dioxide and some form of sulphur.
Solids
Polymorphism. Polymorphism is the occurrence or existence of the same substance in different
crystalline forms. Ability of a substance or drug to exist in different crystalline forms. Different
properties such as melting points, solubility, dissolution rate, density, and stability. Examples of
polymorphism include theobroma oil or cocoa butter exhibit polymorphism.
Amorphous materials. Solids and liquids differ from crystals in that they do not possess long-range
periodicity of packing. They will therefore be isotropic. Window glass, basically SiO 2 is a common
example. Many plastics like PVCs are also amorphous.

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Crystalline versus amorphous form. The amorphous form of a compound is usually more soluble than
the crystalline form. Different polymorphic forms of the same compound may demonstrate different
physical properties including water solubility.

Interfacial Phenomena
The Interface. Interfacial phenomena are attributable to the effect of the properties of molecules
located at or close to the boundary between immiscible phases. The region of influence is referred to
as the interface. Interface may exist between a liquid and a gas (a foam) between two immiscible
liquids (an emulsion), between a solid and liquid (a suspension), between solids, solid and gas, etc.

Wetting Phenomena. A solid is said to be wetted by a liquid if the liquid spontaneously spreads over
the solid. A solid is not wetted by a liquid if the latter cannot spread over the former spontaneously.
The contact angle is an important parameter reflective of the degree of wetting of a solid by a liquid.
This is the angle that a droplet of the liquid makes with the solid surface at the point of contact.

Liquids. With few exceptions, most organic solvents are irritating or toxic. Aromatic hydrocarbons
cause paralysis of the central nervous system and are irritating to the skin.

Methyl alcohol (methanol) and isopropyl alcohol, ethylene glycol is toxic, and butyl and amyl alcohol
are irritating. Volatile ethers paralyse the central nervous system, and are irritating to mucous
membrane increases. Ketones are mildly irritating and the low molecular weight esters are irritating.
Toxicity and irritation limit the many solvents internal use except, Glycerine, ethyl alcohol, and
propylene glycol can be employed for internal use as pharmaceutical solvents.

Aliphatic hydrocarbons, ether, and glyceryl esters of aliphatic acids can be employed for external use
as pharmaceutical solvents.

Propylene glycol has been employed as a solvent for oral and parenteral solutions of drugs such as
antihistamines, barbiturates and vitamins.

Hydrogen bonding (H….N or H….O) increases the likelihood of cohesion in liquids and further affects
their physiochemical behaviour.

Van der Waals forces impose regular arrangement among molecules.

London forces in molecules are weak intermolecular forces in liquid hydrocarbon are not true chemical
bonds.

Critical solution temperature. It is the maximum temperature above which homogenous liquid is
formed regardless to any concentration of phenol.
Viscosity is an internal property of a fluid that offers resistance to flow. Not, all liquids are the same.
Some are thin and flow easily. Others are thick and gooey. Honey or corn syrup will pour more slowly
than water. A liquid's resistance to flowing is called its viscosity.

Gases. The intermolecular forces of attraction in gases are virtually non existence at room
temperature.
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Pressure. Random collision of molecules with boundaries of the system is responsible for pressure.

Ideal gas law. The interrelation among Volume (v), pressure (P) and the absolute temperature (T) is
given by ideal gas law: PV = nRT, where n = number of moles of gas and R = molar gas constant
(0.08205 L atm/mole deg).

Pharmaceutical gases:
• Anaesthetic gases: Nitrous oxide and halothane
• Compressed gases: Oxygen, nitrogen, carbon dioxide
• Liquefiable gases: used as propellants in aerosol (pressurized package) products, eg: ethylene
oxide is gas used to sterilize or disinfect heat-labile objects.

Chemical kinetic & Drug stability

Factors that affect chemical stability: The factors that affect chemical stability include: temperature,
pH, moisture, air (oxygen) and light. Effect of temperatures on drug degradation. The Arrhenius
equation describes the effect of temperature on the rate of drug degradation reaction. Heat increases
rate of chemical reaction. Every 10oC increase normally 2 to 3 times rate of reaction increases.

Arrhenius equation

k = S x e-Ea/RT
Ea =Arrhenius activation energy
T = absolute temperature
e-Ea/RT = Boltzman factor
S = Frequency factor
R= Gas constant

Logarithm
Log k = log S-Ea/2.303 RT
Integration between two limits k 1 and k 2 at temperature T 1 and T 2
Log K 2 /K 1 = Ea/2.303 R x (T 2 -T 1 /T 1 T 2 )

Change pH effect on degradation of drugs. The magnitude of the rate of hydrolytic reaction catalyzed
by acid (H+) and base (OH-) can change with pH. Acid (H+) catalysis predominates at lower pH, whereas
base (OH-) catalysis operates at higher pH.

To determine the effect of pH on degradation kinetics, decomposition is measured at several H+

concentrations. The pH of optimum stability can be determined by plotting the logarithm of the rate
constant (k) as function of pH. The point of inflection of the plot is the pH of optimum stability. The
value is useful in the development of a stable drug formulation.
At pH 1 to 3 (strong acidic) more susceptible to H+ (acidic). At pH 5 to 14 (weak acid and base) more
susceptible to OH- (base).

Change in pH: Hydrolysis reactions are catalyzed by H and OH ions, can change with pH
• Acid (H+) catalysis predominates at lower pH
• Base (OH-) catalysis predominates at higher pH

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The effect of pH on degradation kinetics, decomposition is measured by plotting the log of the rate
constant as function of pH. The point of inflection on the plot is the pH of optimum stability. This value
is useful in development of stable drug formulation.

Modes of pharmaceutical degradation:

Hydrolysis, Oxidation and free radicals results in degradation and photolysis. Antioxidants prevents
free radical propagation (hydrogen peroxide, .OH, and benzoyl peroxides).

Antioxidants:
• Water soluble: Ascorbic acid, sodium bisulfate, and sodium sulfite.
• Lipid soluble: Butylated hydroxyl anisole (BHA), butylated hydroxyl toluene (BHT), propyl gallate,
and the tocopherol (vitamin E 1 ).

Photolysis: Exposure to light wavelength less than 400 nm. Protect using amber glass or opaque
storage. Sodium nitroprusside has a shelf life only 4 hour, if exposed to normal room light, when
protected form light, the solution is stable for at least one year.

Stability, kinetics and shelf Life: Most commonly zero order and first order reactions are encountered
in pharmacy.

Zero order

-dC
= ko
dt

Where Ko is zero-order rate constant [C/t]

C = -Kot + Co
Where Co is the initial concentration of drug

t = C-Co
-Ko
First order
-dC
= kC
dt

Where C is concentration of intact drug remaining, t is time, (-dC/dt) is

the rate at which the intact drug degrades, and k is the specific reaction
rate constant.

-kt
log C = +log Co
2.303

Where Co is the initial concentration of drug

In natural log form:

In C = -Kt + In Co
Shelf life t 10% or t 90% = 0.105/k
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Buffers and Buffer Calculations. A buffer is a compound or a mixture of compounds that has the
ability to resist changes in pH when limited amounts of acid or base are added to the solution of the
buffer or when the solution is diluted with solvent.

Generally, a buffer system consists of a weak acid and its salt of the weak acid, or a weak base a salt of
the weak base. An example of the former is acetic acid and sodium acetate and of the latter is
ammonium hydroxide and ammonium chloride.

Mechanism of action In the example of the acetic acid-sodium acetate buffer combination the acetic
acid is essentially unionized and the sodium acetate is completely ionized. When acid is added to the
buffer system, the hydronium ion reacts with acetate ion to form more unionized acetic acid
CH 3 COOH + H 3 O+ -------> CH 3 COOH + H 2 O
And when base is added to the buffered solution, it will react with acetic acid to form more acetate
ion.
CH 3 COOH + OH- --------> CH 3 COO + H 2 O

Other Types of Systems – The combination of certain salts may function as a buffer system, as for
example, the combination of monobasic potassium phosphate and dibasic potassium phosphate in the
appropriate molar ratio. A study of the mechanism will reveal that the buffer behaviour is essentially
the same as the previous cases mentioned above.

Buffer Calculations – Calculations involving buffer systems are based on the Henderson-Hasselbalch
equation.
pH = pKa + log [base]/ [acid]

The above equation applies to all buffer systems involving a single proton transfer (conjugate acid-
base pair).

If a buffer system, for example, is composed of 0.1 molar acetic acid and 0.1 molar sodium acetate (Ka
for acetic acid is 1.75 x 10-5). The pH of a solution will be pKa is
pH = 4.75 + log (0.1/ 0.1) = 4.75
pKa = -log of Ka
If the concentrations of acetic acid and sodium acetate are equimolar, the pH of the solution will
always be the same, 4.74. However, the higher the concentration of buffer compounds, the greater
will be the buffer capacity or the greater the ability to resist change in pH.

Buffer Capacity. this is a quantitative expression of the ability of a buffer system to resist change in pH.
β = ∆A/∆ pH
where β is the buffer capacity and ∆ A is the addition in gram equivalents per litre of strong acid (or
strong base) to buffered solution to produce a pH change of ∆pH.

Colligative properties. The Colligative properties depend primarily upon the number of particles in
solution. Example of these properties includes.
• Lowering vapor pressure
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• Increase in boiling point

• Decrease in freezing point
• Osmotic pressure
• Lowering of vapour pressure. When a solute is added to a liquid, it will decrease the vapor
pressure of the liquid.
• Increase in boiling point. The effect on the boiling point is just the opposite. That is the boiling
point of a liquid is increased if something is dissolved in it. Boiling is the vapour pressure of liquid
not more than the atmospheric pressure.
• Decrease in freezing point. When a solute or salt is added to liquid, it will decrease the freezing
point.
• Osmotic pressure.
• Isotonic. The solute concentration is the same on both sides of the membrane. The solutions are
said to be isotonic compared to one another.
• Hypotonic. The clinical significance of all this is to insure that isotonic or iso-osmotic solutions do
not damage tissue or produce pain when administered.

Tips
• Arrhenius equation is used for? 
• Water-soluble antioxidants? 
• Fat-soluble antioxidants? 
• Theobroma oil and cocoa butter are? 
• Polymorphs have 
• Arrhenius equation is used for? 
• Water soluble antioxidants? 
• Polymorphs are different in crystalline forms of the same drug, will differ in 
• USP official temperature is 
• Protect from light indicates storage in light resistant container that reduces light transmission in
the range of 
• Pycnometer is used for 
• Hydrometer is used for 
• Boric acid is 
• Tannic acid is 
• Acetic acid is 
• Freon is 

USP (United States Pharmacopea):

• Alcohol USP 94.9% ethanol V/V
92.3% ethanol W/V
• Diluted alcohol 49% ethanol V/V
• Rubbing alcohol 70% V/V absolute alcohol (denatured)

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35
Pharmaceutical Excipients
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Types of water in parenteral preps
• Examples of alkalinizing agents, antioxidants, surfactants, levigating agents, bacterial and
fungal preservatives.
• Definitions of glidant, anti adherent and lubricants
• 1) What type of water is used to manufacturing parenteral preps?
• 2) What type of water is used for multiple use containers?

Water for injection USP

• Prepared by double distillation or reverse osmosis
• Free from pyrogen
• Used as solvent for parenteral solutions in manufacturing.

Sterile water for injection USP

• not >1 liter
• Sterilized and packed in single dose container of type I and II glass.
• Limitation of total solids depends on size of the container.

Bacteriostatic water for injection USP

• Not >30 ml
• Contain 1 or more antimicrobial agent

Packed in single or multiple use dose containers

Sterile water for irrigation USP

 >1 liter
Sterilized and suitably packed
It contain no antimicrobial agents or other added substance

Purified water USP

Prepared by distillation, reverse osmosis, or ion exchange
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Should not contain 10 ppm solid particle

Should have pH between 5 and 7
Used in prescription and finished manufactured product
Not used in parenteral and ophthalmic products

Sterile purified water USP

It is purified water sterilized and packed
It does not contain antimicrobial agents
It is NOT intended for parenteral preparations

The method of preparation of purified water USP must be indicated on the label. [Sterile water for
injection (USP method)].

Excipient Type Use Example

Acidifying agent Used in liquid preparations to provide Acetic acid
medium for product stability. Ammonium chloride
Ascorbic acid
Citric acid
Fumaric acid
Hydrochloric acid
Nitric acid
Alkalizing agent Used in liquid preparation to provide Ammonia solution
alkaline medium for product stability. Ammonium carbonate
Also used for acidic drug (ASA) Diethanolamine
overdose. Monoethanolamine
Potassium hydroxide
Sodium borate
Sodium carbonate
Sodium hydroxide
Triethnolamine
Trolamine
Sodium bicarbonate
Adsorbent An agent capable of holding other Powdered cellulose
molecule onto its surface Activated charcoal
(adsorption) by physical or chemical
(chemsorbtion) means.
Aerosol An agent responsible for developing Carbon dioxide
propellant the pressure within an aerosol Dichlorodifluoromethane,
container and expelling the product Dichlorotetrafluoroethane,
when valve is opened. Trichloromonofluoromethane (CFCs) also
Ozone oxidation mechanism is? free known as freon gas, it is not safe.
radical formation. Hydrofluroalkenes (HFA) are safe.
Topical sprays are n-butane and propane.
Air An agent which is employed to Nitrogen or inert gases (Ar, Ne, Xe, He)
displacement displace Air in a hermetically sealed
contained to enhance stability.
Antifungal Used in liquid and semi solid Benzoic acid
preservative preparations to prevent the growth Butyl paraben
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of fungi. Ethyl paraben

Methyl paraben
Propyl paraben
Sodium benzoate
Sodium propionate
Antimicrobial Used in liquid and semi solid Benzalkonium chloride
preservative preparations to prevent the growth Benzothonium chloride
of microorganisms. Benzyl alcohol
Cetylpyridinium chloride
Ophthalmic preps use benzalkonium Chlorobutanol
chloride concentration 0.004%. Phenol
Phenylethyl alcohol
Phenylmercuric nitrate
Thimerosal
Antioxidant An agent which inhibits oxidation and Water soluble (aqueous):
thus is used to prevent the Ascorbic acid
deterioration of preparations by Sodium ascorbate
oxidative process Sodium bisulphite
Sodium formaldehyde
Solfoxylate
Sodium metabisulfite
Hypophosphorous acid

Lipid soluble (non aqueous):

Ascorbyl palmitate
Butylated hydroxyanisole (BHA)
Butyllated hydroxytoluene (BHT)
Monothiglycerol
Propyl gallate
Tocoferal (vitamin E 1 )
Buffering agent Used to resist change in pH upon Potassium metaphosphate
dilution or addition of acid or alkali. Potassium phosphate Monobasic
Buffers are made with Acid and salt Sodium acetate
of acid or base and salt of base. Sodium citrate anhydrous and dehydrate

Chelating agent A substance that forms stable, water EDTA

soluble complex (chelates) with Edate disodium
metals. Chelating agents are used in Edetic acid
some liquid pharmaceuticals as
stabilizers to complex heavy metals,
which might promote instability. In
such a case they are also
sequestering agents.
Colorant Used to impart color to liquid FD&C
Caramel
Ferric oxide gives red color
Tartazine gives yellow color

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Clarifying agent Used as filtering aid because of Bentonate

adsorbent
Emulsifying Used to promote and maintain the Acacia
agent dispersion of finely subdivided Cetomacrogol
(Surfactant) particles of a liquid in a vehicle in Cetyl alcohol
which it is immiscible. The end
product may be a liquid emulsion or Anionic
semisolid emulsion (e.g. cream). Sodium lauryl sulfate
Emulsifying agents also known as Glycerl monoestearate
surfactants. Sorbitan monooleate
Polyoxyethylene 50 stearate

Non ionic
Tweens and spans

Cationic
Benzalkonium chloride
Encapsulating Used to form the shells for the Gelatin
agent purpose of enclosing a drug Cellulose acetate phthalate (CAP), enteric
substance or drug formulation for coated.
ease of administration. Sorbitol
Flavorant Used to impart a pleasant flavor and Anise oil
often odor. Cinnamon oil
Cocoa
Menthol
Orange oil
Peppermint oil
Vanillin
Strawberry
Humectants Used to prevent the drying out of Glycerin
preparation, particularly ointments Propylene glycol
and creams due to the agent’s ability Sorbitol
to retain moisture.
Levigating agent A liquid used as an intervening agent Mineral oil
to reduce the particle size of drug Glycerin
powder by grinding together, usually
in mortal.
Ointment base The semisolid vehicle into which drug Water soluble base
substance may be incorporated in Hydrophilic ointment
preparing medicated ointment. Rose water ointment
Polyethylene glycol (PEG) ointment

Lipid soluble
Lanolin
Propylene glycol
Petrolatum (Occlusive base)
Hydrophilic petrolatum

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White ointment
Yellow ointment
Plasticizer Used as a component of film coating Diethyl phthalate
solutions to enhance the spread of Glycerin
the coat over tablets, beads and Sorbitol
granules.
Solvent An agent used dissolves another Solvent that are used in parenteral prep.
pharmaceutical substance. Olive oil
Corn oil
Canola oil
Cottonseed oil
Peanut oil
Water for injection USP
Sterile water for injection USP
Normal saline, D5W, Ringer solution.

Solvent in oral prep.

Purified water
Sterile water for irrigation
Ethyl alcohol
Glycerin
Mineral oil
Oleic acid
Stiffening agent Used to increase the thickness or Cetyl alcohol
hardness of ointment Cetyl esters wax
Microcrystalline wax
Paraffin
Stearyl alcohol
White wax
Yellow wax
Surfactant Substance, which absorbs to Benzylalkonium chloride
surfaces or interfaces to reduce Nonoxynol 10
surface or interfacial tension. May Oxtoxynol 9
be used as wetting agents, Polysorbate 80
detergents or emulsifying agents Sodium lauryl sulfate
Sorbitan monpalmitate
Suspending A viscosity increasing agent used Agar
agent to reduce the rate of Bentonite
sedimentation of particles Carbomer
dispersed throughout a vehicle in Carboxymethylcellulose sodium (CMC)
which they are not soluble. Hydroxymethyl cellulose
Hydroxypropyl cellulose
Hydroxypropyl methyl cellulose (HPMC)
Kaoline
Methyl cellulose
Tragacanth
Veegum

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Tablet anti Agent, which prevent the sticking Magnesium stearate

adherent of tablet formulation ingredients. Talc
Silicon dioxide
Tablet coating Used to coat a formed tablet for Sugar coating:
agent the purpose of protecting against Liquid glucose
drug decomposition by Sucrose
atmospheric oxygen or humidity Film coating:
to provide desired release pattern Hydroxethyl cellulose
for drug substance after Hydroxypropyl cellulose
administration, to mask the taste Hydroxyproply methylcellulose
and odor or the drug. Methylcellulose (e.g. Methocel)
The coating may be various type: Ethyl cellulose (e.g. Ethocel)
Sugar coating
Film coating or enteric coating Enteric coating
Sugar coated is water based and Cellulose acetate phthalate
results thickened covering around Shellac (35% in alcohol, “pharmaceutical
a formed tablet. Sugar coating glaze”).
generally starts to break up in Methacrylic acid
stomach. A film coated is thin
cover around a formed tablet or
bead. Unless it is an enteric coated
the film coat will dissolve in the
stomach. An enteric-coated tablet
or bead will pass through the
stomach and break up in the
intestine. Some coating that is
water insoluble may be used to
coat tablets or bead to slow the
release of drug as they pass
through the gastrointestinal tract.
Tablet direct Used in direct compression tablet Dibasic calcium phosphate (e.g. Ditab)
compressing formulation
exipient
Tablet /Capsule Used to render a capsule of a Titanium oxide
opaquant tablet coating opaque. May be
used alone or in combination with
colorant
Tablet polishing Used to impart an attractive sheen Carnauba wax
to coated tablet White wax
Tonicity agents Used to prepare isotonic solutions Sodium chloride and dextrose.
in parenteral, ophthalmic and
irrigation solutions.

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Filler/diluents Filler functions: Increases the bulk volume so that the final product has the proper
volume for patient handling.
Filler requirements: inert, compatible, non-hydroscopic, soluble, cheap,
compactable, and tasteful.
Fillers: Lactose, sucrose, glucose, mannitol, sorbitol, calcium phosphate, calcium
carbonate, and cellulose.
Binder Binders cause the adhesion of the powdered drug and inactive ingredients. Dry
powder added to the mixture prior to the wet granulation process solution that is
used in the wet granulation process.
Binder types. Wet/Solution Binders. Gelatine, cellulose, cellulose derivatives,
polyvinyl pyrrolidone (PVP), starch, sucrose, and polyethylene glycol.
Dry Binders. Cellulose, methyl cellulose, polyvinyl pyrrolidone, polyethylene
glycol, and starch.
Disintegrant Disintegrant are used to ensure that when tablets are in contact with water, they
are rapidly breaking into smaller fragments, facilitating their dissolution.
Disintegrants facilitate water uptake, rupture the tablets.
Disintegrant. Starch, cellulose, crosses linked polyvinyl pyrrolidone, sodium starch
glycolate, sodium carboxymethyl cellulose.
Glidants To improve the flow ability of the powder or granules or both. Example Corn
starch, silica derivatives (silicon dioxide colloidal), and talc.
Glidants properties are measured by “Angle of repose” and X-ray photo electron.
Lubricant To ensure that tablet formation and ejection can occur with low friction between
the solid and the die wall. Example polyethylene glycols, stearic acid, stearic acid
salts (calcium, zinc and magnesium stearate).
Anti-adherent Is used to reduce the adhesion between the powder (granules) and the punch
faces and thus prevent tablet sticking to the punches. Example talc, and starch.
Sorbent Limited fluid sorbing in dry state.

Tips
1 Anti-adherent 2. Polysorbate 3. alkalizing agent
4 lubricant stearic acid 5. Water for injection USP 6. Anionic surfactant

7 improve flow ability 8. ascorbic acid 9. Sodium bisulfate

of granules
10 sorbic acid ester 11. hydrofluoroalkenes HFA
• Triethanol amine is? ( )
• Prevent sticking in die wall is referred as? ( )
• Glidant is? ( )
• Example of water soluble antioxidants are? ( )
• Sodium lauryl sulfate is? ( )
• The type of sterile water used in parenteral preparation in manufacturing? ( )
• In aerosol propellant action is given by? ( )
• Magnesium stearate is? ( )
• Tween is? ( )
• Span is? ( )
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www.Pharmacyprep.com Rheology

36
Rheology
Rheology is study of deformation and flow
of matter. Questions Alerts!
Common questions in pharmacy exam is to ask!
Newtonian Fluids • Thixotropy systems (gel to solution)
• The rate of shear (flow) should be the • Antithixotropy systems (solutions to gel)
directly proportional to the shearing
stress.
• The reciprocal of viscosity is defined as fluidity.
• The units of viscosity are poise. (gm/cm sec).

Non-Newtonian Fluids
The fluids that do not obey the Newton’s law
are described as non-Newtonian fluids.

Non-Newtonian flow is characterized into three

types: plastic, pseudo plastic and dilatants.

Plastic Flow
• The substance that exhibits plastic flow and
does not pass through the origin, it normally
intersects the shearing stress axis.
• The point at which it intersects the shearing stress axis is known as yield value.
• Plastic flow is also known as Bingham bodies.
• Plastic flow materials. They do not start to flow until the applied shearing stress equals the yield
value.
• At stress below the yield value, material act as an elastic material.

Pseudo plastic flow

• Most of the pharmaceutical follow pseudo plastic flow.
• Pseudo plastic flow also known as shear thinning system.
• Flow begins at the origin.

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• The viscosity of material decreases with increase

rate of shear force.
• It is thixotropy. Examples suspending agents such
as ethyl cellulose, carboxymethylcellulose and its
derivatives.

Gel ------>Solution
Viscosity decrease
Flow increase

Thixotropy systems. Two types of systems associated with thixotropy. Products that have thixotropy
with shear stress, decrease in viscosity and increase flow ability.
• Pseudo plastic flow
• Plastic systems
Thixotropy occurs when transformation of gel to solution. Thixotropy is used in formulation of
suspensions dosage form where system remains gel form upon resting and by application of shear
stress this can be converted to solution form.

Gel-------------------->Solution
↓ Viscosity
↑ Flow

Dilatants flow
• Also known as shear thickening systems, it is just opposite to pseudo plastic flow.
• The increase in rate of shear force normally increases resistant to flow.
• Normally suspension with high percentage of dispersed solid particles does follow dilatants flow.
• Examples are suspension containing high concentration of small-deflocculated particles.

Anti-thixotropy systems. Products that exhibit opposite action of thixotropy are referred to as anti-
thixotropy. Anti-thixotropy occurs when solutions to gel transformation. Example dilatants flow.
• Upon shear stress decrease flow and increase viscosity.
• Increase in viscosity thereby decrease flow rate.
• Example products fusidic acid ophthalmic and timolol ophthalmic drops.

Solution ----------------> Gel

↑Viscosity
↓Flow
Tips
1. Bentonite at high conc 2. is increase viscosity with increase 3. dilatants flow
shear stress
4. increase flow 5. decrease viscosity 6. antithixotropy
7. decrease flow 8. thixotropy increases flow and 9. Gel to solution
decrease viscosity
10 Solution to gel

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• Term that referred to non Newtonian flow, increase force will increase difficulty in suspension
flow? ( )
• Pseudo plastic flow ( )
• Thixotropy systems ( )
• Anti-thixotropy systems ( )
• Dilatants flow ( )
• Rheopexy is? ( )
• Agents to prepare dilatants flow ( )
• Shear thickening is? ( )

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37
Pharmaceutical Dosage Forms
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Tablet manufacturing methods (for ASA) and problems
• Soft gelatin and hard gelatin capsules
• Methods of powdering (levigation, trituration, pulverisation)
• Suppository calculation
• Suspending agents and flocculating agents
• HLB for w/o and o/w

Solid Dosage Coarse Dispersion Solution Dosage Miscellaneous

Dosage

Tablets Pills Internal Use

Caplets Inhalants
Suspensions Aerosols
Lozenges Gels

Powder Emulsions External Use

Lotions
Liniments
Capsules Creams
Soft gelatine shell Ointments
Hard shell Vitamin drops

Suppository

Pellet/Bead

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Solid Dosage Form

Tablets Most commonly known dosage form is the tablet.
Advantages Accurate dosage
Lesser manufacturing cost
Easy to pack and ship, Easy to identify, Easy to swallow
Appropriate for special-release forms
Best for large-scale production
Most stable of all oral dosage forms
Tampered proof
Disadvantages Some drugs are hard to compress into tablet
Some drugs may be difficult to formulate to have adequate bioavailability.
Some drugs has foul odour or disgusting taste, so they are preferably done in
forms of capsules.

Methods of tablet preparation. There are 3 methods of tablets preparation

Wet granulation method, Dry granulation method and direct compressions method.
Wet This is a widely employed method for the production of compressed tablets. This
granulation method NOT suitable for moisture sensitive drugs, like ASA, this drug can undergo
hydrolysis in moisture.
Dry In the dry granulation method the granulation is formed by compacting large
granulation masses of the mixture and subsequently crushing and sizing these pieces into
smaller granules.
By this method either the active ingredient or the diluents must have cohesive
properties in order for the large masses to be formed.
Direct Some granular chemicals like potassium chloride and methenamine possess free
compression flowing as well as cohesive properties that enables them to compress directly in a
tablet machine without need of either wet or dry granulation. Vehicle should be
compressible and have good flow. Example dried lactose, mannitol, and starch.

Important Concept!
1) Poorly manufactured tablets may have small “Pinholes” on the surface which occurs when the
tablet powder stick to punch face-picking
2) Air entrapment can causes? Lamination
3) Excessive moisture can cause? sticking
4) Too much pressure or excessive pressure in punching may cause? Capping

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Problems in tablet manufacturing

Capping The partial or complete separation of the top or bottom crown from the main body of
the tablet. Too much pressure or excessive pressure in punching.
Lamination Separation of tablet into two or more distinct layers. Air entrapment results from
excess powders which traps air in the tablet, deep marking or tablet punches. Warm
or imperfect punches. Too much pressure. Moist and soft granulation or unsuitable
formula.
Picking The removal of the surface material of tablet laid a punch.
Sticking An adhesion of tablet material to a die. Picking and sticking results from or these
problems are caused by excessive moisture or the inclusion of substance with low
melting temperature in the formulation.
Mottling The uneven distribution of colour. Degradation of active ingredients can give rise to
mottling.

Evaluation Tests for tablet (quality control)

Hardness Measures the degree of force required to break a tablet and also indicates tensile
strength of tablet. Hardness of tablet greatly effects dissolution and disintegration.

Thickness Measured by capillary scale (Vernier calipers)

Friability Ability of the tablet to withstand abrasion in packing, handling and shipping which is
defined as loss in weight of tablet due to chipping or fragmentation in the form of fine
particles. Tumbler method is used for testing friability.
Weight Measuring weight of tablet.
USP methods include Friability, dissolution, disintegration, hardness and weight variation. USP do not
include thickness of tablets.

Capsules
A solid dosage form in which medicinal or inert substances are put inside a small gelatin shell.
Capsule shell sizes (5 to 000). 000 is the largest size of capsule, its capacity is 600 mg. The smallest
capsule size is 5 is 30 mg. Manufacturer also makes available number 10, 11, and 12 for veterinary use.
The gelatin shell dissolved in 10 to 20 minutes after ingestion.

Capsule. Comes in two types.

Soft gelatine shell manufactured in one piece with drug usually in liquid form inside the shell, e.g. fat-
soluble vitamins A and E, Procardia (nifedipine), etc. soft shell capsule are made from gelatine to
which glycerin or some other polyol, such as sorbitol or propylene glycol has been added as
plasticizer. Spherical or ovoid capsules are sometimes called pearl or globules.

Soft gelatin capsules. Made up of gelatin shell, glycerin or polyhydric alcohol are added to make the
shell elastic and plastic-like. It also contains preservatives to prevent microbe’s growth. Advantages of
capsule dosage form are good for drugs with objectionable taste or odour and easy to swallow.

Hard gelatine shell. The hard shell gelatin capsules are made from the mixture of gelatin, sugar and
water, with without suitable coloring agent. Hard gel caps contain powder and cannot fill liquid. Sulfur
dioxide is used as a preservative. Capsules are made opaque with titanium dioxide. Hard capsule are
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available in variety of sizes and designated by numbers 000 to 5. Manufacturer also makes available
number 10, 11, and 12 for veterinary use.
Trituration The continuous rubbing or grinding of the powder in a mortar with a pestle. This
method is used when working with hard, fractural powders.

Levigation This method is also used to reduce the particle size of insoluble materials when
compounding ointments and suspensions. Reduces the particle size by triturating it
in a mortar or spatulating it on an ointment slab or pad with a small amount of a
liquid in which the solid is not soluble.
The solvent should be somewhat viscous such as mineral oil or glycerin.

Pulverization By intervention it is the process of reducing a substance to a fine powder by means

of utilizing solvent, which can evaporate easily. Used with hard crystalline powders
that do not crush or triturate easily, or gummy-type substances.
Mechanical Ball or pebble mills, wiley mill, hammer mill fluid energy mills.
Comminution

Powders
Particle size Powders generally range from 0.1 to 10 micron (0.1µM to 10 µM) in size. The
screen size indicates the number of openings in the mesh screen per inch. For
example, a # 40 sieve has 40 openings per inch in the screen mesh. Particles that
can sift through that mesh are said to be "40 mesh" size. Very small particles (below
1 µM) posses high surface free energy that results in absolute solubility. Higher the
mesh size, smaller the particle.

Advantages Flexibility in compounding

Good chemical stability
Rapid dispersion of ingredient
Disadvantages Time consuming in preparing powder
The dose is inaccurate
Unsuitable for hygroscopic, deliquescent drugs and unpleasant tasting.

Comminution. The process of reducing the particle size have 3 methods.

Powder mixing methods

Spatulation Small amounts of powder, having the same range of particle sized and densities,
may be conveniently mixed on a sheet or paper or tile with spatula.

Trituration Powders may be mixed in a mortar by gentle trituration with a pestle.

Sifting Where free-flowing, light powders are desired, the ingredients may be brushed
through a sieve. Ordinary household sifters may be used in sifting pharmaceutical
powders.
Tumbling When simple mixing of powders is desired without reduction in particle size.

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Geometric Dissolving in small proportions.

dilution

Special Powders
Hygroscopic A substance that absorbs moisture from the air is termed hygroscopic. (Absorb H 2 O).

Deliquescent Hygroscopic substances, which absorb moisture from the air to the extent that they
liquefy by partially, or wholly forming solution are termed deliquescent. (Absorption
H 2 O).
Efflorescent Crystalline substances, which become powdery and liberate their water of
crystallization are said to be efflorescent. (Liberate H 2 O).

Effervescent Granules or powders consisting of sodium bicarbonate, a suitable organic or inorganic

salts acid, and medicinal ingredients are known as effervescent salts. In the presence of
water, the acid and base react to liberate carbon dioxide, thereby producing
effervescence. (Liberate CO 2 ). Examples of effervescent salts include Alka Setzer (ASA
with NaHCO 3 ), and calcitral.

Eutectic A eutectic mixture is defined as that proportion of components, which will give the
mixtures lowest melting point. Example menthol, and camphor. Compound A 50oC and
compound B 80oC after combining mixture 20oC.

Suppositories
Types of Solid or semi solid dosage form intended to be inserted into body orifice.
suppositories The most common method of suppository preparation is fusion Method.
Rectal Bullet-like shape to moves it inward when rectum contracts, 2 g adult, children
smaller than adult.
Tapered shape and rectal suppository can provide systemic medication

Vaginal Ova shape and 5 g. Have local absorption, but systemic absorption may occur.
Variable size, cylindrical shape, often contain poly ethylene glycol (PEG), water
soluble base
Urethral Long and tapered. Has local effect.
Suppository Criteria:
Bases It should have a narrow or sharp melting range.
It should yield a clear melt just below body temperature or it should dissolve or
disintegrate readily in the cavity fluid.
It should be inert and compatible with wide variety of drugs.
It should be non-irritating and non-sensitizing

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Types of Suppository Bases

Lipid Cocoa butter USP (Theobroma oil, cocoa butter). At 34 to 35oC, it melts to produce a
soluble thin, oily liquid. It is a good base for rectal suppositories, but less ideal for vaginal
suppositories.

Witepsol bases (Lauric acid). Do not exhibit polymorphism.

High melting witepsol can be mixed low melting witepsol to produce 34 to 44oC.
Contain emulsifiers. surfactants in suppositories enhance rate of absorption.

Wecobee bases (coconut oil). These bases are derived from coconut oil.
The incorporation of glyceryl monostearate and propylene glycol monosterate them
emulsifiable.
Water Polymer of ethylene oxide and water, molecular weight range 400-6000
soluble Polyethylene glycol polymers e.g. carbowaxes.
Usually anhydrous, water soluble and washable, non-greasy, non-occlusive
lipid free.
Glycerin suppositories USP consist of 91% glycerin gelled with 9% sodium stearate.
They are available as adult and infant suppositories to evacuate the lower bowel.

Displacement value.
Displacement Value = number of grams of salt to replace one gram of cocoa butter.
Example. ZnO displaces cocoa butter. Two parts of ZnO displaces one part of cocoa butter.

Preparation of suppositories. To prepare 10 suppositories, each containing 300 mg ASA are required
what amount of cocoa butter? Density factor (displacement value) of ASA is 1.1.
Each, mold is 2 ml.
Solution.
3.3 g/1.1= 3 ml ASA
11 suppositories x 2 ml = 22 ml
22 ml–3 ml ASA = 19 ml of cocoa butter

Suspension
Suspension is a two-phase system in which the internal or dispersed phase is solid external or
continuous phase is liquid.

Physical and chemical properties of suspension

Colloidal suspension. A suspension containing particles between 1 nm to 0.5 µm in size.
Coarse suspension. The particle size is between 1 to 100 µm, the suspension.

Purpose. Sustaining effect it necessitates drug dissolution prior to absorption.

• Stability. drug degradation occurs more slowly with suspension compared to solution form.
• It improves the taste.
• Basic solubility, it provides alternative solvents.

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Ideal Suspensions
• A uniform particle size-uniformly distributes
• Suspension that have no particle, particle interaction
• Suspension that have no sedimentation.

Factors for an ideal suspension

• Sedimentation
• Suspending Agent
• Flocculating Agent

Sedimentation. The Stoke’s law can express the relationship of the rate of sedimentation with various
parameters.
V = 2r2 (P1 – P 2 )g
9n
V = velocity of sedimentation in cm/sec
P 1 = density of disperse phase in g/cm3
P 2 = density of dispersion medium in g/cm3
R = radius of the particles in cm
n = viscosity of dispersion medium
g = gravity acceleration 980.7 cm/sec2
The rate of sedimentation is independent of the lipophilic nature of particles.

Summary of Stokes equation. The velocity of sedimentation of particles in a suspension can be

determined by using the Stoke's equation.

Particle size. Larger particles will settle faster at the bottom of the container and too fine particles will
easily form hard cake at the bottom of the container. Larger the particle size increase in
sedimentation. In most good pharmaceutical suspension, the particle diameter is between 1 and 50
µm. Particle size reduction is done by dry milling method.

Density of particles. The settling decreases as (p 1 –p 2 ) approaches zero.

Density of the vehicle. adding the following substances either alone or in combination can increase the
density of the vehicle of a suspension polyethylene glycol, polyvinyl pyrolidone, glycerine, sorbitol, and
sugar. Increase vehicle density  decreases sedimentation. However, the density of the dispersion
medium cannot be altered thereby density of particle is changed.

Viscosity of the vehicle. Adding the suspending agents or viscosity enhancers increases the viscosity of
a suspension. Increase in viscosity of vehicle decrease in sedimentation rate.

Suspending agents (viscosity enhancers). Natural hydrocolloids; acacia, tragacanth, alginic acid, locust
bean gum, guar gum, gelatin and cellulose.
Semi synthetic hydrocolloids. Methylcellulose, sodium carboxymethylcellulose, and carbomen.
Synthetic hydrocolloids. Carbopol.
Clays. Bentonite, veegum

Problems in suspension. Sedimentation, and caking

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Flocculating Agents. The addition of flocculating agents to enhance particle "dispersability".

Flocculating agents are electrolytes, which carry an electrical charge opposite that of the net zeta
potential of the suspended particles. The addition of the flocculating agent, at some critical
concentration, negates the surface charge on the suspended particles and allows the formation of
floccules or clusters as particles are held loosely together by weak Van der Waals forces. The particles
are linked together only loosely. They will not cake and may be easily re-dispersed by shaking the
suspension. Floccules have approximately the same size particles. Examples of flocculating agents are
potassium stearate, potassium laurate, acryl polymers and surfactants.
Addition of viscosity enhancers to reduce sedimentation rate in the flocculated suspension.
Higher volume of sedimentation. NO clear boundary is seen when the particles settle.

Deflocculation Flocculation
Clear boundaries No clear boundaries
Small volume of sedimentation Higher volume of sedimentation
Not ideal suspension Ideal for suspension
Not easy to disperse Easily dispersible

TABLE: Comparison between Deflocculated and Flocculated System

Deflocculated System Flocculated System
Pleasant appearance, because of uniform Somewhat unsightly sediment.
dispersion of particles.
Supernatant remains cloudy. Supernatant is clear
Particles exist as separate entities Particles form loose aggregates.
Rate of sedimentation is slow, as the size Rate is high, as flocs are the collection of
of particles are small. smaller particles having a larger size.
Particles settle independently and Particles settle as flocs.
separately Sediment is a loosely packed network
The sedimentation is closely packed and and hard cake cannot form.
form a hard cake. ) The sediment is easy to redisperse.
) The hard cake cannot be redispersed. )Bioavailability is comparatively less due to
)Bioavailability is higher due to large specific small specific surface area.
surface area.

Emulsions
Emulsion is a two phase system consisting of at least two immiscible liquids. Internal or discontinuous
phase; The dispersed liquid, external or continuous phase; The dispersion medium.
Emulsion is classified as five different categories:
* Water in Oil (W/O). Oil is a continuous phase and water is a disperse phase, i.e., lotions and
liniments. Example. lotions and liniments.
* Oil in Water (O/W). Water is a continuous phase and oil is a dispersed phase, i.e., most of the oral
emulsions to unmask the oily taste of a medication.

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* Microemulsion. Unlike emulsions, microemulsion is transparent with a small particle size. It is

believed to be thermodynamically unstable. The particle size of microemulsion lies between 10 to 200
nm. It is generally used for the solubilization of the drug in pharmaceutical dosage form.
* Nanoparticles. Micro-emulsion- droplets size range 0.01 to 0.1 mm, the particle size of this kind of
emulsion is limited to nanograms. They are useful for the preparation of globulins and toxoids.
Tetanus toxoid and human immunoglobulin G are examples of nanoparticles emulsion.
* Multiple emulsions: Water in Oil in ware (W/O/W), Oil in Water in Oil (O/W/O). The w/o/w
emulsions are generally more preferable for preparation of various pharmaceutical dosage forms.
They are used to prolong the duration of action of various drugs, to localize drug in the body and to
prepare cosmetics

Purpose of emulsion
• Increase drug solubility
• Increase drug stability
• Prolonged drug action
• Improve taste
• Improved appearance

Stability of emulsion. Protect emulsions against the extremes of cold and heat. Emulsions may be
adversely affected by microbial contamination.

Emulsifying agents (surfactants) are categorized as.

• Anionic agent. Sodium lauryl sulphate.
• Cationic agent. Benzalkonium chloride.
• Non ionic. Tween and Spans. Tween is polysorbate and span is sorbital esters.

Problems in emulsion can be classified into three different categories. Creaming, breaking (cracking)
and phase inversion.

Creaming. It occurs due to flocculation of globules of the internal phase. It is not a potential cause of
instability of emulsion, however, occurrence of creaming is a potential step towards complete
breaking of emulsion. The rate of creaming can be expressed by Stoke’s law.

V = d2 (Ps – Po) x g
18n
d = diameter of particle in cm
Ps = density of disperse phase
Po = density of dispersion medium
g = gravitational force
n = viscosity of medium

Breaking. Breaking generally results in separation of the internal and external phase. It cannot be
reformulated.

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Hydrophilic lipophilic balance (HLB) measures the surfactants mixibility in water and lipids.
Classification of surfactants based on HLB values and uses.
0-3----------------------- Antifoaming
4-6-- .................w/o emulsifying
7-9----------------------- wetting
8-18------------- - o/w emulsifying
13-15-------------------- detergent
10-18-------------------- solubilizing agent

Combinations of emulsifiers can produce more stable emulsions than using a single emulsifier with the
same HLB number. The HLB value of a combination of emulsifiers can be calculated as follows.

Example. What is the HLB value of a surfactant system composed of 20 g span 20 (HLB = 8.6) and 5 g
Tween 21 (HLB = 13.3)?

Creams
Cream (W/O). A semisolid emulsion of oil, e.g. lanolin or petrolatum, and water.
These are either water-miscible or readily washed-off, or oily and not so easily
washed off.
Cold cream Cream (W/O) emulsion and vanishing cream (O/W) emulsion
Preservatives Chlorocresol and Hydroxybenzoates, both of which may cause skin allergies.
used
Barrier creams Barrier creams often contain water-repellent substances such as dimethicone or
other silicones. They give protection against irritation or repeated hydration and is
useful in the treatment of napkin rash and bedsores, etc.
Creams should be stored in cool place and supplied in well closed containers that
prevent evaporation and contamination of the contents.
Cream Eumovate, Elocom, Tridesilon Cream.
examples
Substances such as precipitated sulphur, salicylic acid, menthol and camphor,
hydrocortisone powder, hydroquinone, to mention a few, may be incorporated
into creams and/or ointment bases extemporaneously.
Ointments
Mechanism Ointments are semisolid substances that are greasy, normally anhydrous, and
insoluble in water, and intended for external use.
Therapeutic use The most commonly used ointment bases consist of soft paraffin or a combination
of soft paraffin with liquid paraffin and hard paraffin. Due to their anhydrous
nature ointments do not require any preservatives.
They are typically used as emollient that makes skin more pliable
Protective barriers prevent contact to skin from harmful substances.

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Advantages It moisturizes, more occlusive than creams and forming a protective film over the
skin. The occlusive effect tends to prolong and enhance drug penetration.

Disadvantage They are messy to use.

Storage They should be kept in well-closed container that prevents evaporation and
contamination in a temperature not exceeding 25oC. The material making up the
container should be resistant to absorption or diffusion of the contents.
Ointment Levigation to reduce particle size, most commonly used method for
Preparation pharmaceutical compounding.
Levigating agents. Levigating agents used for wet & disperse powder
Main agents: mineral oil, cottonseed oil, and castor oil.
Glycerin: (propylene glycol PEG 400).
Surfactants: polysorbate 80 (Tween 80).
Not all surfactants are compatible
Fusion method: used method if the base contains solid that has higher melting
point.
Some examples ointments are generally used for treatment of hemorrhoids.
Preparations H, Anusol, Anusol HC and Anugesic.
Ointment Water and lipid soluble base. Poly ethylene glycol (PEG)
bases Lipid soluble base Lanoline
Occlusive bases: Petrolatum

Important Concept!
1) Occlusive bases effectively prevent water
evaporation from the skin. Tends to prolong and
enhance drug absorption.

1) Hydrophilic Petrolatum, USP

• Contains cholesterol, stearyl alcohol, white wax and white petrolatum
• Forms water-in-oil emulsions
• 2) Cholesterol is the emulsifying agent

Home work
Creams Ointments
o/w w/o
vanishing Cold cream
Hydrocortisone ZnO

Pastes
Mechanism Pastes are stiff preparations containing a high proportion of finely powdered solids
such as zinc oxide and starch.
Therapeutic They are less occlusive than ointments and can be used in subacute, lichenified, or
use excoriated skin conditions. Due to the stiff nature, they can be applied accurately to
a particular lesion such as chronic eczema and psoriasis, and are therefore useful for
the local application of irritating drugs.

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Examples Anthralin OTC paste 0.025% and 0.2% for seborrhea and psoriasis. Benzoyl peroxide
paste for acne.

Gels
Mechanism Gels are semisolids or solids prepared from high molecular weight polymers in an
aqueous or alcoholic base. They are easy to apply and wash off (example hairy
places).
Therapeutic Gels are useful for promoting wound granulation (example Actovegin Jelly), in
use treatment of acne (example Panoxyl gel) and Scalp psoriasis (example Synalar gel
mix).
Due to their drying effect and especially the alcoholic ones, they may cause irritation
to the skin.
Examples Acne gel preparations. Made of synthetic polymers such as carbo vinyl and
polyoxyethylene laurel ether in hydroalcoholic liquids are used as bases for benzoyl
peroxide in the treatment of acne.
Topical gels. Tretinoin or tretinoin + clindamycin (clindagel), tretinoin + erythromycin
gel should be stored in refrigerator and protect from light.

Panoxyl®, Benazagel®-10, Hormone replacement (Androgel®, Estrogel®).

Diffusimax is a commercially prepared pluronic gel that easily penetrates the skin and
is used as a vehicle to apply such drugs as Diclofenac sodium to ease muscle pains.
Hydrophilic Petrolatum, USP

• Contains cholesterol, stearyl alcohol, white wax and white petrolatum

• Forms water-in-oil emulsions
• Cholesterol is the emulsifying agent

Lotions
Mechanism Lotions are aqueous solutions or suspensions that cool diffusely inflamed
unbroken skin. Finely powdered drugs are suspended in a thin, semi-solid base and
applied to the skin.
Therapeutic Cool skin by evaporation and should be applied frequently.
use Lotions are also used to apply drugs to the skin when only a thin layer of the
preparation is intended to be applied over a large surface area.
Shake lotions (e.g. calamine lotion) that contain insoluble powders are applied to less
acute, scabbed, and dry lesions.
In addition to cooling, they leave a deposit of inert powder on the skin surface.
Examples Benoxyl, valisone and scalp lotion, calamine lotion (Zinc oxide + Ferric oxide).
Counseling Lotions and suspensions require a ‘Shake Well” label and if intended for topical use.
An “External use only” label.

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Liquid Dosage Form

Spirits
Spirits or essences are alcoholic or hydroalcoholic solutions of volatile substances prepared usually by
simple solutions or by admixture of the ingredients (contain 50% to 90% alcohol).
Spirits require storage in tight, light-resistant containers to prevent loss by evaporation and to limit
oxidative changes. Some of spirits are medicinal but mostly are used as flavouring agents.

Tinctures. Natural products or herbal extracts taken orally. They are extracted in alcohol.
Tinctures are alcoholic or hydroalcoholic solutions prepared by mixing chemical
substances like iodine. The alcohol content of the official tinctures varies from
10% to 21% with opium tincture USP; 74% to 80% with benzoin tincture USP.
Glycerin may be added to hydroalcoholic solvent to increase solubility of the
active content and reduce precipitation during storage.

Tincture is categorized as protectant. It is used to protect and toughen skin in

the treatment of bedsores, ulcers, cracked nipples, and fissures of lips and anus.
Tinctures require storage in tight, light resistant containers, away from direct
sunlight and excessive heat (may undergo photochemical change).

Topical tinctures. Iodine tincture, compound benzoin tincture and themerosal

tincture.

Iodine tincture. The iodine tincture is prepared by dissolving 2% of iodine

crystals and 2.4% of sodium iodide to an amount of alcohol equal to half the
volume of tincture to be prepared.

Benzoin tincture Prepared by the maceration in alcohol 10% of benzoin and lesser amounts of
aloe, storax, and tolu balsam totalling about 24% of starting material.

Astringents
Locally applied solutions that precipitate protein. The protein precipitates which
forms serve as a protective coat, allowing new tissue to regenerate underneath. It
causes constriction and reduces secretions therefore they can be used as
astringent. These substances that stop oozing, discharge or bleeding.
Common Zinc oxide used for diaper rash treatment and hemorrhoids. Calamine lotion used
astringents for cold sores or fever blister treatment and poison ivy.
Burrow's solution (Aluminum acetate) used for otitis externa, and dermatitis
treatment.
Calamine Calamine lotion is mixture of zinc carbonate or zinc oxide colored with ferric oxide.
lotion

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Collodions
Collodions are liquid preparations consisting of a solution of proxylin in a mixture
of ether and alcohol. When collodions are painted on the skin and allowed to dry
they leave a flexible film over the site of application.
Therapeutic use Collodions may be used to seal minor cuts and wounds or as a mean of holding a
dissolved drug in contact with the skin for a long time.
Counselling Keep away from fire

Emollients
Emollients are derived from animal or vegetable fats or petroleum products, used to
soften or protect internal or external body surfaces.
Emollients are fats or oils in a two-phase system (one liquid is dispersed in the form of
small droplets throughout another liquid).
Emollients soften the skin by forming an occlusive oil film on the stratum corneum, thus
preventing drying from evaporation from the deeper layers of skin.
Therapeut Emollients are employed as protective and as agents for softening the skin and
ic use rendering it more pliable in conditions like dry eczema, ichthyosis and psoriasis. They
also serve as vehicles for more active drugs.

Gargles
Gargles are aqueous solutions, usually in concentrated forms intended for use,
after dilution, for treatment of infections of oral cavity and throat.
Therapeutic use A gargle does not, however, act as a protective covering to mucous membranes.
Monitoring In the treatment of mucositis, try to avoid a gargle that contains a high
concentration of alcohol as it may produce irritation.
Examples Examples of gargles are thymol gargle, chlorhexidine gargle and difflam gargle.
Gargles may contain a drug to relieve sore throat such as Tantum (Benzydamine):
commercially prepared mouthwashes or saline solution (0.9% sodium chloride)
may be used for stomatitis.
Chlorhexidine: used for stomatitis, mucositis, and gingivitis. Caution: stains teeth
after excessive use. Use chlorhexidine 30 min before or after use of toothpaste.
Chlorhexidine can interact with fluoride and can stain teeth.

Humectants
Mechanism Humectants promote water retention due to their hygroscopic. They act by being
absorbed into the skin and attract water from atmosphere and serve as a reservoir
for the stratum corneum. Commonly used humectants are propylene glycol and
glycerin.

Liniments
Mechanism Liniments are viscous liquid containing substances possessing analgesic, soothing or
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stimulating properties when applied on the skin. They are usually made with a base
of oil, alcohol, or soap solutions.
Example. Methyl salicylate liniment.
Liniments should not be applied to broken skin

Syrups
Sugar in water is syrup.
Counseling. Generally syrup contain sugars solutions, caution diabetic patients and recommend syrup
containing artificial sweeteners such as aspartame, in place of sugar.

Elixir. Contain alcohol

Elixir are clear, sweetened, hydroalcoholic solutions intended for oral use and usually flavored to
enhance palatability.
Elixir is prepared for products that are soluble in water and alcohol. Elixir contains less sugar, less
viscous than syrup.

Rubbing alcohol
Rubbing alcohol contains about 70% of ethyl alcohol by volume, the remainder consisting of water,
denaturants with or without color additives and perfume oils and stabilizers. In each 100 mL it must
contain not less than 335 mg of sucrose octa acetate of 1.4 mg of denatonium bentoate, a bitter
substances that discourage accidental or abusive oral ingestion. It is used as rubefacient externally
germicide for instruments and skin cleanser prior to injection. This product is flammable stored in tight
container far from fire.

Isopropyl rubbing alcohol. Isopropyl rubbing alcohol contains about 70% of ethyl alcohol by volume,
the remainder consisting of water. Can be used as disinfectant.

Tips
1 Has low accumulation 2 Rate of diffusion 3. Burrow solution
.
4. disintegrating agents 5 Pc=octanol water o/w 6. first pass effect
.
7 Stokes equation 8 stability & solubility 9 all oils except
. mineral oil

1 alcoholic and hydroalcoholic 11 Tocoferol alpha 1 anionic surfactant

0 liquid mixtures 2
1 disintegrating agents 14 sodium lauryl sulfate 1 Sterile Water for
3 5 injection USP
1 small intestine>oral>mucus stratum corneum 1 capsule size 000
6 membrane>stomach 17 8
mixing of 2 subs. Leads to 20 glycerin 2 crystallization
1 lowering in melting point, 1
9 example includes camphor and
menthol
2 o/w emulsion
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2
• The definition of tincture is? ( )
• Sodium lauryl sulphate is? ( )
• High HLB values associated with? ( )
• What problem does not occur in suspension? ( )
• Fick's law describes? ( )
• The rate limiting step in ophthalmic drops ? ( )
• Partition coefficient is described as? ( )
• Drug with low volume of distribution? ( )
• The most commonly used humectants is? ( )
• Aluminum acetate is? ( )
• Eutectic mixture is? ( )
• Oils used for parenteral preparations? ( )
• Write the sequence of surface area in GIT ( )
• The largest size of capsule is? ( )
• The rate limiting step for the topical drugs ( )
• Water used in parenteral preparation is? ( )
• What is avoided in transdermal patch? ( )
• What is an example of anionic surfactant( )
• The tablets are disintegrated by? ( )
• Relation of sedimentation and particle size can be explained by? ( )
• What type of tocoferol has the strongest antioxidant properties? ( )
• Complexation can modify which two properties in a drug? ( )
• An example of biphasic include ( )

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38
Drug Delivery Systems
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Solvents in parenteral preparations like types water, and sterilization methods
• Asthma devices in children meter dose inhaler + spacer and nebulizers
• Ophthalmic prep preservatives, viscosity enhancers like HPMC

Route drug
Site/Tips
administration
Oral (PO) By mouth. Whenever possible, safest and most convenient route
Sublingual (SL) Under the tongue. When rapid effect is desired.
Parenteral Other than the gastrointestinal tract (by injection)
Intravenous Administered directly in vein. Aqueous solutions are used. Single small volume
(bolus) or large volume slow iv drip infusion.
Intraarterial Artery.
IM are given in deep into skeletal muscles, generally gluteal or lumbar muscles.
IM Drugs that irritate subcutaneous may be administered by IM.
Volume used is 2 to 5 ml. If require more than 5 ml, administered in divided
dosages at two different sites.

Intracardiac Heart
Instraspinal or Spine
intrathecal
Intraosseous Bone
Intraarticular Joint
Inrasynovial Joint-fluid area
Intracutaneous or Beneath the skin loose subcutaneous (hypodermic) tissue.
Intradermal or Subcutaneous Less than <2 ml volume is used. Liquids, or suspension are used.
Subcutaneous Intradermal. Injection in to the most superficial skin layer. Deliver only limited drug
volume, it is generally restricted to skin test and some vaccines.
Epicutaneous (topical) Skin surface
Transdermal Skin surface
conjunctival Conjunctiva
Intraocular Eye
Aural Ear
Intrarespiratory Lung
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Rectal Rectum
Vaginal Vagina
Urethral Urethra
Sublingual Under the tongue  fastest oral absorption

Bioavailability of parenteral dosage forms

Parenteral preparations
• Preparations intended to be administered parenteral should be sterile, pyrogen free and particulate free.
• Sterility testing are two common methods. Immersion (direct inoculation) and Membrane Filtration.
• Methods of removal of pyrogen are double distillation. LAL test and rabbit tests are used to determine
pyrogen.
• Test for particulate contamination is the light Obscuration Particle Count Test
• Parenteral packing integrity test is Package leak Tests

Parenteral Prep Requirements: Restrictions on buffers, stabilizers, and antimicrobial preservative. Do not use
coloring agents. Sterile and pyrogen free. Must meet compendia standards for particulate matter. Must be
prepared under aseptic conditions. Specific and high quality packaging.

Parenteral Prep Vehicles: Aqueous. Sterile water for injection USP (<1 liter), water for injection (>1 liter).
Non-aqueous. Glycerin, polyethylene glycol, and alcohol. Must not contain paraffin or mineral oil, and methanol.
Fixed oils. Restrictions on fixed oils. Must meet the requirement of iodine number and saponification number.
Iodine number: It represents the number of grams of iodine absorbed, under the prescribed conditions, by 100 g
of the substance. Iodine number indicated the presence of number of double bonds.
Saponification number: It represents the number of mg of potassium hydroxide required to neutralize the free
acids and saponify the esters contained in 1 g of the substance. Saponification number indicates the number of
ester functional groups.

Parenteral solvents: Water for injection, pea nut oil, cotton seed oil, sunflower oil, olive oil, corn oil, and canola.
Do not use mineral oils, and theobroma oil.

IV injection must not be a suspension because of the probability of blockage of a blood vessel.
IV. injection of high concentration of K+ may cause cardiac arrest.

Premixed products: Premixed iv solution contain both diluents and the drug already combined in
single unit-of-use iv bag or bottle. E.g. Minibags metronidazole, gentamycin, ciprofloxacin. LVPs (>100
mL). Heparin, KCl, lidocaine. Gloss bottles. Nitroglycerin.

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Intrapulmonary drugs
Intrapulmonary drug delivery devices includes Metered dose inhalers (MDI), diskus, turbuhaler,
handihaler and nebulizers.
Components of aerosols: Propellants, valves, containers
Formulation of aerosols: Solutions, suspensions, emulsions
Inhalation Therapy: Deposition of particles in the lungs.
Metered dose inhalers (MDI): Contain suspension or liquid. Suspension containing MDI should shake
before use. Safe propellant hydrofluorocarbons (HFA) or HFC. Aerosol flow rate 30 m/s or 100 km/h.
Shake before use. Do not exceed prescribed dose. Good for under 5 year old.

Dry powder inhalers (DPI) also known as turbuhaler:

• No propellant and no need to shake.
• Requires patient’s own inspiratory effort to form aerosol
• Powder is delivered only when the patient inhales.
• Useful in children above 5 years, teenagers & arthritic patients.
• Can be used open mouth and closed mouth technique.

Nebulizers: Turns an aqueous solution of drug into fine mist. Drug will be inhaled with normal
respiration. Medication reaches lower airways more effectively.
Two types. jet & ultrasonic
Jet: Cools during operation, Small aerosol particle size, Less expensive, More noise
Ultrasonic: Heats up during operation, Larger aerosol particle, More expensive, Less noise.

Example Composition Inhalation aerosol Example of Topical Spray

Drug…………………………. Albuterol (bronchodilator) Drug…………………………. Miconazole
Surfactant…………………… Oleic acid, and propylene Surfactant……………………. Glycol
Propellant…………………… HFC (HFA) Propellant……………………..Propane or n-butane
Co-solvent………………….. None Co-solvent…………………… Isopropyl alcohol
Type of output……………… Dry mist Type of Drug output……Wet mist
Example of Vaginal foam Choice of inhalation therapy
Drug: Nonoxenol-9 (Contraceptive) Infants -----------------Nebulizer
Surfactant……………………. Triethanolamine Children
Propellant…………………….. n-butane, and propane < 4 years----Nebulizer
Co-solvent……………………..None 4 year--------DPI/MDI/Spacer
Type of output……………..… Stable foam 7 years-------DPI/MDI
Adults-------------------MDI/DPI
Acute episodes-------Nebulizer

Ranking of various oral dosage (fastest → slowest)

• Solutions (ready for absorption)
• Suspensions (wetted and ready for dissolution)
• Powder [(dispersed + GI fluid → wet) absorbed]
• Capsules (dissolve gelatin cap first → then powder)
• Tablets (disintegration from tab. to smaller granulate then → powder)
• Sustained release tab (barrier of coating materials)

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Whenever a drug is more rapidly and more completely absorbed from a solid form, the rate-limiting
factor is the dissolution process.

Rectal Dosage forms

Rectal route may be preferred over oral route in order to avoid liver by first pass.
• Safe route if patient is vomiting, unconscious or unable to swallow (mainly applies to rectal).
• Often used for local effects e.g. hemorrhoids, local infections.
• Suppositories can provide systemic medication (diffuse through mucosa and transport the
veins and lymph vessels into systemic fluids or tissue. (by pass liver).
• Surfactants in suppositories increase drug absorption.

Rectal ointments: Ointments are generally used for the treatment of hemorrhoids. Some examples
are Preparations H, Anusol, Anusol HC, and Anugesic.

Rectal suppositories. Suppositories are topical dosage forms designed to soften when placed in the
rectum. They may be cylindrical or egg-shaped and are used for local action as laxative.
Suppositories should be protected from heat. Some examples Dulcolax or glycerin, analgesic, Anusol,
Preparation H.
Anti-inflammatory suppositories indomethacin or naproxen. Suppositories are also used for systemic
use when the oral route is either impossible or not desirable. Some examples of drugs available for
systemic use rectally antiemetics such as Gravol, and Stemetil.
Analgesics. Acetaminophen and ASA.

Rectal solutions or rectal suspensions (enemas): Enema is administered in a syringe or disposable

squeeze bottle with an applicator tip. Some examples: Systemic anti-inflammatory effect: 5-ASA
(Salofalk)

Vaginal dosage forms

Vaginal dosage forms include tablets, creams, aerosol foams, jellies, solutions and ovules
(suppositories) and the sponge. The ovule is shaped differently from that of a rectal suppository-the
laxative fleet enema are larger, more oval in shape, and the base is water-soluble.

Vaginal preparations: Most commercial vaginal suppositories use a base of polyethylene glycol o/w.
An excellent choice of diluents for a compressed vaginal tablet would be lactose.

Vaginal products: Vaginal dosage forms for contraception: Delfen Foam, and the sponge Protect Aid.
Some example of anti-infective: Monistat, Canesten, Flagystatin, douches, and Hormone
replacements.

Metronidazole (Flagystatin): Partner should be treated same time, it is important to avoid alcohol.
Metronidazole indicated for trichomonas associated vaginitis.
Miconazole: drug of choice in vaginal candidiasis in pregnancy. Cream is preferable over suppositories
and ovules. Cream effective decrease itching associated with vaginitis.

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Topical Dosage forms

Four bases are used: Hydrocarbons,
which are greasy to the touch Important concept!
(petroleum jelly) 1) Some products may be used in both the ear and eye
Absorption bases, which are also like Sofracort. While otic preps have a glycerin or PEG
greasy but allow the addition of base cannot be used in eye.
liquid usually water or dissolved 2) What type of topical preps requires sterilized preps?
chemicals in aqueous solution. Ophthalmic
Water removable bases, which are 3) Ophthalmic ointments have high contact time so high
oil-in-water mixtures, easily removed absorption than drops.
form the skin with water (Glaxal 4) Percentage of bioavailability from ophthalmic preps is?
Base) and water-soluble bases, 5%
which can be mixed with substances
that will dissolve in water.
(Polyethylene glycol bases).

Ophthalmic Ointments/Solutions/Suspensions: Cornea as a barrier to ophthalmic drug absorption.

Formulation. Isotonic, sterile and pH additive (should be formulated at a pH equivalent to tear fluid
value of 7.4.
Ophthalmic ointments are sterile ointments containing antibiotics or substances to relieve dry eyes.
Only sterile products are used in the eye. The advantage of using an ointment rather than a solution is
that the ointment allows increased contact time in the eye.

Ophthalmic ointments are packaged in 3 or 3.5 g tubes.

Examples Cetamide, Tobra-Dex, Garamycin. Sterile solutions and suspensions are used in the eye
(ophthalmic preparations) to treat infections, allergies, inflammation and dry eyes in the ears (otic
operations) to treat infection. Examples of ophthalmic preparations used in the eye Sulamyd,
Opticrom, Inflamase, prednisolone, and Isopto Tears.

Ophthalmic drops
• Voltaren. Cause stinging and burning, and blurred vision.
• Ketorolac. Cause stinging and burning
• Trifluridine. Store in refrigerator
• Pilocarpine. cause miosis
• Latanoprost (Xalatan). causes pigmentation, and enlargement of eyelashes.
• Latanoprost + Timolol (Xalacom).
• Some products may be used in both the eye and the ear, such as Sofracort, Cortisporin while otic
preparations have a glycerine or propylene glycol base and cannot be used in the eye.
• Examples of otic preparations: Cortisporin Otic, Garamycin Otic, Garasone Otic, Locacorten
Vioform, and Otic Drops.

Controlled/targeted delivery
An ideal controlled release mechanism for a device is the one, which exhibits a zero order drug
release. i.e. the release of drug is independent of time.

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Delayed release (SR) --> repetitive intermittent dosing of IR. (e.g. Bupropion SR).
Extended release (XL)--> maintain therapeutic levels prolong time (e.g. Bupropion XL)
Site specific target-->target to one organ location (enteric coated)
Receptor targeting--> target a drug receptor.

Conventional dosage forms, drug concentration raises rapidly, peaks, and then falls until the next dose
is taken.

Controlled delivery systems: Advantages of controlled delivery systems. Maintenance of optimum

therapeutic drug concentration in the blood or in a cell predictable and reproducible release rates for
extended periods of time enhancement of activity duration for short half-life drugs the elimination of
side effects, frequent dosing, waste of drug, optimized therapy better patient compliance.
Drug may be coated on small inert beads of sugar & starch. Some beads can then be coated with lipids
to delay release. Beads with different coating thickness can then be combined in a capsule to achieve
sustained release, e.g., the Spansule technology (Contac, Dexedrine).

Technological methods: Drug can be embedded in slowly eroding matrix, e.g., SLOW-K (KCl in a wax
matrix), SLOW-Fe etc.
• Two-layered or press-coated tablets for sustained release.
• Drug embedded in inert plastic matrix, e.g. Gradumet
• Drug complexes with ion exchange resins, e.g. Pennkinetic systems
• Floating capsules or tablets, e.g. slow release diazepam (Valrelease), a hydrodynamically balanced
(HBS) drug delivery system.
• Coating or sustained release tablets should not be crushed or chewed.

Osmotic release: Nifedipine (Adalat), and Concerta (Methylphenidate).

Liposomes: The Liposomes are lyotropic liquid crystals composed mainly of ampiphillic bilayers.
Liposomes have the advantage of primarily consisting of lecithin and cholesterol, which are materials
that occur naturally in the human body. Lecithin and cholesterol are also present in the body in large
amounts, and thus demand good bioacceptability. This liposome’s can entrap drugs and may be used
for drug targeting, sustained release, or reduced drug toxicity. Phospholipid can spontaneously form
concentric, bilayer lipid vesicles when dispersed in water. Can be processed into various types & sizes.

Transdermal delivery: involves diffusion of the drug through the skin. The drug properties that are
suitable for transdermal preps are drugs with short half life, lipid soluble drugs.
• Nicotine patch. volatile (may evaporate), Androderm, Estraderm, Habitrol, Nicoderm, Nitro-Dur,
and Estalis.
• Nitroglycerin patch. Use nitrate free period to reduce tolerance (apply 12 hours and 12 hours
without patch). Can be applied on chest. Avoid applying on lower extremities.
• Fentanyl patch. Effective for 72 hours.
• Estrogen patch. Do not apply on the chest. If it falls frequently apply new patch.
• Scopolamine patch. Apply behind the ear, effective for 3 days.
• Oxybutynin Patch. Anticholinergic drug for the treatment of urinary incontinence
• Tolterodine Patch. Anticholinergic drug.
• Clonidine Patch. Centrally acting antihypertensive drugs.

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Implants for drug delivery

Implantable drug delivery systems are being developed to take the place of traditional drug delivery
systems, such as pills and hypodermic injection.
Implantable systems that are currently available include Norplant and various pumps, such as insulin
pumps. The systems are designed to deliver drugs directly into the bloodstream at a controlled rate of
transmission.

Tips
1. it is rapid onset & no 2 8 to 12 hrs 3 drugs that act directly on the
first pass metabolism bronchi & inhalation
anesthetics
4. for drugs that cause GI 5 no shaking but 6 it is the most convenient to both
irritation and N, and prime the patient
uncooperative or and physician
unconscious patient
7. hydrofluoroalkane HFA 8 iv 9 the physical and
chemical characteristics of the
drug
10 the tissue mass, extent 11 it is the fastest acting 12 they provide continuous drug
. of ionization method administration
and no first pass
metabolism
13 im 14 ophthalmic and 15 injection in joints
parenteral
16 salbutamol, fluticasone, 17 the taste and or smell 18 into the spinal column
. budesonide, salmeterol and possible first pass
metabolism and slow
• What are the advantages of oral administration? ( )
• What dosage forms require sterile? ( )
• Intra articular injections ( )
• What propellant used in meter dose inhaler? ( )
• Nitroglycerin patch require nitrate free period for? ( )
• Meter dose inhalers that require shaking ( )
• Nitroglycerin spray require ( )
• What are the disadvantages of oral administration? ( )
• What is the advantage of IV drug administration? ( )
• What are the advantages of sublingual administration of a drug? ( )
• What is meant by the intrathecal administration of a drug? ( )
• Drug distribution into different tissues depends on which factors? ( )
• What is the most direct route of drug administration? ( )
• What factors must be considered in choosing a specific route of administration? ( )
• Which provides a more rapid absorption, IM or SC administration? ( )
• What type of drugs can be given by inhalation? ( )
• What are the advantages of rectal administration of drugs? ( )

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39
Pharmaceutical Analysis
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Chromatography methods like HPLC, GC, TLC
• Spectroscopic methods like mass spectroscopy, or NMR.
• Bioassays like ELISA, gel electrophoresis, western blot, eastern blot and
Polymer chain reaction (PCR) and RtPCR.

Chemical separation or purification techniques include, distillation, chromatography, extractions and

centrifuge.

Chromatography
Chromatography is a method of separation of mixture of chemicals that relies on differences in
partitioning behaviour between a flowing mobile phase and a stationary phase to separate the
components in a mixture. The commonly used chromatographic methods of analysis include: Gas
chromatography, HPLC, TLC, and paper chromatography.

Chromatography instrumental procedures

Liquid
Gas

Column Planar

GLC GSC
HPLC
TLC Paper

Normal phase (NR-HPLC) Reversed phase (RP-HPLC)

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Liquid Chromatography
Liquid chromatography (LC) is an analytical chromatographic technique that is useful for separating
ions or molecules that are dissolved in a solvent.

High Performance Liquid Chromatography (HPLC) Or High Pressure Liquid Chromatography

Used for non-volatile and thermally stable compounds to separates macromolecules, ionic species,
labile natural products, polymeric materials and high-molecular weight compounds.

Diagram.

Solvent Injector Columns

Detector Records
and Pump chromatogram

Mobile phase. Solvent such as methanol, water, ethanol and CCl 4 .

Stationary phase. Silica gel column.
Column. 4 to 5 mm heavy wall, glass-lined metal tubing or 10 to 30 cm.

Detectors
• UV-VIS photometers (diode array detector)
• Fluoviometric detector
• Electrochemical
• Refractometers (RI)
• Conductivity for ion chromatography
• Radiodetector

Parameter that affects resolution.

• Mobile phase. Nature of solvent should be compatible with substance.
• Solubility’s of mixture in mobile phase.
• Concentration of mixture substance.
• Stationary phase, thickness of silica gel, column size and pressure in HPLC.
• Temperature (gas and column chromatography).
• pH of solvent and flow rate.
• Detectors does NOT enhance resolution of separation of mixtures.

Gas Chromatography (GC)

Gas chromatography is a chromatographic technique that can be used to separate volatile organic
compounds. Example volatile liquids, oils and alcohols etc.
Mechanism. The organic compounds are separated due to differences in their partitioning behaviour
between the mobile gas phase and the stationary phase in the column.

GLC (Gas Liquid Chromatography)

• Mobile phase is gas for example, helium, argon, or nitrogen
• Stationary phase is liquid surface on solid

GSC (gas solid chromatography)

• Mobile phase: gas for example helium, argon, or nitrogen

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• Stationary Phase (solid)

• Used: For volatile and thermally stable compounds
Components of gas chromatography; Gas chromatography columns known as capillary columns, Oven,
Detector, and Recorders

Types of detectors in GC.

• TCDThermal conductivity Detectors
• FIDFlame ion detectors
• ECDElectron conductivity detectors.

Thin Layer Chromatography (TLC)

• A simple and rapid method to monitor the extent of a reaction or to check the purity of organic
compounds. The mobile phase is a solvent and the stationary phase is a solid adsorbent on a flat
support.
• Mechanism: Relies on capillary action

TLC Spray Reagent

• Ninhydrin is used for detection of amino acids, amines, and aminosugars.
• Ehrlich's reagent is dimethyl aminobenzaldehyde/hydrochloric acid reagent for detection of
amines, indole derivatives.

Paper Chromatography
• Stationary phase
• Stationary phase is cellulose paper (paper is made from cotton fibres and highly purified about
90% alpha cellulose).
• Properties of stationary phase: Highly hydroxylated polysaccharide, this has great affinity for water
and other polar solvents.
• The tightly bound water is actual stationary phase and as mobile phase passes over the surface of
paper.
• Mobile phase: The solvents used for paper chromatography analysis are similar to those employed
in other forms of chromatography.

Spectroscopic Methods of Analysis

Spectroscopic methods. Instrumental methods that are used to identify chemical structure and
analysis of drugs. The following instrumental techniques are commonly used in drug analysis and
structure determination of new and unknown chemical structures.

Spectroscopic Methods

Mass spectroscopy Ultraviolet light Nuclear Magnetic Other spectroscopy

(MS) spectroscopy Resonance Infrared (IR)
(UV/Vis) (NMR) Atomic Absorption (AA)
Mass Spectroscopy (MS)

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Mechanism. The basics mass spectrometry is that a charged particle passing through a magnetic field
is deflected along a circular path on a radius that is proportional to the mass to charge ratio, and m/e.
(Electronic ionization method).

General Diagram of a mass spectrometer

Collection &
recorder
electron beam

Radius of curvative

Neutral ionized mixed ion beam

Gas Molecules molecules
separated
magnetic field ion beam
Sample Vaporized

Inlet Inlet Mass Ion

System Source Analyze Collection
System

Vacuum Data
System Handling
System

Used in structural determination of unknown chemical structures. Detect molecular weight of

substance.
Advantage. This can detect trace amount of substances.
• Blood sample analysis (alcohol in blood)  GC-MS
• Pharmacokinetics analysis of drug samples.
• Detection of environmental samplesGC-MS
• Probably the most useful information you should be able to obtain from a MS spectrum is the
molecular weight of the sample.
• Used in detection and analysis of unknown chemical structures molecular weight of substances or
drugs.

Type of detectors in mass spectroscopy

• CI-MS; Chemical Ionization mass spectroscopy
• FAB-MS. Fast atomic bombardment mass spectroscopy
• EI-MS. Electron impact mass spectroscopy

Ultra Violet/Visible light spectrophotometer

• Wavelengths (λ) 190 and 800 nm

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• Ultraviolet radiation <400

• Visible light 400 to 700 nm
• Chromophore any group of atoms that absorbs light whether or not a color is thereby produced.
• Auxochrome. A group, which extends the conjugation of a chromophore by sharing of nonbonding
electrons.
• Bathochromic shift. The shift of absorption to a longer wavelength.
• Hypsochromic shift. The shift of absorption to a shorter wavelength.
• Hyperchromic effect. An increase in absorption intensity.
• Hypochromic effect. A decrease in absorption intensity.

Processes or Equipment Radiation

• Welding arcs UV, visible, and IR
• Lasers UV, visible, and IR
• Bactericidal lamps in ultra pure water systemUV
• Radiant heat sources; boilers, IR lampsIR

Infrared spectrophotometer
• Infrared  >700 nm
• Infrared light lies between the visible and microwave portions of the electromagnetic spectrum.
• Infrared light has a range of wavelengths, just like visible light has wavelengths that range from red
light to violet.

Atomic-absorption spectroscopy
Atomic-absorption (AA) spectroscopy uses the absorption of light to measure the concentration of gas-
phase atoms. The analyte concentration is determined from the amount of absorption.

The Beer-Lambert law

• The Beer-Lambert law (or Beer's law) is the linear relationship between absorbance and
concentration of an absorbing species.
• A = a (λ) * b * c
Where
• A is the measured absorbance
• a (λ) is a wavelength-dependent absorptive coefficient
• b is the path length
• c is the analyte concentration.

Nuclear Magnetic Resonance Spectroscopy (NMR). NMR techniques are used to identify unknown
chemical structure.
Magnetic Resonance Imaging (MRI). MRI is used to scan tumours, minor blood clots etc.
CAT scan (computer assisted tomography).

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Bio and Immunoassay Methods

ELISA, Western blot, and PCR.

Immunoassay are an assay (test) that detects antigens (Ag) or antibodies (Ab). Immunoassays
described into various types based on their different techniques such as radioimmunoassay, enzyme
immunoassays etc.
Radio immunoassay are more sensitive assay (0.0001 to 0.001 µg/ml, 0.1 to 1 ng/ml) .
This makes it suitable for measuring hapten size drugs and hormones in the blood, things you can't get
in large concentrations needed for precipitation or agglutination.

Enzyme Immunoassay (EIA) is a laboratory test that detects specific antigens or antibodies utilizing
enzyme tagged antigens or antibodies, and in the presence of a specific substrate, it produces a colour
change that indicates a positive reaction. Example ELISA.
ELISA. The name stands for Enzyme- Linked Immunosorbent Assay (ELISA). It is a useful and powerful
method in estimating ng/ml to pg/ml antigens (Ag) or antibodies (Ab) in the solution, such as serum,
urine and culture supernatant. Used for diagnosing viral infections.

Gel electrophoresis: It is a method that separates macromolecules either nucleic acids or proteins on
the basis of size, electric charge, and other physical properties.

Western blot Easter blot Northern blot Southern blot

Using antibodies For analysis of For detection of For detection DNA
separate mixture post translational RNA
of proteins. proteins, Lipids.
Blot consisting of a Blot consisting of a Blot consisting of a Blot consisting of a
cellulose derivative cellulose cellulose derivative cellulose derivative that
that contains spots derivative that that contains spots contains spots of DNAs for
of antibodies for contains spots of of RNAs for identification by suitable
identification by proteins for identification by molecular probe.
suitable molecular identification by suitable molecular
probe suitable molecular probe.
probe.
PAGE: Polyacrylamide gel electrophoresis system is used for protein and protein mixture separations.

Polymer chain reaction (PCR) is used for magnifying DNA. PCR utilizes Taq polymerase and this
produced by Thermos aquatics.

Titration’s
Non-aqueous solvents. Acid base titration in non-aqueous solvents. Three types of solvents:
Amphiprotic, non-ionisable, and aprotic or inert.

Amphiprotic: Autoprotolysis produce both an acid and base species, or solvent dissociates such that it
produces cation and anion species. Example: H 2 O, methanol, ethanol and acetic acid
H 2 O  H+ + OH-

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CH 3 OH  CH 3 O- + H+

Non-ionisable-with basic properties: No autoprotolysis, but solvent has a group that can react with
acids. No reaction bases. Only act to transport on pairs. E.g. pyridine, ethers, benzene, esters, ketenes,
and aldehyde

Protic Upon reaction provides H+ ion. Example: Methanol, Acetic acid. Water etc.

Aprotic or inert There is no reaction with acids or bases, they simply provide medium in which the
sample species or titrant are soluble (only contribute solubility).
Example: CCl 4 (Carbon tetrachloride)

Levelling effect Regardless of the type of acid and basis, the actual acid strength is actually determined
by the strength of H 3 O+.

Equilibrium reactions
• At equilibrium hydrolytic reaction
• The rate of forward reaction is equal to backward reaction
• Example. In aproteolytic reaction of acetic acid with water, the rate of forward reaction increased
as the hydronium ions are depleted or when acetate ions are depleted

Gravimetric Analysis
The quantitative determination of a substance by precipitation followed by isolation and weighing of
the precipitate.

The basic method of gravimetric analysis

A weighed sample is dissolved after which an excess of a precipitating agent is added.
The precipitate which forms is filtered dried or ignited and weighed.
From the mass and known composition of the precipitate, the amount of the original ion can be
determined.

Criteria for successful determinations

The desired substance must be completely precipitated. In most determinations the precipitate is of
such low solubility that losses from dissolution are negligible. An additional factor is the common ion
effect; this further reduces the solubility of the precipitate.

Example:When Ag+ is precipitated out by addition of Cl- the (low) solubility of AgCl is reduced still
further by the excess of Cl-, which is added, pushing the equilibrium to the right.
Ag+ + Cl- =<-> AgCl (s)

Extraction Methods
Liquid/liquid
• Examples of liquid/liquid extraction methods are fractional distillation, which functions based on
boiling points of solvents

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• Mixture of two volatile liquids can be separated using fractional distillation techniques
• Example: Ethanol in water, Hexanes in Chloroform
• Immiscible liquids: this mixture can be separated by using separating funnel.
• Example: Hexanes in water (Organic solvents in water)

Solid phase extraction (SPE)

• A solid sorbent material, typically an alkyl bonded silica, is packed into a cartridge or imbedded in
a disk and performs essentially the same function as the organic solvent in liquid-liquid extraction.
• Example,
• Reverse-phase SPE employed to extract non-polar compounds, pesticides for instance, from polar
samples such as water generally utilize a solid sorbent containing non-polar functional groups such
as octadecyl (C 18 ) or octyl (C 8 ) bonded silicas.

Tips
1. PCR 2. Molecular weight 3. purification and analysis of pharmaceuticals
4. GC-MS 5. protein separation 6. protein isolation
7. Enzyme linked 8. HPLC 9. UV, DAD, Fluorescent & RI
immunosorbent assay
10. Gas Chromatography 11. capillary action 12. amine, amino sugars and proteins
13. Salting in 14. Salting out 15. Detectors, printers
16. Detection of HIV 17. Mass Spectroscopy 18 Lyophilization (freez drying)
infection
• Pump is present in what type of chromatography? ( )
• Types of detectors used in HPLC? ( )
• Drugs present in blood samples can be detected by? ( )
• Increase in solubility by addition of salt is? ( )
• Decrease in solubility by addition of salt is? ( )
• Mechanism of TLC is based on? ( )
• Ninhydrin is used to detect? ( )
• What are the factors that does not affect resolution in HPLC? ( )
• What device is used for analysis and detection of volatile chemical in samples ( )
• Electron impact (EI) ionization mass spectroscopy is? ( )
• HPLC is used for? ( )
• ELISA is? ( )
• Enzyme linked immunosorbent assay (ELISA) is used for? ( )
• Western blot test for? ( )
• Gel electrophoresis separates? ( )
Electronic ionization (EI) mass spectorscopy results in well-established fragmentation pattern that
are useful in identification of unknown?
• What technique is used to dry wet powders, which are heat sensitive drugs

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www.Pharmacyprep.com Canadian Healthcare System

40
The Canadian HealthCare
System
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Role of governments in healthcare
• Canadian Health Act (CHA) five principles Comprehensiveness, Universality, Portability,
Public administration and Accessibility.
• Drug Benefit Programs. Federal drug benefit programs and provincial drug benefit
programs.
• Federal drug benefit programs covers natives, veterans, inmates, refugees and RCMP.
• Provincial drug benefit programs covers seniors over 65 yo, and social welfare recipients.
• Financial support for healthcare in Canada. Federal, and provincial taxes.

This chapter provides information about Canadian healthcare system; explore key concepts around
health care delivery system and health care professionals. This chapter is focus on Canadian health act
(CHA), the role of federal, provincial, & territorial government in health care.

Federal Provincial Municipalities

Making federal law and bill HealthCare (Medicare) Police/Fire/
International affairs Education Roads/Parks etc
Canadian safety Flu vaccination District health officer
Drug Approvals in Canada (Health
Canada) DIN,NPN
Public health Agency

RCMP Provincial police City/regional

Health Canada is a federal agency. it is responsible for drug quality, safety and efficacy
The Health Protection Branch (HPB) or The Health protection Food Branch Inspectorate (HPFBI) of
Health Canada regulates drugs imported into and manufactured for sale in Canada.

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The Canadian health care system

The Canadian health care system is universal health care, this mean that all citizens and immigrants
will have access to health care regardless of their ability to pay. All Canadian are insured on equality
basis and offered health in all ten provinces and three territories.

Canadian health act (CHA). Canada health act (1984) unanimously passed in parliament, with
adherence to the 5 principles, enforced by threat of withholding funds. Extra billing is banned as a
restriction on access.

Canadian health act five principles

• Universality
• Public administration
• Portability
• Accessibility
• Comprehensiveness

Universality All insured parties are entitled to equal access to essential services.

Public administration Healthcare insurance is to be administered on a non-profit basis by a public

authority responsible to the province and subject to audit. The Canadian healthcare delivery is
decentralized and offered for provincial delivery of care.

Comprehensiveness  The insurance must cover all insured services supplied by hospitals, medical
practitioners and essential services dentists. Each province determines which services are insured.

Portability  A series of obligations on provinces which essentially guarantee any Canadian resident
(after a maximum wait of three months upon first becoming a resident) access anywhere in Canada on
the same basis as local residents.

Accessibility  Charges or other obstacles must not impede access to insured services.

The CHA covers

• Medically necessary hospital services.
• Medically required physicians services.
• Medically or dentally required surgical-dental services requiring a hospital for proper performance.
• The coverage reflects the two-stage evolution of public health care insurance in Canada. The 1959
Hospital Insurance and Diagnostic Services Act and the 1966 Medicare Act respectively brought
hospital and medical insurance to the federal level.

CHA does not cover

The following services are not covered under the CHA. Services delivered by health-care
professionals other than doctors, particularly outside of hospitals (some provinces do cover some
of these services, but are not obligated to do so under the CHA). Services in sectors outside the
hospital. These include long-term care facilities and home care. Pharmaceuticals, rehabilitation
services and dental care are also not covered when provided outside of hospitals.

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Drug benefit program. Provincial drug benefit programs and Federal drug benefit programs

Provincial Drug Benefit Programs covers. People age over 65 year old and Social Assistance (welfare),
disabilities. Long term illness.

Federal Drug Benefit Programs covers

• Natives or aboriginals (covered by NIHB)
• Inmates
• Refugees?
• Veterans
• Royal Canadian Mounted Police (RCMP)

Non insured health benefit (NIHB) programs

The role of federal government in health care. The federal government sets and administers national
principles of healthcare system through Canada health act. Federal government gives funds to
provincial and territorial health care services through fiscal transfers.

Delivers health care services to specific groups e.g. first nations (aboriginal), inuits. Canadian forces
and veterans, refugee claimants and penitentiary inmates, and RCMP. Provides other health related
functions such as public health/health promotion programs and health research.

Role of provincial and territorial health care as CHA principle is public administration this means the
administration and delivery of health care services is the responsibility of each province and territory.
Provinces and territories fund health services with assistance from the federal government in the form
of transfer payments and some times equalization payments.

Some examples of essential services that offered by provinces and territories are Physicians, diagnosis,
and other health care services in primary clinics and emergency services in hospitals.

Drugs coverage plans for specific groups, such as seniors, and social assistance. Some provinces have
supplementary health benefits.

Federal Health Portfolio: The Minister of Health is responsible for maintaining and improving the
health of Canadians. This is supported by the Health Portfolio which comprises;
• Health Canada
• Public health agency of Canada
• Canadian Institute of health research
• The Patented Medicine Prices Review Board
• Canadian Food Inspection Agency

Public health Agency of Canada

• Health promotion and disease prevention
• Health promotion is the process of enabling people to increase control over, and improve their
health. Disease prevention focuses on efforts to avoid disease and injury.
• provincial plans

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Some examples of the disease prevention include smoking cessation programs, breast cancer
screening (mammogram), Pap smear screening, prostate specific antigens (PSA) and colonoscopy.

Healthcare financing: Provincial, Federal, health premium and charities.

Distribution of health Expenditure in Canada

Distribution of funds %
Hospital 29.9%
Other institutions 9.9%
Physician salaries 12.8%
Other professionals 10.7%
Drugs (Rx and OTC) 17.5%
Other health spending 6.1%
Public health 5.5%
Capital 4.2%
Administration 4.1%

Canadian health human resources 2010

Total physicians in Canada ~80,000 The third highest public sector expenditure
Total registered nurses in Canada ~240,000
Dentist/dental hygienist 45,554 The highest private section expenditure
Pharmacist 38,700
Optometrists 4,841
Source National Health Expenditure Database, Canadian Institute for Health Information

Tips
1. Pharmaceuticals 2. Non essential services 3. Federal
4. Provincial or territories 5. Comprehensiveness 6. Universality
7. Portability 8. Public administration 9. Accessibility
10 Natives or aboriginals 11 Inmates 12 Refugees
13 Veterans 14 RCMP

• What are the five Canadian health act principles? ( )

• Federal Drug Benefit Program covers ( )
• What is not covered in CHA? ( )
• Funding for healthcare system is paid by? ( )

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41
Pharmacy Regulations
Questions Alerts!
Common questions in pharmacy exam is to ask!
• National Drug Model or Harmonized Drug Model. NAPRA categorized drugs into Schedule
I, II, III and unscheduled drug.
• Food and Drug Act (F&DA) and Control Drug Substance Act (CDSA) regulates narcotics,
benzodiazepine & targeted substance, and control substances.
• Narcotics are categorized as straight narcotics, narcotic preps, and exempted narcotics.
• Benzodiazepine and targeted substances like all benzodiazepine
• Control substances have 3 parts. The part 1. CNS stimulants part 2. barbiturates part 3:
anabolic steroids.

Canadian Federal Regulations

Control Drugs and Food and Drug Act NAPRA Tips
Substance Act (F&DA) National
(CDSA) Association of
pharmacy
regulatory
authority
Narcotics, BZDs, Manufacturing Pharmacy
Control drugs, conditions and profession
sales, Rx and advertising. regulation sales
disposing.

Schedule I Schedule A
Schedule II Schedule B
Schedule III Schedule C
Schedule IV Schedule D
Schedule V Schedule E
Schedule VI Schedule F part 1 Schedule 1 Schedule F part1. Prescription drug
advertisement standards
Schedule F Part 2 FDA part 2. Veterinary drug

Schedule VII Schedule G

Schedule VIII Schedule H
Schedule 2 Behind the counter (BTC), under the

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counter
Schedule 3 Over the counter or self selection area or
10 meter rule
Unscheduled Corner store

Federal regulations: Three federal regulations are F&DA, CDSA, and NAPRA applies to pharmaceuticals
in Canada.

Food and Drug Act (F&DA). This federal legislation controls the manufacture of all drugs in Canada.
Also, the act controls manufacturing conditions, packaging, advertising standards and the sale of
foods, drugs, cosmetics and therapeutic devices. As with all the laws in Canada, the law exists to
protect the consumer or the public. Drugs regulated by the F&DA are grouped into A to H schedules.
• Schedule A. Disease which treatment may not permit to public.
• Schedule B. Describe official standard.
• Schedule C. Radiopharmaceuticals. Drugs other than radionuclides for use in preparation of
radiopharmaceuticals.
• Schedule D. Allergic substances, vaccine, blood and blood derivatives.
• Schedule F. Food and prescription drugs. Advertisement standards.
• Schedule G. Controlled drugs
• Schedule H. Restricted drugs

The Controlled Drugs and Substances Act (CDSA). The Controlled Drugs and Substances Act, 1997, is an
act sets standards for the control of narcotics, controlled drugs and targeted substances. It is a federal
act and the strictest of all the acts that govern the pharmacy industry.
Drugs regulated by the CDSA are grouped into 8 schedules.
• Schedule I. Narcotics, opium poppy, cocaine, phenylpiperidine (pthedine)
• Schedule II. Cannabis and cannabis preparations
• Schedule III. Amphetamines, methylphenidate, LSD plus other listed psychoactive substances.
• Schedule IV. Barbiturates, specific anorexiants, benzodiazepines, and anabolic steroids.
• Schedule V. Phenylpropanolamine and others
• Schedule VI. Ephedrine, ergotamine, pseudoephedrine and others
• Schedule VII. Cannabis that serves enforcement purposes regarding possession and trafficking.
• Schedule VIII. Cannabis that serves enforcement purposes regarding possession and trafficking

Narcotics regulations have categorized as straight narcotics, narcotic prep, and exempted narcotics.
Straight narcotics. Opioids like morphine, codeine, methadone, fentanyl, Suboxone, OxyNeo, Tylenol #
4 (acetaminophen 300 mg + codeine 60 mg), ketamine etc.
• Given by written Rx only.
• No repeats
• No Rx transfers
• Need sales report

Narcotic preparations or verbal narcotics. opioid + 2 non opioid. Tylenol # 2, (acetaminophen 300 mg+
codeine 15 mg + caffeine 15 mg). Tylenol # 3 (acetaminophen 300 mg + codeine 30 mg + caffeine 15
mg), Fiorinal c 1/4 , Fiorinal C1/2
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• Given by verbal or phone

• No Repeats
• No Rx transfers

Exempted narcotics or OTC narcotics. Opioid + 2 non opioid

Tylenol # 1 (acetaminophen 300 mg + codeine 8 mg + caffeine 15 mg) (codeine 19.6 mg/30 mL).
No Rx needed

Benzodiazepines and Targeted substance. All benzodiazepines are included. Can be unlimited refills.
One transfer is allowed. Prescription expires in one year.
• Can be verbal or phone
• Can be transferred once only
• Can have unlimited refills
• Rx expires in a year.

Control drugs. The drugs are categorized as control drug part 1 to 3.

• Part 1. CNS stimulants like amphetamines, dexamphetamine, and methylphenidate require sales
report .
• Can be given verbally
• Repeats are allowed(Refills are allowed with specified intervals).
• No Rx transfer
• Need to keep sales report

• Part 2. Barbiturates (Phenobarbital, thiopental, primedone), Fiorinal

• Can be given verbally
• Repeats are allowed
• No Rx transfer

• Part 3. Androgens (anabolic steroids performance enhancing drugs), Androgel

• Can be given verbally
• Repeats are allowed
• No Rx transfer

National Association of Pharmacy Regulatory Authorities (NAPRA) or The Harmonized

National Drug Model. The National Association of Pharmacy Regulatory Authorities (NAPRA) is an
association comprised of mainly the provincial regulatory authorities (the registrars of each province
that has a college of pharmacy that licenses and regulates its member pharmacists). NAPRA is
incorporated under the Canada corporation act as a voluntary, not for profit associations. Mission of
NAPRA is to evaluate the activities of the pharmacy regulatory activities by representing the common
interests of the member of organizations. Serving as a national resource centre and promoting the
national implementation of progressive regulatory programs and standards.
All provinces have similar conditions of sale.
• Schedule I Require prescription.
• Schedule II Pharmacist intervention  behind the counter or under the counter
(recommended by pharmacist).

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• Schedule III  Pharmacist intervention  Over the counter, self selection or 5 to 10 m rule.
Lock and leave.
• Schedule U  Unscheduled Drugs  Can be sold from any corner store.

Schedule I
The Highest risk, these drugs require a prescription for sale and are provided to the public by a
pharmacist in a pharmacy. Most drugs in schedule F (FDA) and some drugs that were listed under
Schedule E. Some drugs are listed in Schedule I of the NAPRA schedules, but are not listed under
Schedule F, The Food and Drugs Act Regulations.

Schedule II
Prescription is NOT required. Requires professional intervention from the pharmacist and possible
referral to a physician. Need direct pharmacist supervision. The decision to sell a schedule II product
must be made by the pharmacist. (e.g., injectable epinephrine for anaphylactic reactions).
The drugs are retained in a non-patient access area (behind the counter) no opportunity for patient
self-selection and have no public access to the public.

Example.
• Tylenol # 1 (Codeine 8 mg + Acetaminophen 300 mg + caffeine 15mg)
• Nitroglycerin SL
• Regular Insulin
• Epipen
• All Vaccines
• Iron supplement (>30 mg)
• Lactulose
• Vitamin D 3 drops
• Vitamin B 12 inj.

Schedule III. Over the counter

• The lowest risk however, may present risks to certain populations.
• Prescription is not required. Need direct pharmacist supervision.
• These drugs may be stored in a self-selection area of the pharmacy
• The pharmacist should be accessible, and approachable to assist the patient in making an
appropriate self-medication selection or to refer physician.
• Example. Plan B. Emergency contraception

Unscheduled Drugs
• May be sold from any corner store.
• Labelling is considered sufficient to ensure safety of drug.
• No pharmacy knowledge required.

Pharmacy related professional associations in Canada

• Canadian Pharmacist Association (CPhA) (www.pharmacists.ca)
• Voluntary national association.
• Identify, respond to emerging issues of importance to the profession, assisting and acquiring
new technologies and using information.
• Create educational and professional development tools.
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• CPhA publications include:

• Canadian Pharmacy Journal (CPJ)
• Compendium of Pharmaceutical Specialties (CPS)
• Therapeutic choices (TC)
• Patient selfcare (PSC) or Therapeutic Choice for Minor Ailments.
• Compendium of patient self-care products (CPSP)
• E-therapeutics

Canadian Society of Hospital Pharmacist (CSHP)

• Voluntary national association.
• Develop continuing education programs, residency training programs.

Institute of Safe Medication Practices Canada (ISMP). Gather information about medical incidents and
develops, recommendations in Canada.

Adverse Drug Reaction. Reporting (ADR reporting). New side effects and rare serious side effects of
drugs should be reported through ADR forms to manufacturer and Health Canada's "MedEffect"
program.

Tips
Find answers from the table.
1 Institute of Safe Medication 2 NAPRA 3 CPhA
Practices Canada (ISMP)
4 Narcotics 5 Benzodiazepine & Targeted 6 Control Substances
Substance

• National Association of Pharmacy Regulatory Authority ( )

• Examples of pharmacy associations, where pharmacist can be a member? ( )
• Examples of medication incident reporting systems in Canada? ( )
• Who regulates pharmacy profession in Canada? 
• Who regulates pharmacist and its members in Canada? 
• Morphine, codeine, meperidine are regulated under ( )
• Lorazepam, and Diazepam are regulated under ( )
• Methylphenidate and amphetamine are regulated under ( )

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42
Social, Behavioral,
Economics Aspects of
Pharmacy Profession
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Patient behavior models toward therapy. Transtheoretical model.
• Pharmacist should always think as professionals
• What factors that effects on patient compliance on medication therapy?

Professionalism is described as the competence and skill expected and required of a professional.
Professions have a formal knowledge base that is continually upgraded and practitioners usually
require a long period of preparation and hands on training before they become independent
practitioners. To become professional a candidate must meet certain educational standards, usually
these set by regulatory bodies.

Professions are committed to the public through their code of ethics. Healthcare professions are
constantly changed with latest developmental technologies, identification of new diseases &
treatments consequently there is emphasis on adopt to change and meet the rising expectations.

• Personal attributes of professionals

• Practice ethics and high moral standards
• Reflection and self-awareness.
• Responsibility and accountability of actions.

• Cooperative attributes of professionals

• Respect for patients.
• Working as team.
• Taking social responsibility.

A report on professionalism in medicine, the CMA (2001) states that, professionalism is:
• A strong commitment to the well being of others.
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• High moral, ethical, integrity standards.

• Mastery of body of knowledge and skills and continue education, or lifelong learning.
• A high degree of autonomy.

Professional boundaries: Professional boundaries are the defining lines that separate the
professional relationship from any other behavior. The professional relationship is a
purposeful relationship in which the client’s healthcare needs are priority. There are warning
signs, which can prompt professional. It is health professional responsibility identifies and
deals with boundary of violations if they arise.

Patient and pharmacist relation is covenant. (trust worthy, privacy, confidential)

• Some warning signs that professional boundaries are being crossed are:
• Noticing sexual content in interactions with the client.
• Favouring one client’s care at the expense of another’s.
• Giving/receiving gifts or continued or continued contact after discharge.
• Acting and or feeling possessive about the client. Giving special attention, treatment to
this client, which differs from that given to other clients.
• Denying the fact that you have crossed the boundaries from professional relationship to
non-professional relationship.

Reporting requirements. Reporting wrong behavior of healthcare professional protect public

and reputation of healthcare system. Each regulatory body have set different requirement for
reporting by the members of the profession.

Professional expectations. Public expect professional to offer activities with responsibilities

and the best care.

Here are some situations you may be expected to report.

• Sexual abuse of patients
• Misconduct, incapacity, incompetence
• Unsafe practice

Reporting requirement about abused patients. Sexually abused adult patient, pharmacist should
report or give contact number of support groups or support agencies to patient.

Reporting requirement about sexually abused child. Contact child associate society (CAS).

QAlerts!
Patients centred care values
• Respect. Respecting patients, wishes, concerns and strength
• Human dignity. Caring for patients as whole or unique
• Experts. Patient are experts of their own lives
• Timelines. Needs deserve a prompt response

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Regulated health professions in Canada

• Pharmacist
• Physician
• Physiotherapist
• Chiropractor (spine)
• Respiratory therapist
• Podiatrist (Chiropodist) or Foot doctor
• Registered Massage Therapist (RMT)
• Optometrist
• Midwife
• Veterinarian

Prescription scope of practice of some healthcare professions

• Pharmacist
• Physicians
• Veterinarians
• Dentists
• Registered Nurses
• Midwife
• Optometrist

Health Belief Model (HBM): It was first proposed by Rodenstock and later modified by Becker.
According to this model, the authors have hypothesized that people generally do not engage in
preventive healthcare practices or participate in health detection and screening programs unless they
view themselves vulnerable and/or have certain kinds of health relevant problems.
• There are three categories of behavior related to healthcare, these include:
1. Health behavior
2. Illness behavior
3. Sick-role behavior
Health behavior: It is defined as any activity undertaken by an individual who believes himself or
herself to be healthy, for the purpose of preventing illness.
• Weight reduction screening program
• Exercise program
• Stress reduction
• Regular self-examination for breast or testicular cancer
• Change in diet to reduce fat or cholesterol consumption

Illness behavior: It is defines as any activity undertaken by an individual who believes he/she may be
ill.
• Discussing health problems with a family member, friend or pharmacist
• Making an appointment to see physician
• Self testing to determine blood pressure or blood sugar level
• Experimenting with OTC products

Sick-role behavior: It is defined as an activity undertaken by an individual who considers them to be ill
or who have been diagnosed by a health professional as being ill.
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• Following medical advice

• Taking medication as prescribed
• Selecting an appropriate OTC product
• Staying home from work or school

Transtheoretical model
Pre-contemplation
(Not thinking about, taking information..)

Contemplation
(Thinking about taking medication in 6 mo)
(Motivate and assist)

Preparation
(Getting ready to take medications)
(Show and tell), Set quit date

Action
(Taking medications)

Maintenance. Support
(Has been taking medication for past >6 mo)
(4 or more session)

Termination (Relapse. Don’t give up)
(No longer to take medications)

Tips____________________________________________________________________________
• The transtheoretical model of behavior change is starts with precontemplation & ends up with
termination.
• Health behavior is defined as any activity undertaken by an individual who believes himself or
herself to be healthy, for the purpose of preventing illness.
• Professionalism is described as the competence and skill expected and required of a professional.

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43
Pharmacy Management
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Types of pharmacy ownership and formats of pharmacy
• Financial statements like income statement and balance sheet
• Human resources management and delegation
• Inventory management (calculating turnover rate)

Pharmacy management in the community pharmacy

Pharmacy management in retail stores comprises several business issues, those discussed include:
terminology commonly used in pharmacy business. Starting and managing pharmacy business,
financial management, human resource management, merchandise and inventory management.

Starting and managing a pharmacy business

Starting any business requires clear understanding and knowledge of the business. However, it is clear
that lay people start pharmacy business. Like any other business, starting pharmacy business requires;
business plan, organizing, staffing, and budgeting.

Business plan
Business plan comprises. Business structure, Market area analysis, Business products and services,
Competitive strategy, Positioning, Financing, Human resources, Operation and monitoring of
performance.

Types of business ownership

Sole proprietorship
• Advantage. Sole owner, low start up cost
• Disadvantage. Unlimited liabilities

Partnership
• Advantage. Skills and knowledge can be shared
• Disadvantage. Rate of conflicts is high.

Corporations and Limited Liability Companies (Inc). The most common business form, business name
often ends with “Inc”.
• Advantage. Legal entity, several directors (several owners), and limited liabilities.
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• Disadvantage. Higher government involvement.

Franchises . Associate franchises or banner franchises.

Associate have fixed term and payment plan from franchise corporations.
Owner of specific franchise location
Fixed and secure salary
Additional bonus or commission on performance.
No capital investment (do not own physical assets)
Central distribution

Banner franchises own locations and pay franchises fee or commission to corporations.
Capital investment because you own physical assets.
No fixed salary
Franchise provide name and marketing
No central purchase

TYPES OF PHARMACY OWNERSHIP STRUCTURES INCLUDE Retail pharmacy, Banner pharmacy, Chain
pharmacy, Franchise pharmacy, Food store pharmacy, Mass merchandise, Specialty pharmacy, mail
order pharmacy and central fill facilities (in hospital).

BUSINESS LOCATION ANALYSIS.

Methods applied in locating community pharmacy decision focused on.
• Region. Broad geographical area example country, and provinces.
• Market area analysis. Basic information about market like population, sites consideration, and
trading areas.

Population. Trading area, business area, and market area analysis. Population is of interest to business
and professional practice.

Site considerations. There are scientific methods (techniques) to assess the site location.

Trading area. Once location decisions are made regarding regional and market area, it is necessary to
select particular trading area, type of retail operation desired. Example outlets, supermarkets,
discount stores, national departmental stores (already established stores).

Site considerations: Important consideration in site selection is the relationship of cost to productivity.
Physical characteristics of space in a building under consideration should be scrutinized. The shape of
the space, its width and depth, exposed pipe and ductwork. Parking is a key concern. Techniques in
assessing site locations. The use of ratios as rule of thumb is fairly common. Another rule of thumb
deals with convenience and distance. Example sales per square feet.

Financial Statements. There are three basic financial statements. A balance sheet, an income
statement and a statement of retained earnings.

Income Statement or profit and loss statements

Income statement is an indicator of sales, total sales, cost of the good sold, gross margin, expenses,
total expenses, profit (net income), profit and loss statements.

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• Unit price x unit volume = Sales

• Unit volume x unit cost = Cost of goods sold
• Sales – cost of goods sold = gross margin or gross profit
• Gross margin – expenses = Net profit

Balance sheet. Balance sheet is a important indicator of assets and liabilities. Balance sheet is an
indicator of current assets (cash, current inventory, prepaid expenses), total current assets (fixture,
furniture), liabilities (account payable), and long-term liabilities (over one year).

• Total liabilities. Net worth = assets – liabilities.

• Cash + Account receivable + Inventory + Prepaid expenses = Total Current Assets
• Total current assets + Fixed assets = Total Assets
• Accounts payable + Notes payable + Accrued expenses = Total current liabilities
• Total Current liabilities + Long term liabilities = Total liabilities
• Total liabilities + net worth (owner equity) = Total liability and net worth

Retained Earnings Statement. The

Retained earnings statement indicates business retained earning that includes dividend payments
(share profit to share holders) that will reduce retained earnings, and net income that will increase
retained earnings.

Basic Management Principles

Basic Management Functions includes
• Recruiting/Staffing/Human Resource Management
• Accounting
• Strategic Planning/Organizing
• Purchasing/ Negotiating
• Inventory/Merchandising
• Marketing
• Dealing with regulatory officials

Recruiting/Staffing/ Human Resource Management

Described three commonly used steps in human resources. Job analysis, position description and job
description.

Job Analysis
Job analysis is a concise and factual study of pharmacy’s staffing need. The scope of each job must be
delineated, anticipated problems outlined, and hierarchy of position established.
A thorough job analysis will possess all areas of the work to be done, and alert the pharmacy owner on
duplication of functions. On long run, it will determine the responsibility of each employee and help
prevent conflict.

Position Description (Job advertisement). The position description outlines the main components of
each position. A good position description should be relatively short (no more than two pages).
General description of the job includes. Nature and the scope of the position, the main areas of
responsibility, required qualification, experience, and other job related skills.

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Job description. The detailed job description should list, the entire task to be accomplished, in order
of importance and described in detail.

Pharmacists manager are responsible for the supervision of the activities of pharmacy and non-
pharmacist staff in their activities of pharmaceutical services. This is useful in establishing the priorities
of job functions within each position.

A pharmacist manager maintains appropriate job description. Ensure adequate staff coverage for
pharmacy activity levels.

Delegation. Authorizing job to others. The principle of delegation consists of three components
responsibility, authority, and accountability.
• Responsibility. Assigning a task or a project.
• Authority. Given certain authority to operate a business. Like hiring personnel’s.
• Accountability. Manager or staff pharmacist is accountable for completion of task or project.
scope of pharmacy technician?

Employee motivation. The manager who supervises, controls, and motivates a management team.
Basic principles of employee relation and motivations aspects are described by Maslow’s hierarchy.

Maslow’s theory describes that every person has five basic levels of needs. Physiological needs, Safety
and Security, Social needs, Esteem Needs, Self-actualization needs.

Physiological needsthe most basic level

Safety and SecurityPerformance report

Social needs every employee wants to become part of the group.

An employer may ask the following questions: What degree of sharing of information about the
business and it goals will be?

Esteem NeedsIf the three levels are satisfied, employees will become interested in addressing
higher levels, through recognition of groups as leader or experts in a particular area.

Self-actualization needsthis is the highest level of needs, wherein employees will strive toward
greater accomplishment and responsibility, because it gives them personal satisfaction.

Workplace safety
Workplace safety and Insurance board (WSIB)
Workplace Hazardous Materials Information Systems (WHMIS)
Material Safety Data Sheet (MSDS)
Spill kits

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Risk Management

Strategic Planning
SWOT Analysis
• SWOT (Strength, Weaknesses, Opportunities, Threat) analysis.
Strength Weakness

Opportunity Threat

Project Management: The project management functions, risk management, human resource
management, and communication management.

Quality Management: Four principles of quality management "P-D-C-A" Plan, Do, Check and Act.

Merchandising. Visual selling or visual display merchandise using floor plan (Plannogram).

Inventory and merchandise management

• SKUs. Stock keeping unit of each size, strength, format of stock items in one unit.
• Individual items of inventory are referred to SKU.
• UPC. Universal product code.

ABC analysis (Pareto’s law).

• Category A. 20% of products stocked represent 80% of the inventory cost.
• Category B. 15% of the products represent 15% of the inventory cost.
• Category C. 65% of the products stocked represent 5% of the inventory cost.
• By closely monitoring the 20% of the items in category A, control is gained over 80% of the
inventory costs. Identify your top 20% SKUs and maximize inventory control efforts on these.
Some of the items in the 80% category of SKU should be probably not be stocked or sold on a
special order basis.

Third Party Insurance. The payment system can be classified into two different categories.
Retrospective payment and Prospective payment.

Retrospective payment (reimbursement) System. In this type of payment service, payment is

generally made after the service has been provided by the hospital. The payment depends on the
service actually provided by the hospital. The payment depends on the service actually provided by
the hospital during the patient’s stay. There is little incentive for a hospital to keep a patient in the
hospital for long because payment increases as more costs are incurred. It is not preferred by third
party insurances.

Prospective payment (reimbursement) system (PPS). This was introduced in 1982. A form of
payment (reimbursement) system usually pays the hospital on the basis of DRG (Diagnostic Related
Group) services. DRG includes lists of different kinds of illnesses and a fair amount of cost is required
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to treat such illnesses. Under this payment service, the hospital will reimburse a predetermined
amount specific to the DRG in which the patient is classified. This single payment will cover the entire
episode of care regardless of the patient’s stay in the hospital, the number of tests performed, or the
number of drugs that are used.

Commercial third party insurances: They offer a variety of services with the condition that an initial
certain amount of money should be spent by the consumer which is known as “deductible”. Also,
most of them do not cover charges for certain types of services. They also collect the prepaid fixed
monthly fees from the enrolled customers.
Maximum allowable cost (MAC): The maximum amount that will be paid by a third party to a
pharmacy when the drug is available from more than one source.
Estimated acquisition cost (EAC): the third party estimate of the prices paid by a pharmacy for a
particular drug product.
Actual acquisition cost (AAC): The actual price paid by the pharmacy after all trade, volume and cash
discounts.
Average wholesale price (AWP): The published list price of a particular product.

Cash flow: a summary of cash receipts and disbursements of a business, for a defined period of time.

Cash management. freeing up funds for operating purposes by minimizing assets and maximizing
liabilities and specifically accounts payable.

Coinsurance: It is one type of cost sharing plan in which patient pay a specific percent of all expenses.

Co-payment: It is one type of cost sharing plan in which patient has to pay fixed amount each time a
service is provided. OR patient pays fixed amount for each prescription.

Deductible: It is one type of cost sharing plan in which patient has to pay a specified amount during a
specific period of time. Before benefits are paid by third party.

Business Indicators and Financial analysis

Functions of ratios that indicates overall financial position of pharmacy:
Ratios indicating profitability
Ratio indicating efficiency
Ratio indicating liquidity and solvency
Ratio indicating financial position

Ratios indicating profitability:

• Net profit to net sales (NP:NS): The normal ratio lies between 3 to 7%.
• Net profit to total assets (NP:TA): The normal acceptable ratio lies between 10 to 15%.
• New profit to inventory (NP:IN): The normal acceptable ratio lies between $0.21 to $0.27.
• Net profit to net worth (NP:NW): The ratio lies between 20 to 25%, and 15% is acceptable for older
pharmacies and 40% is attainable for newer pharmacies.

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Ratio indicating efficiency

• Inventory turnover rate (IN:TOR). It is normally calculated by dividing the cost of goods sold by
the average beginning and ending inventory. The inventory turnover rate should be 4 as a
minimum, with a target of 6 or higher. Theoretical number of times during a special period, usually
one year, that inventory is bought and completely sold.
• Average turnover rate is for retail pharmacy 4 min and 6 max or more. For hospitals turnover rate
is 8 to 10.
• Inventory turnover rate = Cost of goods sold/average inventory capital .

or
Inventory turnover rate = Cost of goods sold
Beginning inventory (opening stock) + End of inventory (closing stock)
2
Example if inventory purchased two times a year, one at beginning of inventory and end of
inventory.

Net sales to networking capital (NS:NWC). The normal ratio range is 4 to 8. Ratios greater than 8 are
considered inadequate capitalization or overtrading. A value below 4 indicates under trading or too
much capitalization.
Net sales to inventory (NS:IN). The ratio normally ranges from 6 to 9.

Net sales to net worth (NS: NW): The normal ration range is from 3 to 8. Greater than 8 is considered
under capitalization and overtrading while below 3 indicates under trading.
Net Sales to net worth = Net sales/ Net worth
Account receivable collection time (A/R CT): This ratio is a direct measure of efficient credit
management. Normally, a 30-day collection period is a reasonable target.

A/R =Year end account receivable/ Mean credit sales per day

Account payable remittance time (A/P RT): This is normally calculated by dividing year end accounts
payable divided by mean credit purchase per day.

A/P = Year end account payable

Mean credit purchase per day

Ratio indicating liquidity and solvency

Liquidity normally measure’s a pharmacy’s ability to meet its current liabilities with little or no
interruption in the regular conduct of business.

Solvency measures a pharmacy’s ability to meet current liabilities with moderate change in the
composition of current assets.

Acid test ratio. It is also known as quick ratio. The normal ratio is 1:1.

Current ratio. The minimum standard value is 2:1.

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Inventory to networking capital (IN: NWC). Mean inventory is the average of the beginning and ending
inventory for the accounting period. This ratio is an indirect measure of liquidity and solvency. A high
ratio indicates low liquidity and too much inventory. A ratio if 80% is a reasonable target.

Ratio indicating financial position

Total liabilities to net worth (TL: NW). It is the most direct measure of the financial position of the
pharmacy. A ratio of 50% or lower is acceptable.

Founded debt to networking capital FD: NWC). It is also expressed as a percentage. Long term
liabilities are defined as liabilities extending longer than one year. The normal acceptable value of a
ratio is 20 to 25.

Fixed assets to net worth (FA:NW). This helps to identify over investment in fixed assets. A high value
indicates over investment in fixed assets while a low value indicates there is a need for remodelling.
The target value would be a 20% or less.

Prescription pricing system

Calculating markup% = [(sales price-cost)/cost]x100

Calculating sales price = Cost+(Cost x %markup)

Calculating cost of drug = Sales price/(1+%markup)

% gross margin = [(Total sales- COGS)/COGS]x100

Marketing in pharmacy “4 Ps “of marketing management. These activities, which are under the direct
control of the business, were known as the “4 Ps” of marketing product, place, price, and promotion.

Promotion. The methods of promotions are door-to-door flyers, local radio, TV, posters and news
papers.

Management use of Structure-Process-Outcome component (SPO)

Measure of SPO
• Structure component. Examples. Facilities, equipment, staffing, and personal qualification
• Process component. Examples. Provider, healthcare system etc.
• Outcome component. Examples. Mortality, morbidity, and consumer satisfaction

Tips
1. POS 2. salaries 3. income statement
4. Balance sheet 5. Turnover rate 6. 4 to 6
7. Nature and scope of position 8. Market area analysis 9. Corporation
10 Sole proprietor 11 Partnership 12 Franchise
13 Cash 14 Account receivable 15 Furniture
16 Building
• What are the forms of business structure in Canada? ( )
• What is banner pharmacy ownership? ( )
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• What is the most important in business location analysis? ( )

• What financial statement includes sales of prescription drugs? ( )
• What financial statements include assets and liabilities? ( )
• Examples of current assets include? ( )
• Examples of fixed assets include? ( )
• What is the most expensive in pharmacy business? ( )
• Cost of goods sold/average inventory capital ( )
• The average turnover rate for a pharmacy ( )
• Staffing need is described as? ( )
• Position description includes ( )
• Point of sale system is ( )

Select True or False Statements

Backorder is (If an order is received, and an item has 'BO' means that item is out of stock at the
supplier. The 'BO' signifies that the supplier will ship when the item becomes available or it may need
to be re-order).

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44
Pharmacoeconomics
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Definition. A study of affordability of drugs to society.
• Pharmacoeconomic methodologies like cost effective analysis (CEA), cost minimization
analysis (CMA), cost utility analysis (CUA), and cost of illness analysis (COA).

Pharmacoeconomics is “the description and analysis of the costs of drug therapy to

healthcare systems and society.” Pharmacoeconomics research, identifies, measures, and
compares the costs and consequences of pharmaceutical products and services.

Pharmacoeconomic Methodologies. There are some scientific methods are used to evaluate
pharmacoeconomics.
• Cost-benefit analysis (CBA)
• Cost-effectiveness analysis (CEA)
• Cost-minimization analysis (CMA)
• Cost-utility analysis (CUA)
• Cost-illness analysis (CIA)

Methodology Cost Outcome unit

(spend)
Cost-benefit analysis Dollar Dollar
Cost-effectiveness Dollar Units such as blood pressure mm Hg, blood glucose or units of
analysis. clinical effects (example costs per year of life saved). The most
commonly used in PE calculations.
Cost-minimization Dollar Assumed to be equivalent in comparative groups. Only cost is
analysis compared, so cheap intervention will be chosen.

Cost-utility analysis Dollar Quality-Adjusted Life Year (QALY). This is used when the impact a
health related quality of life is important outcome to treat a
condition.
Cost of illness analysis No comparison is made. Choose the best one.

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Quality-Adjusted Life Year (QALY). The results of CUA analysis are normally expressed in terms of
quality adjusted life year gained. QALY includes both improvements in quantity of life and quality of
life, QALY is used when, Quality of life is the only outcome. Quality and quantity of life are health
outcomes. When intervention affects both mortality and morbidity and combined unit of outcome is
desired.

Cost-benefit analysis (CBA)

It is a basic tool that helps to improve the decision-making process in the healthcare program.
Cost and consequences:
• The outcome is measured in dollars. This study calculates all of the possible benefits that may
occur from the program. All the benefits must be expressed in dollar value.
Disadvantage: (require the economic evaluation of a human life.)
• It is very difficult to assign dollar values to non-financial benefits, e.g. benefits of the program
that may improve a patient’s life.

Cost-effective analysis (CEA) (dollars  clinical effects

• This technique is used to make a decision in order to select the most cost effective
intervention from the available alternative.
• Cost and consequences
• The output measure of this type of study is a health related measure rather than a financial,
example blood pressure, mm Hg, or blood glucose.

Cost-minimization analysis (CMA) (dollars  equal in both groups

• It is defined as: when two or more interventions are examined and assumed to be equivalent
in terms of a given outcome. Cost associated with each intervention may be examined and
compared.
Example. The comparison of cost of two ca-channel blockers, which may successfully produce
similar blood pressure reduction, patterns in a selected group of patients.

Cost-utility analysis (CUA) (dollars  QALY)

• It is an economic tool that measures the consequences in terms of outcome of the program in
terms of quality and quantity of life QALY.
• Cost and consequences
• The outcome measured in CUA is cost per QALY (Quality Adjusted Life Year).
• When the objective is to compare a gold standard intervention that already has the cost per
QALY. QALY is calculated by multiplying the utility value obtained for the specific health
condition with quantity of life year spent in that specific health condition. Comparison can be
made for program and intervention.

Cost of illness analysis (COI or CIA)  does not address both cost and consequences.
• It is very important for evaluating new therapies.
• No cost and consequences

Healthcare Outcome Research

• Outcome research (OR): The study of health care interventions (treatments, such drug therapy,
surgery, palliative therapy etc) and healthcare quality that are evaluated to measure the extent to
which optimum desirable outcome can be reached.

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• The purpose of OR is to assess the value of a program or therapy under study:

• ECHO model: Provides framework for comprehensive evaluation of outcome.
• Economic outcome: Acquisition cost associated with care, labor cost associated with care, treat
side effect reactions, cost of treatment failure, hospital readmission, cost of emergency room,
clinic visits.
• Clinical outcomes: length of hospital stay, side effect reactions, hospital readmission and death.
• Humanistic Outcome: Patient satisfaction, functional status of validated instruments, quality of life
assessment.

Health Related Quality of Life (HRQOL):

• QALY focuses on all aspects of life. However, HRQOL only focuses on patient non- clinical
information such as functional status, well being, perception of health, return to work from illness
and other outcome that are effected by illness
• Health Related Quality of Life (HRQOL): According to the WHO (world health organization),
health is defined as complete physical, mental and social well-being.
• HRQOL normally focuses on non-clinical components of healthcare such as functional status,
well-being, and other important health- related outcomes.
• HRQOL has a very large database. This database is prepared either by personal interviews, by
telephone interviews, or by postal survey.
• Personal interviews, telephone interviews and postal surveys are defined standardized
questionnaires or instruments of HRQOL.

Techniques of pharmacoeconomic assessment

Short Form 36 (SF 36). The SF 36 was designed for use in clinical practice and research, health policy
evaluation, and general population survey.

Budget impact analysis (BIA)

Multi-attribute Utility Theory (MAUT)

• Used in assessing utilities. This include, clinical, financial effects as well as quality of life. Example.
A hospital administrator may view clinical outcome 20%, financial outcome 70% and the quality of
life 10%. The individual perspective will have a major impact on the final decision made, based on
varying levels of priority chosen for evaluation.

Willingness To Pay (WTP)

• This technique is used to assess the perceived value or benefit of a product and service.

Pharmacoeconomic Resources

Methods for Economic Evaluation of Health Care Programmes, 3rd ed. Michael F. Drummond, Mark J.
Sculpher, George W. Torrance, Bernie J. O'Brien, and Greg L. Stoddart. Oxford University Press.

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Review example of Cost Benefit Analysis (CBA)

Drug A Drug B
Cost drug $1000 $1100
Administration $100 $10
Monitoring $50 $0
Side effects $75 $0
Total cost $1225 $1110
Benefit Days at work ($)
Extra months of life ($) 750 1200
C/B = <1 is beneficial
C/B = 1 no benefit or no loss
C/B = >1 is loss

Review example of Cost effective analysis (CEA). A marginal cost effectiveness ratio is
calculated by determining the added cost divided the added benefit.

Drug A Drug B
Cost dose $300 $300
Hospitalization $300 $300
Stay require $600 $600
Total cost
Outcome Extra years of life 2 6
Cost effectiveness ratio 600/2 600/6
$300 $100

or
cost for 12 month Lowering LDL for 12 month
Drug A $1000 2 mmol
Drug B $1500 3 mmol

Review example Cost Minimization analysis (CMA)

Drug A Drug B
Cost Drug $250 $430
Administration $75 $0
Monitoring $100 $10
Side effects $100 $15
Sub total cost $525 $455
Outcome
Antibiotic effectiveness 80% 80%
Result = Cost Drug A>Cost of Drug B

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Review example. Cost utility analysis. A CUA takes patient preferences, also referred to as
utilities, into account when measuring health consequences. The most common unit used in
conducting CUA is QALYs, which incorporates both quality and quantity of life.
Drug A Drug B
Cost
Drug $250 $430
Administration $75 $0
Monitoring $100 $10
Side effects $100 $15
Total cost $525 $455
Utilities Extra years of life 2 3
Quality of life 0.33 0.25
QALY 0.5 0.40
Cost utility ratio $525/0.5 $455/0.4
$1050 $1137

QALY = Quality Adjusted Life Years

Review example of cost benefit analysis (CBA)
Drug A Drug B
Cost
drug $1000 $1100
Administration $100 $10
Monitoring $50 $0
Side effects $75 $0
Total cost $1225 $1110
Benefit 750 1200
Days at work ($)
Extra months of life ($)
C/B = <1 is beneficial
C/B = 1 no benefit or no loss
C/B = > 1 is loss

Review example of Cost effective analysis (CEA)

Drug A Drug B
Cost
dose $300 $300
Hospitalization $300 $300
Stay require
Total cost $600 $600

Outcome
Extra years of life 2 6
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Cost effectiveness ratio: 600/2 600/6

$300 $100

Review example cost minimization analysis (CMA)

A B
Cost
Drug $250 $430
Administration $75 $0
Monitoring $100 $10
Side effects $100 $15

Subtotal cost: $525 $455

Antibiotic 80% 80%

effectiveness
Result = Cost Drug A>Cost of Drug B
Note: usually used for calculating different methods surgical techniques.

Review example cost utility analysis

A B
Cost
Drug $250 $430
Administration $75 $0
Monitoring $100 $10
Side effects $100 $15
Total cost $525 $455
Utilities
Extra years of life 2 3
Quality of life 0.33 0.25
QALY 0.5 0.40
Cost utility ratio $525/0.5 $455/0.4
$1050 $1137
QALY = Quality Adjusted Life Years

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Tips

1. Units 2. Society 3. Short Form 36

4 Cost Minimization 5. Quality Adjusted Life 6. Dollars
Analysis Years
7 cost utility analysis
• What is QALY ( )?
• Pharmacoeconomics is the study that determine affordability of drugs to ? ( )
• Cost minimization analysis outcome is measured in? ( )
• Cost effectiveness analysis outcome is measured in? ( )
• QALY is outcome of? ( )
• What is SF 36? ( )
• To compare cheaper intervention, what methodology is used? ( )

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 www.Pharmacyprep.com Drug Development Process

45
New Drug Development
Process
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Role of Health Canada. Drug market authorization in Canada
• Drug approval process Clinical trials phase 1 to phase 4
• Adverse drug Reaction Reporting
• Label indication and off label indications

Pre market ……………………………………………………………………….. … Post-market

Physician Physician Physician

Prescribing prescribing prescribing

Clinical Regulatory
Pre-clinical
trials product Market Public access
studies
(phase I, submission authorization Public and
II, and III By health private drug Prescribing
Canada plans/policie practices
Clinical trial Submission s listing and
applications Notice of reimbursem Real-world use
review studies (phase
Compliance ent
(NOC). decisions IV) by ADR
Drug Product CADTH Pharmacovigilanc
New drug submission (NDS) or abbreviated
NDS (generic products) or supplemental Database Common e.
Labelling and Drug Review Therapeutic cost-
NDS (changes in existing products)
product (CDR) effectiveness
monograph

Surveillance, inspection, and

investigation for safety and
regulatory compliance

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Notification issued indicating that manufacturer has complied with FDA regulations. Notice of
compliance (NOC) is issued following satisfactory review of submission.

Pre-clinical research (in animals)

↓
Phase I trials (small healthy human population, PK, Safety)
↓
Phase II trials (small disease human population, safety, effectiveness)
↓
Phase III trials (safety, dosage info, decisive phase)
↓
Trial review and approval
↓
Phase IV trials (post marketing surveillance), adverse drug reaction (ADR) monitored

NO phase I trials for chemopreps.

Preclinical Research
Stage # of patients Duration Purpose
Pre-clinical research None 18 months - 3 years Laboratory investigation for
efficacy and toxicity

Phase I trials
Stage # of patients Duration Purpose
Phase I 20-100 Up to 2 years Safety and dosage
• Human Healthy volunteers
• Small or limited population
• Designed to establish the effects of new drugs in humans, specifically determine a
pharmacokinetic studies, drug toxicity, absorption, distribution and metabolism.

Phase II trials
Stage # of patients Duration Purpose
Phase II 100-300 Several months-2yrs Some shows term
safety but mainly
effective
• Test on disease patients
• Slightly larger but limited population
• Tested safety and efficacy in slightly larger populations who afflicted with the disease or
conditions, which the drug is developed.

Phase III Trials

Stage # of patients Duration Purpose
Phase III 100-3,000 2-3 years Safety, relative
effectiveness dosage
• Tested on Disease patient
• Larger population than phase II

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• Last pre-approval round of testing. Test the new drug with comparison of standard drug. The
results of new trials usually provide the information that included in the package insert labelling.
• After approval drug from phase III, this can be sold in market.
Trail Review and Approval
Stage # of patients Duration Purpose
Review and None 1-2 years Safety, effectiveness,
Approval dosage

Phase IV Study
Stage # of patients Duration Purpose
Phase IV 100- several thousand No limit Safety, effectiveness dosage
After drug has been approved. Studies are conducted to compare the drug to a competitor. Explore
addition side effects.

Tips
1. Notice of Compliance 2 Phase III 3. Disease patient, large number
of patient, it is decisive phase

4. Animal studies 5. Post marketing, 6. Health Canada

inspection of safety and
regulatory
compliance
7. Patented Medicine 8. Pharmacy 9. Healthy volunteers,
Price Review Board Manager/Owner pharmacokinetics & safety
PMPRB
10 Disease patient and 11 NPN 12 Natural Product
smaller number Directorate
• Who approves and authorizes the sale of medications in Canada? ( )
• Who sets the prices of prescription drugs in Canada? ( )
• Who sets the prices of over the counter drugs in Canada? ( )
• Pre-clinical studies is done in? ( )
• Phase I clinical studies is done in? ( )
• Phase II clinical studies is done in? ( )
• Phase III clinical studies is done in? ( )
• Phase IV clinical studies is done in? ( )
• What is notice of compliance (NOC)? ( )
• Decisive Phase in clinical trials is ( )
• Approves the prescription & OTC medications ( )
• Natural Products Number is ( )
• Drug identification number (DIN) is used for?
• Natural product number (NPN) is used for?
• Product identification number (PIN) is used for?

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www.PharmacyPrep.com Epidemiology

46
Epidemiology
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Cross sectional, case control and cohort studies
• Clinical study designs like parallel and cross over designs
• Types of bias and confounders
• Types of blinding
• The credible clinical studies are randomized double blind

General Design Elements. These are the several important tools that researchers use to improve the
validity of a clinical trial, its ability to achieve the clinical endpoints, and its ability to provide the
highest possible level of evidence.

Clinical Studies

Descriptive studies Explanatory Studies

Case reports Case series Meta analysis Observational Experimental

Cross sectional (or)

prevalence (now) Case control or retrospective or past. Cohort or follow up
Good for rare disease, initial etiology. No future or prospective
Collect the data after both
disease and exposure. incidence and prevalence. Outcome is Get incidence and estimate. Calculate
Determine prevalence rate measured by odds ratio method. the risk
No incidence rate Example. Antibiotic resistance pattern for Example post marketing surveillance
the past 10 yrs. (ADR monitoring)

The strongest sequence of strength (the most credible) clinical trial design is A>B>C>D>E.

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Important concepts
Epidemiological study designs to study drug use and outcomes in large populations.
Prevalence. Collect data after both disease and exposure. Measured by cross sectional study.
Incidence. Collecting data from exposed. Measured by cohort studies.
Cross sectional examples
• Determines or identifies the risk factors and etiological agents or disease or conditions.
• To evaluate receiver characteristics of diagnostic procedure.
• To evaluate a new laboratory tests.
• Advantage: results appears at the time of study

Fig 55.1

Fig 55.2

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Case control study: A case control study compares a population of patients with a specific pre-existing
condition to a similar population without – to establish the influence of a disease or other event (e.g.
Intervention, hospitalization, death). Data collection is usually done using medical records and patient
interviews. Example. Studies of antibacterial resistant for the treatment of pneumonia.
This study often the best way to study rare diseases that develops over a long period of time. It can be
less reliable than randomized controlled trials or cohort studies because the difference that can be
made about the influencing factors is limited by bias.

Pros and Cons

• (+) Requires fewer subjects than cross-sectional trials
• (+) Only way to study long-term, rare disorders
• (+) Fast and inexpensive
• (-) Difficult to select control
• (-) Potential bias form patient selection and recall
• (-) Exposure status relies on records and recall

Odd Ratio (OR). The odds represent the number of patients in a given group with an event divided by
number of patient in the same group without it.
The 2 x 2 table

OUTCOME
Exposure Yes No

Yes A B
NO C D

OR = (a/b)/(c/d)
OR = AD/BC

A= number of exposed cases

B=Number of exposed NON cases
C=Number of unexposed cases
D= Number of unexposed non cases

Tips. always divide experiment by control (goes down in table)

Cohort Studies: An observational study that allows a large population of patients with a specific pre-
existing condition or treatment for a period of time, comparing them with another group unaffected
by the affliction or the treatment.
Cohort studies are employed when it would be unethical to test the effects of a condition or treatment
on otherwise healthy patients (e.g. obesity in children), often in the etiology or prognosis of a disease.
Pros and Cons
• (+) Lower cost, easy administration (compared to RCTs).
• (+)Can establish time and direction of events
• (+) Ethical
• (-) Not randomized, difficult to blind
• (-) Control difficult to identify

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• (-) Differences can take a long time to develop.

• (-) Participants can withdraw, develop other conditions, or die.

Randomized Controlled Trials (RCTs)

A clinical trials that answers questions about the effectiveness of different therapies by studying the
effect of an intervention on randomized patients. This can be achieved by using 2 possible
methodologies designed to reduce bias and promote comparison between the intervention group and
1 or more control groups (also known as ‘arms’) treated with a placebo and/or the current standard of
care. RCTs are the standard trial design for answering clinical questions about therapy effectiveness.

Randomization: Participants are selected by computer codes, randomization improves the validity of a
trial’s results.

Stratification: In some trial designs, patients may have important differences that researchers know
will affect the outcome of the intervention, such as different stages in disease state or concurrent
conditions. In such a case, patients may first be intentionally divided into 2 or more groups, example
“smokers and non-smokers” or diabetics and non-diabetics”.
Stratification enables researchers to evaluate how an intervention affects both groups by studying
whether or not there is a difference in the subgroup.

Population. Population, from which trial subjects will be selected.

Sample size. The total number of participants included in a clinical trial is determined by the change
the researchers want to observe in the chosen primary outcome.

Placebo. A placebo is a device that imitates the active intervention but has no therapeutic value. The
placebo effect is important when discussing adverse events (AEs) with a healthcare practitioner. AEs
from the group taking the placebo can be compared with those from the group taking the intervention
to determine to what degree adverse events are really attributed to the active agent.

Multi-Centre Trials: Multi-centre trials are conducted at more than one location, often by more than
one investigator, but using one central protocol. When conducted at multiple centres in more than
one country they are referred to as multi-centre, multi-national trials.

Systematic Reviews: Are critical assessment and evaluations of primary research trials that use
rigorous methods to combine the current best evidence to answer a specific question on a clinical
topic.
• A comprehensive literature survey of the topic is conducted
• Primary trials of sound methodology and the highest level of evidence are identified (eg.
Randomized controlled trials)
• The results of each trial are appraised
• All results are summarized using predetermined, explicit, reproducible methodology.
A systemic review shares many common characteristics with the first 4 steps of the evidence-based
medicine process: phasing a clinical question (endpoint); researching the answer; evaluating the
evidence; integrating and applying the evidence (conclusion).

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Study designs:
Parallel group design: The more common of the 2RCT designs, the parallel group design, is often used
for confirmatory trials. Participants are randomized into 2 or intervention, the other treated with
placebo or current standard of care.

Pros and Cons

• (+) Randomized improves statistical analyses
• (+) Unbiased distribution
• (+) Can be blinded
• (-) Requires extensive resources
• (-) Can present ethical challenges
• (-) Nature of volunteers can bias trial

Crossover Design: Participants are randomized into 2 or more groups. However, each group receives
all the treatment (e.g. Intervention, standard, placebo) in a random order with a “washout” period in
between, a period of time between two active treatments when the patient receives a placebo in
order to remove the residual effect of the
previous treatment before initiating the Important Concept!
next active treatment. The basic crossover Cross over design all participants get treatment
design is 2 x 2, in which 2 groups receive 2 and placebo in crossover design. Reduce error
consecutive. treatments. variance
Pros and Cons
• (+) Reduced error variance, reduced
sample size
• (+) All participants serve as own control
• (+) All participants treated
• (+) Can be blinded
• (+) Comparative studies
• (-) All participants receive intervention, standard, and placebo
• (-) Cannot be used for intervention with permanent outcome (like irreversible side effects)
• (-) Length washout period
• (-) Long duration

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Fig 46.3

Fig 46.4

Meta Analysis: It thoroughly examines data from a number of valid trials that are similar enough to
permit them to be combined and analyzed as one large trial. The evaluation of quantitative evidence
from 2 or more trials involves combining the raw data or the summary of statistical results using a
special statistical methodology.

The meta analysis trial design provides the highest level of evidence of any trial design because part of
its methodology includes the analysis, critical appraisal, and summary of the results of many selected
randomized controlled trials.

Pros and Cons

• (+) Top ranking in the levels of evidence
• (-) Trials demonstrating a positive effect are published more often than those that don’t exposing
a meta-analysis to a publication bias.
• (-) Results from different trials do not always agree.
• (-) Authors of a meta analysis could unconsciously or intentionally omit trials that may or may not
support the clinical question.

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• (-) “Grouping” results from trials with different designs, statistical analyses, and patient
populations may be problematic.

Bias
Bias is systemic error or distortion of a test measurement.
Interview bias. Because of blinding of interviewers response may be influenced, known as interview
bias.

Recall bias. Differentials in the memory capabilities. Example case control studies.
Lead time bias. The selection of cases from both of these groups introduces a form of non-random
error known as lead-time bias.

Berksons bias (admission rate bias). Distortion in risk ratios occurs as result of different hospital
admissions.

Confirmation bias. Linking directly to results.

Selection bias. The selection of subjects into your sample or their allocation to treatment group
produces a sample that is not representative of the population, or treatment groups that are
systematically different.

Publication bias. Not publishing negative results.

Confounder. A factor that is prognostically linked to the outcome of interest and is unevenly
distributed between the study groups. Example. If study is examining the effect of age on ulcer relapse
rate and several ulcer also smokers (smoking could be confounder).

Blinding. It helps limit or eliminate factors that could unconsciously influence results. Blinding
minimizes bias in several ways.

Single blind. One if the most basic forms of

blinding in which trial participants have no
Important Concept!
knowledge of intervention (example patients
Who is NOT blinded? Biostatistician
cannot distinguish between the intervention,
placebo, or active product used to compare
different treatment regimens.

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Double blind. Neither the trial participants nor the investigators have knowledge of the assignment to
the various trial groups of the interventions, placebo, or active product used to compare different
treatment regimens.

Triple blind. Neither the participants, the investigators, those monitoring the safety, nor any of the
personnel involved in the selection of participants or evaluation of the outcomes have knowledge of
the assignment of the interventions and placebo to the various trial groups.

Tips format 002: Epidemiology

1. case-control 2. cross-sectional 3. prospective
4. Cohort 5. Single-blind studies 6. Double-blind
7. Randomization of the 8. Parallel Studies 9. crossover studies
sample
10 Dependent variable 11 Meta analysis 12 Prevalence
13 Case report 14 15
16 17 18
• Factors reduces best bias ( )
• The odds ratio associated with ( )
• A study designed to determine the relationship between emotional stress and ulcers used the
records of patients diagnosed with peptic ulcer disease versus controls over the period from May
2009-May 2010. This is an example of what kind of study? ( )
• Twelve patients are given a drug or a placebo to determine the effect of medication on blood
pressure. The dependent variable in this study is ( )
• A study was undertaken to determine if prenatal exposure to marijuana is a cause of low-birth
weight. Mothers of 50 infants weighing less than 5 lbs (low-birth weight) and 50 infants weighing
more than 7 lbs (high-birth weight) were questioned about their use of marijuana during
pregnancy. The study found that 20 mothers of low-birth weight infants and only 2 mothers of
high-birth weight infants used the drug during pregnancy. This is an example of what kind of
study? ( )
• In this study, the odds ratio associated with smoking marijuana during pregnancy is (16)
• The odds ratio is 16 and is calculated as follows
• Mother smoked marijuana Mother did not smoke marijuana
• Low-birth weight babies A = 20 B = 30
• High-birth weight babies (normal) C = 2 D = 48
• Odds ratio = (A)(D) or (20)(48) = 960/60 = 16
• (B)(C) or (30)(2)
• Combining data from several studies (often via a literature search) to achieve greater statistical
power. ( )
• is the number of people who have an illness at a specific point of time ( )

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47
Biostatistics
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Statistical significance. Probability of error (P) or level of significance and confidence
intervals
• Hypothesis testing. Types of error like Type 1 (alpha) and Type 2 (beta) errors.
• Calculating risk reductions like absolute and relative risk reductions
• Calculating number needed to treat (NNT) or number needed harm (NNH).

Characteristic of data: Descriptive statistical measurements are often used in medical literature to
summarize data statistical distribution. Frequently used in clinical medicine are symmetrical
distribution, measuring central tendency and measures of dispersion.
99%
Symmetrical distribution: The symmetrical distribution is
also known as normal (Gaussian) distribution or bell shape 95%
curve. The dispersion or spread form the mean is
68%
represented by the standard deviation 68% (two thirds) of
the value falls within one standard deviation of the mean.
95% of the values are found within two standard deviations
of the mean. 99% of the values are found within three
standard deviations of the mean.

SD1 is 68%
SD2 is 95% -3 -2 -1 0 +1 +2 +3
SD3 is 99%
Number of standard deviations from the mean value

Bimodal = Two lumps

Positive skew = Mean> median> mode: Tail on right handed side
Negative skew = Mean < median <mode): Tail on left handed side

Measures Of Central Tendency (middle of distribution).

A measure that describes a typical value in a set of data is referred to as a measure of central
tendency. Three measures of central tendency describe such values when they are found in a
normally distributed sample mean, median and mode.

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Mean. The sum of the scores divided by the number of scores that is, the average score.
Mean. Sum of the score/number of scores = 3 + 5 + 5 + 8 + 9 = 30/5 = 6

Median. Midpoint of the sequence = 5 (if there is an even number of values, the mean of the middle
two numbers becomes the median), 4, 3, 8, 5, 5
3, 4, 5, 5, 8 (arranged in increasing order)

9, 4, 3, 2, 1, 5
1, 2, 3, 4, 5, 9 (arranged in increasing order)
3+4/2 = 3.5

Mode. The score that occurs most frequently or repeats is referred as mode. Note. All measures of the
central tendency may be altered by the addition of very high or very low values is distribution, the
mode is usually unaffected by such values, and the mean is susceptible to the greatest degree of
change.
3, 4, 5, 6, 6,7------Mode is 6
4, 4, 8, 5, 5-----Mode is 4 and 5, this is referred as bimodal
1, 2, 3, 4, 5, 9  No mode

Examples. In a follow up study of five patients admitted to the coronary care unit with diagnosis of
acute myocardial infarction, the length of stay was found to be 5, 3, 8, 5 and 9 days. Calculate the
mean, median, and mode for these sample patients. First arrange the data in ascending or descending
order; 3, 5, 5, 8, 9
Mean = 3, 5, 5, 8, 9 = 30/5 = 6
Median = 5
Mode: The score that occurs most frequently = 5

Measures Of Dispersion
A measure that described the spread or variation of the observations is referred to as a measure of
dispersion. Four measures of dispersion that are used in clinical epidemiology and medicine are range,
standard deviations, variance, and standard error of mean.

Range. The difference between the highest and lowest observation

Example. 99, 105, 115, 125, and 130.
Range: (130-99) = 31

Standard deviation: The standard deviation is another way to calculate dispersion. This is the most
common and useful measure because it is the average distance of each score from the mean. The
formula for sample standard deviation is as follows.
For sample data 5, 6, 8 and 9, what is the standard deviation?
Correction = x bar

SD = √ (5-7)2 + (6-7)2 + (8-7)2 + (9-7)2 S= ε (x - x)2

3 n-1
SD = √ (2) + (1) + (1) + (2)2
2 2 2

3 Where X = sample score, S = mean of the sample and

SD = √ 10/3 n = sample size
SD = 1.8
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Variance. The third method of measuring dispersion. Compare the two-variance formula with their
corresponding standard deviation formula. Variance is the square of the standard deviation.

Coefficient of variance SD
Coefficient of variance = x 100
Given (x bar) and standard deviation (SD), calculate of %
X
of variance coefficient.

Standard error of the mean (SEM). The standard error of the mean plays an important role in many of
the statistical procedures used in epidemiology and clinical medicine. It is used for confidence limit
determination and becomes and estimates of standard deviation of population through. As the
standard error of the mean decreases as the size of the sample increases.
S
S = Standard deviation, N = Sample size SEM =
n
Statistical tests analysis. Statistical test can be divided into three categories that are parametric and
non-parametric tests and meta analysis.

Statistical tests

Parametric tests Non-parametric tests

Mean and standard deviation and t-test Chi Square, median, and mode

Parametric statistical tests

The parametric statistics are the most popular data analysis procedures that assume that data are
from populations that are normally and independently distributed. The population of parametric tests
must have the same variances. Examples of parametric statistic are t-tests, mean, and standard
deviation.

t tests. The t tests is used for comparing the means of 2 treatment, even if they have different
number of replicates. The student’s t tests used to compare the means of small (n <30) independent
samples for the purpose of determining the statistical significance (p value) of the observed findings.
• T-test checks difference between the means of 2 groups.
• The degree of freedom (DF) in paired t test can calculated by (n-1)
• The degree of freedom in two independent sample t-test would be (n 1 -1) + (n 2 -1)
• Example. A drug is used to treat 50 placebo and 50 patients. Find out the degree of freedom.
Analysis of variance (ANOVA). It is also known as F test and is used to compare means of three or
more samples or groups for the purpose of determining the statistical significance of the observed
findings. Degree of freedom can be calculated by (n-2). Consist of positive value.

Non-parametric statistical tests

The non-parametric statistics are also known as “distribution free” statistics. They do not require
assumption of same variances. Their observations are independent. Examples of non-parametric
statistics are mode, median and chi square tests.
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Chi Square test. The chi square test is used for comparing two or more dependent proportions within
two or more groups making it useful for multi group comparisons. Compares percentage (%) or
proportions. (not mean values). The degree of freedom is defined as (R-1) x (C-1). Here, R = row and
C= column. Example find out the degree of freedom in chi-square tests in 2 x 2 contingency table.
(R-1) x (C-1) = (2-1) (2-1) = 1.
Used to test differences of two proportions from two independent samples can calculate by

Chi-square can be calculated by:

X2 = ε (observed frequency-expected frequency)2
Expected frequency

The Wilcoxon signed-rank test. Non-parametric statistical hypothesis test used when comparing two
related samples or repeated measurements on a single sample to assess whether their population
means differ.

Hypothesis Testing
Statistical Significance. It’s important to determine whether a treatment effect is really caused by the
study intervention or whether it is merely due to chance. A result is said to be statistically significant
when it is reasonably unlikely to be due to chance alone.

There are two main measurements that can help us i.e. p-value (probability of error) and 95%
confidence interval.
The statistically significance results is one in which the observed p is less than 5%, which is formally
written as p<0.05.

Null hypothesis (Ho). State that there is no difference between. Example smokers and non-smokers
with respect to the risk of developing lung cancer.

Alternate hypothesis (HA) (relationship hypothesis). The alternate hypothesis states that there is
difference between smokers and non-smokers with respect to the risk of developing lung cancer.

Types of error

Types of error

Type I (α-error) Type II (β-error)

False + ve False -ve
Chance Sample size

Type I (α-error). False positive error. Stating that there is a difference when NO difference exists. Or
mistakenly accept the experimental hypothesis and reject null hypothesis. Rejecting null hypothesis
when Ho is true.
Investigator can error in concluding that there is difference between treatment group and control
group when, in fact, no such difference exist. In statistical terminology it is called a type I error and
the probability of making such an error is referred to as alpha level.
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• P = Probability of making type I error, also referred level significance.

• The level significance is set at a 5% level or 0.05 levels. The alpha error is set in advance.
• The α error is commonly chosen as 5%, however, sometime it may set up to 1%.
• P = 1/20 = 5/100 = 0.05 = not significant
• P <0.05 significant
• P = 0.0005 = Highly significant

p-value (probability of error)

if p is 0.05 or 5% means, 1 in 20 results are by chance.

if p is 0.01 or 1% means. 1 in 100 results are by chance.

Type II (β-error) or False -ve. Stating that there is NO difference when different exists. Accepting null
hypothesis when it is false. Beta is probability of making type II error. The β-error is the probability of
declaring no difference between the observed value and the hypothesized value of an experiment.
Parameter, a difference of error delta exists. Accepting null hypothesis when null hypothesis (Ho) is
false.

Confidence interval
Confidence interval (CIs) are inversely proportional to p-value, therefore p-value 0.05 is expressed as a
confidence interval 95%.
CIs are provides range within which the true treatment effect is most likely to occur across trial
population.

Measure Of Risk

Risk Reduction

Absolute Risk Relative Risk Attributable Risk

Measure of risk. Factors that are likely to increase incidence, prevalence or mortality of disease are
called risk factors.

Absolute Risk (AR). The difference in risk between exposed and unexposed groups that is also
percent of disease occurrences that are result of the exposure (example smoking causes 1/3 cases of
pneumonia). Allows to separately calculating the incidence of a particular disease in both populations
of a risk factor study for the purpose of making individual risk comparisons for each population.
The absolute risk = A/(A+B) i.e. A = Drug, B = Placebo

Absolute risk reduction (ARR). The difference between treatment group and control group.
• The difference in the absolute risk between the intervention and control groups.
• ARR = (treatment events) – (placebo events) or EER – CER
• EER = Experimental event rate (treatment event), CER = control event rate (placebo events)
• NNT = Number needed to treat = 1/ARR
• NNT = Number of patient needed to be treated to prevent one bad outcome

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A study experiment event rate or treatment reduced 10% risk and control reduced 7.5% risk. What is
absolute risk reduction?
ARR = EER-CER or 10-7.5 = 2.5%
NNT = 1/ARR = (1/2.5) x 100 = 40

Relative Risk (RR). Relative probability of getting a disease in the exposed group. Calculated as percent
with disease exposed group divided by percent with disease unexposed.
• Relative risk = a (a+b)/c(c+d)
• Relative risk gives risk as a ratio of incidence among subjects exposed to a particular risk factor
divided by the incidence among subjects who were not exposed to the risk factor.

Relative risk reduction (RRR). Reduction in adverse outcomes in the treatment group relative to those
in the control (placebo) group.
• RRR = [EER-CER]/EER
• RRR= ARR ÷ EER
RRR = [1x CER]/NNT
• RRR = Relative Risk Reduction

When experimental treatment When experimental treatment

reduces risk of bad event increases probability of good
event
RRR (CER-EER)/CER (EER-CER)/EER
ARR CER-EER EER-CER
NNT 1/ ARR 1/ARR

Clinical trial project example

Variable Independent variable Dependant variable
Patient Patient hypertension
Age Age
Gender Gender
Demography Demography
Body weight Body weight
hypertension

Tips
• When will be the results on the same point in symmetrical curve-->
• P = Probability of making type I error, also referred level significance.
• Chi square test: The degree of freedom is defined as (R-1) x (C-1)
• The absolute risk = A/(A+B); A = drug, B = placebo
• ARR = (placebo events) – (treatment events) or (treatment event) - (placebo event)
• RRR = [EER-CER]/EER
• RRR=ARR ÷ placebo events.
• RRR = (1 x CER)/ NNT

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• Example: A statistical data mean is 100, median is 100, and mode 100, the statistical distribution
is? Indicates symmetrical distribution
• A statistical data mean is 200, median is 150, and mode 100, the statistical distribution is?
• What are the examples of parametric tests are 
• What are the examples of non-parametric tests are 
• False +ve test is 
• Type I error can occur by 
• Type II error can occur by 
• Probability of error is presented as 
• What is precision 
• What is specificity 
• What is accuracy
• What is validity
• The Wilcoxon signed-rank test is a? 

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48
Hospital Pharmacy
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Managing Drug Distribution and Workflow (Electronic medication records (EMR),
medication administration records (MAR).
• Unit dose system, Ward Stock.
• Formulary systems.Hospital committees (P&T committee prepares formularies, medical
advisory committee or MAC).
• Inventory management (Perpetual inventory is used for narcotics), POS
• Medication Reconciliation (gathering patient medication history)
• Quality Assurance. Drug utilization review (DUR)s. Reporting medical incidence to
Canadian Institute of Health Information (CIHI). ISMP. Institute of safe medication
practices) Canadian Medication Incident Reporting Services (CMIRS). IV admixture and
sterile preparations. FMEA and RCA
• Failure Mode and Effect Analysis (FMEA). Before error occurs analysis
• Root cause analysis (RCA). After error occurs analysis.

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Hospital organization structure

Board of Trustees
(board of director)

CEO

CFO COO CMO

VPs

Director of
Pharmacy

Pharmacy
manager

Hospital Committees: Most common committee in hospital are Pharmacy therapeutic committee (P&T),
Formulary committee, Paramedical committee, Pharmacy Therapeutics and Nutritional support
committee

Common examples of committee of hospitals and their functions

Hospital Committee Functions
P&T committee P&T committee is responsible for managing drug-related issues for the organization or
hospital represented by the committee. Developing and preparing formulary listing.
Medical Advisory The role of the MAC generally is to advise the hospital board on matters of the quality of
Committee (MAC). care being provided to patients. The MAC is required to supervise the practice of medicine
in the hospital and report to the Board on such matters.
Ethics committee The Ethics Committee provides consultation to care providers and patients concerning
ethical questions, educates health care workers on how to resolve ethical dilemmas, and
addresses organizational ethical issues, among other functions.
Risk Management or This committee monitors the hospital-wide incident reporting system; develops processes
incident reporting to reduce actual or potential patient risk; identifies trends among incidents and provides
committee recommendations to the appropriate committees for further action.
Patient Safety This committee develops and implements policies and processes related to patient safety
Committee in the hospital; reviews hospital risk reduction activities; and creates patient safety
education programs.

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Responsibilities of the Pharmaceutical and Therapeutics (PT) committee

• The evaluation and selection of all drugs currently in use in the hospital
• Setting of use for all medications in the hospital
• Evaluating drugs based on drug studies, available literature and financial considerations.
• Education program for staffs.

Formularies: A formulary is a list of drugs approved by a third party for reimbursement. Formularies are
developed to help control costs and improve the quality of the drug therapy patients receive (i.e., cost-
effective therapy).
The formulary contains important information to assist the pharmacist which includes: Identification of
generic name products, Identification of product concentration and Identification of package size.

The formulary serves as a valuable reference in determining all aspects of product information required
in a pharmaceutical purchasing system.
The potential benefits of a hospital formulary system are: Economic, therapeutic and educational.
Formularies help physicians reach clinically and economically appropriate prescribing decisions for their
patients. Each province has a formulary, or list of drugs that are covered under its plan. The drugs on the
formulary vary among the provinces.

Formulary responsibility. It is pharmacy’s responsibility to carry the drugs listed in the formulary and
physicians and residents. Check the formulary to determine which drugs are available.

QAlerts
1. Formulary is up to date listing of pharmaceuticals
2. Automatic substitution policy developed by P&T committee and approved by MAC (Medical Advisory
Committee)

Non-Formulary Drugs: The non-formulary drugs are drugs that are commercially available but not
included in the hospital formulary.

Investigational drugs
• New products that have been evaluated and tested
• Forms must be submitted by physicians
• Not yet been approved for marketing in Canada.
• Investigational drugs are not marketed since they are not approved.

Emergency Release Drugs: The drugs commercially available in other countries but not in Canada. These
drugs are released to specific practitioners for a specific patient with a serious medical condition where
the disease is refractory (non-responding) to traditional treatments in Canada. These drugs are
accessed through the Health Canada’s Special Access Program (SAP). Once the request has been
submitted to government by the physician and approval has been made by SAP then pharmacy is
responsible for receiving, storing, preparing, distributing, recording patient information in profile.

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Compassionate release drugs: These drugs are provided on individual basis by manufacturers for
patients who need the drug but are unable to pay for it. Generally supplied to the hospital pharmacies
only. These people are not eligible for any government programs or benefits that would help subsidize
the drug product.
QAlerts!
Investigational drugs, emergence release drugs or drugs that are discontinued can be obtained from?
Special Access Program

Automatic Stop Orders (ASO’s): Policy developed by P&T Committee that limit the amount of
medication dispensed for potent drug classifications such as narcotics, anticoagulants, antipsychotic
agents or mood modifying drugs, injectable and anti-infective. The purpose of this regulation is to avoid
prolonged administration of certain drugs; use of these drugs for each patient are reviewed regularly.
Although the days supply may vary in each hospital, the following serves as an example of the
classifications of drugs that are affected by Automatic Stop Orders.

Drug class ASO

Anticoagulants 1 day
All inject able and Narcotic & Controlled drugs 3 days
Antibiotics 7 days
All regular meds , e.g. Antipsychotic agents, mood 10 days
modifying drugs, sedatives, hypnotics

Automatic therapeutic interchanges (ATI) is common practice in hospital or closed settings, however
generally there is no provision of automatic interchange in community pharmacy setting. When
therapeutic interchange is done take in consideration drug interactions and patient specific factors such
as kidney functions and liver function. Pharmacy technician should always refer to pharmacist for any
questions related to therapeutic interchange.

Unit dose dispensing

• In unit dose dispensing, medication is dispensed in a unit of use package that is ready administer to
patient.
• The unit dose system is part of the hospital’s system of drug distribution in which medications are
dispensed for a 24‐hour period.
• CIVA (centralized intravenous admixture). This utilized prepackage iv drug admixture.

Unit Dose System Ward Stock System (Floor Stock)

Delivered in unit dose for 24 hr for Stocking commonly used medication in
a specific patient. nursing floor.
Expensive but effective Short shelf life cannot be stored in ward
stock
Less wastage More wastage
MAR (Medication Administration
Record) is used for administration.
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Technician fills unit dose or robots

(automation) fills unit dose
Nurses retrieve and check
medication against MAR before
administration.

The technical responsibilities of preparing patient specific unit dose and floor stocks medication are
done by the pharm. technician.

Drug Information Centres: Healthcare professional or public may have some questions urgently or some
of questions require detail literature search using electronic search programs, and journals to find out
up-to-date information on variety of topics.

• Availability and uses of different medications

• Side effects of medications
• Drug interactions
• Mixing intravenous medications
• Current approaches to therapy
• Controversial topics on medical use

Poison information centres

• Pharmacist working in poison information centres answer questions from other healthcare
professional and public about poisons, toxicities and overdoses of drugs.
• Management of accidental ingestion of medications by children
• Antidote to medications
• Management of overdoses
• Contents of household products
• Identification of unknown medication ingestions
• Poison prevention tips

Medication reconciliation: Gathering patient medication information at the time of hospital admission,
transfer ICU and discharge. ISMP recommend to use Best possible medication history (BPMH) chart to
gather information. Medication reconciliation is performed by pharmacy technician.

Drug Utilization Review (DUR). Examine the following quality and efficiency of;
• Quality and efficiency of a unit dose drug distribution system
• Quality and efficiency of clinical pharmacy services
• Quality and efficiency of antibiotic drug use in a hospital
• Quality and efficiency of a centralized IV admixture program

DUR are conducted both perspective and retrospective. The perspective DUR involves setting up
parameters such as dosing too high or drug-drug interactions that sent to dispensing pharmacist at the
time and point of service to alert the potential problems.
Retrospective DUR. Performed by the clinical pharmacist reviewing claims of patient several weeks or
months following dispensing of medication to track clinical problems and excess use of high cost
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medications.

Hospital Financing: Health care in Canada is public administration. It is owned and managed by
provincial governments. However provincial, federal, offers hospital funding from health premiums, and
charities.

Distribution of funds %
Hospital 29.9%
Other institutions 9.9%
Physician salaries 12.8%
Other professionals 10.7%
Drugs (Rx and OTC) 17.5%
Other health spending 6.1%
Public health 5.5%
Capital 4.2%
Administration 4.1%
Pharmacy technician Role
• Med. reconciliation
• Sterile preparation can be prepared independently
• Preparing unit dose system
• Final check before delivering to wards

Tips

• Pharmacist functions in hospital pharmacy 

• Pharmacist role in P&T committee 
• Therapeutic equivalent drugs in hospital 
• What is least likely pharmacist functions in hospital pharmacy 
• Who is the last person to check medications in hospital ward 
• A patient in hospital is using different brand of drug, then hospital formulary. Patient wants same
drug? 
• Hospital funding -->
• Medication Reconciliation: gathering medication information from patient at the point of hospital
admittance and discharge.
Can doctor determine price of drug from drug formularies? yes

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Part 4

Pharmacy Practice

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49
Basic Pharmacy Calculations

Question Alerts!
Common questions in pharmacy exam is to ask!
• Conversions
• Ratios and Proportions and Concentration
• Active drug quantity
• Conversion of dosage forms
• Dose Tapering
• IV Rate of infusion

Units
In Metric System Volume
Weight 1 pint = 473 ml = 16 fluid ounces
1 fluid ounce = 29.6 ml = approximately 2
1 Kilogram = 1000 grams
tablespoonfuls
1 Gram = 1000 milligrams
1 fluidram = 3.75 ml scientifically
1 Milligram = 1000 micrograms
1 teaspoonful = 5 ml
1 Microgram = 0.001 milligrams
1 tablespoonful = 15 ml
1 Milligrams = 0.001 grams
One wine glassful = 60 ml
1 Microgram = 10 -6 grams
One tea cupful = 120 ml
1 Nanogram = 10 -9 grams
One full glass = 240 ml
1 Grain (1 gr) = 65 milligrams
4 cups = 1 pint
1 kg = 2.2 lbs
8 pints = 1 gallon
1 gallon = 3.8 L
An "official" dropper contains 20 drops/ml (of
water)

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Pounds and Kilograms or Kilograms (Kg) and Pounds (lbs)

• To convert lbs into Kg = divide by 2.2

• To convert Kg to lbs = multiply by 2.2

Example.
1) A newborn child weighs 10 lbs. What is weight in kg? 10/2.2 =

2) A child weighs 22 lbs, and doctor wants to give 1 mg/kg/day bid drug, how much you should give
per dose?
a. 10 mg/day B. 5 mg/day C. 15 mg/day D. 20 mg/day E. 25 mg/day
22/2.2 = 10 kg= 10 mg
10 mg/day
each dose is 5 mg

A patient weight 180 lbs has admitted to emergence for congestive heart failure and severe edema.
Patient was give furosemide iv infusion for the past 24 hours. After discharge the patient weight was
173 lbs. How many kg patient weight is lost?
A. 7 kg B.3.2 kg C. 2.2kg D. 172 kg E. 173 lbs

180 lbs-173 lbs = 7 lbs

7/2.2 = 3.2 kg

Body Surface Area

"BSA" stands for "body surface area." units are m2. BSA is sometimes used in dosing of medications
(more on this later). A universal equation for calculating BSA of both kids and adults is
BSA in m2 = (H0.3964) (W0.5378) (0.024265)
Where height is in centimetres and weight in kilograms.
BSA in m2 = √ H x W/3600
Height is in centimeters and weight in kg
A prescription order of acyclovir 750 mg/m2, IV tid. The patient weighs 75 kg and is 162 cm tall.
Calculate the dosage to administer?

BSA in m2 = √ (162 cm x 75 kg)/3600

= √ (12,150)/3600
= √3.37 = 1.84 m2
BSA = 1.84 m2
= 750 mg/m2 x 1.84 m2 = 1380 mg tid

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Body Mass Index (BMI)

BMI = weight in Kg/height m2 or Weight in Kg/height m x height m
• BMI = normal 18.9 to 24.9
• BMI = overweight >26 to 30
• BMI = obese >30
• BMI = morbid obese >35

Example.
1) A person body weight is 180 lbs and height is 4 ft 6 in? What is right BMI?
A) normal
B) over weight
C) obese
D) morbid obese
E) none

4.5/3.3 = 1.36 m

180/2.2 = 81 kg

81/ (1.36x1.36) = 44

1 m = 3.3ft (3.28 ft) i.e. the conversion factor from meters to feet is 3.28
or
3.3 ft = 1 m
1 ft = 12 inch
1 m = 39.37 inches
100 cm = 1m

Density (specific gravity)

• Density = Weight/volume (D = W/V)
• Volume = Weight/Density
• Weight = Volume x Density
Water density 1 g/ml

Examples. Water 1000 ml, its density is 1, what is weight water in grams?
so 1000 ml = 1000 g of water or 1 Kg

Glycerine 1000 ml, its density is 1.2, what is weight in g of glycerine?

Weight = Volume x Density
Weight = 1000 ml x 1.2 g/ml = 1200 g

A winter green oil density is 0.9, what is the weight of 1000 ml oil?
Weight = volume x density

Weight = 1000 ml x 0.9 g/ml = 900 g

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A prescription order for glycerine 1200 ml, to prepare suppository in base. Glycerine density is 1.1.
What is weight of glycerine in suppository?

Weight = volume x density = 1200 ml x 1.1 g/ml = 1320 g

Fractions to decimal numbers

To convert fractions to decimal numbers  divide top number by bottom number
• Example: ½ = 0.5
• Example: 3/10 = 0.3
• Example: 10/3 = 3.3

Mixed numbers to decimal number

To convert mixed numbers to decimal number
Example: 2 ¾ = 11/4 = 2.75 or 11 ¾ = 11.75
• Step 1 multiple bottom number by whole number and add with top number.
• Step 2  divide top number by bottom number

Decimal to mixed number

To convert decimal to mixed number
Example: 3.5 = 3 ½
• Step 1  Write the decimal number over one, dividing with one = 3.5/1
• Step 2  Move the decimal point in the top as many places as to right as necessary to form a
whole number.
• Move the same in bottom. 35/10
35/10 = 7/2 = 3 ½
Example: 1.25 = 125/100 = 5/4

Teaspoons (tsp) and Tablespoons (Tbsp)

The physician has prescribed 1 Tbsp of Riopan. The unit dose container available contains 30 ml of this
medication.
The correct dose is _____ ml.
The client has been taking 25 ml of a medication in the hospital. In preparing him to administer this
medication in the home setting, you would teach him to take ___ tsp of this drug.

Milligrams and Grains

You are to administer phenobarbitol gr ¾ . There are scored 60 mg tablets available in floor stock.
You would administer __mg or _____ tablet(s).
65mg x 3/4 = 48 mg

45 mg
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Morphine sulfate gr 1/8 IM is to be prepared from a solution containing 10 mg/1 ml. The volume to be
given is _____ ml.
Ans:
65 (1/8) = 8 mg
10 mg.....................1 ml
8 mg...................?
= 0.8 ml

Millilitres and Ounces

The physician has ordered ss ounce of a laxative. The correct dose is _____ tbsp
ss = one half
ounce = 30 ml
tbsp = 15 ml
Ans. 1 tbsp

You are to administer 5 ml of ferrous gluconate that must be diluted in water to protect the client’s
teeth and gastrointestinal track. The directions in your drug reference state that each ml of this
medication must be diluted in 20 ml of water. Once diluted, the total volume to be administered is
105 ml.
Note.
Diluted in, added to, added in may increase total volume or weight.
Dilute up to, quantity sufficient or qs, mark up to the volume should not increase volume.

Calculations involving percentage, ratios, proportions

Percentage: To convert percent to fractions

25% = 25/100 = ¼
0.25 . 100% = 25%
50% = 50/100 = ½
200% = 200/100 = 2
To convert fraction to percentage: multiply by 100
3/4 . 100 = 75%

Ratios. Relation between two quantities

W/W 1 gram in 100 grams = 1g:100 g = (1/100) x 100 = 1%W/W
W/V 1 gram in 100 ml = 1 g:100 ml
V/W 1 ml in 100 grams = 1 mL:100 g
V/V 1 ml in 100 ml = 1 mL:100 mL

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Ratio Strength

For solids in liquids For liquids in liquids For solids in solids (w/w)
(w/v) (v/v)
Grams /1000 ml of ml / 1000 ml of liquid Grams /1000 grams of Mixture
mixture Or Grains/1000 grains of
mixture

Example
1) Express 0.02% as ratio strength
Solution: 0.02100 ml
210 000 than 15000
2) Dissolving 4.8 g of NaCl in water can make how many millilitres of a 1:1500 solution?
Solution:
We have 1 gram for every 1500 ml of solution
So for 4.8 we will give x ml of solution
X ml = 4.8 * 1500 /1=7200 ml

3. Syrup is an 85% w/v solution of sucrose in water. It has a density of 1.313 g/ml. How many grams of
water should be used to make 125 ml of syrup? (D = W/V)
A. 85 g B. 106 g C. 125 g D. 164 g E. 58 g

125 ml x 1.313 g/ml = 164 g

100 ........... 85
125.............?
= 106
164-106 = 58 g

Working:
• Density of solution =mass/volume
• Density of solution = Weight of solution/125
• 125 x 1.313 = 164 g
• Therefore the weight of the solution will be 164 g
• Now we have 85 grams of sucrose in 100 ml of solution
• Therefore for 125 ml of solution we need (125x85)/100=106 grams the weight of sucrose in this
•
• 100 ml .......... 85 g
• 125 ml............?
• =106 g
• solution =164 –106 = 58 ml

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Ratio percent: W/W%

• Example: 5 g of glucose in 50 mL water, what is ratio percent 10% W/V
(5/50)x 100 = 10%W/V
• Examples: 50 g of glucose in a 1 kg glycerine, what is ratio percent 5% W/W
• Example: If 2% of glucose in water, what is ratio? 2 g/100 ml = 1/50 = 1:50 W/V
• 12.5 g glucose in 100 ml Water, what is ratio percent?= 12.5% w/v
• Example: 2.5% glucose in 80 ml of water? Glucose?

2.5g -------------- 100 ml

?--------------------80 ml
= (80 ml x 2.5 g)/100 ml = 2 g of glucose is present in 80 ml

Example: if 10% of dextrose in water, what is ratio? 1g :10ml W/V

Example: if 50g/L glucose, what is ratio percent? 5%W/V
Example: 100g/1L water, what is ratio percent? 10%
= 5g/50 mL = 5:50 or 1:10
Example: 50 grams of glucose in 1 L?
= 50g/1L =50:1000 = 5:100 = 1:20

Example: Convert 5 grams of glucose in 100 mL into percent?

• 5g/100mL. 100 = 5 W/V%
• 5 grams of glucose in 1L water, what is ratio percent?
• 5/1000 . 100 = 0.5 W/V%
• 50 gram of glucose in 500 ml of water, what is ratio percent?
• 50/500 .100 = 10 W/V%

5 grams of glucose in 500 mL water, what is ratio percent? 5/500 .100 = 1 W/V%

Convert 10 grams of glucose in 10 ml into percent? 10 g/10 mL = 100/1 = 100 w/v%

A drug x is 1 mg/10 ml present. What %W/V? 0.01% W/V
Two ratios with the same value are equivalent.
1/3 x 2/2 = 2/6 = 1/3
If two ratios are equal, then their reciprocal are equal:
If 1/3 = 2/6 then 3/1 = 6/2
Proportions. (two ratios) relation of two ratios is the proportion

Example: How many mg (?) of glucose in 500 mL if this is a equal to 1 g in 1000 ml of water.

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Unknown Known

x mg 1000 mg__
500 ml 1000 ml

X mg = 500 ml x 1000 mg
1000 ml
= 500 mg

How many g (?) of glucose in 250 mL if this is a equal to 1 g in 1000 ml of water?.

Proportion and Percent Calculations

Weight / weight Weight / Volume Volume / Volume

W/W% W/V% V / V%
Number of grams of substance Number of grams of Number of milliliters of a
in 100 grams of solvent or constituent per 100 ml of substance in 100 ml of the
mixture. solvent. solvent

1-How much drug should be added to 30 ml of water to make 10% w/w solution?
Solution:The mass of the final solution in this case in unknown, we only have the mass of solvent
(water) as 30 ml will weight 30 grams.
So know we need a solution which contains 10 grams (10%) of drug in 100 grams of the solution
(solvent + drug).
In this case the solvent will represent 100 –10 = 90%
So if 90% 30 grams, how much is 10 %?
The weight of the drug is = 10* 30/90 = 3.33

2-What is the percentage strength of an injection that contains 50 mg of pentobarbital sodium in each
millilitre of solution?
Solution: [(50 mg / 1 mL) x 1 g /1,000 mg] x 100 = 5 % w/v

3-If an injection contains 0.5% w/v of diltiazem hydrochloride; calculate the number of milligrams of
the drug in 25 mL of injection.
Solution: [(0.5 g / 100 mL) x ( 1,000 mg/ 1 g)] x 25 mL = 125 mg

4-How many grams of potassium permanganate should be used in compounding the following
prescription?
Rx
Potassium permanganate 0.02% w/v
Purified water ad 250 mL
Solution: (0.02 g / 100 mL) x 250 mL = 0.05g = 50 mg = 50, 000 µg

Parts Per Million (ppm)

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Occasionally, you will see a number followed by the term "ppm." This stands for "parts per million"
and is most often used to indicate the amount of trace substances in water. The standard dilution for
fluoride added to a municipal water source, for example, is 1ppm. In every 1,000,000 ml of water,
therefore, there is 1 g of fluoride.

1) Express 5 ppm of iron in water as ratio strength and in percentage strength

Solution: 5 ppm = 5 parts in 1,000,000 parts
Ratio strength: 5:1,000,000 = 1:200,000
Percent strength: (5 /1,000,000) x 100 = 0.0005%

2) Express 10 ppm, in percent strength? 0.001%

10:1,000,000 = 0.001%

3) Express 0.0001% in how many ppm? 1ppm

4) Express 0.0005% of iron in water as parts per million (ppm)?

(0.0005 x 1000000)/ 100 = 5:1000, 000 = 5 ppm

5) Express 0.023% of iron in water as ppm? [0.023 x 1,000, 000]/100 = 230 ppm
____________________________________________________________________

1-A parenteral solutions used in TIPS pharmacy. If 100 g of parenteral solution dissolved in 900 mL of
petrolatum (Density of petrolatum is 0.9 g/mL), the concentration of parenteral solution is: D = W/V
900 mL x 0.9 g/mL = 810 g
810g+100g = 910g
100g/910g .100 = 10.9%
____________________________________________________________________

2) If 500 mL of a 15% v/v solution is diluted to 1,500 mL, what is the resultant percentage strength?
Q 1 (quantity) x C 1 (concentration) = Q 2 (quantity) x C 2 (concentration)
500 (mL) x 15 (%) = 1,500 (mL) x? (%)
1,500 x = 7,500
x = 7,500 / 1,500
x = 5% v/v
___________________________________________________________________
3. If syrup containing 65% w/v of sucrose is evaporated to 85% of its volume, what percent of sucrose
will it contain?

Note any convenient volume of syrup may be selected, say 100 mL. Then, 85% x 100 mL = 85 mL (V 2 )
C1 = 65
V1 = 100
C2 = ?

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V2=85
C2 = ( C1V1)/V2

C2= 76.47% w/v

_____________________________________________________________________________
If 1 gallon of a 30% w/v solution is evaporated so that the solution has strength of 50% w/v, what is its
volume in milliliters?

C1 = 30
V1 = 3800 mL
C2 = 50
V2=?
V2 = (C1V1)/C2
= (30 x 3800 mL)/50
= 2280 mL

Solution: Q 1 x C 1 = Q 2 X C 2
3,785 (mL) x 30 (%) = x (mL) x 50(%)
x = 2,271 mL

5) A pharmacist mixed 100 mL of 37% w/w concentrated hydrochloric acid (specific gravity, 1.20) with
enough purified water to make 360 mL of diluted acid. Calculate the percentage strength (w/v) of the
diluted acid.
100 mL x 1.20 (specific gravity) = 120 g of concentrated acid
120 g x 37% w/w = 44.4 g HCI
(44.4 g / 360 mL) x 100 = 12.33% w/v
________________________________________________________________________

Drug Strength Expressions. Units (International units) or IU. Insulin, Penicillin G, Vitamin K, Vitamin E,
Vitamin A, Vitamin D, Heparin, LMWH (Fragmin), interferon alpha, Nystatin, Polymixin, and Bacitracin.

Example. U-100 insulin contains 100 units/mL

Rx
Insulin 40units
For 60 days and bid.
How many ml of insulin you dispense?
Solution: (1 mL/100 units) x 40 units = 0.4 mL
For 60 days and two times a day = 48 mL

If U-500 insulin (Humulin R U-500) is ordered for patient, a 1 ml syringe should be used. Dr prescribed
40 U of Humulin R U-500 insulin. How many ml of insulin is drawn in syringe?
500 .............. 1 mL
40.................?
= 0.08 mL
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2.How many millilitres of a heparin sodium injection containing 200,000 heparin units in 10 mL should
be used to obtain 5,000 heparin units?
Solution:
200,000..........10 ml
5000............?
(10 mL/200,000 units) x 5,000 units = 0.25 mL

Practice calculations

1. In dosing the drug gentamicin in pediatric patients, for every 1 mg/kg of gentamicin administered,
serum drug concentrations are expected to increase by 2.5 µg/ml. What would be the expected serum
drug concentration following an administration of a 2.5 mg/kg dose of gentamicin?
A) 5 µg/ml B) 6.25 µg/ml C) 10 µg/ml D) 2.5 µg/ml

2) An elixir is to contain 250 mg of an alkaloid in each teaspoonful dose. How many grams of the
alkaloid will be required to prepare 5 liters of the elixir?
A) 0.25g B) 5g C) 250g D) 2.5g

3-A pediatric product contains 100 mg of erythromycin ethylsuccinate in each dropperful (2.5ml) of
the product. How many kilograms of erythromycin ethylsuccinate would be required to prepare 5000
pint-size bottles?
A-74.6 kg B-84.6 kg C-99.5 kg D-94.6 kg

4-A physician places a patient on a daily dose of 48 units of U 80 insulin (80units/mL). How many ml
should the patient inject each day?
A-0.4 mL B-0.5 mL C-0.6 mL D-0.25 mL

5-A 20-ml vial of biologic solution is labeled “2.0 megaunits.” How many units of drug are present in
every ml of solution?
A) 2000 B) 1000 C) 100,000 D) 10,000

6-A prescription calls for 10 units of a drug to be taken 3 times a day. How much will the patient have
taken after 7 days?
A-21.0 units B-0.21 units C-2.10 units D-210 units

7-A physician orders Meprobamate 0.2 g. How much is to be administered if the dose on hand is 400
mg. in each tablet?
A-do not dispense B-give 2 tablets C-give 1 tablet D-give ½ tablet

8-The usual initial dose of chlorambucil is 150 µg per kg of body weight once a day. How many
milligrams should be administered to a person weighing 154 lbs.?
A-10.5 mg B-18 mg C-15 mg D-8 mg

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9-An initial heparin dose of not less than 150 units/kg of body weight has been recommended of open
heart surgery. How many ml of an injection containing 5000 heparin units per milliliter should be
administered to a 300 pound patient?
A-5.1 µl B-4.1 µl C-5.1 ml D4-.1 ml

10-The pediatric dose of cefadroxil is 30 mg/kg/day. If a child is given a daily dose of 2 teaspoonful of
a suspension containing 125 mg of cefadroxil per 5 ml, what is the weight in lb. of the child?
A-19.5 lbs. B-18.8 lbs. C-18.3 lbs. D-18.1 lbs.

11-If the loading dose of Kanamycin is 7 mg/kg of body weight, how many grams should be
administered to a patient weighing 130 lbs.?
A-0.492 g B-0.414 g C-414 g D-0.485 g

12-The adult dose of a liquid medication is 0.1 ml/kg of body weight as single dose. How many
teaspoonfuls should be given to a patient weighing 220 lbs.?
A-2 tsp. B-2.5 tsp. C-2 tbsp. D-2.5 tbsp.
13-If a prescription order requires 25 g of concentrated HCI (Density 1.18g/ml), what volume should
the pharmacist measure?
A-29.50 ml B-0.0212 ml C-23.0 ml D-21.2 ml

14-If the dose of a drug is 0.5mg/kg body weight/day, how many mg will a 35lb infant receive per
24hours?
A-7.9 mg B-7.1 mg C-7.2 mg D-7.4 mg

15-What is the weight of 60 ml of oil whose density is 0.9624 g/ml?

A-5.770 g B-57.7 g C-6.0 g D-0.577 g

16-A prescription calls for 0.3 g of phosphoric acid with a specific gravity of 1.71. How many milliliters
should be used in compounding the prescription?
A-0.5 B-0.7 C-0.18 D-0.3
17-How many ml of 0.9% (w/v) NaCl solution should be prepared from 250 ml of 25% (w/v) solution?
A-3750 B-2500 C-6944.4 D-9

18-A patient is determined to have 0.8 mg of glucose in each milliliter of blood. Express the
concentration of glucose in the blood as mg%.
A-800 mg% B-0.8 mg% C-8 mg% D-80 mg%

19-How many mL of a 1:400 (w/v) stock solution should be used to make 4 liters of a 1:2000 (w/v)
solution?
A-1000mL B-200 mL C-800 mL D-1600mL

20-If a patient is determined to have 100 mg % of blood glucose, what is the equivalent concentration
in terms of mg/dL?
A-1 B-10 C-40 D-100

21-Strong Iodine Solution USP contains 5% w/v iodine. How many mg of iodine are consumed daily if
the usual dose is 0.3 mL t.i.d.?
A-15 B-90 C-22.5 D-45
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22-Express in percentage the fluoride concentration in drinking given in 0.6 ppm.

A-0.06% B-0.00006% C-0.0006%

23-How many grams of dextrose are required to prepare 4 liters of a 5% solution?

A-0.2g B-200g C-2g D-20g

24-Change to percent the number 1/300.

A-3% B-33% C-3.3% D-1/3%

25-A Pharmacy tech adds 75 mL of strong iodine solution USP (5.0% w/v) to 1 liter of sterile water for
irrigation. What is the % w/v of iodine present?
A-0.35% B-0.375% C-0.53% D-0.60%

26-How many grams of potassium citrate are needed to prepare 1 liter of 10%?
A-1000 g B-50 g C-100 g D-10 g

27-How many grams of a drug are required to make 120 mL of a 25% solution?
A-30 g B-10 g C-12.0 g D-12 g

28-Calcium Hydroxide Topical Solution contains 170 mg of calcium hydroxide per 100 mL at 15º C.
Express this concentration as a ratio strength.
A-1: 688 B-1: 888 C-1: 588 D-1: 788

29-How many mg of isofluorophate are contained in 15 g of a 1: 10,000 ophthalmic solution of

isoflurophate in peanut oil?
A-1.7 mg B-1.9 mg C-1.8 mg D-1.5 mg

30-Express 0.2 % in a ratio strength.

A-1: 5000 B-1:50 C-1: 500 D-1:5

31-How much of a substance is needed to prepare 1L of a 1: 10,000 solution?

A-0.1 g B-10 g C-0.01 g D-1.0 g

32-A cupric chloride injection (0.4 mg Cu/mL) is used as an additive to IV solution for TPN. What is the
final ration strength of copper in the TPN solution if 2.5 mL of the injection is added to enough of the
IV solution to prepare 500 mL?
A-1: 500 B-1:5000 C-1: 500,000 D-1: 50,000
33-How many milliliters of a 23.5% (w/v) concentrate of Sodium Chloride solution should be used in
preparing 650 mL of a stock solution such that 30 mL diluted to liter will yield a 1: 5000 solution?
A-0.2 mL B-4.33 mL C-18.44 mL D-11.75 mL

34-You have a stock solution of 50% Sodium citrate and you were asked to prepare 300 mL of a 10%
solution. How many mL is needed?
A-20 B-15 C-30 D-60

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35-How many milliliters of 1:16 solution of sodium hypochlorite should be used in preparing 5,000 mL
of a 5% solution of sodium hypochlorite for irrigation?
A-800 ml B-2500 ml C-4000 ml D-300 ml

36) Prepare 1000 ml of KMnO 4 1:12,000 compresses out of KMnO 4 1: 8,000.

A-Add 333.3 mL water to 1000 mL KMnO 4 1: 8,000
B-Add 666.6 mL water to 333.3 mL KMnO 4 1: 8,000
C-Add 333.3 mL KMnO 4 1: 8,000 and enough water to make final volume 1000 mL
D-Add 333.3 mL water to 666.6 mL KMnO 4 1: 8,000

37-How many milliliters of 24% (w/v) concentrate of saline solution should be used in preparing 600
mL of a solution such that 10 mL diluted to a liter will yield a 0.09% solution?
A-300 ml B-150 ml C-50.0 ml D-225 ml

38-The only source of Sodium Chloride is in the form of tablets, each containing 5.0 g. How many
tablets should be used in preparing 3000 litres of a solution of such strength that 20 mL diluted to 100
mL with water will yield a 0.9% (w/v) solution?
A) 60,000 tablets B) 27,000 tablets C) 12,000 tablets D) 9,000 tablets

39-How many grams of 10% (w/w) ammonia solution can be made from 1800 g of 28% (w/w) strong
ammonia solution?
A) 6428.57 g B) 5040 g C) 50,400 g D) 642.86 g

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 50
Dosage Calculations
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Tapering dosage for prednisone
• Number of tablets for prophylaxis therapies
• Calculating dosages of loading dose of antibiotics
• Calculating dosages for contraceptives pills

One of the most common calculations in pharmacy practice is that of dosages. The available
supply is usually labeled as a ratio of an active ingredient to a solution:
active ingredient (available)/solution (available)

The prescription gives the amount of the active ingredient to be administered. The unknown
quantity to be calculated is the amount of solution needed in order to achieve the desired
dosage of the active ingredient. This yields another ratio:
active ingredient (to be administered) / solution (needed)

The amount of solution needed can be determined by setting the two ratios equal:
[active drug/Solution available] = [active drug (to be administered)/ solution (needed)]

When solving medication-dosing problems, use ratios to describe the amount of drug in a
dosage form (tablet, capsule, or volume of solution). It is important to remember that the
numerators and denominators of both fractions must be in the same units – for example,
mg/ml, 5 mg/ml or mg/tablets = mg/tablets.

CHILDREN DOSES:
1. Young’s Rule: Child dose = Age/Age + 12 x Adult’s dose
2. Cowlings Rule: Infant dose = [Age (at next birthday) x Adult’s dose]/ 24
3. Frieds Rule: Infant dose = [Age (in months) x Adult’s dose]/ 150
4. Clarks Rule: Child dose = [ weight (in pounds) x Adult’s dose)]/150
Tips: Rarely applied now, generally dose for children is depending on weight of pt. & the
technician should ask the agent or caregiver about the weight of pt. so that the pharmacist can
check the dose.
Example
If the adult dose of X, is 5 mg. What is the dose for child of 8 years?
Since we know according to
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Young’s rule: Child dose = AgexAdult’s dose

Q&A
1. A prescription calls for 10 units of a drug to be taken 3 times a day. How much will the
patient have taken after 7 days?
A-21.0 units B-0.21 units C-2.10 units D-210 units
Ans: D
10 units x 3 x 7 = 210 units

2. A physician orders Meprobamate 0.2 g. How much is to be administered if the dose on hand
is 400 mg. in each tablet?
A-do not dispense B-give 2 tablets C-give 1 tablet D-give ½ tablet
Ans: D
Tips: 200 mg/400 mg = 1/2 tab

3) Prednisolone each tablet containing 5 mg. Start 35 mg and then taper by 5 mg every 1 day.
How many tablets are needed?
A) 20 tab B) 56 tab C) 14 tab D) 28 tab E) 8 tab
Ans: D
Tips: 7 + 6 + 5 + 4 + 3 + 2 + 1 = 28 tablets for 7 days

4) Prednisolone each tablet containing 5 mg. Start 35 mg and then taper by 5 mg every 2 day.
How many tablets are needed?
A) 20 tab B) 56 tab C) 14 tab D) 28 tab E) 8 tab
Ans: B
Tips: 7+7+6+6+5+5+4+4+3+3+2+2+1+1 = 56 tablets

5) Doctor prescribed a dose of 180 mg TID of Amoxicillin suspension for 10 days. Best Amoxicillin
suspension size to pick up and reconstitute is
A) Amoxicillin 250 mg/5 ml, 100 ml size
B) Amoxicillin 250 mg/5 ml, 150 ml size
C) Amoxicillin 125 mg/5 ml, 100 ml size
D) Amoxicillin 125 mg/5 ml, 150 ml size
Ans.(B)
(180 x 5 ml)/ 250 =3.6 ml 3.6 ml x 3 doses= 10.8 ml 10.8 x 10= 108 ml
Tips. So it is better to pick out 250 ml/5 ml, 150 ml size.
********
7) A patient who is 3 year old experiencing sore throat. His Dr. prescribed for him:
Rx
Zithromax 200 mg
1 QD for 5/7 days
Best bottle of Azithromycin suspension to choose for reconstitution is:
A) Azithromycin 300 mg which is 100mg/5ml
B) Azithromycin 600 mg which is 200mg/5ml
C) Azithromycin 900 mg which is 200mg/5ml
D) None of the above
Ans. (B)
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Tips: Since give for 5 days will constitute 1000mg so 2 bottles of Azithromycin 600mg is ok.

8) A 3-year-old boy with otitis media. Doctor prescribed Amoxicillin suspension in a dose of 90
mg/kg for 5 days. Child weight is 56 lbs. If the product in the pharmacy is 250 mg/ 5ml and the
Doctor wants to give it in a 3 divided doses. How much is the total volume required.
A) 100 ml of 250 mg/5ml
B) 150 ml of 250 mg/5ml
C) 200 ml of 250 mg/5ml
D) 200 ml of 125 mg/5ml
E) 225 ml of 250 mg/5ml
Ans. (E)
56 lbs /2.2 lbs = 25 kg
90 x 25 = 2,250
250 mg________5 ml
2,250________X
X= 2250 x 5 / 250= 45 ml per day
45 ml x 5 = 225

9) 3 parts per million of CO 2 in water is equal to

A) 0.3 mg b) 3 mg C) 3 g d) none of the above
Ans. (A)
3 parts g-------------1000 000
X-----------------100
X= 300/1000 000 = 3 x 10-4 g = 0.3 mg

10) 0.05 mg of glucose in 1L of water equal to:

A) 50 parts per million
B) 5 parts per million
C) 0.5 parts per million
D) 10 parts per million
Ans. (A )

0.05mg-------------------1000ml
x----------------------------1000000
hence, 50 parts per million

11) A patient who is 3 year old experiencing sore throat. His Dr. prescribed for him:
Rx
Zithromax 200 mg
QD for 5/7 days
Best bottle of Azithromycin suspension to choose for reconstitution is:
E) Azithromycin 300mg which is 100mg/5ml
F) Azithromycin 600mg which is 200mg/5ml
G) Azithromycin 900mg which is 200mg/5ml
H) None of the above
Ans. (B )
Since give for 5 days will constitute 1000mg so 2 bottles of Azithromycin 600mg is ok.
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12) 20 mg of Gentamycin Sulfate inj. In 2 ml of water was added to 500ml glucose water. The
concentration of Gentamycin is going to be:
A) 0.08mg b) 0.16mg c) 0.09mg d) none of the above
Ans. (A)
(20mg) x (2ml) = (500ml) x (X)
X= 40/500 =0.08 mg of Gentamycin Sulfate in 500 ml of glucose water.

13) Rx
40mg M.S contin I BID for 10days
Available MS contin 20mg.
The number of M.S contain given
A) 20 B) 40 C) 10 D) None of the above
Ans. (B )
40 x 2 = 80 x 10 = 800 mg
800 ÷20 mg= 40 tab

14) 50 grams of Griseofulvin HCl was added to 20ml of Glycerine to form a paste. Density of
Glycerine is 1.25. The final concentration of Griseofulvin in the paste dosage is:
A) 80% w/w
B) 40% w/w
C) 66.7% w/w
D) 33.3% w/w
Ans. (C )
20ml x 1.25 = 25gm of Glycerine
50% w/w = wt of solute / (wt of solute + wt of solvent)
=[ 50 / (50 + 25)] x 100% = 5000 / 75= 66.7% w/w

15) Rx
Ratio-prednisolone 1% ophthalmic drops
Mitt: 5ml
Sig. Gtt ii.o.s
On the label the instruction should be:
A) Instill 2 drops on the right eye
B) Instill 2 drops on both eye
C) Instill as directed
D) Instill 2 drops on the left eye
Ans. (D)

16) A 3 year old boy with otitis media. His doctor prescribed for him Amoxicillin suspension in a
dose of 90mg/kg for 5 days. His weight is 56 lbs. If the product in the pharmacy is 250mg/ml
and the Doctor wants to give it in a 3 divided doses. How much is the total volume required.
A. 100ml of 250mg/5ml
B. 150ml of 250mg/5ml
C. 200ml of 250mg/5ml
D. 200ml of 125mg/5ml
Ans. (B)
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36 lbs/2.2 lbs = 16.36 kg
90 x 27.27 = 1472

250 mg________5ml
1472.7________X
X=[(1472.7 x 5) ÷ 250] = 29.45ml per day
29.45 x5 = 147.25

17) Rx
Desyrel 50 mg tablet
S: take 1 tab H.S
M: 1 month
The correct label is
A) 25mg Desyrel, take 2 tabs once daily
B) 25mg Desyrel, take 2 tabs at bed time
C) 100mg Desyrel, take ½ tab everyday
D) 100mg Desyrel, take ½ tab at night
Ans. (B)
Tips: It is better to give 2 tabs than half tablet.

18) A Doctor prescribed Hyderm 1% to be mixed with clotrimazole 1% as 2:1 ratio, and the total
weight of the mixture is 100gm. The label should be:
A) 66.7gm of H.C 1% and 33.3 Clotrimazole 1%
B) 75gm of H.C 1% and 25% of Clotrimazole 1%
C) 100gm of H.C 2% and 25% Clotrimazole 1%
D) None of the above
Ans. (A)
H.C 1% 66.7gm Clotrimazole 1% 33.3gm

66.7g / 33.3gm 33.3g/33.3 g

= 2parts =1part
Hence 2:1

19) Rx
Betaderm 1% in Glaxal base (4:1)
Mitt: 100gm
Sig: ud
The quantities of Betaderm and Glaxal base should be:
A) Betaderm 70 g and Glaxal base 30 g
B) Betaderm 20 g and Glaxal base 80 g
C) Betaderm 80 g and Glaxal base 20 g
D) None of the above
Ans.(C )
4:1 means 5 parts
5: 100 g
100 g ÷ 5= 20 g

thus: Betaderm 80 g and Glaxal base 20 g

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Betaderm Glaxal base
80 g / 20 g 20 g /20 g
4parts 1part

20) Patient taking hydroxyzine tablet 20mg 2 times daily. The doctor wants to switch him to
hydroxyzine syr. 10 mg/5ml to be given 5ml 4 times for 10dyas.
The volume of Hydroxyzine given is:
A) 50 ml B) 100ml C) 150ml D) 200ml
Ans (D)
20mg TID x 2 = 40mg per day
Syrup:
5ml x 4 = 20ml i.e. 40 mg since the syrup is 10mg/5ml.
20ml x 10 days = 200 ml.

21) A 9 year old child was given Cephalexin 250mg/5ml to use it as 10ml. 4 times daily. His
doctor want to switch him to Cephalexin 500mg 4x daily for 1 week. The number of capsules
should be:
A) 28 cap of Cephalexin 500 mg
B) 56 cap of Cephalexin 250 mg
C) Both A and B
D) None of the above
Ans. (C )
250 x 2 = 500mg each dose
500mg x 4 = 2000mg per day , the child is using from suspension.
The switching to cap will require 500 x 4 = 2000mg Cephalexin cap thus 4 cap of 500mg
Cephalexin and since it is for 7 days, then 4 x 7 = 28 cap.

22) Rx
Apo- Hydrochlorothiazide 25mg
Sig: IAMPC
The Latin abbreviation mean
A) 1 tablet in the morning before meal
B) I tablet in the morning after meal
C) 1 tablet in the morning and in the evening
D) None of the above
Ans ( B)

23) 50 ml of 10% Calcium gluconate was diluted 6 times. The conc. of the resulted Calcium
gluconate will be
A) 20 % B) 1.67% C) 5% D) 4%
Ans. (B)
50ml x 10% =300ml (X)
X= 500 ÷ 300 =1.67%

24) A Patient profile:

Topiramate 1QD HS 100mg tablet
Sodium valproate 1QD 30 tablets
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Tramacet 1 TID 30 tablet
Paxil 20mg 1 QD HS 30 tablet
All medications filled in a dosette weekly.
New prescription:
Tylenol # 3 30 tablets
1-2 Q 4-6h prn
The pharmacist should fill in:
A) 5 medications
B) 6 medication
C) Call doctor to confirm whether Tylenol # 3 should be dispensed in a dosette or not.
E) None of the above.
Ans. (A)
Tips: Tylenol # 3 is on need basis and hence cannot be dispensed in a dosette but in a vial.

25) Rx
Amoxicillin 100mg TID for 7 days.
Available: 125mg/5ml 100ml suspension
125mg/5ml 150ml suspension
250mg/5ml 100ml suspension.
A) Use 125 mg/5ml (150ml) suspension
B) Use 125mg/5ml (100ml) suspension.
C) Use 250 mg/5ml (100ml) suspension
D) None of the above.
Ans. (B)
100mg x 3 = 300mg is the dose/day
125 mg ……. 5ml
300mg ……… x
X = 12 ml x 7 = 84ml

26) Cefuroxime axetil 50mg BID for 10 days

Available as: 150 mg (100ml), 250mg/5ml (150ml), 150mg/5ml (75ml)
A) Use 250 mg/5ml (150ml) suspension.
B) Use 150 mg/5ml (75ml)
C) Use 250 mg/5ml (100ml)
D) None of the above.
Ans. (B)

50 mg X 2 = 100 mg is the total daily dose.

150------------ 5 ml
100 mg ----- X
X = 3.3 ml
3.3 x 10 = 33 ml
Thus 75 ml is sufficient.

27) Rx
Endocet 5-325 mg
1-2 tablet QID prn for 10 days.
Maximum allowed quantity is:
A) 40 tablets
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B) 80 tablets
C) 100 tablets
D) None of the above
Ans. (B)

28) Rx
Fluticasone inhaler 100 mcg BID for 3 months.
Content of each inhaler is 60 doses. Pharmacist should dispense:
4 inhalers B) 6 inhalers C) 3 inhalers D) None of the above.
Ans. (C)
Tips: Two doses per day means 60 doses per month and this is available in each inhaler. Thus for
3 months 1 x 3 = 3 inhalers.
Each puffer contains 100 mcg.

29) Rx. Cephalosporin suspension 25 mg QID for 10 days.

Dose of Cephalosporin is 25-50 mg/kg.
Weight of child 6 lbs.
A) Dose is within normal range.
B) Dose is exceeding the normal range.
C) Dose is less than the normal range.
D) Dose is in the toxic level.
Ans. (A)
Tips: (6 lbs x 1 kg) / 2.2 lbs = 2.73 kg
25 mg x 4 = 100 mg is the daily dose.
25 x 2.73 = 68 mg is the minimum dose.
50 x 2.73 = 136 mg is the maximum dose
so the range of the dose must be 68-136 mg.
Doctor prescribed 25 mg QID that means 25 x 4 = 100 mg. The dose is within the normal range.

30) Rx. Amoxicillin Clavulanate 875/125

Each tsp is equivalent to that strength.
Doctor wants to give 1 tsp TID for 10 days. The volume that is required is:
A) 75 ml B) 100ml C) 125 ml D) 150 ml
Ans. (D)
1 tsp = 5ml
TID = 3 x 5 = 15 ml
15 x 10 days =150 ml

31) In the above question, if the patient weighs 60 lbs and doctor wants to give him a dose of
90mg/kg. The daily dose in ml will be:
15 ml B) 14 ml C) 10 ml D) 5 ml
Ans. (B)
60 lbs x 1 kg/2.2 lbs = 27.3 kg
90mg/kg x 27.3kg = 2457 mg
So 875 mg Amoxicillin is in 5 ml
2457 mg is in _____X
X = 14 ml

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32) Four family members want to use a cream (Permethrin) volume of 60 ml/person. The family
consists of 2 adults and 2 kids. The volume of mix cream is 60 ml. The amount required for the
family considering all have existing lice.
A) 240 ml B) 180 ml C) 300 ml D) None of the above
Ans. (D)
60 x 4=240ml (to be repeated after 7-9 days)
: 240x2= 480 ml

33) In the above question if only one of the kid had existing lice and he is a bedmate with his
sister. The family should buy considering Nix is in 60ml.
240ml B) 180ml C) 120ml D) 150ml
Ans. (A)
Tips: The bedmate has the tendency to get the lice.

34) 100 gram of Sulfur 5% is required to apply for whole body of a child 5 years old having
scabies. The infection is only in his hands and arms. If his hands and arms represent 1/5 of his
body and the treatment is for 3 consecutive days. The amount of Sulfur 5% to be used is:

A) 60 g B) 300 g C) 15 g D) 20 g
Ans. (B)
Tips: The whole body must be applied with Sulfur even though infection is on hands only. Thus
for 3 days is 100gm x 3 = 300gm.

35) How many teaspoonfuls would be prescribed in each dose of a medicine of fluidounce VI
contained 16 dose?
A)
6 x 30 = 180
180 ÷ 5 = 36 teaspoonful
36 ÷ 16 = 2.25 teaspoonful in each dose
or
We know each teaspoonful equals 1/6 of a fluidounce therefore = 29.573 ÷ 6 = 4.928833 ml. In
other words each fluidounce = 6 teaspoonful
6 x 6 36 teaspoonful, and 36 ÷ 16 = 2.25 teaspoonful has to be taken
________________________________________________________________________
51-How many drops would be prescribed in each dose of a medicine if 15 ml contains 60 doses?
The dispensing dropper calibrates to 32 drops/ml
15 ÷ 60 = 0.25 ml, and 0.25 x 32 8 drops per dose
________________________________________________________________________
52-How many milliliter of medicine is needed to produce if 2 tablespoonfuls twice a day for 8
days
2 x 2 x 8 x 15 = 480 ml or 2 x 2 x 8 = 32 tablespoonful is required for the treatment and if 323 is
divided by 2 we will get the volume in fluidounce, 32 ÷ 2 = 16 fl oz.
No. of doses = 2 times/day x 8 days = 16 doses
Volume of each dose 16 ÷ 16 = 1 fl oz or 30 ml
________________________________________________________________________
53-How many mgs of a drug are needed to prepare 72 doses of 1/12 gr. Each.
72 x 1 ÷ 12 = 72 ÷ 12 = 6 gr., we know each grain is 65 mgs therefore,
6 x 65 = 390 mg is required
5-If 125 tablets contain 0.05 gram of a drug. How much is contained in a tablet?
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0.05 x 1000 = 50 mg, if 50/125 = 0.4 mg or 400 microgram
________________________________________________________________________
54-Given the following prescription
Codeine phosphate 0.6 g
Ammonium Chloride 6.0 g
Cherry syrup ad. 120 ml
SIG: 1 teaspoonful prn cough
Tips: Always the domestic measured should be accompanied by mls. so we say one teaspoonful
(5ml).
______________________________________________________________________
55-How much medications are contained in each dose?
0.6 x 5 ÷ 120 = 0.025 g or 25 mg of Codeine
6 x 5 ÷ 120 = 0.25 g or 250 mg
_______________________________________________________________________
56-How many grams of a chemical are needed to make 120 ml of a solution in which each
teaspoonful will contain 3 mg of chemical?
120 ÷ 5 = 24 teaspoonful, then 24 x 3 = 72 mg, which means 72 ÷ 1000 = 0.072 grams
________________________________________________________________________
57-The dose of a drug is given as 3 mg/kg of weight. How much medication should be given to a
patient weighing 154 lb.?
154 x 454 = 69919 grams or 69916 ÷ 1000 = 69.916 kg
69.946 x 3 = 209.748 mg each dose about 210 mg
________________________________________________________________________
58-A powder is divided into 36 capsules, if each capsule contains 0.5 mg of X and 15 mg of Y and
enough of Z to make 0.3 gm. How much of each drug is in the original powder?
0.3 x 1000 = 300 mg of total powder in each capsule
0.5 + 15 = 15.5 mg of X and Y, 300-15.5 = 284.5 of Z in each capsule
0.5 x 36 = 18 mg of X in original powder
15 x 36 = 540 mg of Y
284.5 x 36 = 10242 mg of Z
_______________________________________________________________________
59-If the dose of a medicine is 5 mg/kg of weight. How much is the dosage expressed in
mg/pound?
5 ÷ 2.2 = 2.273 mg/lb.
60) Dr. prescribed a dose of 180mg TID of Amoxicillin suspension for 10days. Best Amoxicillin
suspension size to pick up and reconstitute is
a) Amoxicillin 250mg/5ml, 100ml size
b) Amoxicillin 250mg/5ml, 150ml size
c) Amoxicillin 125mg/5ml, 100ml size
d) Amoxicillin 125mg/5ml, 150ml size
Ans.(B)
(180 x 5ml)/ 250 =3.6ml 3.6ml x 3 doses= 10.8ml 10.8 x 10= 108ml
So it is better to pick out 250ml/5ml, 150ml size.

63) Valproic acid syrup is available as 250 mg/5 cc. If a patient were taking 1000 mg in the
morning and 750 mg in the evening, how many cc of syrup would you dispense for a 30-day
supply ?
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A. 1500 cc B. 1050 cc C. 500 cc D. 480 cc
Ans: B- 1050cc. In this type of calculation first find out number of cc required for 1 day.
Morning dose
Drug ml of solution
250 mg present 5 cc of solution
1000 mg ?
1000 x 5 cc / 250 = 20 cc of solution.
Evening dose
Drug ml of solution
250 mg present in 5 cc of solution
750 mg ?
750 x 5cc / 250 = 15 cc of solution.
For a 30 day supply of Valproic acid
(20 cc (am) + 15 cc (pm) ) x 30 = 1050cc.

64) A prescription calls for 10 units of a drug to be taken 3 times a day. How much will the
patient have taken after 7 days?
A. 21.0 units B. 0.21 units C. 2.10 units D. 210 units
Ans: D
Tips: 10 units x 3 x 7 = 210 units
__________________________________________________________________
Drug Strength Expressions
Units (International units): Some examples of drug measured in international units (IU). Insulin,
Penicillin G, Vitamin K, Vitamin E, Vitamin A, Vitamin D, Heparin, LMWH (Fragmin), interferon
alpha, Nystatin, Polymixin, and Bacitracin.
________________________________________________________________________

65) U-100 insulin contains 100 units/mL

Rx
Insulin 40units
For 60 days and bid.
How many ml of insulin you dispense?
Solution:
(1 mL / 100 units) x 40 units = 0.4 mL
For 60 days and two times a day = 48 mL
________________________________________________________________________
66-How many milliliters of a heparin sodium injection containing 200,000 heparin units in 10 mL
should be used to obtain 5,000 heparin units?
Solution: (10 mL / 200,000 units) x 5,000 units = 0.25 mL
________________________________________________________________________
67. If the suggested continuous infusion rate of a drug is 10 mg/kg/hr q8h, how many ampoules
of the drug would be needed daily for a 100 kg patient if each 25 mL ampoule has a
concentration of 10 mg/mL?
a) 4 b) 8 c) 25 d) 96
Ans: D
Working:
Interpreting data
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 i. Infusion rate is 10 mg/kg/hr; for a 100 kg patient 1,000 mg/kg/hr are required, or 8,000
mg q8h.
ii. Each 25 ml ampoule contains 10 mg/ml = 250 mg per ampoule.

Calculate
iii. 8,000 mg are contained in (8,000/250) = 32 ampoules q8h (4 ampoules per hour) = 96
ampoules per day.

68) You have on hand 10ml ampoule of isoproterenol 1:5000 solution. How much of this solution
would be needed to give 500ml of 0.25mg/100ml of the solution?
0.25 mg 100ml
x 500ml
x = 1.25 mg
1000mg 5000 ml soln
Thus 1.25 x 5 ml
x = 6.25 ml
69) How long would you infuse a phenytoin dose of 20mg/kg in a 33 lb child at a rate of
0.5mg/kg/min.
33 lb x 1 kg = 15 kg x 20 = 300 mg dose
2.2 lb
0.5 mg/kg/min x 15 kg = 7.5 mg/min
7.5 mg = 1 min
300 mg x
x = 300mg/ 7.5
= 40 mins.

70) You have on hand 10ml ampoule of 1/2000 solution. How much of the solution would be
needed to give 500ml of 0.35mg/100ml of the solution?
0.35mg = 100ml
X 500ml
X= 1.75mg
1000mg = 2000ml
1.75mg X
X= (1.75 / 1000) x (2000)
= 3.5ml

71) Using a vial containing 200,000 units of penicillin G potassium how many mL of solvent
should be added to the dry powder to prepare a solution having a concentration of 25,000 units
per mL.
a) 8 b) 10 c) 15 d) 25
Ans: A
Working:
i. vial contains 200,000 units of penicillin G
ii. Each mL of reconstituted solution will contain 25,000 units. Therefore, you will need
(1/25,000) x 200,000 = 8mL to produce a solution containing 25,000 units / mL

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51
Dilution, Concentrations
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Dilution from Stock C1 x V1 = C2 x V2 or Q1 x C1 = Q2 x C 2
• Using Allegation methods to prepare ointments.
• Converting from milliequivalent to milligram mEq = [mg x valence/M. wt (mg)]
• Converting from milligram to milliequivalent mg = [mEq x M. wt/Valence]

Stock solution. Solutions of known concentration that are prepared in the most concentrated
form. Sometimes a stock solution will be pure drug in powder or crystalline form. At other times
it will be a liquid or a solid paste or cream.
Stock solutions and additives. Here are some common IV stock solutions. A pharmacist or
pharmacy technician will withdraw a calculated number of milliliters from the vial and place it
into a bag of fluid, thereby diluting the original concentration of the stock solution. These stock
solutions are also called "additives" because they are added to another IV solution.
Most commonly dilution and concentration can be solved by inverse proportion method and by
determination of percentage or ratio strength. The following formula can be used to calculate
dilutions and concentrations:
Q1 (quantity) X C1 (concentration) = Q2 (quantity) X C2 (concentration)
Or We can use the equation = C 1 * V 1 = C 2 * V 2
C1* V1= C2 * V2
C1 = stock concentration
V1= stock volume
C2 = final concentration
V2 = final volume

C1 = (C2 V2)/V1

or

V2 = (C1V1)/C2

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Examples:
1) A prescription for hydrocrotisone cream 0.1%. Pharmacy has 0.25% available in 30 g tube.
How many grams diluents base (vanishing cream) should be added?
A) 30 g
B) 45 g
C) 50 g
D) 75 g
E) 25 g

C1Q1 = C2Q 2
so 0.25% x 30 g = 0.1% x g?
g? = 0.25% x 30 g / 0.1% = 75 g
but the added tube contains 30 g
so the used base = 75 g - 30 g = 45 g

2) Dexamethasone is available as 4 mg/mL preparation. in infant is to receive 0.35 mg. Prepare a

dilution so that the final concentration is 1 mg/mL. How much diluents will you need if the
original product is in a 1mL vial and you use the full vial?
A) 4 ml B) 3ml C) 1ml D) 0.35ml
Ans: B

Step1: determine the volume of final product. Since dexamethasone is 4mg/mL, a 1 ml vial have
4mg of drug
X ml/ 4 mg = 1 ml/1 mg = 4 mL

Step2: subtract the volume of concentrate from the total volume to determine the amount of
diluents needed.
4 ml-1ml = 3 mL

3-If a 600 ml of a 15% (v/v) solution of methyl salicylates in alcohol are diluted to 1500 ml what
will be the percentage strength.
Q1 * C1 = Q2 * C2
C 2 = Q 2 /Q 1 *C 1
1500 mL / 600 mL = 15 % / X % = 6%

4-If a potassium chloride elixir contained 20 mEq of potassium ion in each 15 mL of elixir, how
many milliliters will provide 25 mEq of potassium ion to the patient?
Solution/Answer:
20 mEq = 25 mEq
15 mL x mL

x = 15 x 25 x = 18.75 mL
20
5-How many grams of dextrose are required to prepare 4,000 mL of a 5% w/v solution?
Equivalent factor: a 5% w/v solution = 5 g in 100 mL of solution.

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Solution/Answer
(5 g / 100 mL) x 4,000 mL = 200 g

Calculations involving dilution and concentration of Stock solutions

A solution of known concentration that is prepared in the most concentrated form is referred as
stock solutions. Sometimes a stock solution will be pure drug in powder or crystalline form. At
other times it will be a liquid or a solid paste or cream.

1-How many mL of a 1:500 (w/v) stock solution should be used to make 4 liters of 1:2000 (w/v)
solution?

Solution/Answer : 1:500 = 0.2%

4 liters = 4000 mL
1:2000 = 0.05%
0.2% /0.05% = 4000 mL / x mL = 1000 mL
2) A parenteral solutions used in hospital pharmacy. If 250 g of parenteral solution dissolved in
1000 mL of glycerin (density of glycerin is 1.25 g/mL), the concentration of parenteral solution
is?
A) 8%
B) 20%
C) 24%
D) 16%
E) 32%
• To find out concentration: %C = [Solute/Solute + Solvent] x 100
D = M/V
M=DxV
M = 1.25 x 1000 mL = 1250 g
Then
250 g+1250 g = 1500 g (total volume)
(250g/1500 g) x 100 = 16%

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Allegation Method
Allegation medial. A method for calculating the average concentration of a mixture of two or
more substances.

1) What is the final percentage of ZnO ointment made by mixing ZnO ointment of the following
strengths?
200 g of 10% + 50 g of 20 % +100 g of 5%
Solution:
+200 * 10% = 20 +
+50 * 20% =10 +
+100 * 5% = 5+
Therefore we have 350 g of the ointment which contain 35 g of ZnO
Therefore the percentage is 35/350=10%

Ointment mixture of 15 g of 70%, 5 g of 90%, 10 g of 40%, 5 g of 10%, what is final concentration

of this mixture?
15 g + 5 g + 10 g + 5 g = 35 g
(15 x 70)/100 + (5x 90)/100 + (10 x 40)/100 + (5x10)/100 =
10.5 + 4.5 + 4 + 0.5 = 19.5
(19.5 /35 g) x 100 = 55%

ALLEGATION ALTERNATE. A method of calculation of the number of parts of two or more

components of known concentration to be mixed when the final desired concentration is
known.
Which proportion of 95% alcohol and 50% alcohol should be used to make a solution of 500 mL
of 70% alcohol?
Solution:

95% .................................. 20 parts of 95 %

70 %
50% .............................. 25 parts of 50%

the final proportion is 20:25 = total 45 parts

Take 95%: (20/45) x 500 ml = 223 ml
Take 50%: (25/45) x 500 ml = 277 ml

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Prescriber orders to prepare 1% hydrocortisone 60 g. Your pharmacy has stock of 0.5%

hydrocortisone and 2.5% hydrocortisone. How many each part should be taken?

0.5 1.5
1
2.5 0.5

2.5% of HC ...........( 0.5/2) x 60 = 15 g

0.5% of HC............(1.5/2)x60 = 45 g

Rx
Hydrocortisone 1% 60 g

Your pharmacy has 2.5% hydrocortisone and petrolatum base. What fraction of each
hydrocortisone needed use to prepare above prescription

2.5 1
1
0 1.5

2.5% HC = 24 g
petrolatum base = 36 g

Rx
Hydrocortisone 1% 60 g

Your pharmacy has 0.5% hydrocortisone and hydrocortisone powder. What fraction of each
hydrocortisone needed to use to prepare above prescription

0.5% 99

1%

100% 0.5

0.5% of HC = 59.7 g
HC powder = 0.3 g

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Calculation involving electrolyte solutions

Mole: molecular weight in grams One mole of NaCl = 58.5 g
Reference atomic weights: Na = 23, C = 12, O = One mole of KCl = 74.5 g
16, K = 39, Cl = 35, Ca = 40 One mole of HCl = 36 g
One mole of Na2CO3 = 106 g
One mole of CaCl2 = 111 g
Eq. wt = Molecular Weight/Valence

Converting between milligrams (mg) and milliequivalent (mEq)

Number of mEq = Weight of substance in mg/mEq weight

Molarity
Molarity is the expression of the number of moles of solute is dissolved in litre of
solution. Molarity can be calculated by diving the moles of solute by the volume of
solution in litres.
One mole dissolved in 1liter solution is 1M.

1M HCl = 36.5g of HCl dissolved in 1L

1M NaCl = 58.5g of NaCl dissolved in 1L

One mole of substance dissolved in a liter solution

Molarity = molecular weight in grams/ Litres

1molar NaCl = 58 grams in litre

1) To prepare 100 mL of 1M NaCl, how many grams of NaCl (Mol. wt of NaCl = 58.5g)
needed?

Solution: 58.5 / 1000x 100 = 5.85g

________________________________________________________________

2-To prepare 28 mL of 0.5M NaCl, how many grams of NaCl needed? (M. Wt of Na =
58.5)
Solution: 58.5/2 = 29 g
29/1000 x 28 mL = 0.8 g

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1-How many mEq of magnesium sulphate are represented in 1 g anhydrous magnesium

sulfate? (M. wt of MgSO 4 =120)
A) 120 mEq B) 32 mEq C) 16.6 mEq D) 33.2 mEq E) 66.6
mEq
Ans: C
Tips:
1 g = 1000mg
mEq = [(weight) (valence)] / Molecular weight
= [(1000 mg) (2)] / 120= 16.6 mEq

2-A solution contain 10 mg% of Ca2+, describe this concentration in mEq/L. (Atomic
weight = 40 and valence = 2

10 mg% is = 10 mg/100 ml
10 mg% for 1L is 100 mg/L

mEq/L = [(mg/L) (valence)] / atomic weight

[(100 mg/L) (2)] / 40 mg = 5 mEq/L

3-What is the concentration in g per ml of a solution containing 4mEq of calcium

chloride (CaCl 2 x 2H2O) M. wt = 147

Mg /L = [(4 x 1470)]/ 2= 294 mg = 0.294 g /L = 0.002 g/mL

Millimole
Q. Millimole (mmol)/L = Molecular Wt in milligrams/Litres

1 mmol of NaCl solution contain how many milligram of sodium chloride? 58.5 mg /L
1 mmol of 100 mL NaCl contain how many milligram of NaCl? 5. 8 mg
0.5 mmol of NaCl contain how many milligram of NaCl? 29 mg

Magnesium has an atomic weight of 24, what is weight of 1 mmol? 1mM = 24 g/1000 = 0.024 g =
24 mg.

Normality
A method of dealing with acids, bases, and electrolytes which involves the use of
equivalents. One equivalent of acid is the quantity of that acid that supplies or donates

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of mole of H+ ions. One equivalent of base is quantity that gives off one mole of OH-
ions.
One equivalent of acid (H+) reacts with one equivalent of base (OH-). Equivalent can be
calculated for atoms or molecules.
Equivalent wt dissolved in 1L Valence
Na, K, Li = 1
Equivalent Wt = M. wt in g/Valence Ca, Mg = 2
Al = 3
1N HCl = 36 g of HCl dissolved in 1L
The salts with valence 1 have the same molarity and normality. The valence in salts is
referring to metal ions.
The salts with valence 1: NaCl, HCl, KCl, Li 2 CO 3 , Na 2 CO 3 , NaHCO 3
The salts with valence 2: CaCO 3 , CaCl 2 , MgCl 2 , Mg (OH) 2 , ZnCl 2
The salts with valence 3: Al, citrate

One mole of NaCl contain one equivalent of Na+ (Na mol. weight 23 g)
One mole of NaCl contain one equivalent of Cl- (Cl mol. Weight 35 g)
0.9 % NaCl contain 0.9g of NaCl in every 100 mL
0.9% NaCl contain 9 g of NaCl in every 1liter

MilliEquivalent. The amount in mg, of a solute equal to Magic formula!

1/1000 of its gram equivalent weight per unit volume. mEq = [mg x valence]/(Mol.Wt)
Converting milliequivalents per unit volume to weight mg = [mEq x (mol.wt)]/valence
per unit volume.

1. How many milliequivalents of sodium is in 92 mg of NaCl salt? M.wt of Na = 23

mEq = [mg x valence]/(Mol.Wt)

mEq = 92/23
= 4 mEq

Number of mEq = weight of substance in mg/mEq weight

92/23 = 4 mEq

2) What is the concentration in mg/ml of a solution containing 2 mEq of KCl per millilitres (KCl
M.Wt = 74.5)?

2 mEq. Of KCl= 74.5 mg × 2 = 149 mg/ml

OR
mg/ml = 2 (mEq/ml) × 74.5 = 149 mg/ml

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2) What is the concentration, in grams per milliliter of a solution containing 4 mEq. Of

CaCl 2 .2H 2 O per milliliter?
(M. weight of CaCl 2 .2H 2 O = 147)

Eq. wt. Of CaCl 2 .2H 2 O = 147/2 = 73.5

1 mEq. CaCl 2 .2H 2 O = (1/1000) × 73.5 g = .0735 g
4 mEq. Of CaCl 2 .2H 2 O = 0.0735 g × 4 = 0.294 g/ml
OR
by mg/ml = [4 x 147]/ 2 = 294 mg/ml = 0.294 g/ml

Converting Milligram % to mEq/L

1-A solution contains 10 mg% of K+ ions .Express the conc. In terms of mEq/L?
Solution:
Atomic weight of K+ = 39
Equivalent weight of K+ = 39
1 mEq. Of K = (1/1000)x39 g = 0.039 g = 39 mg
10 mg% of K + = 10 mg K + per 100 ml
= 100 mg per liter
100 mg x 39 = 2.56 mEq/L

Or
MEq/L = [100 mg/L × 1 ] / 39 = 2.56 mEq/L

2-A solution contains 10 mg % of Ca ++ ions .Express this concentration in terms of mEq/Liter

mEq/Liter = [100 mg /L ×2 ] / 40 (atomic weight of Ca ++)

Converting weight to milliequivalents

1-How many mEq. Of KCL are represented in a 15 ml dose of 10 % w/v KCL elixir ? Mol. Weight
KCl = 74.5 g
Solution:
Equivalent weight = 74.5 g
1 mEq of KCL = 0.0745 grams =74.5 mg
15 ml dose of 10 % w/v elixir = 1.5 g or 1500mg KCL
74.5 mg -- 1 mEq
1500 mg --x x = 20.1mEq

Milliosmole
It is the unit of measuring the osmotic concentration. Osmotic pressure is directly proportional
to the number of particles in the solution.

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Osmotic pressure ∝ Number of Particles in solution

Osmol/L = wt. Of substance in g/L X number of species

Molecular weight in g

mOsmol/L = Wt. Of substance in g/L x number of species x 1000

Molecular weight in g

Solutes, which dissociate exert osmotic pressure based on the number of particles present in the
solution after they have dissociated.

Some Example salts:

For NaCl, the number of species =2
NaCl  Na+ + Cl-

For CaCl2 , the number of species = 3

CaCl 2  Ca2+ + 2Cl-

For Li 2 CO 3 the number of species = 3

Li 2 CO 3  2Li + + CO 3 2-

For MgSO 4 the number of species = 2

For Solutes which do not dissociate, the milliosmole = millimole
________________________________________________________________
1) Solution contains 5% anhydrous dextrose in water injection. How many milliOsmoles per litre
are present in this concentration? (M. wt = 180 g).

Solution:

mOsmol/L = 50 g x 1 x 1000 = 278 mOsmol/L

180
Note: dextrose, gluconate are examples of substances that do not dissociates. However salts
dissociates into ions.
________________________________________________________________
2) How many milliosmoles per litre are present in 0.9% NaCl solution.

Solution:
0.9% NaCl is 0.9g in 100ml, however, solution in one litres, thereby NaCl concentration is 9 g
(9 x 2 x1000)/ 58.5 = 307 mOsmol/L

Isotonic solutions preparations

Isotonic  "Normal saline" and is 0.9% NaCl concentration
Hypotonic Less than 0.9% NaCl concentration
Hypertonic  More than 0.9% NaCl concentration

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Tonicity is affected by number of particles in solution. Substances that dissociate have greater
tonic effect than non-dissociated substances. Greater the dissociation greater the osmotic pressure
and greater the tonic effect.

2-How much NaCl must be added to the following Rx to make it isotonic? NaCl equivalent of
ZnSO 4 =0.16, NaCl Equivalent of phenylephrine=0.29.
Rx
ZnSO4 ----------1/4 %
Phenylephrine--1/8 %
NaCl----------------Q.S.
Aq. Distilled ad to 30 mL
you have to follow the steps as follows :
First step:
Calculate the amount of each ingredient in the prescription
so if we look at the prescription you will find that the final volume is 30 ml .
so for ZnSo4 , we need 0.25 for each 100 ml so for 30 ml we need 30 * 0.25/100=0.075
grams. now for phenylephrine do the same so we will need 30 * 0.125/100 = 0.0375 grams.

Second step:
By using the NaCl equivalent of each of them calculate the contribution of these salts to the
isotonicity of the solution .
now for ZnSo 4 : 1 gram of ZnSo 4 is equivalent to 0.16 grams of NaCl , but in our prescription we
have only 0.075 so this makes the solution as if it contains
1 gram ------> 0.16 NaCl
0.075 gram -------> x NaCl
x = 0.075 * 0.16 / 1= 0.012 NaCl
Applying the same for phenylephrine: 0.0375 *0.29 / 1 = 0.0108 NaCl
therefore total contribution of the salts = 0.012 + 0.0108 = 0.022875 NaCl
Third step:
Find the amount of NaCl needed to make 30 ml - which is the volume of the final solution -
isotonic.
so we need 0.9 grams NaCl for every 100 ml ...so for 30 ml we need :
0.9 g --------100 ml
x g ---------30 ml x= 30 * 0.9/100 = 0.27g NaCl
therefore the amount of NaCl needed = 0.27 - 0.022875 =0.247 grams = 247 mg NaCl

2) You are given ZnCl 2 0.7%, phenylephrine 0.1% and boric acid 1.1% with E values 0.16, 0.32
and 0.5 respectively. This solution will be:
A) Hypotonic
B) Hypertonic
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C) Isotonic
D) Non isotonic

Solution.
[(0.7 x0.16] + [(0.1 x 0.32] + [ (1.1 x 0.5)]
= 0.112 + 0.032 + 0.55 = 0.694
= 0.9>0.7 = Hypotonic
How much NaCl required making isotonic solution?

0. 9 - 0. 7 = 0. 2 or 2 mg

Dissociation factors
The dissociation factor is the measure of the number of particles resulted in when a substance is
placed in aqueous solution.

Non-electrolyte substances have low dissociation factor. Dissociation factor for non-electrolytes
substances are assigned a value of 1.
Substance dissociate into two ions dissociation factor (i) = 1.8
For three ions (i) = 2.6
For four ions (i) = 3.4
For five ions (i) = 4.2

Salts that dissociate into two ions: NaCl, KCl, LiCl, NaHCO 3
Salts that dissociate into three ions: Li 2 CO 3 , Na 2 CO 3 , ZnCl 2 CaCl 2 , Mg(OH) 2

Sodium chloride equivalent

1-Calculate the sodium chloride equivalent for fluorescein sodium, which dissociates into three
ions and has a molecular weight of 376.
i factor for sodium chloride = 1.8
i factor for fluorescein sodium = 2.6
Mol. wt of sodium chloride x i factor of substance = sodium chloride equivalent
i factor of sodium chloride Mol. wt of substance

58.5 x 2.6 = 0.22

1.8 376
NaCl equivalent (E) = 0.22

1) Zinc sulfate is a two-ion electrolyte, dissociating 70% in weak solutions. Calculate its
dissociation factor.
ZnSO 4  Zn + SO 4 + ZnSO 4
 80+ 80 +20
180/100 = 1.8

Example. If 80% Li2CO3

Li 2 CO 3  Li + Li+ CO 3 + Li 2 CO 3
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 80+ 80 + 80 + 20
260/100 = 2.6

Solution:
On the basis of 70% dissociation, 100 particles of zinc sulphate (ZnSO 4 ) yield:
70 zinc ions
70 sulphate ions
30 undissociated particles
170 total particles

Because 170 particles represent 1.7 times as many particles as were present before dissociation,
the dissociation factor is 1.7.

Calculations involving Balance sensitivity

1) What is the minimum quantity that can be weight on a balance with sensitivity requirements
of 15 mg of a 5% error is permissible?

Sensitivity Requirement = Weight x Error

15 = weight x 5 / 100 = 300 mg

Weight = (15/5) x 100 = 300 mg

2) What is the sensitivity of a balance that can weight 120 mg of a substance and has a
permissible error of 5%?
SR = Weight x Error
SR = 120 mg x 5 /100 = 6 mg

Error = sensitivity requirement/weight

Weight = sensitivity requirement/error

What is the sensitivity of a balance that can weight 120 of substance and has accuracy of 98%?

Sensitivity requirement = weight x error

120 X 2/100 = 2.4

Tips Practice format 002: Electrolyte Solutions

________________________________________________
Molarity = molecular weight in grams / Litres

________________________________________________________________________
Millimole (mmol) / L = molecular wt in milligrams / Litres
________________________________________________________________
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Converting milliequivalents per unit volume to weight per unit volume

mEq = [mg x valence]/(Mol.wt)

mg = [mEq x (mol.wt)]/valence
________________________________________________________________________
mOsmol/L = Wt. Of substance in g/L x number of species x 1000
Molecular weight in g
________________________________________________________________________

Sensitivity Requirement = Weight x Error

Error = sensitivity requirement/weight
Weight = sensitivity requirement /error
________________________________________________________________________

Practice Calculations

1-In dosing the drug gentamicin in pediatric patients, for every 1 mg/kg of gentamicin
administered, serum drug concentrations are expected to increase by 2.5 µg/ml. What would
be the expected serum drug concentration following an administration of a 2.5 mg/kg dose of
gentamicin?
A-5 µg/ml B-6.25 µg/ml C-10 µg/ml D-2.5 µg/ml
Ans: B

_1 mg/kg__ = 2.5 mg/kg

2.5 µg / ml X µg /ml
X = 6.25 µg /ml

2-An elixir is to contain 250 mg of an alkaloid in each teaspoonful dose. How many grams of the
alkaloid will be required to prepare 5 litres of the elixir?
A-0.25g B-5g C-250g D-2.5g

Ans: C
= X g / 5000 ml = 0.25 g / 5 ml
X= 250 g

3-A pediatric product contains 100mg of erythromycin ethylsuccinate in each dropper (2.5ml) of
the product. How many kilograms of erythromycin ethylsuccinate would be required to prepare
5000 pint-size bottles?
A-74.6 kg B-84.6 kg C-99.5 kg D-94.6 kg
Ans: D
1 pint = 473 ml
480 ml x 5000 = 2, 365,000 ml
0.0001 kg / 2.5 ml = X/2, 365,000 ml _ X = 94.6 kg

4-A physician places a patient on a daily dose of 48 units of U 80 insulin (80units/mL). How
many ml should the patient inject each day?
A-0.4 B-0.5 C-0.6 D-0.25

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Ans: C
U- 80 INSULIN
80 U / 1ml = 48 units/ X
X= 0.6 ml

5) A 20-ml vial of biologic solution is labelled “2.0 megaunits.” How many units of drug are
present in every ml of solution?
A-2000 B-1000 C-100,000 D-10,000
Ans: C
I Megaunit = 1000,000 U
20 ml --- 2000000 units
1 ml ---- ?
X= 2 x 1000 x 1000 = 100,000 units
20
1Megaunit = 1000KU
1KU = 1000 units

2.0 M units x 1000 KU_ x 1000 units = 1000,000 units

1M units 1KU

8-The usual initial dose of chlorambucil is 150 µg per kg of body weight once a day. How many
milligrams should be administered to a person weighing 154 lbs.?
A-10.5 mg B-18 mg C-15 mg D-8 mg
Ans: A

154 lbs x (1 kg/ 2.2 lbs) = 70 kg

150 g / 1 kg = X / 70 kg
X = 10, 500 µg
= 10.5 mg
9) An initial heparin dose of not less than 150 units/kg of body weight has been recommended
of open-heart surgery. How many ml of an injection containing 5000 heparin units per milliliter
should be administered to a 300 pound patient?
A) 5.1 µl B-4.1 µl C-5.1 ml D-4.1 ml
Ans: D
300 lbs x (1kg / 2.2 lbs) = 136.36 kg

150 units = _ X___ = 20, 454.54 units

1 kg 136.36 kg
_5000 u_ = 20454.54 u
1 ml X
X= 4.1 ml

10) The pediatric dose of cefadroxil is 30 mg/kg/day. If a child is given a daily dose of 2
teaspoonful of a suspension containing 125 mg of cefadroxil per 5 ml, what is the weight in
lb. of the child?
A-19.5 lbs. B-18.8 lbs. C-18.3 lbs. D-18.1 lbs.
Ans: C
(125 mg /5 ml) x 2 = 250 mg
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250 mg/ X = 30mg/ 1 kg

X = 8.33 kg
8.33 kg x (2.2 lbs /1 kg) = 18.33 lbs

11) If the loading dose of Kanamycin is 7 mg/kg of body weight, how many grams should be
administered to a patient weighing 130 lbs.?
A-0.492 g B-0.414 g C-414 g D-0.485 g
Ans: B
130 lbs x 1kg /2.2 lbs = 59.09 kg
7 mg /1 kg = X/ 59.90 kg
X= 413.63 mg
= 0.414 g

12-The adult dose of a liquid medication is 0.1 ml/kg of body weight as single dose. How many
teaspoonfuls should be given to a patient weighing 220 lbs.?
A-2 tsp. B-2.5 tsp. C-2 tbsp. D-2.5 tbsp.
Ans: A
220 lbs x (1 kg_ / 2.2 lbs) = 100 kg
0.1 mL / 1 kg = X/100 kg
X = 10 ml
= 2 tsp

13-If a prescription order requires 25 g of concentrated HCI (density 1.18g/ml), what volume
should the pharmacist measure?
A-29.50 ml B-0.0212 ml C-23.0 ml D-21.2 ml
Ans: D
W= 25 g
D= 1.18 g/ml
V= M/D = 25/ 1.18 = 21.2 ml

14-If the dose of a drug is 0.5mg/kg body weight/day, how many mg will a 35lb infant receive
per 24hours?
A-7.9 mg B-7.1 mg C-7.2 mg D-7.4 mg

Ans: A
35 lbs x 1 kg / 2.2 lbs = 15.9 kg
0.5 mg / 1 kg = X / 15.9 kg
X = 7.9 mg
15-What is the weight of 60 ml of oil whose density is 0.9624 g/ml?
A-5.770 g B-57.7 g C-6.0 g D-0.577 g
Ans: B
V = 60 ml
D = 0.9624 g/ml
D = _M_/V
M=DxV
= 0.9624 x 60 = 57.7

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16-A prescription calls for 0.3 g of phosphoric acid with a specific gravity of 1.71. How many
milliliters should be used in compounding the prescription?
A-0.5 B-0.7 C-0.18 D-0.3
Ans: C
D = M/V = g/ ml
V = M / D = 0.3 g/ 1.71 g/ml
X = 0.18 ml

17) How many mL of a syrup having a specific gravity of 1.350 should be mixed with 3000 mL of
a syrup having a specific gravity of 1.250 to obtain a product having a specific gravity of
1.310?
A-3500 mL B-4500 mL C-4600 mL D-5500 mL
Ans:

1.35....................... 0.06
1.31
1.25........................ 0.04

0.04........... 3000 ml
0.06..................?
= 4500 ml

18-A patient is determined to have 0.8 mg of glucose in each milliliter of blood. Express the
concentration of glucose in the blood as mg%.
A-800 mg% B-0.8 mg% C-8 mg% D-80 mg%
Ans:D
0.8 mg /1 ml = X/100 ml
X = 80 mg %

19) How many mL of a 1:400 (w/v) stock solution should be used to make 4 litres of a 1:2000
(w/v) solution?
A) 1000mL B) 200 mL C) 800 mL D) 1600mL
Ans: C
1 g/ 2000ml = X/ 4000mL = 2 g
X mL / 2g = 400 mL/ 1g = 800 mL

20) If a patient is determined to have 100 mg % of blood glucose, what is the equivalent
concentration in terms of mg/dL?
A-1 mg/dL B-10 mg/dL C-40 mg/dL D-100 mg/dL
1dL = 100mL
Ans: D
mg / dL = mg /100 mL
=100 mg /dL

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21-Strong Iodine Solution USP contains 5% w/v iodine. How many mg of iodine are consumed
daily if the usual dose is 0.3 mL t.i.d.?
A-15 mg B-90 mg C-22.5 mg D-45 mg
Ans: D
_5_ = _X_
100 0.9
X = 0.045 g x 1000
= 45 mg
22-Express in percentage the fluoride concentration in drinking given in 0.6 ppm.
A-0.06% B-0.00006% C-0.0006% D-0.006%
Ans: B
___0.6g____ = _X_
1,000,000 100
X = 0.00006%

23-How many grams of dextrose are required to prepare 4 litres of a 5% solution?

A-0.2 g B-200 g C-2 g d-20 g
Ans-B
x / 4000 mL = 5g /100 mL

24) Change to percent the number 1/300.

A-3% B-33% C-3.3% D-1/3%
Ans: D
1/ 300 = X /100
(1/3)/ 100= 0.33%

23-How many grams of petrolatum should be added to 250 g of a 25% sulphur ointment to
make a 5% ointment?
A-1000 g B-1250 g C-500 g D-100 g
Ans: A
Given: 250 g of 25 %

5 parts = 20 parts
250 mg X

X = 1000 g

25% 5
5%
0% 20

26-How many grams of potassium citrate are needed to prepare 1 litre of 10%?
A-1000 g B-50 g C-100 g D-10 g
Ans: C
_X_ = _10_
1000 100
X = 100
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27-How many grams of a drug are required to make 120 mL of a 25% solution?
A-30 g B-10 g C-12.0 g D-12 g
Ans: A
_X_ = _25_
120 100
X = 30

28-Calcium Hydroxide Topical Solution contains 170 mg of calcium hydroxide per 100 mL at 15º
C. Express this concentration as ratio strength.
A-1: 688 B-1: 888 C-1: 588 D-1: 788
Ans: C
170 mg → 0.17 g = 1_
100 ml 100 ml X
X = 588 ≈ 1:588

29-How many mg of isofluorophate are contained in 15 g of a 1: 10,000 ophthalmic solution of

isoflurophate in peanut oil?
A-1.7 mg B-1.9 mg C-1.8 mg D-1.5 mg
Ans: D
___1 g__ = _ X_
10,000 mg 15 g
X = 1.5 mg
30-Express 0.2 % in ratio strength.
A-1: 5000 B-1:50 C-1: 500 D-1:5
Ans: C
_0.2_ = _1_
100 15 g
0.2 X = 100
X = 500
31-How much of a substance is needed to prepare 1L of a 1: 10,000 solution?
A-0.1 g B-10 g C-0.01 g D-1.0 g
Ans: A
_ 1_ = _ X _
10,000 1000
X = 0.1 g

32-A cupric chloride injection (0.4 mg Cu/mL) is used as an additive to IV solution for TPN. What
is the final ratio strength of copper in the TPN solution if 2.5 mL of the injection is added to
enough of the IV solution to prepare 500 mL?
A-1: 500 B-1:5000 C-1: 500,000 D-1: 50,000
Ans: C

_0.4 mg__ = X___ 0.001 g = _1_

1 ml 2.5 ml 500 ml X
X = 1 mg ≈0.001 g X = 500,000
1: 500,000

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33-How many millilitres of a 23.5% (w/v) concentrate of Sodium Chloride solution should be
used in preparing 650 mL of a stock solution such that 30 mL diluted to litre will yield a 1: 5000
solution?
A-0.2 mL B-4.33 mL C-18.44 mL D-11.75 mL
Ans: C

_ 1_ = __X_ X = 0.2 g
100 5000

0.2 g_ = _ X _ X = 4.33 g
30 ml 650 ml

23.5 = 4.33 g X = 18.44 ml

100 X

34-You have a stock solution of 50% Sodium citrate and you were asked to prepare 300 mL of a
10% solution. How many mL is needed?

A-20 B-15 C-30 D-60

Ans: D
Q1C1 = Q2C2
X (50) = 300(10)
X = 60
35-How many millilitres of 1:16 solution of sodium hypochlorite should be used in preparing
5,000 mL of a 5% solution of sodium hypochlorite for irrigation?
A-800 ml B-2500 ml C-4000 ml D-300 ml
Ans: C
Q1C1 = Q 2C2
(X) 6.25% = (5000)(5%)

X = 5% x 5000mL
6.25%
X = 4000 ml

36-Prepare 1000 ml of KMnO 4 1:12,000 compresses out of KMnO 4 1: 8,000.

A-Add 333.3 mL water to 1000 mL KMnO 4 1: 8,000
B-Add 666.6 mL water to 333.3 mL KMnO 4 1: 8,000
C-Add 333.3 mL KMnO 4 1: 8,000 and enough water to make final volume 1000 mL
D-Add 333.3 mL water to 666.6 mL KMnO 4 1: 8,000
Ans-D

C1V1 = C2V2

1000 x 1/12000 = 1/8000 x V 2

V2 = 666 mL of KmnO 4

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37) How many milliliters of 24% (w/v) concentrate of saline solution should be used in preparing
600 mL of a solution such that 10mL diluted to a litre will yield a 0.09% solution?

A) 300 ml B)150 ml C) 50 ml D-225 ml

Ans: D

(0.09 g/100) = (X/1000) X = 0.9 g

0.9 g/10 ml = X/600 ml X = 54 g

24 /100 = 54/ X X = 225 ml

38) The only source of Sodium Chloride is in the form of tablets, each containing 5 g. How many
tablets should be used in preparing 3000 litres of a solution of such strength that 20 mL diluted
to 100 mL with water will yield a 0.9% (w/v) solution?
A-60,000 tablets B-27,000 tablets C-12,000 tablets D-9,000 tablets
Ans: B

_ 0.9_ = __X_ X = 0.9 g

100 100

0.9 g_ = _ X _ X = 135,000 g
20 ml 3,000,000 ml
(135,000 g / 5 g) = 27,000 tabs

39-How many grams of 10% (w/w) ammonia solution can be made from 1800 g of 28% (w/w)
strong ammonia solution?
A-6428.57 g B-5040 g C-50,400 g D-642.86 g
Ans: B
Q1C1 = Q 2C2
(10) X = (1800)(28)
X = 5040 g
40) How many ml of 0.9% (w/v) NaCl solution should be prepared from 250 ml of 25% (w/v)
solution?
A-3750 ml B-2500 ml C-6944.4 ml D-9 ml
Ans: C
Q 1C1 = Q2 C2
(X)(0.9)= 250(25)
X = 6944.4 ml

41) A Pharmacy tech adds 75 mL of strong iodine solution USP (5.0% w/v) to 1 litre of sterile
water for irrigation. What is the % w/v of iodine present?
A) 0.35% B) 0.475% C) 0.53% D) 0.60%
Ans: A
Q1C1 = Q2C2
75 (5) = (1075) X
X = 0.35%
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42) Determine the specific gravity of a mixture of 900 mL of syrup with a sp. Gr. of 1.1898, 700
mL of elixir with a sp. Gr. of 0.975 and 1150 mL of glycerin with a sp. Gr. of 1.240.
a) 1.1349 b) 1.1486 c) 1.1486 d) 1.1561
Ans: d
900 ml x 1.1898 = 1070.82
700 ml x 0.975 = 682.5
(1150 ml/3179 ) x 1.240 = 1426
3179./ 2750= 1.1561

43)What is the percentage alcohol in a mixture of 2000 mL of 50% (v/v) alcohol, 500 mL of 70%
(v/v) alcohol and 2.5 L of 95% (v/v) alcohol?
a) 71.67% b) 73.25% c) 72.50% d) 74.5%
Ans:
2000 ml x 0.5 = 1000
500 ml x 0.7 = 350
(2500 ml /5000 ml) x (0.95 / 3725) = 2375
(3725 /5000) = (X/100)
X = 74.5

44) If 800 g of 5% coal tar ointment is mixed with 1200 g of a 10% coal tar ointment. What is the
concentration of coal tar in the finished product?
a) 8.5 % b) 9.5% c) 8% d) 9%

Ans: C
800 x 0.005 = 40
1200 x 0.001 = 120
160/ 2000 = X/100
X = 8%

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www.PharmacyPrep.com Generic and Brand Names

52
Generic and Brand Names
Antiemetics: to treat vomiting
Generic Name Brand Name Generic Name Brand Name
Dimenhydrinate Gravol (generics) Metoclopramide Generics
Meclizine Bonamine Scopolamine Generics
Ondansetron Zofran Domperidone
Prochlorperazine Stemetil (generics) Diclectin (vitamin B6 + doxylamine)
Promethazine Phenergan

Cardiovascular Drugs
Antiarrhythmics: To treat irregular heart rhythms
Generic Name Brand Name Generic Name Brand Name
Amiodarone Cordarone (generics) procainamide PronestylSR, Procan (generics)
Disopyramide Rhythmodan (generics) Quinidine Biquin (generics)
Lidocaine Xylocaine Propafenone Rythmol (generics)

Antihypertensive: to treat high blood pressure

Diuretics (water pills): There are five types of diuretics i.e. Thiazides, Loop diuretics, potassium sparing, osmotic
and carbonic ahnydrase diuretics
Generic Name Brand Name Generic Name Brand Name
Hydrochlorothiazide Generics Furosemide Lasix (generics)
Metolazone Zaroxolyn

Potassium Sparing Diuretics

Generic Name Brand Name Generic Name Brand Name
amiloride + Moduret (generics) Triamterene + generics
hydrochlorothiazide hydrochlorothiazide
spironolactone + Adactazide (generics)
hydrochlorothiazide

βeta Blockers (suffix "lol")

Generic Name Brand Name Generic Name Brand Name
Acebutolol Monitan, Sectral (generics) Nadolol Corgard (generics)
Atenolol Tenormin (generics) Pindolol Visken (generics)
Bisoprolol Mococor Propanolol Inderal (generics)
Carvedilol Coreg Sotalol Sotacor (generics)
Labetalol Trandate (generics) Timolol generics
Metoprolol Lopresor, Betaloc (generics)

Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) (suffix "pril")

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Generic Name Brand Name Generic Name Brand Name

Benazepril Lotensin Lisinopril Zestril, Prinivil (generics)
Captopril Capoten (generics) Perindropril Coversyl
Cilazapril Inhibace Quinapril Accupril
Enalapril Vasotec Ramipril Altace
Fosinopril Monopril Trandolapril Mavik

Angiotensin II, AT 1 Receptor Blockers (ARBs) (Suffix "sartan")

Generic Name Brand Name Generic Name Brand Name
Candesartan Atacand Losartan Cozaar
Eprosartan Teveten Telmisartan Micardis
Irbesartan Avopro Valsartan Diovan

Calcium-Channel Blockers (CCBs) (suffix "dipine, except verapamil and diltiazem)

Generic Name Brand Name Generic Name Brand Name
Amlodipine Norvasc Non-Dihydropyridines
Nifedipine Adalat XL Diltiazem Cardizem CD (generics)
Felodipine Plendil, Renedil ER Verapamil Isoptin SR (generics)

Vasodilating Agents
Generic Name Brand Name Generic Name Brand Name
Hydralazine Apresoline (generics) Nitroglycerin SL spray Nitrolingual Spray
(generics)
Isosorbide dinitrate Cedocard SR Minoxidil Loniten
(generics)
Isosorbide mononitrate Imdure
Nitroglycerin SL tablet Nitrostat

Centrally Acting Antihypertensive Agents

Generic Name Brand Name Generic Name Brand Name
Methyldopa Aldomet (generics) Clonidine Catapres (generics)

Alpha-Adrenergic Blockers (alpha1 receptor blockers) (Suffix "zosin")

Generic Name Brand Name Generic Name Brand Name
Alfuzosin Xatral Prazosin Minipress (generics)
Doxazosin Cardura (generics) Tamsulosin Flomax
Terazosin Hytrin (generics)

Antihyperlipidemic Agents (HMGCoA reductase inhibitors suffix "statin"): To treat high cholesterol, there are 4
categories of drugs i.e. statins, fibrates, niacin and resins
Generic Name Brand Name Generic Name Brand Name
Atorvastatin Lipitor Fluvastatin Lescol
Bezafibrate Bezalip Gemfibrozil Lopid (generics)
Cholestyramine Questran (generics) Lovastatin Mevacor (generics)
resin
Fenofibrate Lipidil (generics), Pravastatin Pravachol (generics)
Lipidil Supra
Rosuvastatin Crestor
Simvastatin Zocor (generics)

CNS drugs
Opiates & Other Narcotics
Generic Name Brand Name Generic Name Brand Name
Codeine generics Meperidine Demerol
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PharmacyPrep.
www.PharmacyPrep.com Generic and Brand Names

Dextropropoxyphene Darvon N, 642, Morphine MS Contin and generics,

(generics) M.O.S.
Hydrocodone and Hycodan, Hycomine Oxycodone preps Percocet (generics)
preps Novahistex DH,
Novahistine DH,
Tussionex
Hydromorphone Dilaudid (generics) Pentazocine Talwin
Fentanyl Duragesic Oxycodone Oxycontin

Anticonvulsants (antiepileptics or antiseizure drugs)

Generic Name Brand Name Generic Name Brand Name
Carbamazepine Tegretol (generics) clobazam Frisium (generics)
Phenytoin Dilantin clonazepam Rivotril (generics)
Gabapentin Neurontin (generics) diazepam Valium (generics)
vigabatrin Sabril lorazepam Ativan (generics)
phenobarbital Generics primidone Mysoline (generics)
divalproex Epival (generics) lamotrigine Lamictal (generics)
valproic acid Depakene (generics)

Antiparkinson Drugs: To treat Parkinson's disease

Generic Name Brand Name Generic Name Brand Name
levodopa/carbidopa Sinemet (generics) Amantadine Symmetrel (generics)
levodopa/benserazide Prolopa pergolide Permax
bromocriptine Parlodel (generics) pramipexole Mirapex
trihexyphenidyl generics ropinerole ReQuip
benztropine Cogentin (generics) selegiline Eldepryl (generics)

Antidepressants: SSRIs, TCAs, SNRIs and MAOIs

Monoamine Oxidase Inhibitors (MAOIs)
Generic Name Brand Name Generic Name Brand Name
phenelzine Nardil
tranylcypromine Parnate

Tricyclic Antidepressants
Generic Name Brand Name Generic Name Brand Name
Amitriptyline generics maprotiline Generics
clomipramine Anafranil (generics) nortriptyline Aventyl (generics)
desipramine Norpramin (generics) trazodone Desyrel (generics)
doxepin Sinequan (generics) trimipramine Surmontil (generics)
imipramine Tofranil (generics)

Selective Serotonin Re-uptake Inhibitors (SSRIs)

Generic Name Brand Name Generic Name Brand Name
Citalopram Celexa fluvoxamine Luvox (generics)
Fluoxetine Prozac (generics) paroxetine Paxil
sertraline Zoloft (generics)

Serotonin norepinephrine reuptake inhibitors (SNRI) and Dual action antidepressants

Generic Name Brand Name Generic Name Brand Name
Venlafaxine Effexor Bupropion Wellbutrin SR, Zyban
Mirtazapine Remeron Buspirone BuSpar (generics)
Reversible Inhibitors of Monoamine Oxidase (RIMAs)
Moclobemide Manerix and generics

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Psychotropic (neuroleptic) agents (Antipsychotic drugs, antischizophrenia drugs)

Generic Name Brand Name Generic Name Brand Name
Chlorpromazine Novo-Chlorpromazine Hydroxyzine Atarax (generics)
Fluphenazine Moditen (generics) Lithium Lithane, Duralith (generics)
Haloperidol generics pericyazine Neuleptil
loxapine generics perphenazine Trilafon (generics)
pimozide Orap prochlorperazine Stemetil (generics)
thioridazine generics trifluoperazine generics
thiothixene Navane
Second generation antipsychotics
quetiapine Seroquel risperidone Risperdal
olanzapine Zyprexa, Zyprexa
Zydis OD

Benzodiazepines (suffix "am") sleeping pill

Generic Name Brand Name Generic Name Brand Name
Alprazolam Xanax (generics) Temazepam Restoril (generics)
Chlordiazepoxide generics Triazolam Halcion (generics)
Diazepam Valium (generics) Clonazepam
Flurazepam Dalmane (generics) Bromazepam
Lorazepam Ativan (generics)
Oxazepam Generics
Barbiturates (suffix "tal")
Generic Name Brand Name Generic Name Brand Name
Phenobarbital Thiopental

Stimulants
Generic Name Brand Name Generic Name Brand Name
dextroamphetamine Dexedrine methylphenidate Ritalin (generics), Ritalin SR

Gastrointestinal Drugs
Antacids
Generic Name Brand Name Generic Name Brand Name
Aluminum hydroxide Amphogel Magnesium hydroxide Milk of Magnesia
Aluminum and magnesium Maalox, Mylanta, Sodium/potassium Alka seltzer
hydroxide Gelusil bicarbonate
Calcium carbonate Tums® Alginic acid/aluminum Gaviscon
hydroxide
Dihydroxy-aluminum Rolaids®
sodium carbonate

H 2 -Receptor antagonists (Suffix "tidine")

Generic Name Brand Name Generic Name Brand Name
Cimetidine generics Nizatidine Axid (generics)
Famotidine Pepcid (generics) Ranitidine Zantac (generics)

Proton pump inhibitors (suffix "azole"): To treat ulcers

Generic Name Brand Name Generic Name Brand Name
esomeprazole Nexium omeprazole Losec
lansoprazole Prevacid pantoprazole Pantoloc
rabeprazole Pariet

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Gastroduodenal Cytoprotective Agents

Generic Name Brand Name Generic Name Brand Name
sucralfate Sulcrate misoprostol Cytotec

Prokinetic Agents (antiemetics)

Generic Name Brand Name Generic Name Brand Name
metoclopramide generics domperidone generics

Hormones
Thyroid Hormones
Generic Name Brand Name Generic Name Brand Name
Levothyroxine Synthroid, Eltroxin Levothyroxine sod Cytomel
sodium
Thyroid Thyroid

Sex hormones
Androgens
Generic Name Brand Name Generic Name Brand Name
Danazol Cyclomen Testosterone Andriol, Androgel, Androderm
Depo-Testosterone, Delatestryl

Estrogen
Generic Name Brand Name Generic Name Brand Name
estradiol-17β Estraderm®, conjugated estrogens Premarin, C.E.S.
Estrace®, Estalis®,
Estrogel®
estradiol-17β Climera hormone replacement Fem-HRT® Premplus®
micronized
estradiol Estring, Vaginal Ring

Progesterone
Generic Name Brand Name Generic Name Brand Name
levonorgestrel Mirena megastrol acetate Megace® (generics)
medroxyprogesterone Provera (generics), norethindrone Norlutate® Micronor®
acetate Depo-Provera
progesterone Prometrium

Combined Oral Contraceptives

Generic Name Brand Name Generic Name Brand Name
Ethinyl estradiol and Alesse Demulen®
Levonorgestrel
Brevicon® Marvelon®
cyproterone acetate Diane-35 Ortho-Cept®
and ethinyl estradioL
Ortho7/7/7 Min-Ovral®
Triphasil® Synphasic®

Diabetes: Insulin
Generic Name Brand Name Generic Name Brand Name
Iletin® Humulin R,N,U Humalog® Humalog Mix25
Novolin® Mixtures of 30/70; NPH (intermediate)
20/80; 50/50; 40/60
Glargine (long Lantus

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acting)

Oral Hypoglycemic Agents

Generic Name Brand Name Generic Name Brand Name
acarbose Prandase pioglitazone Actos
metformin Glucophage (generics) rosiglitazone Avandia
repaglinide GlucoNorm chlorpropamide Generics
gliclazide Diamicron® Diamicron MR® glimepiride Amaryl®
(generics)
glyburide Euglucon®, Diaβeta® (generics)

Neuromuscular Blocking Agents

Generic Name Brand Name Generic Name Brand Name
pancuronium Pavulon succinylcholine Quelicin
bromide

Anticholinergic Drugs
Generic Name Brand Name Generic Name Brand Name
Atropine generics Ipratropium Atrovent
benztropine Cogentin (generics) Oxybutinin Ditropan
dicyclomine Bentylol Tiotropium Spiriva

Adrenergic Drugs (Decongestants)

Generic Name Brand Name Generic Name Brand Name
norepinephrine Levophed pseudoephedrine Sudafed
bitartrate
(levarterenol)
oxymetazoline Claritin Eye drops phenylephrine Prefrin, Mydfrin
xylometazoline Otrivin

Anti-infective agents: Penicillin's

Generic Name Brand Name Generic Name Brand Name
amoxicillin generics bacampicillin Penglobe
ampicillin generics cloxacilin Generics
penicillin V generics pivampicillin Pondocillin®

Anti-infective agents: Cephalosporin's

Generic Name Brand Name Generic Name Brand Name
cefaclor Ceclor (generics) cefuroxime Ceftin (generics)
cefazolin Kefzol cephalexin generics
cefixime Suprax cefprozil Cefzil
cephradine Velosef

Anti-infective agents: Macrolides

Generic Name Brand Name Generic Name Brand Name
azithromycin Zithromax clarithromycin Biaxin
erythromycin Eryc (generics)

Anti-infective agents: Amino glycosides

Generic Name Brand Name Generic Name Brand Name
gentamicin Garamycin (generics) tobramycin Nebcin®

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amikacin Amikin

Anti-infective agents: Tetracycline

Generic Name Brand Name Generic Name Brand Name
minocycline Minocin (generics) tetracycline generics
doxycycline Vibra-Tabs (generics)

Anti-infective agents: fluroquinolones

Generic Name Brand Name Generic Name Brand Name
Ciprofloxacin Gatifloxacin
Norfloxacin Ofloxacin
Moxifloxacin

Anti-infective agents: Others

Generic Name Brand Name Generic Name Brand Name
clindamycin Dalacin (generics) vancomycin Vancocin
metronidazole Flagyl (generics)

Anti-infective agents: sulfa drugs

Generic Name Brand Name Generic Name Brand Name
co-trimoxazole Septra (generics)

Antifungals
Generic Name Brand Name Generic Name Brand Name
Amphotericin B Fungizone® griseofulvin Fulvicin® U/F
clotrimazole Canesten® (generics), otraconazole Sporanox
Lotrimin- OTC
fluconazole Diflucan (generics) ketoconazole Nizoral (generics)
Single dose
Miconazole Monistat, Micatin® terbinafine Lamisil (generics)
OTC
Nystatin Nilstat, Myocostatin tolnaftate Tinactin OTC
(generics)
undecylanate Desemex OTC

Anti-Viral Agents
Generic Name Brand Name Generic Name Brand Name
abacavir Ziagsen® lamivudine Heptovir®
amprenavir Agenerase® nelfinavir Viracept®
amantadine Symmetrel® nevirapine Viramune®
(generics)
acyclovir Zovirax (generics) oseltamivir Tamiflu
delavirdine Rescriptor® ribavirin Rebetron®
didanosine Videx® ritonavir/ lopinavir Kaletra®
efavirenz Sustiva® saquinavir Invirase®
famciclovir Famvir stavudine Zerit®
ganciclovir Cytovene® valacyclovir Valtrex®
indinavir Crixivan® zalcitabine Hivid®
zidovudine Retrovir® zanamivir Relenza®

Anti-neoplastic Drugs

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Generic Name Brand Name Generic Name Brand Name

bleomycin sulfate Blenoxane® ifosfamide Ifex®
busulfan Myleran® methotrexate generics
carboplatin Paraplatin mitomycin Mutamycin®
chlorambucil Leukeran® mitoxantrone Novantrone®
cisplatin Cisplatin® paclitaxel Taxol®
cyclophosphamide Cytoxan®, Procytox® tamoxifen Nalvodex® (generics)
cytarabine Cytosar®, ARA-C® vinblastine sulfate Vinblastine®
dacarbazine DTIC® vincristine sulfate Vincristine®
daunorubicin Cerubidine® idarubicin Idamycin®
doxorubicin Adriamycin® 5-fluororoucil Adrucil®, Efudex®, 5-FU
fludaribine Fludara®
phosphate

Antihistamine/Decongestant Products
Generic Name Brand Name Generic Name Brand Name
cetirizine Reactine (generics) fexofenadine Allegra
chlorpheniramine Chlor-Tripolon® hydroxyzine Atarax (generics)
desloratadine Aerius®* loratadine Claritin
dimenhydrinate Gravol® (generics) meclizine Bonamine®
diphenhydramine Benadryl®,
Allerdryl®

Coughs and Colds Drugs

Generic Name Brand Name Generic Name Brand Name
Neo Citran® Actifed® Drisdan® Tylenol Cold and Sinus®
Drixoral® Contac®

Anti-emetics
Generic Name Brand Name Generic Name Brand Name
droperidol Droperidol® prochlorperazine Stemetil® (generics)
metoclopramide generics promethazine Phenergan®
ondansetron Zofran®

Antipyretics, Analgesics; Non-steroidal Anti-inflammatory Drugs

Generic Name Brand Name Generic Name Brand Name
acetylsalicylic acid, Aspirin® ibuprofen Motrin®, Advil® (generics)
enteric coated ASA Entrophen®, indomethacin Indocid® (generics)
Novasen®
celecoxib Celebrex® ketoprofen Orudis® (generics)
diclofenac Voltaren® (generics) ketorolac Toradol®
diflunisal generics meloxicam Mobicox®
floctafenine Idarac® (generics) naproxen Anaprox®, Naprosyn® (generics)
flurbiprofen Ansaid® (generics) piroxicam Feldene® (generics)
tolmetin Tolectin® sulindac generics
tiaprofenic acid Surgam® (generics)

Antidiarrheal
Generic Name Brand Name Generic Name Brand Name
diphenoxylate/atropine Lomotil® psyllium mucilloid Metamucil®, Prodiem®,
Mucillium®
attapulgite Kaopectate® bismuth subsalicylate Pepto-Bismol®
loperamide Imodium® (generics)

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Laxatives
Generic Name Brand Name Generic Name Brand Name
bisacodyl Dulcolax® magnesium citrate Citro-Mag®
cascara sagrada magnesium hydroxide Milk of Magnesia®
castor oil magnesium sulphate Epsom Salts®
docusate sodium mineral oil (heavy)
docusate calcium polyethylene glycol GoLytely®, Colyte®
products
lactulose Acilac® psyllium Metamucil®, Prodiem®,
(generics) Mucillium®
senna Senokot®

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www.pharmacyprep.com Prescription Processing

53
Prescription Processing
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Definition of prescription
• Essentials in prescription. prescriber name and address, patient name, date and medication and
directions, repeats (regulations). Prescriber signature.
• Directions of ophthalmic and ear drop
• Directions that often causes errors

The prescription. Written direction from a registered medical practitioner to a pharmacist for
preparing and dispensing a drug.
The prescription: A written direction from a registered medical practitioner to a pharmacist
for preparing and dispensing a drug.
Typical prescription flow include a prescription intake and processing is initial phase of
process, such as receiving a new prescription at the pharmacy by the patient. A new
prescription from doctor via phone or fax. Refill request via telephone by the patient. The
information then usually requires manual data entry into the pharmacy/dispensary software
for processing and adjudication.
Some Information that require to process prescription are as follows:
Prescriber’s name & title
Prescriber’s office address
prescriber’s number
Rx
Patient’s name & address
Date on which Rx was written
Patient’s age/child body weight
Drug name, strength
quantity to be dispensed
Sig: Directions to 1 pt
Refill instructions
Prescriber’s signature and initials

Upon receiving prescription, the pharmacy technician is responsible for checking:

Five rights: Right Patient; Right Drug; Right dosage form/route; Right Dose and Right Prescriber.

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When a customer brings a new prescription, a pharmacy technician gathers the following information
and input in computer software.
• Any allergy
• Address/ Phone number (demography)
• Demographics
• Weight of patients (for children only)
• Current medication
• Medical conditions
• Previous medications.

Commonly use abbreviations

Abbreviation Meaning Latin Phrase Abbreviation Meaning Latin Phrase
a Before Ante b.i.d. Twice a day
ac Before meals Ante cibum q every quaque
pc After meal Post cibum q.a.m. Every morning
c with D= dexter qd Everyday Quaque die
cc With food S=sinister q.o.d. Every other day
AD Right ear qid. Four times a day Quarter in die
AS Left ear bis in die
AU Both ear
OD Right eye cum p.o. By mouth Per os
OS Left eye pr Per rectum
OU Both eyes p.r.n. As needed Pro re nata
dr Dram pt Pint
dx Diagnosis
g Gram Q2h Every two hours
gr Grain qt quart
gtt Drop rx, Rx prescription
h Hour s without sine
hr Hour ss One half (1/2)
h.s. At bed time Hora somni stat immediately
hx History supp suppository
ID Intradermal sx symptoms
IM Intramuscular T, Tbsp or tbs tablespoon
IU International units t, tsp teaspoon
unit
IV Intravenous t.i.d 3X a day ter in die
IVPB IV piggyback T.O. Telephone order
kg Kilogram tr tincture
L Liter tx treatment
lb Pound ung ointment
mcg Microgram µg VO Verbal order
mEq Milliequivalent aa/aaa Of each/ apply
affected area
mg Milligram Ad lib As desired Ad libitum
ml Milliliter ud As directed
oz Ounce Q8H
p post post

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Abbreviation Meaning Abbreviation Meaning

IHD ischemic heart disease LFT liver function test
TIA transient ischemic attack CXR chest x ray
CRF chronic renal failure PUD peptic ulcer disease
C/O complains of CBC complete blood count
FBS fasting blood sugar GTT glucose tolerance test
FHX family history FUO fever of unknown origin
Hx history IBS irritable bowel syndrome
U.F. until finished HCTZ Hydrochlorothiazide
u.g. until gone BZD Benzodiazepines
s.os. if necessary CNS Central nervous system
SOB shortness of breath WNL within normal limits
PA past history INR International Normalization Ratio
CVA cerebral vascular accident UA urine analysis
HA headache MAR Medication Administration Record
NTG- Nitroglycerine MS Morphine Sulphate
qs ad a sufficient quantity to make pulv Powder
as up to ASO Automatic stop order
INH Isoniazid ASA Acetyl salicylic acid
SSRI Selective serotonin reuptake NSAIDS Non steroidal anti-inflammatory drugs
inhibitors

Interpreting Directions of prescriptions

Direction Interpretation
caps ii tid pc Take two capsules three times a day after meals (after food).
suppos I pr q6h prn Unwrap and insert 1 suppository into the rectum every 6 hours as
needed.
tabs ss stat. tabs I q6h cc Take one half tablets to start (at once), then take 1 tablet every 6
hours with food.
fl.oz I tid cc Take two tablespoonful three times a day with food
gtts ii ou qid for 7 days Instill 2 drops into both eyes 4 times a day for 7 days
For a child. 10 mL stat, then 5 mL give 2 teaspoonful at start then 1 teaspoonful three times a day for
tid for 10 days 10 days.
gtts IV au qid for 7 days Instill 4 drops in both ears, 4 times a day for 7 days
tabs ii qam ss at noon & tabs ii Take 2 tablets every morning, half tablet at noon and two tablets
qhs at bed time.
fl.oz IV stat; fl.oz II q4h ud Take teacupful (120 mL) at start: four tablespoonful every 4 hours
as directed.
app ung sp aa tid Apply ointment sparingly to affected area three times a day.
10 gtts x po q12h ud Give 10 drops orally every 12 hours as directed

Direction of administration of prescription order

For adults
For eye drops, and nasal drops use instill or place
For tabs and capsules Take
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For liquid Take

Suppositories unwrap and insert 1 suppository into the rectum or
into vagina
Ointment and cream, topical Apply
Aerosols Inhale
Sublingual tablets place or dissolve one tablet under the tongue
Effervescent dissolve one tablet in water and take
For Children
Oral liquid, tablets, or capsules use "give"
Chewable tablets Use "chew"

QUANTITIES IN PRESCRIPTIONS:
Example
0/7 For days 3/7 means 3 days
0/52 For weeks 1/52 means 1 week
1/12 For month 1/12 means 1 month
1/24 For hours 3/24 means 3 hours

Clarify with patient

• The following information should be added to the prescription if missing or clarified.
• Patient demographic information
• The correct spelling of the patient’s full name (last and first)
• The patient address
• The patient home phone number
• Payment
• The age and date of birth (DOB)
The physician full name (last and first)
The physician address and telephone number

Clarify with doctor

• Drug interactions and contraindication
• Potential side effects to patient medical conditions.
• Interchangeable. (except generic and brand)
• To verify dose, missing information of prescription drug (dosage form, strength, duration) and
route administration.

Expanded scope of practice include

• Dispensing emergence medication (advancing)
• Extending Prescription (Rx fee can be charged).
• Pharmaceutical opinion
• Ordering, Monitoring and interpreting Lab Test to optimize medication management.

QAlerts!
Prescribed dosage form does not exist.
Prescribed dosage release form is not available?
What is prescription adaptation (expanded scope of practice)?
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Suspicious prescription of forged narcotic prescription?

What if doctor signature is not legible?

The following Information added to the prescription at the time of dispensing:

• The prescription number. Retail price (cost + professional fee = total)

Label. The information, which must be on the prescription label include:

• Patient full name (first and last)
• Prescription number
• Instruction for the patient use of the medication
• Name of drug
• Manufacturer (if drug was ordered by generic name).
• The quantity
• The strength
• Filling date
• Physician name/initial
• Drug Identification Number
• Pharmacist name/initials
NOT on label. expiry dates

Package insert: The package insert is a document that is included in the medication's surrounding box
or wrapper.

Tips
1. OD 2. pc 3. OS
4. ac 5. prescription 6. expiry dates
7. ex aqua 8. OU 9. AD
• What is prescription? 
• Written direction from a registered medical practitioner to a pharmacist for preparing and
dispensing a drug ( )
• The information which must be on the prescription label includes: (patients full name,
prescription number, instruction for the patient use of medication, name of drug, manufacturer,
quantity, strength, date, physician name or initial, drug identification number, pharmacist
name/initial (optional)
• What is not prescription label ( )
• Prepared in water ( )
• before meals ( ); after meal ( ); right eye ( ), left eye ( ), both eyes ( ), right ear ( )

Select True or False Statement

• Abbreviation "AU" is mistaken for? "OU".
• Abbreviation "o.d" or "OD" is mistaken for "right eye" use daily
• Abbreviation "per os" intended meaning is? orally or by mouth
• Abbreviation "µg" when handwritten is misinterpreted as? microgram "mcg"

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www.pharmacyprep.com Safety of Medications in Special Populations

54
Safety of Medications in Special
Populations
Infants, pregnant, seniors (geriatics)

Geriatric Population

Pharmacokinetic factors
Increase with age Decrease with age
Gastric pH (basic) or Lean body mass
achlorhydric Acid secretion
Body fat or lean body mass GI motility
ratio Renal function (CrCl)
Serum albumin
Total body water
Cytochrome P450 enzyme
First pass metabolism
Serum creatinine
Decrease cardiac out

Note. Serum creatinine is not a good predictor because creatinine production decreases with
age.

Drug absorption: Rate of absorption: may be altered in some patient and Extent of
absorption: No effect.
Distribution
• Decrease in total body water. decreases water distribution of water-soluble drugs.
(e.g. acetaminophen)
• Lipid soluble drugs (diazepam, propranolol) distribution increases.

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• Albumin levels are decreased with age therefore albumin bound drugs have
greater free concentration.
• Renal function: Renal function (renal excretion) decrease with age.
• 50% decrease of renal function by age of 70.
• Geriatic patients have sensitive reaction drugs cause.
• Anticholinergic effects and should be avoided

Pharmacokinetic changes related to aging Decreased Increased

Heart - Decrease Cardiac out put
Renal-Decreased blood flow
Liver-Reduced enzyme production
GI - pH increased (alkaline)

Vitamins in seniors: Vitamin B 12 supplements is recommended

I. Methods to improve compliance to medication.

A. Reduce number of daily doses (once daily is best)
B. Time doses to meal times
C. Establish partnerships to ensure compliance
1. Patient
2. Family (educate on indications and adverse effects)
3. Pharmacists
4. Home health aids
D. Use devices that aid taking of medication
1. Pill boxes and pill calendars
2. Label containers with large type
3. Pill containers should open easily
4. Keep accurate medication list
E. Ensure easy access to medications
1. Affordability
2. Medication delivery
F. Evaluate for patient factors affecting compliance
1. Dementia
2. Major Depression

↓ dose due to decreased renal Decreased hepatic clearance in the older

clearance in the elderly adults
Aminoglycosides Benzodiazepines
Vancomycin Calcium Channel Blockers
Fluoroquinolones Lidocaine
Penicillins Phenytoin
Imipenem Celecoxib
Digoxin Theophylline
ACE Inhibitors Imipramine or desipramine, and trazodone
Beta Blockers (Atenolol, Nadolol) Isoniazid
Sotalol Procainamide
Glyburide
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Ranitidine, Cimetidine, Famotidine

Lithium

Beers criteria: Describes the list potential inappropriate medications to elderly.

• Anticholinergic drugs
• Benzodiazepine
• Beta blocker
• Glyburide
• Sedating Antihistamines
• Ticlopidine
• Methyldopa
• Reserpine
• Disopyramide (Norpace)
• Meperidine (Demerol)
• Propoxyphene (Darvon)
• Barbiturates (e.g. Fiorinal, Nembutal, Seconal)
• Meprobamate
• Sedating Antidepressants
• Methylphenidate (Ritalin)
• Antiemetics (Phenergan, Tigan)
• GI antispasmodics (e.g. Donnatal, Bentyl, Levsin)
• Antidiarrheals (Lomotil)
• Urinary antispasmodics (Ditropan)
• NSAIDs (especially indocin, toradol, ponstel, feldene)

Drugs in Pregnancy and Lactation

Biogenesis The first 15-21 days after fertilization. Cleavage, and germ layer formation.
Embryotoxic. Most critical period in pregnancy for drugs therapy 14 to 56
days (2 to 8 weeks).

Organogenesis 2-8 wks. The major organ start developing. (congenital defects or hereditary
birth defects). e.g. down syndrome, cleft palate, septal defects. Basic steps of
organogenesis affected and damage irreparable. Can cause structural
abnormality.
Fetal period at 9th wk, the embryo referred to as fetus. Most critical period of fetotoxic
drugs Ninth week to birth. (affect on fetal growth or formed organs or
functional maturation organs thus affects.

On function of organ rather than gross structural damage. Example

Behavioral teratogenicity due to phenytoin, antidepressants, or alcohol.

Teratogenic Drugs: Risk is highest in 1st trimester. Teratogenicity causes mental and physical
deformation to the developing fetus. Examples. Isotretinoin, tretinoin, warfarin, tetracycline,

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finasteride, dutasteride, and quinolones, Hormones (estrogen, progestin, androgen), oral

contraceptives, plan B, ACEi, ARBs, statins, misoprostol and antidiabetic drugs.
The most teratogenic antibiotic:
• Nalidixic acid derivative as quinolone
• Fluroquinolones
• Amantadine
• Tetracycline

Drug Factors that affect on teratogenicity:

• Teratogens must reach the developing conceptus.
• Drugs must be able to diffuse across lipid barriers to enter the fetus. The transfer of drugs,
nutrients and oxygen through placenta occurs via passive diffusion.
• Large molecules with Mol. Weight >1000 (e.g. heparin) do not cross placenta.
• Factors that affects rate and extent of placental transfer include polarity, lipid solubility, and
existence of specific carrier protein (P-glycoprotein) binding, Molecular weight, pH, drug
distribution.

FDA classification:
Category A  Safe. Adequate clinical controlled trials, has not evidence of harm.
Category B  Animal studies showed safe. Can be safe in human?
Category C  Animal studies shows risk, but human data not available?
Category D  Demonstrate risk to fetus
Category X  Positive evidence of risk to fetus in clinical well controlled trials.

Category X: The positive evidence of risk to fetus. Contraindicated in woman who are pregnant
or who may become pregnant.
• Vitamin A derivative (isotretinoin, and tretinoin)
• ACE inhibitors, ARBs, and statins
• Warfarin causes Fetal Warfarin Syndrome (first trimester)
• Estrogen and androgen, can cause genital tract mal formation.
• Methimazole and carbimazole.
• Leflunomide
• Finasteride and dutasteride
• Methotrexate and chemotherapeutic drug
• Alcohol in large quantities can cause abnormalities in growth, cardiac, skeletal development.
Fetal alcohol syndrome (FAS).
• Misoprostol
Drugs not used in pregnancy
Drugs Affects
Tetracycline Mottling of teeth (taken by mother after 18 week of pregnancy).
Metronidazole Use in first trimester must be evaluated carefully. Completely
contraindicated for Trichomoniasis in 1st trimester.
Quinolones Not recommended in pregnancy due to arthropathies (cartilage erosion)

QAlerts!
What antibiotics can be used in pregnant? Erythromycin, Cephalexin, Ampicillin, Amoxicillin

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Alteration of organ function in pregnancy Increases Decreases

Heart-increase CO and blood volume
Renal-increased blood flow
Liver-placenta and fetal liver contribute to
metabolism
GI-Increased HCL production and N&V.
Decreased peristalsis

Drugs in lactation: Factors that effect on drug Affects

secretion into breast milk
Lipid solubility
Membrane permeation
Low Molecular weight
Base drugs has high excretion into breast milk
because breast milk is weak acidic. This
cause ionization increase excretion.
Protein binding affinity

Drug of choices in pregnancy

• Nausea and vomiting (morning sickness)  Diclectin (vitamin B 6 +doxylamine)
• Anti hypertension  Methyldopa, hydralazine, and labetalol
• Diabetic Type I and II  Insulin
• Epilepsy  Carbamazepine
• Hyperlipidemia  Cholestyramine
• Hyperthyroidism  Propylthiouracil (PTU)
• Ulcerative colitis  5ASA or sulphasalazine
• Constipation  Psyllium (bulk laxative), and stool softener
• Stomach ulcers  Antacids, H 2 blockers, and PPI.
• Vulvovaginitis candida  Clotrimazole (except 1st trimester), miconazole or nystatin.
• Migraine, fever and pain  Acetaminophen, NSAID’s (avoid full anti-inflammatory dose in
3rd trimester.
• Depression  Fluoxetine
• Urinary tract infections  Cephalosporin's (cephalexin), cotrimoxazole (Possible increase in
the risk of neural tubule and cardiovascular, oral cleft in 1st trimester exposure, this can be
minimized by folic acid supplements), and Nitrofurantoin.

Tips
1 2 to 8 wks 2 Urinary tract infection 3 Diclectin
4 decreased renal clearance 5 Dimenhydrinate 6 body fat/lean muscle mass ratio
7 fiber diet 8 stool softeners 9 lactulose
10 Calcium citrate 11 Vitamin B 12 12
13 ginger root 14 There is decreased rate 15 Neurotubular defect
of absorption as well
as change in drug

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distribution
16 16)Category X 17 Folic acid & 18 morning sickness
multivitamins
• Pharmacokinetics factors that increase with age? ( )
• Calcium supplements that are preferably given to seniors? ( )
• What vitamin supplements are recommended to seniors? ( )
• What therapy recommended for constipation in seniors? ( )
• Most critical period in pregnancy for drugs therapy ( )
• Drugs that should be discontinued in pregnancy? ( )
• Supplements that should be recommended in pregnancy? ( )
• Folic acid supplements in pregnancy prevents? ( )
• Nausea and vomiting in pregnancy also referred as? ( )
• Drug of choice therapy against nausea and vomiting in pregnancy is? ( )
• OTC drug therapy against nausea and vomiting in pregnancy include? ( )
• Cranberry juice is used against? ( )
• How do pharmacokinetic characteristics in the very young differ from that of an adult? ( )
• What pharmacokinetic characteristics change in elderly? ( )
• What is the significance of the placental barrier? ( )
• Herbal products that is recommended for nausea & vomiting in pregnancy? ( )

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www.Pharmacyprep.com Prevention and Intervention in Medication Overdose

55
Clinical Toxicology
Questions Alerts!
Common questions in pharmacy exam is to ask!
Drugs often cause overdose and managing overdose problems
• Acetaminophen
• Iron
• Tricyclic antidepressants
• Benzodiazepines
• Opioids
• ASA
In case of overdose, what to do?

The commonly overdose toxicities associated medications are:

Tricyclic antidepressants
Iron supplements
ASA
Acetaminophen
Opioids
Benzodiazepines

Tricyclic Antidepressant (TCA). Amitriptyline, Nortriptyline, imipramine, desipramine

• Overdose symptoms. TCA are extremely toxic in overdose. Consultation with poison control center
is recommended.
• Symptoms. Mydriasis and anti-cholinergic symptoms, and severe arrhythmias (AV node)
(cardiopulmonary toxicity) exhibit tachycardia.
• Treatment is symptomatic and supportive, arrhythmias and CNS involvement pose the greatest
risk.
• Toxic dose is variable but in general 10 to 20 mg/kg may result in serious toxicity and may be
lethal.
• In child 50 mg dose can manifest the overdose symptoms.
• There are 15% mortalities with overdose of TCA are reported. Toxicity begins within 2 hours of
ingestion.
• Initial symptoms are mild and can precipitate to CNS and cardiac symptoms. All cases of
accidental, pediatric or adult overdose. Should be monitored at healthcare facility.

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Opioids Overdose
• Symptoms. Lethargy, sedation, coma, bradycardia, hypotension, hypoventilation (respiratory
depression), pinpoint pupils (miosis), cool skin, decreased bowel sounds, and flaccid muscles.
• Antidote is naloxone, and full opioid antagonist
• Opioids withdrawal is treated by methadone (partial agonist mu receptors and NMDA antagonist).
• Naltrexone is used for chronic alcohol withdrawal treatment.

Acetyl Salicylates Overdose

• Overdose more than 4 g/day can cause toxicity.
• Symptoms of overdose. Mild rapid, deep breathing, nausea, vomiting, vertigo, tinnitus, flushing,
sweating, thirst, and tachycardia.
• Severe acid base imbalance, respiratory alkalosis, metabolic acidosis, fever, hemorrhage,
excitement, and confusion.
• Acute ASA intoxication can result from single ingestion of 150 mg/kg or more chronic ASA
intoxication also known as salicylism can occur. Salicylism can occur in high dose >100 mg/kg/day
for 2 or more days.
• Salicylism most often occurs in elderly, being treated for chronic conditions such as rheumatoid
arthritis.
• Treatment. Acute symptoms of overdose should be treated by supportive therapy by removal of
unabsorbed ASA from gut.
• Management. Decontamination, alkaline diuresis, Hemodialysis.
• ASA overdose is treated by NaHCO 3 diuresis.

Acetaminophen Overdose
• In adult hepatotoxicity may occur after ingestion of a single dose of more than 7.5 g (adults), or
150 mg/kg (children).
• A dose of 10 g or more is potentially fatal. However reports have indicated hepatic necrosis with
single dose of 6 g and death occurring with single dose of 13 g.
• Treatment. Consider consultation with poison control centers.
• Consultation with toxicologist is highly recommended in cases of hepatotoxicity associated with
sub acute acetaminophen overdose.
• Antidote. Acetylcysteine, it is administered within 8 hours of overdose.

Clinical presentation of acute acetaminophen poisoning.

Phase 1. Nausea, vomiting, GI bleeding and abdominal discomfort within 1 to 12 hr after
ingestion.
Phase 2. Clinical improvement in seen in 6-24 hr of ingestion.
Phase 3. Metabolic acidosis, renal and hepatic failure, sepsis, pulmonary edema and death.
Ref. Pharmacotherapy, 7th ed.

Iron supplement overdose (Fe fumarate 33%, Fe sulfate 20%, Fe. gluconate 12%)
• Toxicity is based on the amount of elemental iron. Toxicity can occur at 60 mg/kg may cause GI
symptoms.
• Clinical overdose symptoms are nausea, vomiting, and diarrhea. melena, hematemesis may cause
hemodynamic instability.
• If GI symptoms does not occur within 6 hours of ingestion suggest, it is non-toxic dose.
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• Management. Decontamination for iron overdose should NOT be treated by charcoal. Treat by
ipecac.
• Antidote is deferoxamine (it works by chelation)

Benzodiazepine
Antidote. Flumazenil
Overdose. Sedation, drowsiness, sleepy, confusion and ataxia.
Withdrawal symptoms are insomnia, delirium and anxiety, autonomic hyperactivity (sweating, pulse
>100 bpm), increased hand tremor, and restless.
Symptoms begins within 1-2 d of abrupt discontinuation. or 5- 10 d for long acting.

Non toxic drugs

Amoxicillin
3 g daily maximum
Symptoms. diarrhea

Nystatin.
Nystatin cream or suspension 30 g (3 mU) or more can cause stomach upset.

Tips
1. opioids 2. TCA’s 3. Deferoxamine
4. lethargy 5. sedation 6. coma
7. bradycardia 8. hypotension 9. hypoventilation
10. pinpoint pupils (miosis) 11. cool skin 12. decreased bowel sounds
13. flaccid muscles 14. mydriasis 15. anticholinergic
symptoms
16. severe arrhythmias 17. charcoal 18. NaHCO 3 diuresis
19. Naloxone 20. Removal of 21.
benzodiazepines with
lavage, treatment with
charcoal & treatment
with Flumazenil
22. Flumazenil 23. 8 hrs of overdose of 24.
acetaminophen
CAMH: Canadian Addiction and Mental Health
• Iron overdose should not be treated by? ( )
• What is ASA antidote? ( )
• What is the acetaminophen antidote? ( )
• N-acetylcysteine should be administered within? ( )
• Benzodiazepine antidote is? ( )
• Benzodiazepine overdose treatment? ( )
• Opioid antidote ( )
• Pinpoint pupil is overdose symptoms of? ( )
• What drugs overdose can cause proarrhythmias? ( )
• What is true about charcoal? ( )

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• Iron overdose is treated by? ( )

• TCA overdose symptoms ( )
• Increase surface area, increase adsorption, decrease impurities on surface of charcoal increase
adsorption. However, increase temp on surface of charcoal increase adsorption

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www.Pharmacyprep.com Communication Skills

56
Communication Skills
Questions Alerts!
Common questions in pharmacy exam is to ask!
• The best communications skills is verbal and writing
• Barriers in communications are environmental barriers, personal barriers, and
financial and administrative barrier.
• Cultural competence or cultural diversity.

Type of communication methods.

• Verbal communication methods
• Non-verbal communication methods

Verbal communication
• Verbal communication comprise speaking and listening
• The sender. One who transmits a message to another person
• The message. It is an element that is transmitted from one person to another
• The receiver. One who receive message from sender
• Feedback. It is the process of replying to sender

Barriers in communications. The interference that affects the receiving, sending transmitting of
message.
• Environmental barriers (noise, music, counter heights, poor lighting etc).
• Personal barriers (no confidence, shy, incompetence)
• Patient barriers (knowledge)
• Administrative and financial barriers

Environmental barriers: Distraction in environment often can result into environmental barriers like
height of prescription counter separating the patient from the pharmacist.
• Crowded and noisy prescription areas inhibit one to one communications.
• Presence of support workers like technician who stands between pharmacist and patient.
• Distraction or loud noise, telephone rings, music, and traffic.
Check the following potential factors that are associated with environmental barriers:
• Is pharmacist visible?
• Is counter top or stuff on counter tops blocking pharmacist visible?
• Does it easy to get pharmacist attention?

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• Is it private counseling area available to conduct private interview?

• Is that lost background noise or distractions?
• Is it easy to get pharmacist attention?

Recommendation to minimize environmental barriers

• Place computers terminal near the patient counseling area to minimize distractions.
• Create a quite private counseling area.
• Make countertops wider to accommodate computers, printers etc.

Personal barriers
• Low self confidence.
• Cultural differences (cultural competent).
• Discomfort to sensitive situations
• Conflicting values of therapy
• Shyness

Patient barriers: The following are the examples of patient barrier.

• Patient perceive being as knowledgeable?
• Patient perception about pharmacist knowledge?
• The perception of impersonal atmosphere
• Patient perceptions about their medical conditions as minor?
• Patient may be anxious about their conditions.

Administrative and Financial barriers

There are several factors of administrative and financial aspects effects pharmacy practice. Like
bureaucracy can be administrative barrier.
• Pharmacist are not paid directly for educating or communicating with patients, therefore many
managers perceive the task of talking with pharmacist is expensive service and not a high priority.
• Pharmacy policies that encourage minimum number of pharmacist.
• Excessive tasks to pharmacist by typing label, count medications, talk on phone, and completing
other tasks while communicating with patients.

Time barriers
• Setting inappropriate timing of appointment.
• Large number of prescription needs to be filled in short time.

Non-Verbal Communication
• Communication does NOT require verbal language.
• The elements of non-verbal communication kinesis and proxemics.

Kinesics or body language: The manner in which one uses her/his eye contact, arms, legs, hands head
to convey a message to receiver.
Example. Relaxed posture, slight lean toward the other person, eye contact, smile.

Proxemics: The distance between two interactive people put more emphasis on content of
communication, and it is defined as proxemics.

Written. It is powerful nonverbal communication tool.

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Tips
1. Low self-confidence 2. Distractions 3. language
4. Promotion sales 5. Telephone 6. Noise
7. Verbal 8. Written 9. Cultural differences
10. Discomfort to 11. Conflicting values to 12. Shyness
sensitive situations therapy

• The best communication skills are? ( )

• Examples of communication barriers includes? ( )
• Examples of communication distractions includes? ( )
• Examples of personal barriers includes? ( )

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www.Pharmacyprep.Com Pharmacy practice and management

57
Bioethics and Professional Ethics

This chapter provides basic understanding of ethical principles, code of ethics, professional
responsibility and liability. You will learn how to make ethical decisions. Lecture presentation includes

Questions Alerts!
Common questions in pharmacy exam is to ask!
• Beneficence = doing good or doing the very best to patient
• Nonmaleficence = preventing harm
• Autonomy = patient right to choose (paternalism breaks autonomy)
• Veracity = honesty or telling the truth without deception.
• Justice = equality or first come first service (fairly).

scenarios of ethical decisions and professional liability and legal issues.

Difference in ethics and regulations

Law (Rules or regulations) Ethics (conducts/moral/character)
Described in constitution Professional judgement in the best of
interest patient in the ethical principles
Must be followed Followed or uphold/broken

Beneficence
Beneficence. to do good or doing well or doing the very best to patient.
The health professional should act in the best interest of the patient. Decisions made with perception
are based on what patient needed.

In other words:
• Acting in the patient’s best interest. Current thinking is to involve patient letting the patient
determine what is in their best interest.
• Pharmacists demonstrate beneficence whenever they provide critically needed prescription drugs
to their patients in emergency situations without regard to possible legal consequences.

Nonmaleficence
Nonmaleficence is do no harm or prevent harm. Pharmacists who refuse to fill a prescription order
because of their concern for patient safety or well being observed the principle of nonmaleficence.
Professional interventions on drug related problem that can prevent harm is action of
nonmaleficence.

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Harm reduction services such dispensing syringes to drug addicts. Receiving narcotics to destroy from
customers.

Autonomy. Whether like to not like to take?

Letting the patient have the final decision, even if it is not in their best interest i.e. refusing treatment,
surgery, etc. In other words. Patient’s right to self-determination. To choose what will be done to
them.

Respect for life and autonomy of patient. Contraception, emergence contraception, abortion.

Palliative care, pain management, and end-of-life care.

Euthanasia = Assisted suicide or planned death.

Mental capacity To assess patient's capacity to make decision.

An Alzheimer patient comes to pharmacy with caregiver. Should pharmacist ask patient to authorize
to discuss with caregiver about their medications?

Living will or advance directive?

Autonomy is opposite of Paternalism.

Paternalism
When one fails to respect another’s autonomy, and acts with disregard to the individual rights.
Substitute their own beliefs, opinions and judgment to that of another. Claim they acted in the
person’s best interest.

Honesty and Veracity. Act with honesty without deception.

The patient has the right to the truth medical condition, course of the disease and treatments.

Code of ethics states that a pharmacist, “has the duty to tell the truth and to act with conviction of
conscience” Rapport is built on trust, which is based on honesty.

Rx
Obecalp

Fidelity (loyal)
In other words fidelity is the right of a patient to have health professionals provide services that
promote patient interests rather than their own. The right of patients to have practitioners provide
services that are in the patient’s best interest.

Infidelity from a prescriber could be recommending vitamins that patients don’t need. Failing to
confront a doctor with an inappropriate prescription out of fear that the doctor will direct his/her
patients elsewhere.

Justice or Fairness
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First come first serve. It means providing services equally.

Professional Ethics
Informed Consent and decision making
Three types of consents implied, express, and informed.

Requires honesty and autonomy to exist. Patients have the right to full information of all relevant facts
and must give explicit consent before treatment.
Informed consent exists when.
• All relevant information has been provided
• The patient understands the information
• Consent is freely given and there is no coercion
• The patient is capable of understanding the information
• Note. Often, practitioners rely only on the disclosure part of the list!

Confidentiality
Federal regulations of confidentiality is personal information protection and electronic documentation
act (PIPEDA).

Provincial regulations is personal health information protection act. (PHIPA).

From the patients perspective this is “self-disclosure” and they should be the ones making this
decision.

In other words the principle of confidentiality serves to assure the patient that information about their
health, medical condition, treatment will not be given to individuals without their permission.

Confidentiality of patient Information. The pharmacist preserves the confidentiality of information

about individual patient acquired in the course of his or her professional practice, and does not divulge
this information except where authorized by the patient or required by law.

Spouses. If someone is asking a copy of his or her spouse’s prescription information, get permission
from the patient whose information is being released.

Example Case
An adult son brings prescription for his dad?
A daughter comes for moms refill?

Exceptions of confidentiality based on your reasoning? Cognitive impairment (advance directives

require or care giver)?
Patient decision making capacity should be assessed by health care professionals

Unconscious patients (circle of care)? mental illness (alert family) ? HIV patients (imply information)?

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Tips
1. Violating autonomy 2. Tell the truth 3. Right of determination
4. Beneficence 5. Ethics 6. Equality with everyone
7. preventing harm 8. Best interest of patient 9. honesty without deception

• Doing good ( )
• Non maleficence ( )
• Autonomy ( )
• Honesty ( )
• Veracity ( )
• Justice ( )
• Fidelity ( )
• Paternalism ( )
• Code of conducts or morals ( )

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www.Pharmacyprep.com Drug Information Resources

58
Drug Information Resources
Questions Alerts!
Common questions in pharmacy exam is to ask!
Types of literature primary, secondary and tertiary.
• Canadian drug references like compendium of pharmaceutical specialties (CPS).
• Compendium of Therapeutic choices (CTC) and Compendium of Therapeutic for Minor
Ailments (CTMA).
• USP DI vol.1 drug information for health care professionals.
• Motherisk program. Safety of drugs in pregnancy.
• References like Cochrane data base (Cochrane Collaborative Library) an evidence base
medicine database . Medline is used for new drugs and therapies and off lable use.
• Martindale. Foreign drugs.
Response to drug information request? What reference is appropriate for minor ailment
treatment? CTMA
selection of suitable references for foreign drug and information sources?

Peer review. Assessment of a clinical trial by experts for scientific merit, participant safety, and ethical
considerations.

Literature. It is defined as an extensive, heterogeneous collection of resources, which provide

information about drugs. Drug information sources can be categorized into primary literature,
secondary literature and tertiary literature.

Primary Sources. Consist of original information about clinical trials or research. Examples Scientific
Journals containing clinical trial information
• Peer reviewed articles are published in scientific journals. The primary source literature provides
latest and current information.
• Examples. Canadian Medical Association Journal (CMAJ), Canadian Pharmacy Journal (CPJ), Journal
of American Medical Association (JAMA). Pharmacy connection, Clinical research data, Journal of
Informed Pharmacotherapy, Canadian Family Physician, Canadian Journal of Clinical
Pharmacology, Etc.
• Benefits: Gives most current information and keeps up latest development and research in
pharmacy. It is good resource of continuing education.
• Limitation: Does not guarantee that the article is accurate, however respected journal enhances
the credibility of information contained in the article.
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Secondary Sources. Examples Indexes, bibliography and abstracts.

• Information published in secondary sources obtained from various primary sources and compiled
as abstracts and indexed into publications.
• Example. Internet search, Medline.
• Current Content (Abstracts), Index Medicus (Index); Monthly Biomedical research- results.
• Clin-Alert (Index). Abstracting service as a newsletter edition semi monthly (bi weekly) Adverse
reaction.
• Current content: Weekly-Clinical practice
• International pharmaceutical abstracts—Monthly and quarterly pharmacy practice
• Online sources. MedLine or Pubmed (recent drug information, and off label use)
• Benefits: It is an important resource for quick and selective screening of primary literature for
specific information, or article.
• Limitations. Each indexing service provider may provide specific list of journals, so this can limit
and thoroughness of literature search.

Tertiary Sources. Examples text books and compendia

• Information published in tertiary sources such reference book and textbooks are obtained from
primary and/or secondary sources.
• Example: Compendium of pharmaceutical specialties (CPS). United States pharmacopeia (USP-DI),
Martindale, Remington, Compendium of Therapeutics choice, all text books,
• Benefits: Provide easy and comprehensive topics in one textbook.
• Limitation: No recent information.

Compendium of Pharmaceuticals Specialties or eCPS

• Compendium of Therapeutic Choices (CTC)

• Compendium of Therapeutic Minor Ailments (CTMA)
• United States Pharmacopeia DI-Vol.1 (USP-DI Vol.1)
• Martindale
• Cochrane data base or reviews
• Health Canada Drug Product database
• Drugs in pregnancy and lactation or Motherisk program

Pharmacy Practice Reference Resources

Compendium of pharmaceuticals specialties

• Discontinued products
• Brand and generic name index (green pages)
• Therapeutic guide (pink pages)
• Product identification (pages containing photographs of the medicines)
• Directory (Yellow pages)
• Clini-info (Lilac pages)
• Monographs (white pages)
• Appendices (white pages at the end of the CPS)
• Drugs that have peanut and soya proteins, lecithin’s preps, and ethanol.
• Drugs that can be crushed and chewed.

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Health Canada (Notice of Compliance – NOC)-Drug product database (DPD). Published recent
approved drugs or new drug information.

Drugs manufactured in United States

• USP-DI volume I
• The American Drug Index (updated annually)
• Drug Facts and Comparison (updated monthly and bound annually)
• Drug Topics Red Book (released monthly and bound annually)
• Physician desk reference (PDR) (updated annually)
• AHFS Drug Information. American Hospital Formulary Society (supplemented quarterly and
updated annually).

Drug Manufactured in foreign countries

• Martindale. The complete drug reference
• Index Nominum
• USP Dictionary
• USAN

For Investigational Drugs

• Medline or Pubmed and Health Canada website
• Martindale. The complete drug reference
• Drug facts and comparison
• Unlisted drugs
• FDA website. The new drug application (NDA) pipeline
• Health Canada
For unknown drugs. Try to identify them by physical characteristics such as special marks, color, shape
etc. and or recommend chemical analysis.
• USP DI volume I
• The PDR
• Drug facts and comparison
• Manufacture
• Laboratory

Side Effects
• Compendium of pharmaceutical specialties
• USP DI Vol. I: Drug Information for the Health Care Professional
• Clin-Alert
• Meyler's Side Effects of Drugs
• AHFS Drug Information

Drug-Drug Interactions
• Drug Interaction Facts (Tatro)
• Drug Interactions. Compendium of Pharmaceuticals and Specialties
• Clin-Alert (Generali)
• Hansten and Horn's Drug Interactions Analysis and Management
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• Drug-Drug Interactions. Handbook of Clinical Drug Data (Anderson)

• Handbook of Adverse Drug Interactions
• Drug Interactions: A Source Book of Adverse Interactions, Their Mechanisms, Clinical Importance
th
and Management (Stockley: 6 ed. 2003)
• EDI: Evaluations of Drug Interactions
• Concise Guide to Cytochrome P450 System: Drug Interaction Principles for Medical Practice

Drug-Lab Test Interactions

• American Hospital Formulary Society (AHFS) Drug Information
• Effects of Drugs on Clinical Laboratory Tests (Young: 5th ed. - 2000)
• Drug-Laboratory Test Interferences. In: Handbook of Clinical Drug Data (Anderson)

Drug-Food Interactions
• Drug Interaction Facts (Tatro)
• USP-DI volume I
• Reference Guide to Drug and Nutrient Interactions
• Food Medications Interactions Handbook (Pronsky)
• HIV Medication-Food Interactions Handbook (Pronsky)

Drug-Herb Interactions
• Database of Natural product
• Herbs: Everyday Reference for Health Professionals (CphA)
• Herb Contraindications and Drug Interactions (Brinker)
• Herb-Drug Interactions Handbook (Herr)
• Drug Interaction Facts: Herbal Supplements and Food
• Interactions between Drugs & Natural Medicines: What the Physician and Pharmacist Must Know
About Vitamins, Minerals, Foods and Herbs (Meletis)

Compounding or Extemporaneous prep

• Remington: The Science and Practice of Pharmacy
• Merck index
• A Practical Guide To Contemporary Pharmacy Practice
• Pharmaceutical Dosage Forms and Drug Delivery Systems
• Pharmaceutical Practice
• The Art, Science, and Technology of Pharmaceutical Compounding
• The Pharmaceutical Codex

Formulas For Compounding

• United States Pharmacopea-National Formulary (USP-NF)
• Merck index
• British Pharmacopoeia Vol. 2
• Contemporary Compounding Compendium

Extemporaneous Oral Liquid Dosage Preparations (CSHP)

• The Ghen and Rains Physicians Guide to Pharmaceutical Compounding
• Extemporaneous Formulations (Children's hospital of Philadelphia)

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• Pediatric Drug Formulations

• Pocket Book of Extemporaneous Formulations
• Allen's Compounded Formulations: The US Pharmacist Collection
• The Art, Science, and Technology of Pharmaceutical Compounding
• Trissel's Stability of Compounded Formulations (Recommended for parenteral solution stabilities)
• Minutes from manufacturer

Characteristic Of Specific Chemicals/Drugs

• The Merck Index
• Martindale. The Complete Drug Reference
• Remington. The Science and Practice of Pharmacy
• Handbook of Pharmaceutical Excipient
• The Pharmaceutical Codex
• The United States Pharmacopeia/The National Formulary
• Trissel's Stability of Compounded Formulations Compounding
• Extemporaneous Ophthalmic Preparations
• Guidelines for Preparation of Sterile Products in Pharmacies (CSHP)
• Handbook on Injectable Drugs (Trissel)
• Principles of Sterile Product Preparation (ASHP)
• Sterile Dosage Forms (Turco)

Compatibility And Stability Of Parenteral Drugs

• Handbook on Injectable Drugs (Trissel)
• Parenteral Drug Therapy Manual (Ottawa General Hospital)
• Trissel's Tables of Physical Compatibility
• Pocket Guide to Injectable Drugs (Trissel)
• IV Index System (Micromedex) subscription required.

Pharmacokinetic Monographs
• Compendium of pharmaceutical specialties
• USP-DI Volume I. Information for the Health Care Professional
• AHFS Drug Information
• Handbook of Clinical Drug Data

Patient Counseling
• Patient self care (CPhA) for over the counter products
• USP DI: Volume II: Advice for the patient in lay language
• Communication skills in pharmacy practice: a practical guide for students and practitioners
(Tindall: 4th ed. 2002) .
• Communication skills for pharmacists: building relationships, improving patient care (Berger)

Pregnancy and Lactation

• Drugs in Pregnancy and Lactation (Briggs)
• Mother Risk Program (Sick kids hospital, Ontario)
• AHFS Drug Information
• Clinical Therapy in Breastfeeding Patients (Hale)
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• Nausea and Vomiting of Pregnancy: State of the Art 2000

th
• Teratogenicity and Drugs, in Breast Milk. In Applied Therapeutics: The Clinical Use of Drugs (7 ed.
2001)
• USP DI - Volume I. Information for the Health Care Professional
• Breast-Feeding Precaution Listing. USP DI-Vol. II (22nd ed. 2002)
nd
• Pregnancy Precaution Listing. USP DI-Vol.II (22 ed. 2002)

Pediatrics
• Manual of Clinical Problems in Pediatrics (Roberts)
• Manual of Pediatric Therapeutics (Graef)
• Martindale: The Complete Drug Reference
• Nelson Essentials of Pediatrics
• Nelson's Textbook of Pediatrics
• Neofax
• Pediatric Dosage Handbook
• Pediatric Pharmacology
• Problems in Pediatric Drug Therapy
• Red Book 2000: Report of the Committee on Infectious Diseases
• Rudolph's Pediatrics
• The Harriet Lane Handbook
• The Pediatric Drug Handbook (Benitz)

Poisoning and Toxicology

• Refer to poison control centers: Addresses are found in Yellow pages CPS.
Casarett and Doull's Toxicology: The Basic Science of Poisons (6th edition - 1996)
• Clinical Management of Poisoning and Drug Overdose (3rd edition - 1998)
• Comprehensive Review in Toxicology for Emergency Clinicians (3rd edition - 1998)
• Drug Toxic kinetics
• Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning (2nd edition - 1997)
• Poisoning and Toxicology Handbook (APhA - 1997)
• Principles and Methods of Toxicology (4th edition - 2000)

Veterinary Medicine
Compendium of Veterinary Products
Current Therapy in Equine Medicine (Robinson)
Current Veterinary Therapy 4: Food Animal Practice (Howard)
Development and Formulation of Veterinary Dosage Forms (Hardee)
The Exotic Animal Drug Compendium: An International Formulary
Handbook of Comparative Veterinary Pharmacokinetics and Residues of Pesticides and Environmental
Contaminants
The Veterinary Formulary: Handbook of Medicines Used in Veterinary Medicine
Veterinary Drug Handbook (Plumb)

Doses And Drug Administration

Physician desk reference (PDR)
Drug facts and comparison

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Martindale: The extra pharmacopia

Intravenous and Intramuscularly Compatibilities

Handbook of injectables drug (Tresel)
Martindale: The extra pharmacopia

Teratogenicity
Physician desk reference (PDR)
Drugs in Pregnancy and Lactation (Briggs)

Indexes
Drug Interaction Index
FDA/Manufacturer Alert Index
First Report Index
Legal Action Index
Newly Marketed Drugs: 1997-2000
Drug Index

Summaries of some important reference sources

Martindale. The complete reference. Reference books contained with complete source of information
about foreign drugs and approved and off labeled drugs.

Martindale’s Extra Pharmacopoeia is probably one of the most comprehensive, international, single
volume references on drugs and drug products. Martindale’s is divided into three parts:
The first part consists of monographs on drugs and ancillary substances. (Although drugs that are
manufactured in the England are stressed, generic and propriety products from many other countries
are included). The monographs include chemical data, storage, incompatibilities, uses, doses, and
toxic effects.
The second part contains a supplementary discussion of new drugs, obsolete drugs, and miscellaneous
substances.
The third part lists formulas of OTC products sold in the England. There is also a directory of
worldwide pharmaceutical manufacturers.

Merck Index: Contained information about chemical properties and compounding.

Merck Manual: Basic information about anatomy, physiology and pathophysiological conditions.
USP DI
Available USP DI® Drug Reference Guides include:
Volume I: Drug Information for the Health Care Professional
Volume II: Advice for the Patient in lay language
Volume III: Approved Drug Products and Legal Requirements

USP DI Volume I

USP DI® Volume I. Drug Information for the Health Care Professional contains
• In-depth monographs cover dosing
• Indications
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• Interactions
• Pharmacology/pharmacokinetics
• Side/adverse effects
• Patient counselling guidelines
• Labelled and off-label uses are discussed to facilitate third-party reimbursement.

USP DI Volume II

USP DI® Volume II: Advice for the Patient - Drug Information in Lay Language. Provides patient-
oriented drug information to help patients understand and successfully follow their drug regimens.
These include brand names, descriptions, proper use, and precautions, Side effects. Instructions for
how to handle missed doses are included, as are guidelines for when to seek medical assistance or
supervision.

USP DI® Volume III

USP DI® Volume III: Approved Drug Products and Legal Requirements. Staying apprised of federal
guidelines and legislations related to prescribing and dispensing drugs are time consuming. This is a
single, easy-to-use reference containing all the information you need including the complete FDA
"Orange Book." USP DI Volume III helps you quickly identify a drug's chemical properties, determine if
a drug has been discontinued, or select an appropriate generic substitute for a more expensive brand
name drug. Excerpts from USP-NF offer data on quality, packaging, storage, and labeling requirements.
Contains guidelines and laws governing the safe handling and distribution of drugs.

USP Dictionary

USP Dictionary Content Overview

United States and international drug names

The USP Dictionary is the authoritative source for generic drug names established by the United States
Adopted Names (USAN) Council. The dictionary also provides other types of drug names used
worldwide: Brand names. Chemical names. International Nonproprietary Names (INNs). British
Approved Names (BANs). Japanese Accepted Names (JANs). Official USP-NF names. FDA-established
names.

The Medical Letter

Its newsletters, The Medical Letter on Drugs and Therapeutics and Treatment Guidelines from The
Medical Letter, publish critical appraisals of new drugs and comparative reviews of older drugs.

Clin-Alert
The adverse drug reaction events reported by Clin-Alert during the year 2000 have been compiled,
organized, re-formatted, indexed, and published in a convenient one-volume reference book

Drug Interaction Facts

Drug Interaction Facts loose-leaf edition provides drug-drug and drug-food interaction information in a
quick reference format.

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Drug Interaction Facts covers more than 20,000 brand and generic drugs and more than 70
therapeutic classes.
Drug significance ratings are also included.
Drug Interaction Facts now includes
Drug Interaction Facts: Herbal Supplements and Food. Which covers over 100 monographs and
discusses the interactions' significance, onset, severity, documentation, mechanism, and more.
Updated quarterly.

Remington. The Science And Practice Of Pharmacy

This textbook has been the definitive reference for all aspects of the science and practice of pharmacy,
and is used for pharmaceutics, therapeutics and pharmacy practice courses in primary curricula.
Remington covers many education and practice issues, from the history of pharmacy and ethics, to
industrial pharmacy and pharmacy practice.

Tips
1 Second use of drug or 2. CPS 3. Therapeutic
unapproved use of drug Choices
4 Drug monographs. 5. CPS or Immunization 6. Patient self care.
Guide of Health
Canada
7 Clinical practice 8 Remington; The 9 Antibiotic
recommendations for diseases science and practice of recommendations
such as cardio, neuro, pharmacy or clinical practice
psycho, respiratory, GI etc. trial
recommendations

• Children immunization schedule is found in? ( )

• Dental prophylaxis clinical practice guidelines can be found in? ( )
• Initial treatment can be recommended by using? ( )
• Off label indication is? ( )
• Compendium of pharmaceuticals specialties ( )
• What is found in compendium of pharmaceuticals specialties? ( )
• What is found in patient self care (PSC)? ( )
• What is not present in patient self care? ( )
• Compounding reference ( )

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www.Pharmacyprep.com Medication Errors

59
Medication Errors
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Institute of Safe Medication Practices (ISMP). The ISMP is a non-profit independent
agency established for the collection and analysis of medication error reports and
development of recommendation of enhancement of patient safety.
• Dangerous abbreviations and High alert drugs
• Near missed errors

This chapter focuses on errors that occur during the medication use process that includes the
prescribing, dispensing, and administration phases of medication use. Monitoring the patient for
expected and unexpected drug related problems and patient compliance. It reviews common causes
of medication errors and suggest measures to safe and effective use of medications/strategies to
prevent dispensing errors.

The Canadian organizations involve in medication safety?

• Health Canada's Med effect (advisories, withdrawal, recall)
• Health Canada's pharmacovigilence (ADR)
• Canadian Institute of Health Information (CIHI)
• Institute of safe medication practices (ISMP-Canada)
• Canadian patient safety institute (CPSI)

Types of medication errors: According the American System for Hospital Formulary ASHP guidelines
on preventing medication errors in hospitals, medication errors can be categorized into 11 types.
• Prescribing errors
• Omission errors
• Wrong time errors
• Unauthorized drug errors
• Improper dose errors
• Wrong dosage form errors
• Wrong drug preparation errors
• Wrong administration errors
• Deteriorated errors
• Monitoring errors
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• Compliance errors
• Other errors

Prescribing errors: A prescribing error occurs at the time a prescriber orders a medication for specific
patient. These errors may include the selection of incorrect drug, dose, dosage form, route of
administration, length of therapy, or number of doses.
Omission errors
Failure to administer an ordered dose to a patient in hospital, nursing home, or other facility before
the next scheduled dose is considered an omission error.

Wrong Time: Timing of administration is critical to effectiveness of some medications. Maintaining an

adequate blood level of some drugs such as antibiotics, frequently depends on evenly spaced, around
the clock dosing.

Unauthorized drug error: Administration of a medication to a patient without proper authorization by

a prescriber is categorized as an authorized drug error

Improper dose: Improper dose error occur when a patient is given a dose that is greater or less than
prescribed dose

Wrong dosage form errors: Doses administered or dispensed in a different form from the ordered by
the prescribed are classified as wrong dosage form error.

Wrong drug preparation errors: Drugs requiring reconstitution (adding liquid to dissolve a powdered
drug), dilution or special preparation prior to dispensing or administration are subject to wrong drug
preparation.

Wrong Administration Technique Errors: Doses that are administered using an inappropriate
procedures or incorrect technique are categorized as wrong administration technique error.

Preventing dispensing errors: In order to prevent dispensing errors, pharmacy should have policy and
procedures in place.
College of Pharmacists and professional regulatory agencies provide guidelines to prevent dispensing
error. All pharmacy staff should obey and discuss those guidelines.

Before you dispense any medication, check the following (7 point check)
Name of patient
Name of medication
Name of doctor
Pharmacist and technician initials (check expiration date)
Check DIN
Quantity of medication
Number of refills
3 point check during preparation
read label when taking drug from shelf
read label before preparing label
read label when placing back on the shelf

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www.Pharmacyprep.com Medication Errors

Strategies in reducing dispensing errors

• Procedures and policies must be developed to deal with these errors, keeping in mind that the
patient safety is paramount.
• Discuss commonly dispensing error drug with staff.
• Bringing the common drugs that may have dispensing problems to others attention, that means
everyone is extra careful as they are dispensing them.
• Drugs that look similar separate and label them.

Dispensing error occurred.

• When dispensing errors occur, rapid resolution of the problem is essential, including the recall of
the product.
• Inform the pharmacist manager immediately for any misfills or other serious problems. Do not try
to handle the situation yourself.
• Inform patient
• Inform manager
• Inform doctor if patient have taken wrong medication.
• Documenting all errors and discussing them with all staff helps keep everyone aware of mistakes
that are easily made.

Resolving dispensing errors: Pharmacy should have policies and protocol about resolving dispensing
error. Follow the guidelines provided by the provincial college of pharmacists. However, this is a
general discussion to help you get started understanding resolving dispensing errors.

In case an error has occurred the patient needs to be informed of the error that has occurred that the
medication she is taking is not the correct medication as the pharmacy has made an error in
dispensing the medication she was supposed be taking Diclectin as the doctor has prescribed but the
pharmacy dispensed dicetel 7 by mistake. Tell her to stop taking the medication, Ask her how many
dicetel 7 she has taken, apologize for the mistake that has happened, take reasonability for the
mistake, Call the doctor and report the mistake, replace the medication with the right medication,
speak to the staff about the error that has occurred.

Examples of medication error that could occur if auxiliary labels are not used or used inappropriately:
1) Codeine containing medication auxiliary label: dizziness may occur be careful when operating
machinery, A car accident may occur if the patient is not aware that this medication may cause
dizziness.
2) Fosamax auxiliary labels: drink with plenty of water, remain upright for about ½ hour after taking
the dose, take on an empty stomach, If the patient is to take the medication and lie down right after
taking it then the patient may experience oesophageal adverse experiences
3) Ventolin auxiliary labels: shake well; don’t take too much of the medication
If the patient is to take too much of the medication then the patient may experience adverse drug
reactions such as palpitations, tachycardia, tremors, nervousness, hypokalemia.
4) Flovent auxiliary labels: shake well, rinse mouth after using this inhaler. If you don’t wash your
month a pharyngeal candidiasis fungal infection in the mouth may occur in the mouth.
5) Lipitor auxiliary label: avoid grapefruit juice. Grapefruit juice may have the potential to increase
plasma levels of HMG CoA reductase inhibitors metabolized by this isoenzyme causing increased
potential for adverse effects such as muscle weakness and pain.

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Medications that should be taken with plenty of water:

Sulphonamides: Recommended for sulphonamides to decrease likelihood of crystalluria.
Expectorants: Expectorants to enhance viscosity reduction of bronchial secretions
Bulk laxatives: Bulk laxatives to increase stool bulk and decrease the likelihood of compaction
Irritating drugs: Such as potassium supplements, Chloral hydrate, theophylline
and some antibiotics.

Take with food or milk: Recommended for the drugs that cause stomach upset when this effect may
be decreased by taking medication with food.
Medication examples include:
• NSAIDs, and ASA
• Erythromycin
• Nitrofurantoin
• Valproic acid

Take Medication on an empty stomach, 1 hour before or 2 to 3 hours after 3 hours after meals unless
or otherwise directed physician.
Recommended for drugs that have decreased absorption or increased destruction in stomach when
taken with food.
Examples of drugs that should be taken empty stomach like ampicillin and tetracycline.

Actions that should be taken o resolve dispensing errors;

• Discuss with all staff to keep everyone aware of mistake
• Discuss and identify drugs that have similar names such as:
• Biaxin  one tablet twice a day (500 mg)
• Biaxin  2 tablets once a day (500 mg)
• Lasix (furosemide)
• Losec (omeprazole)

• Procedure and policies must be developed to deal with these problems.

• Check DIN (Drug Identification Number)
• Cautionsame DIN for different quantity packaging
• Expiry date
• Check patient name and date of birth
• Check allergy
• Paediatric dose child weight

Handling Returned Products: It is against the law to replace returned medication as stock bottle once it
has been dispensed and given to the patient. Exceptions are hospital pharmacies.
• Prescription drugs may not be returned by a customer and placed back in stock.
• Sometimes, the manager’s attention needs to be drawn to a complaint. In other cases, policies will
need to be developed e.g. for product recalls and dispensing errors.

Expired drugs. Do not sell expired drugs.

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A customer presents a Rx. ciprfloxacin 500 mg bid for 3d at your pharmacy at night. No other
pharmacy is open and doctor clinic is closed. Your pharmacy has expired ciprofloxacin. Patient request
to give expired cipro? What is appropriate to do?

Medical incident reporting: Institute of Safe Medication Practices (ISMP) is a non-profit independent
agency established for the collection and analysis of medication error reports and development of
recommendation of enhancement of patient safety.
Reference. American Society of Hospital Pharmacists. ASHP guidelines on preventing medication errors in hospitals, Am. J Hosp Pharm. 1993;
50: 305 to 14.

ISMPs dangerous drug abbreviations:

• Use units instead "U" or "IU"
• Use "daily" instead of "o.d"
• Use mcg instead of "µg"
• Use "0.5" instead of ".5"
• Use "5" instead of "5.0"
• Use "qd" instead of "d"
• "D/C" is used for discharge but confused with discontinue
• "CC" is intended for "cubic centimeter" mistaken for units
• "@" is intended for "at", mistaken for 2 or 5
• ">" is intended for greater than mistaken for 7

Dangerous abbreviation Mistaken as Recommended

IU IV or 10 Units
OD Right eye Daily
"µg" mg mcg
".5" 5 0.5
"5.0" 50 5
@ 2 at
D/C Discontinue discharge
> 7 Greater
CC

High alert drug: Opioids, warfarin, digoxin, insulin, epinephrine, KCl solution, TCA, pregnancy x
category drug, pediatric liquid formulation that require measurements. anticancer drugs and Lithium.
To avoid error. Label as high alert

Look alike drugs errors: Tallman letters are used for lookalike or sound alike name drugs to avoid
medication errors.
BuPROPIon and BuSPIROne
ALPRAZOLam and LORAZEPam
ClomiPHENE and ClomiPRAMINE
DAUNOrubicin and DOXOrubicin
INFLIximab and RITUximab
HydrALAzine and HydrOXYzine
diPHENhydramine and diMENhydrinate
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www.pharmacyprep.com Health promotion

60
Health Promotion and Disease
Prevention
Questions Alerts!
Common questions in pharmacy exam is to ask!
A role of public health agency.

Levels of health care delivery systems. It can be categorized as primary, secondary and tertiary health
care delivery systems.

Primary care. This is first contact a person makes a with the system when a person feels the necessity of
health care. This usually occurs through the family physician, pharmacist, or nurse at medical centers.

Secondary care. This is specialized service from a specialist. This requires referral from primary health
care levels.

Tertiary care. This is specialized in diagnosing and highly technical care and treating complicated or
unusual health problems. This generally takes place in hospital setting where generally diagnostic and
complicated therapies can take place.

Public Health units of public health agencies (PHA) offer health promotion and disease prevention
programs to help Canadian of all ages learn more about health, including healthy lifestyles,
communicable disease control and immunization.

The role of public health agencies is to promote health;

• Prevent and control chronic diseases and injuries.
• Prevent and control infectious diseases.
• Prepare for and respond to public health emergencies.
• Serve as a central point for sharing Canada’s expertise with the rest of the world.
• Apply international research and development to Canada’s public health programs and Strengthen
intergovernmental collaboration on public health and facilitate national approaches to public health
policy and planning.
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www.pharmacyprep.com Health promotion

Health promotion (Wellness). a process enabling people to increase control over and to improve their
health. In health promotion, pharmacists provide information and skills to individuals so that they can
prevent specific diseases and participate in services for early detection and treatment of disease. The
process involves a behavioural change approach such as in advising individuals on the importance of
preventing and managing obesity.

Health promotion activities from community pharmacies include the organizing of workshops, clinics
where patients are advised on a specific topics, and written and other visual aids are available in the
pharmacy for further information and for shop window dressing.
Topics for health promotion in community pharmacy includes;
• Smoking cessation
• Diet, exercise, body weight
• Cardiovascular risk factors and prevention
• Sun exposure or sunscreen
• Travel Medicine
• Patient compliance for treatment
• Immunization or vaccination programs
• Screening Programs or Tests (Pap smear test, mammography, PSA, DRE), colorectal cancer
screening.
• Alcohol, drug abuse prevention

Home work:
Screening test For detection of
Pap smear
PSA
DRE

Factors influencing health promotion (wellness) activities in community pharmacy

Positive factors Negative Factors
Accessibility of pharmacy Lack or resource material, Lack of space
Communication skills of pharmacist Lack of confidentiality
Strong pharmacist and patient relation Improper time management of pharmacy
personal
Environment within pharmacy conducive
to health promotion

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 61
Collaboration and Teamwork
Questions Alerts!
Common questions in pharmacy exam is to ask!
Examples of collaborative models.
Goal of academic detailing?

A Collaborative care involves a number of health professionals working to treat a patient. The team
generally comprises a physician, pharmacist, nurse practitioners, physiotherapist etc. To address this
issue there were several collaboration models have been studied.

Examples of collaborative traditional patient care models include biomedical model, bio-psycho-social
model.

Biomedical model. In this model, disease is defined as biophysical malfunction and goal of treatment is
to correct the malfunction in order to cure the disease. The biomedical model includes pathophysiology
of disease, objective tests and therapeutic interventions at centre of patient care. However biomedical
model offers one dimensional approach to patient care that excludes the patient experience of illness
and how this affects the other facets of life such as work disability, finances, and social networks
because they are believed to lie outside of medicines responsibility and authority.

Bio-psycho-social model (BPS). The bio-psycho-social model (body and mind) includes bio, psychological
and social dimension of patient into the care plan. The biological component of this model examines the
cause of the illness and how it affects the functioning of body. The psychological component of the
model explores any potential psychological causes for the illness (example lack of self-control, emotional
stressors, negative-thinking). The social component considers how different social factors (e.g.,
socioeconomic status, religion, culture) impact illness. In order to address all aspects of this three-
dimensional model, an integrated team approach involving allied healthcare professionals, such as
physicians, nurses, psychologists, pharmacists, social workers and rehabilitation specialists, are critical
for ensuring that more comprehensive patient care is provided.

Recovery Model. In this model the patient is involved in a lifelong recovery process that involves a
number of incremental steps across various facets of his or her life. The primary illness is seen as only
one dimension in the patient’s recovery process. Other key aspects of this model include negotiating
treatment approaches between patients and practitioners such that the patient feels empowered.
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Patient-centred cared model (PCC). In this model the patient individuality is central. The patient has
right to have his or her needs, desires, beliefs, values, and goals respected and placed at centre of the
care plan. Respect for patient individuality is part of the team commitment to understand the patient
perspective of his or her own health status and continued care.

Model for Collaborative working relationship (CWR)

There are five stages in CWR
Stage 0: Professional awareness
Stage 1: Professional Recognition
Stage 2: Exploration and Trial
Stage 3: Professional Relationship Expansion
Stage 4: Commitment to the collaborative working relationship

Stage 0: exchange is minimal. Example pharmacist calling for refill request or alerting physician for
possible side effects, drug interactions.
Stage 1: The efforts are mostly from pharmacist. Example as pharmacist develop new services,
pharmacist may be visiting physician to ask for referral of patients.
Stage 2: Pharmacist still continues to be initiator. Recommend high quality and priority
recommendations to physician. Value added services like Med check, screening.
Stage 3: Continue developing relationship to offer patient care.
Stage 4: Relatively high input, lengthy duration and great consistency.

Pharmaceutical Care Delivery System

• The major pharmaceutical care activities takes place in the following systems
• Community pharmacy
• Hospital pharmacy
• Long term care facilities
• Specialty hospital units

Community Pharmacies:
• Community pharmacies are considered one of the important components of the pharmaceutical
care delivery system. However, health related services are primarily limited to dispensing
medications and patient counselling.

Pharmacist collaboration
Pharmacists needs to work in collaborative relationship with physician and other healthcare providers.

Academic detailing (AD) defined as process of outreach in which a knowledgeable heath professional
(pharmacist) visit physicians to discuss issues of drug use and (often) overuse. AD is also known as
counter detailing. The goal of academic detailing is to enhance appropriate prescribing practices.

Soumerai and Avorn described eight components that contribute the success of academic detailing.
• Establish credibility of agency developing the intervention
• Conduct interviews with physicians to establish baseline knowledge
• Focus the intervention on educational outreach, university-based educational detailing, and public
interest detailing specific physicians.
• Define clear objectives for intervention
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• Stimulate physician interaction during the detailing visit
• Use concise graphic educational material during the presentation
• Highlight and reinforce the essential messages during presentation
• Provide positive reinforcement with a follow up visit to the physician

Pharmaceutical opinion. Pharmacist identify a potential drug related problem for patient and then
provide the prescriber with a clinical recommendation to resolve the problem.
Documentation is prepared in SOAP or FARM formats.

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www.Pharmacyprep.com Sterile Preparations

62
Sterile Preparations
Questions Alerts!
Common questions in pharmacy exam is to ask!
• The most common source contaminants in laminar airflow hood is personals.
• Types of needles, syringes, vials and ampoules. The “gauge” measures the size of needle. The
higher the gauge tinier the needle.
• Cytotoxic preparations precautions.
• Cytotoxic products sterile preparations use vertical laminar airflow hood and clean rooms.

Sterilization methods

Dry heat Steam Filtration Gaseous Radiation

Dry heat sterilization

• Equipment. Oven
• Method. Dry heat sterilization is carried out at 240 °C to 250 °C for 2 to 4 hrs.
• Application. Glassware, fixed oils, glycerine, petrolatum, liquid petroleum (mineral oil), paraffin,
and various heat stable powders, glassware and surgical instruments.
• Dry heat method of choice when dry apparatus or dry containers are required, as in the handling
of packaging of dry chemicals or non-aqueous solutions.
• Advantages & disadvantages. Sterilization by means of heat requires higher temperatures and
longer exposures than sterilization by steam. Heat transfer is slow, small volume of oil and thin
layers of powder should be used.

Steam (wet) sterilization

• Equipment. Autoclave
• Temp. 121oC 15 min, pressure 15 to 20 lbs

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• Method. In the presence of moisture, microorganisms are destroyed at a lower temperature than
in dry heat. This is the method of choice when product can withstand such treatment.
• Application. Solutions sealed in containers. Ampoule, vials, bulk solutions, glassware, surgical
dressing, and instruments.
• Advantages. Rapid, inexpensive, effective, large volumes can be sterilized.
• Disadvantages. Cannot use for oily preparation (oil base ointment), cannot use for moisture
sensitive preparations.

Filtration sterilization
• Physical removal of microorganisms by adsorption on the filter medium. Used for heat sensitive
materials.
• Equipment. Porcelain filters, siliceous earth filter, sintered glass filters, asbestos filters membrane
filters.
• Bacterial filtration. Microbial filter used in water filtrations 0.22 microns.

Application. Thermo labile solutions of low viscosity.

Advantages & Disadvantages. Depend on filter media, thermo labile solutions can be sterilized such as
hormones, proteins.

Gaseous sterilization
• Equipment. Special oven, for admission of gas and humidity & hermetic.
• Method. ethylene oxide
• Ethylene oxide gas require 4 to 16 hours
• Humidity of less than 20% RH
• Ethylene oxide-carbon dioxide, pressure 30 psi, temperature 20 to 55 °C.
• Application: Thermo labile powder, plastic/polymers, ophthalmic preparations, subcutaneous,
vaginal inserts, plastic syringes, and tubing sets.

Advantages & Disadvantages: Explosive hazard, toxic, not appropriate for solutions
Radiation sterilization
• Equipment: Ultraviolet lamp (laminar airflow hood), ionization (beta rays, gamma rays-from
nucleus, X-rays)
• Application: Thermo labile drugs (powdered)
• Disadvantages: Highly specialized equipment required, effect of irradiation on products and their
containers.

Sterile Preparations
To make sterile preparations aseptic techniques are procedure conducted under controlled condition
to minimize the chance of contamination.

Sterility is the freedom from bacteria and other microorganisms. Formulations must be sterile, which is
not a relative term an item is either sterile or not sterile. The word “sterile” refers to as free of living
microorganism.

If the sterile formulation is a solution, it must be free of all visible particulate material.
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Pyrogen free  Pyrogen is a chemical substance that is produced by microbial cell wall.
Heating to high temperatures and double distillation can eliminate pyrogen.

Aseptic preparation area: A limited access room of area in which laminar airflow hood is situated.
Usually separated from other pharmacy high traffic areas. Special measures should be taken to reduce
airborne particles.

Laminar Flows Hoods (Biological Safety Cabinets) that used for sterile preparations categorized as two
types based on direction of airflow. Horizontal laminar airflow hood and vertical laminar airflow hood.

Vertical laminar airflow hood is recommended for cytotoxic, anticancer antibiotics like doxorubicin
and microbial preparations.

Horizontal Flow Hood Vertical Flow Hood

HEPA filter. A HEPA filter is described as a high efficiency particulate air filter. It is employed with
laminar flow for preparation of aseptic parenteral products. It has an efficiency of removing 99.97%
particles of 0.33 microns or diameter larger.

Class 100 clean room. A class 100 clean room is defined as an environment that contains no more than
100 particles per cu. Ft. of 0.5 microns or larger diameter size.

Hypodermic Needle
• HUB. extension of needle that fits onto the syringe.
• Bevel. portion of the needle that is ground
• Heal. the back portion of the bevel
• Cannula. shaft portion of the needle (made of steel)
• Lumen. the needle hole.

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• The gauge is thickness or the outer diameter of the bore of needle and ranges from 27 to 13. The
smaller the number the greater the diameter.
• Needles discarded in sharp container.

Insulin needle gauge 31 is the thinnest needle available. The 30G is thinner than 28G.

Types of Glass
Type І glass is made of borosilicate the material, more resistant to water attacks.
Type II glass Is specially treated soda-lime glass
Type III glass Is the typical soda-lime glass
NP glass Non parenteral ie. not suitable for injection

Type II glass is prepared by dealkalinizing the surface of type III glass by sulfur dioxide which will
improve its resistance to breakdown and migration of alkali parenteral product. This internal coating
will be weakened by repeated sterilization or exposure to alkaline detergents.

Tips
1. filtration and 2. dry heat 3. Vertical laminar
radiation air flow hood
4. ethylene oxide 5. dealkalinizing by sulfur dioxide 6. For microbial filtration
0.22mm in sterile H 2 O
7. Distillation 8. microorganism, 9. absolute form
pyrogen & particulate
10. free from bacteria 11 Autoclave, 121oC 12 heat sensitive products
At least 15 min.
13 Rabbit test and LAL 14 pyrogen free, sterile, particulate 15 0.22mm
test free, and isotonic
16. needle

• How do you prepare type II glass, from type III glass? ( )

• Filtration sterilizations ( )
• Steam (wet) sterilization autoclave temperatures ( )
• Gas sterilization ( )
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• Radiation methods ( )
• Pyrogen test ( )
• Hormones ( )
• Tubing’s sterilization method ( )
• Proteins sterilization methods ( )
• Petrolatum, waxes are sterilization methods ( )
• Parenteral solutions should be: ( )
• Sterility is? ( )
• Cytotoxic drug preparations should be done in? ( )
• Doxorubicin is an anticancer antibiotic prepared in? ( )
• The size of HEPA filter that is used in laminar airflow hood? ( )
• Parenteral preparations should be free from? ( )
• Pyrogen are eliminated by? ( )
• What part of the syringe that should not be touched? ( )

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63
Drug Storage and Handling
Proper storage is very important to maintain the Drug’s storage condition and proper handling.
To ensure for all Drugs Standardization, Storage, and Distribution.

Proper storage is very important key component of Quality Assurance to maintain medicines
efficacy, stability. The drug is affected by the factors such as temperature, light sensitivity,
chemical reactions.
• Drug storage areas must maintain proper temperature and humidity conditions to ensure
stability of all medications as recommended by manufacturer.
• Temperature in refrigerators and freezers should be monitored and documented daily.
• Before preparing any medication, each drug, ingredient and container should be visually
inspected for damage defects and expiry date.
• All the drugs and supplies use in the sterile room should be unpack before brining into the
sterile room.
• All the medications and supplies should be stored on shelves, cabinets, and cart, not on the
floor. That way, the floors can be clean properly.
• Chemo/toxins should be stored on an eye level or on lower shelves in order to avoid
breakage.
• All the drugs, supplies and equipment should be storage as the manufacturer indicated on
the label.
• All high-alert medications are safeguarded and that known safety requirements for storage,
availability and labeling are followed.

Stability: Refers to the extent that a pharmaceutical preparation retains specified properties and
characteristics within specified limits that it possessed at the time of compounding or
preparation.
Cold Temperature: Temperature that does not exceed 8º C
Cool Temperature: Temperature that is between 8º C to 15º C
Refrigerated Temperature: Temperature that is between 2º C to 8º C
Room Temperature: Temperature that is between 15º C to 30º C

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Temperatures: The temperature in refrigerators and freezers should be monitored and

documented daily.
• All the drugs and supplies use in the sterile room should be unpack before brining into the
sterile room.
• All the drugs, supplies and equipment should be storage as the manufacturer indicated on
the label.
Drug Recommended Storage Stability at room temperature
Insulin Refrigerate at 2° to 8° C 28 days
Triflurdine (Viroptic) Refrigerate at 2° to 8° C
Idoxuridine Room temperature
Xalaton Prior to dispensing or unopened After first use, store at a room
refrigerate at 2° to 8° C temperature not to exceed 25°C
for up to 6 weeks
Xalacom Prior to dispensing or unopened After first use, store at a room
refrigerate at 2° to 8° C temperature not to exceed 25°C
for up to 10 weeks
Etonogestrel/ethinyl estradiol Refrigerate at 2° to 8° C After dispensing, store at 25°C
vaginal ring (Nuvaring) for up to four month
Infliximab

Vaccine Recommended Storage Stability at room temperature

Dukoral Refrigerate at 2° to 8° C
Influenza virus Refrigerate at 2° to 8° C
Influenza live vaccine (FluMist) Refrigerate at 2° to 8° C
MMR Refrigerate at 2° to 8° C
Diluent may be stored in fridge
or room temperature. Do not
freeze.
Hepatitis a Refrigerate at 2° to 8° C
Hepatitis B Refrigerate at 2° to 8° C
Hepatitis A and B Refrigerate at 2° to 8° C

Powdered antibiotics require reconstitution with distilled water, added at the time of
dispensing. While many of these medications are stored in the refrigerator, some are not.
Reconstituted products Recommended Storage Stability at room temperature
Azithromycin suspension Room temperature for 10 days
Amoxicillin suspension Refrigerate at 2° to 8° C for 14
days
Amoxicillin/clavulin 400 mg Refrigerate at 2° to 8° C for 7
days
Amoxicillin/clavulin 250 mg Refrigerate at 2° to 8° C for 10
days
Clarithromycin suspension Room temperature for 14 days
Erythromycin suspension Refrigerate at 2° to 8° C
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Clindamycin suspension Room temperature for 14 days

Phenytoin suspension
Metronidazole suspension Room temperature stable for 1
month
Chloramphenicol suspension Room temperature for 2 weeks
Ciprofloxacin suspension Room temperature for 2 weeks
Furosemide solutions
Cefuroxime axetil suspension Room temperature for 2 weeks
Cotrimoxazole suspension Room temperature until expiry
Norfloxacillin Room temperature for 2 weeks
Cloxacillin Room temperature for 2 weeks
For cold chain follow National Guidelines for Vaccine Storage and Transportation.
Short dated products are those which will expire before the patient will finish using them.

Q&A
1) When should pharmacy staff defrost refrigerator?
A) More than 10 cm ice in the freezer compartment
B) More than 5 cm ice in the freezer compartment
C) More than 1 cm ice in the freezer compartment
D) It should be never defrosted
Ans. C

2. Storage of Dukoral should be:

A. At room temp
B. In the fridge
C. Away from light
D. In a safe cabinet
Ans (B)
Tips: It is a vaccine.

3. All the drugs and supplies use in the sterile room should be unpack ?
A. After bringing into the sterile room
B. Before brining into the sterile room.
C. Anytime and anywhere can be unpacked
D. Manufacturer should not pack supplies that are used in sterile preps
Ans. B

5. The temp of the fridge in the pharmacy should be recorded at least

A. Once per day
B. Twice per day
C. Three times per day
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D. Once every other day

Ans. ( B)
Tips: It should be recorded once in the morning and once in the night

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64
Pharmaceutical Care or
Patient Care
Patient care describes specific activities (job description) and services which an individual pharmacist
offer services to patients that include dispensing, collaborating, implementing, developing and
monitoring therapeutic plan that will produce specific therapeutic outcome for the patient.

Patient care process include? Assessment--> Care Plan --> Follow up evaluation, documentation
Essential component of patient care?
• Pharmacist -patient relationship
• Pharmacist workup of drug therapy (PWDT). include data collection, develop therapeutic plan,
identify DRPs or DTP, and documentation of patient care (SOAP note).
The pharmaceutical care is the services rendered by the pharmacist to improve patient quality of life
within reasonable economic expenditure. Pharmaceutical care requires the pharmacist to incorporate
some essential skills in practice, that include.
• Prescription processing and dispensing.
• Making sure that the patient understands how to use the product, to ensuring that use of a
medication will have the outcome desired.
• Skills in assessment of patient health status.
• Identification of potential and actual drug related problems (DRP)
• Identification of drug related problem and therapeutic choices
• Developing and implementing therapeutic care plan.
• Monitoring and evaluating patient progress with therapy
• Documentation of finding and follow ups

Professional relationship with patient. A pharmacist must develop a professional relationship with the
patient, by collaborative efforts between pharmacist and patient. Offering empathy is an important
component of developing interaction. The pharmacist encourages patients to participate in decisions
about their health and supports the patient's right to make choices.
The pharmacist develops professional relationships with patients and/or patient’s agents and/or
health care providers:

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Gathering patient information and Maintenance Of Patient Records:

A pharmacist must gather patient information and assess its relevance to patient care. This process is
often described as pharmacists workup of drug therapy (PWDT). The PWDT contains the thought
processes necessary for pharmaceutical care.

The patient specific information that gives a basis for or leads to the recognition of a pharmacotherapy
problem or indication of pharmacist intervention.
In short PWDT can be presented as FARM Note and SOAP Note.

FARM stands for F= Finding, A = Assessment, R = Resolution/recommendations, M = Monitoring.

Information collection and maintenance of patient records.

The pharmacist collects and discuss the following information for new prescription or when made
necessary by profession judgment. This information includes:
• Confirmation of the identity of the patient
• Current medical condition(s) being treated
• Name, general description of the drug dispensed
• Direction for use to get the maximum benefit of drug
• Common or important side effects and appropriate management, and storage requirements
• The pharmacist should respect the patient’s rights to confidentiality and privacy by taking all
reasonable steps to ensure that personal health information is communicated in a manner in
which others cannot overhear the discussion. Pharmacist should offer a semi-private area with
suitable traffic and/or noise barriers or a private counselling room
• The pharmacist should communicate using effective and appropriate communication skills while
respecting the patient’s personal, cultural and educational difference. The pharmacist should
demonstrate flexibility in recognizing the unique qualities of each patient in order to find workable
solutions.
• Informed consentTaking permission and store personal information consent with conscious.
• ConfidentialityInformation provided by patient is the property of patient; maintain information
confidentiality essential by the pharmacy. However, information may disclose to physician,
pharmacist, and insurance with the consent of patient.

Developing therapeutic plan: A pharmacist must develop therapeutic plans, recommending

therapeutic options, doses, scheduling/administration, required drug devices and compliance aids.
Therapeutic plan types: CORE pharmacotherapy plan:
CORE stands for:
C = conditions (medical conditions)
O = Outcome desired for that conditions
R = Regimen (treatment required to achieve outcome)
E = Evaluation parameters to assess outcome treatment

Drug-related problems (DRPs) or Drug therapy problem (DTP). The pharmacist’s focus is on the
patient’s use of a product, to the patient’s situation as a whole including his or her need for the
medication, the appropriateness of the product as prescribed, factors that could affect the patient’s
use of the medication as prescribed, and whether the desired outcome will be achieved (from both the
patient’s and physician’s points of view). An important part of this focus for the pharmacist involves
the identification of current or potential drug related problems and their subsequent resolutions.

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Drug-related problems (DRPs). that are described in the concept of pharmaceutical care include:
1. The patient is taking/receiving a drug for which there is no valid indication (require drug but not
receiving it).
2. The patient requires drug therapy for an indication and is not receiving it (includes symptoms of
disease and of side effects).
3) The patient is not taking/receiving the appropriate drug (includes allergies, contraindications, or a
drug that is not cost-effective, not working or not the drug of choice).
4) The patient is taking/receiving too little of a drug (includes insufficient dose, frequency and drug
disease interactions, drug food interactions).
5) The patient is taking/receiving too much of a drug (includes excessive dose, inappropriate frequency
and drug-disease interactions).
6) The patient is not taking/receiving the prescribed drug appropriately (economic constraints,
dispensing or administration error, non-compliance).
7) The patient is experiencing an adverse drug reaction (non-dose-related).
8) The patient is experiencing a drug-drug, drug-food or drug-laboratory test interaction.

Documentation of pharmaceutical care. Formulate a FARM or SOAP progress note to describe and
document the interventions intended or provided by the pharmacist.
S = subjective
O = objective
A = Assessment
P = Plan

SOAP stands for Subjective data (S) separated from objective data (O), A = assessment P = Plan
S = Subjective (summary of case). MP is a 55-year-old man, receiving treatment of hypertension. MPs
doctor prescribed hydrochlorothiazide 50 mg daily
O = Objective: (findings) Current BP 150/90, SrCr (80), FBG 6.5 mmol.
A = Assessment. MP using HCTZ 50 mg and have still high BP and require additional antihypertensive
drug.
P = Plan. MP Doctor adds Ramipril 10 mg.

Tips
1. ARBs 2 Refer to doctor 3 Pharmaceutical care
4. FARM 5 SOAP 6 improving patient quality of life

• Is the services offered by the pharmacist to improve patient quality of life within reasonable
economic expenditure ( )
• Finding, Assessment, Resolution, Monitoring ( )
• Subjective data, Objective data, Assessment, Plan ( )
• Pharmaceutical care should be focus to? ( )
• A 50 year old patient currently using enalapril for hypertension. Experiencing dry cough. What
alternative therapy should you recommend? ( )
• A customer searching for OTC antidiarrheal medications. If you realized diarrhea is associated with
clindamycin, what is appropriate action? ( )
• Pharmaceutical care should be focus to 
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• Write examples of drug related problem (DRP) 

• A 50-year-old patient currently using enalapril for hypertension. Experiencing dry cough. What is
alternative preferably therapy is recommended?
• A customer searching for OTC antidiarrheal medications. If you realized diarrhea is associated with
clindamycin, what is appropriate action? 

Write the most common DRPs of the following drugs and patient presentations:
• Alendronate -->
• Statins -->
• Metformin -->
• Insulin -->
• Salbutamol -->
• Steroid inhalers -->
• Anticholinergic drugs (ipratropium) -->
• Contraceptive pills -->
• Methotrexate -->
• Minocycline -->
• Metronidazole -->
• NSAIDS -->
• Warfarin -->
• Accutane -->

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65
Adverse Drug Reactions
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Clinical significant adverse drug reactions like most common and serious side effects

ADRs affecting the cardiovascular system

Cardiovascular Causative drug Comments
disorder
Hypertension Venlafaxine dose dependant
hypertension, sympathomimetics and
mineral corticoids. Licorice.
Postural hypotension Alpha-blockers, ACEi, diuretics, • Caution on standing
(syncope) antipsychotic (α 1 blockade), • Take first dose of alpha-blockers
vasodilator (hydralazine, nitrates) and and ACEi on at bedtime
opioids.
Myocardial ischemia Levothyroxine, adenosine, • In patients with hypothyroidism
amphetamines, beta agonist, beta- and cardiovascular disease, the
blockers (withdrawal), caffeine, initial dose of levothyroxine
ergotamine, nifedipine (short-acting), should be low and increased every
theophylline, verapamil. Oral 4 wks.
contraceptive pills.
Peripheral Beta-blockers • Choose a more cardio selective
vasoconstriction (DVT, agent such as atenolol, which has
Raynaud's less affinity for beta 2-
phenomenon) adrenoceptors
• Choose a beta-blockers with
vasodilators actions, e.g. carvedilol
and labetalol
Hemorrhagic stroke Anticoagulants, thrombolytic and • These should be avoided
antiplatelet drugs

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Arrhythmias; Antiarrhythmic: amiodarone, • Risk of torsade de pointes (QT

prolonged QT interval disopyramide, procainamide, interval prolongation) or sudden
propafenone, quinidine, sotalol. death due to ventricular
fibrillation
Antihistamines (Terfenadine, • Recommended doses for
astemizole), antibacterials Terfenadine should not be
(clarithromycin, erythromycin, exceeded.
cotrimoxazole), fluroquinolones • Terfenadine should be avoided in
(moxifloxacin and levofloxacin) hepatic impairment, hypokalemia
antifungals (ketoconazole, and pre existing QT interval
itraconazole), antimalarials prolongation or with grapefruit
(chloroquine, quinine), antipsychotics juice in addition to the risk factors
(chlorpromazine, haloperidol, listed above.
pimozide, thioridazine),
antidepressants, Tricyclic,
(amitriptyline and imipramine and
Ziprasidone), cisapride, pentamidine,
tacrolimus, terodiline.
Atrial fibrillation Antidepressant (trazodone, fluoxetine), • Drug causes are rare. Other
(Lab test is. absence of and alcohol. includes hypertension,
P wave) hyperthyroidism, rheumatic heart
disease, infection and pneumonia.
Bradycardia Beta blockers (including eye drops), H 2 • Serious interaction between beta-
receptor antagonists, carbamazepine, blockers and verapamil leading to
clonidine, digoxin, diltiazem, and a systole. Risk of bradycardia with
verapamil. beta-blockers and diltiazem
(carefully monitoring required).
• Adjust dose of digoxin to keep the
heart rate above 60 beats/min.
• Watch HR for ABCD
AV node arrhythmias TCAs • Amitriptyline is proarrhythmic

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ADRs involving hematological system

Hematological Causative drugs Comments
disorder
Aplastic anemia (total Antidiabetic (chlorpropamide, Reduced red blood cell (anemia), white cell
or partial failure of the tolbutamide), Antiepileptics (leucopenia), and platelets
bone marrow) (carbamazepine, phenytoin, (thrombocytopenia) counts.
lamotrigine), anti-inflammatory Often irreversible despite drug withdrawal.
(diclofenac, gold, indomethacin,
penicillamine, phenylbutazone,
piroxicam, sulindac, sulfasalazine),
Antimicrobials (chloramphenicol, co-
trimoxazole, sulphonamides),
antiplatelets (ticlopidine),
antipsychotics (chlorpromazine),
antithyroid agents (methimazole,
propylthiouracil)
Agranulocytosis Antibiotics (penicillin's, Recovery usually 2 to 3 weeks after drug is
(profound reduction of cephalosporin's, cotrimoxazole, withdrawn; repeat exposure to causative
granulocytes with chloramphenicol, sulphonamides), drug not recommended due to
neutrophil count less antidepressants (imipramine, sensitization.
than 0.5 x 109/L clomipramine, desipramine),
antiepileptics (carbamazepine,
phenytoin), anti-inflammatory (gold,
penicillamine, leflunomide,
sulfasalazine, NSAIDs), antipsychotics
(chlorpromazine, thioridazine,
clozapine), antithyroid drugs
(methimazole, propylthiouracil),
captopril, procainamide, and
ticlopidine.
Thrombocytopenia Antimicrobials (chloramphenicol, co- May present as easy bleeding, bruising or
(reduced platelets to trimoxazole, trimethoprim, penicillin's, purpura; prolong bleeding time but INR
less than 150 x 109/L). sulphonamides, rifampicin), remains normal. Usually occurs 7 to 10
antiepileptics (sodium valproate), anti- days after drug started. Avoid future
inflammatory (gold, penicillamine), exposure to the causative agent.
diuretics (thiazides, furosemide) ASA and NSAIDs reduce the effects or
tolbutamide, digoxin, methyldopa, remaining platelets and therefore should
heparin (less likely with low molecular be avoided during thrombocytopenia.
weight heparin), and quinidine.
Pure red cell aplasia Azathioprine, phenytoin, isoniazid, Anemia with a marked reduction in
(Total or partial failure penicillamine, chlorpropamide, reticulocytes (immature RBC). The Coombs
or red cell production) chloramphenicol, erythropoietin, test is used to distinguish immune
cephalosporin's, penicillin's, mechanism also G6PD deficiency.
tetracycline’s, insulin, methotrexate, Red cells usually return to normal after 2 to
isoniazid, quinidine, quinine, rifampin, 3 weeks.
sulphonylureas, methyldopa,
mefenamic acid, drugs with oxidant Marked increased of reticulocytes
effect on cell membrane (particularly indicates? anemia
in G6PD deficiency).

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Megaloblastic anemia Acyclovir, alcohol, antiepileptic, Impaired DNA synthesis usually due to
(large abnormal form methotrexate (dose dependent), folate or vitamin B 12 deficiency.
or precursors to RBC) nitrofurantoin, oral contraceptives, Use folic acid supplements to treat patients
proguanil, sulphasalazine, taking antiepileptic drugs.
trimethoprim (usually due to
worsening of pre-existing folate
deficiency) and phenytoin.

Home work. Drugs that require vitamin supplementation during therapies.

ADRs leading to psychotic problem

Psychiatric Causative drugs
problem
Depression • Alcohol, amantadine, CNS stimulants (amphetamine withdrawal).
• Antimicrobials (ciprofloxacin, sulphonamides)
• Cardiovascular (lipophilic beta blockers (Propranolol), alpha blockers, CCB,
digoxin, methyldopa, statins).
• Benzodiazepines, carbamazepine, levodopa, phenothiazines).
• Hormones (corticosteroids, estrogens, progesterone)
• Disulfiram, isotretinoin, mefloquine, metoclopramide, and NSAIDs.
Psychosis • Amantadine, .amphetamines, anticholinergics (includes 1st generation
antihistamine), antiepileptics, bromocriptine, chloroquine, clonidine, digoxin,
disulfiram, donepezil, ganciclovir, isoniazid, levodopa, mefloquine, NSAIDs,
quinidine, quinolone, zolpidem, and drugs of abuse.
Mania • Baclofen, bromocriptine, chloroquine, corticosteroids, dopaminergic agents,
isoniazid, levodopa, and antidepressants.
Behavioural • Lamotrigine (cognitive SEs), dextromethorphan (children), diphenhydramine,
toxicity chlorpheniramine, vigabatrin.
Confusion • Antiparkinson's drugs, barbiturates, beta-blockers, benzodiazepines, cimetidine,
corticosteroids, diuretics, H 2 -receptor antagonist, hypoglycemics, MAOis,
NSAIDs, opioids, and 1st generation and antihistamines.
Dementia or • Most common are benzodiazepines withdrawal symptoms, corticosteroids,
delirium opioids, anticholinergics and drug with anticholinergic effects including TCAs,
or delirium antiarrhythmics, antiparkinson agents, conventional antipsychotics, ipratropium
tremens (high doses), oxybutynin, tolterodine and sedating antihistamines.
Neuroleptic • Dopamine antagonists (antipsychotics, most common are phenothiazines and
malignant butyrophenones).
syndrome
Sedation • Most common are antiparkinson’s drugs, antipsychotics (phenothiazines,
particularly chlorpromazine), barbiturates, benzodiazepines, carbamazepine,
opioids, antidepressants (amitriptyline, trazodone), 1st generation
antihistamines, and alpha blockers.

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ADR leading to Neurological disorder

Neurological Causative drugs Comments
disorder
Headache Vasodilators (CCBs like nifedipine, • Tolerance usually develops during
nitrates), indomethacin, MAOi vasodilator treatment and patients
interaction (hypertensive crisis), should persist with treatment if possible
analgesics (rebound after daily
administration, especially with
caffeine), triptans (overuse),
ergotamine (withdrawal), and
SSRIs.
Aseptic meningitis NSAIDs, vaccines, ciprofloxacin, • Particularly in patients with systemic
azathioprine, penicillin, isoniazid, lupus erythromatus
cotrimoxazole. • Difficult to distinguish clinically from
bacterial/viral meningitis, therefore a
drug history should be considered in all
cases.
Benign intracranial Amlodipine, corticosteroids • Symptoms include headache, edema of
hypertension (including topical), danazol, optic nerve head, nausea, vomiting,
etedrinate, nalidixic acid, tinnitus and visual disturbances
nitrofurantoin, oral • Usually resolves on cessation of
contraceptives, tetracycline’s, treatment
isotretinoin, vitamin A (at high
doses and deficiency)
Reduction of Bupropion, 1st generation • Early drug withdrawal improves
convulsion antihistamines, antipsychotics, prognosis
threshold and baclofen, chloroquine, • Risk factors include diabetes mellitus,
increasing the risk of cyclosporine, corticosteroids alcoholism, vitamin deficiency (vitamin
seizures (systemic), donepezil, isoniazid, B 1 , B 12 ), reduced renal/hepatic function,
lithium, mefloquine, ecstasy poor acetylator status (hydralazine,
agents (amphetamines), NSAIDs, isoniazid).
oral contraceptives, penicillin's,
quinolone antibiotics,
antidepressants (SSRIs, and TCAs),
stimulants and anorectics,
theophylline, tramadol, vaccines.
Withdrawal effects of alcohol,
baclofen, barbiturates, BZD.
Guillain-Barre’ Captopril, corticosteroids, gold • Rare paraesthesia of toes or fingers
syndrome (disease salts, hepatitis B vaccine, influenza progresses to upper and lower limb
of peripheral nerve) vaccine, MMR vaccine, oxytocin, followed by total body weakness
penicillamine, streptokinase
Myasthenia gravis Corticosteroids (high-dose), • Avoid in myasthenia gravis
(chronic muscle phenytoin, amino glycosides,
weakness involving quinolone antibiotics
reduced activity of (ciprofloxacin), beta-blockers,
acetylcholine at lithium, anticholinergic
neuromuscular
junction)

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st
Extra pyramidal 1 generation antipsychotics such • Apparent lower risk of drug-induced
symptoms and as haloperidol (also following parkinsonism with newer antipsychotics
Parkinson’s disease withdrawal), antiemetics (clozapine, quetiapine risperidone,
"PATD" (metoclopramide, olanzapine).
prochlorperazine), CCB (verapamil, • Dose-related
amlodipine, diltiazem), lithium, • Metoclopramide should be avoided in
methyldopa, antidepressants patients’ with age less than 20 years.
(TCAs and SSRIs), and valproate
Tinnitus NSAIDs, including ASA, and
antimalarials.

ADRs affecting Respiratory system

Respiratory disorder Causative drugs Comments
Cough ACEi • All ACE inhibitors
• Angiotensin receptor antagonists
(ARBs) may be suitable
alternatives
• Renin inhibitors (Aliskiran)
Nasal congestion (stuffy Chronic use of topical nasal • Prolonged used of topical
nose) decongestants (ephedrine, decongestant vasoconstrictors
xylometazoline, oxymetazoline) causes tolerance and rebound
Antidepressants, antihypertensive congestion due to in part to down-
(methyldopa, prazosin, hydralazine, regulation of alpha-adrenoceptor.
propranolol), antipsychotics, oral • Dilation of nasal vasculature
contraceptives, ASA, and NSAIDs. produces tissue edema.
Bronchoconstriction Anticholinesterases, Antibiotics (e.g. • Particularly in asthma and COPD
penicillin's and cephalosporin's), patients.
Aspirin, NSAIDs, dipyridamole, non- • Allergic reaction to penicillin's may
selective beta-blockers, (including also occur with other beta lactam
eye drops), ACE inhibitors, antibiotics. (cephalosporin's,
pharmaceutical excipients carbapenems and monobactams).
(tartrazine, benzoates,
phenylmercuric salts, paraben,
benzalkonium chloride and
metabisulfite), general anesthetics
and muscle relaxants Radiological
contrast media ACE.
Reflex Ipratropium, inhaled beta2-agonist, • Direct irritation of bronchial
bronchoconstriction corticosteroids, cromoglicate, mucosa
zanamivir
Lung parenchyma- Methotrexate, nitrofurantoin, • Generally allergic reactions
interstitial pneumonitis amiodarone, gold salts, paclitaxel, presenting as cough,
penicillamine, sulphasalazine breathlessness and wheeze
• Patients on methotrexate should
not receive nitrofurantoin due to
synergy of ADR
• Early diagnosis and treatment
improve recovery

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Lung parenchyma- Anticancer agents (bleomycin) • Direct toxicity causes

pulmonary fibrosis Amiodarone, gold, sulphasalazine, inflammation and fibrosis leading
nitrofurantoin, bromocriptine and to significant morbidity and
pergolide. mortality.
• Dose and duration of treatment
are important
Pulmonary edema (adult IV beta-agonists (salbutamol iv and • Increased pulmonary vascular
respiratory distress terbutaline), amphotericin, permeability presenting as cough,
syndrome, ARDS) haloperidol, hydrochlorothiazide, breathlessness and frothy sputum.
mannitol, urea, indomethacin, • Close monitoring of women
methadone, naloxone, and receiving IV beta-agonists in
protamine. premature labour, especially in the
presence of fluid overload.
Pulmonary eosinophilia Nitrofurantoin, NSAIDs, antibiotics, • Symptoms include cough, dyspnea
antineoplastics. and fever.
• Patients improve on cessation of
treatment.
• May be treated with
corticosteroids.
Respiratory failure Opioids, CCB, beta-blockers, anti • Opioids depress the rate and
(neuromuscular) rheumatics, aminoglycoside and depth of respiratory centre in the
polymyxin antibiotics, and diuretics. brain to increase blood CO 2 .
• Impaired respiratory muscle
function.
• Patients at risk include those with
pre-existing impaired respiratory
muscle function, renal failure and
myasthenia gravis.
• Reversible on cessation of
treatment.
Pulmonary and Combined oral contraceptives May present as sudden collapse,
thromboembolism pleuritic pain, breathlessness, cyanosis
and hemoptysis.

ADR affecting Endocrine System

Endocrine effects Causative drugs
Altered glucose
control
Thyroid dysfunction
Adrenal function Corticosteroids, ketoconazole (reduced), rifampin (reduced)
Aldosterone synthesis Carbenoxolone, lithium, loop diuretics, oral contraceptives,
spironolactone, thiazides
Hypoaldosteronism ACEi (including Angiotensin II receptor antagonist), NSAIDs, heparins

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Gonadotrophin Ovarian and testicular:

release and gonadal Corticosteroids (reduced), danazol (increased free testosterone),
function ketoconazole (reduced testicular steroidogenesis)
Gynecomastia-estrogenic:
Clomiphene, digoxin, estrogens, spironolactone
Gynecomastia - (due to reduced testosterone):
Alcohol, alkylating agents, cyproterone, flutamide, phenytoin,
spironolactone, ketoconazole, cimetidine.
Gynecomastia: Antipsychotics (chlorpromazine), CCB, isoniazid,
marijuana, methadone, methyldopa, protease inhibitors, stavudine, and
TCA.
Hyperprolactinemia or Methadone, morphine, antidepressants, antipsychotics, anti ulcer drugs
galactorrhea (e.g. cimetidine, ranitidine), benzodiazepines, estrogens, methyldopa,
and verapamil.
SIADH-syndrome of Psychotropics, carbamazepine, cytotoxics, and hypoglycemics
inappropriate (chlorpropamide, tolbutamide).
secretion of
antidiuretic hormone

ADR affecting musculoskeletal tissue

Musculoskeletal pathology Causative drugs Comments
Statins, fibrates, nicotinic acid, • Myalgia presents as muscle pain,
Myalgia (muscle pain), amiodarone, carbimazole, tenderness and/or muscle weakness.
cramps or myopathy cyclosporine, cimetidine, • Increase creatine kinase (CK-MM) is
colchicine, corticosteroids an indicator of muscle damage (10 x
(withdrawal), danazol, diuretics, normal level may indicate
opioids, penicillamine, quinine, myopathy).
chloroquine, quinolones, and
zidovudine.
Metabolic bone disease: Corticosteroids, heparin, thyroid • Lowest-effective dose of
osteomalacia (rickets, hormones corticosteroids should be used
abnormal bone softening). • Consider vitamin D supplement for
housebound and frail elderly.
Metabolic bone disease: Aluminium salts (including • A lack or defective metabolism of
osteomalacia (rickets, prolonged ingestion of vitamin D.
abnormal bone softening). antacids), barbiturates, • Poor diet and lack of sunlight are
bisphosphonates (overdose), contributing factors.
phenytoin, long term total
parental nutrition.
Arthralgia (joint pain Penicillin, CCB, carbimazole, • May accompany any drug-induced
without swelling). isoniazid, procainamide, skin eruption.
quinidine, quinolone antibiotics, • Severe joint pain with swelling is a
rubella vaccine, BCG. component of serum sickness (e.g.
penicillin)
Arthralgia. Acute gout Thiazide diuretics, low-dose • Caused by the arthritis (includes
salicylates, niacin and inflammation and swelling) of acute
cyclosporine gout.

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Arthropathy (erosion of Quinolone antibiotics • Restricted indications in children,

articular cartilage) growing adolescents and avoid in
pregnancy.
• Usually reversible on cessation of
treatment.
Tendinopathy (particularly Quinolone antibiotics (ofloxacin) • More common in people in over 50
Achilles tendon) years of age increased risk if renal
impairment and/or corticosteroids
treatment
Retroperitoneal fibrosis ASA, beta-blockers, • Symptoms include persistent pain in
(development of fibrous bromocriptine, codeine, the loin and groin, oliguria, pain on
tissue behind peritoneum) ergotamine, haloperidol, micturition, myalgia and edema.
methysergide • Symptoms improve on withdrawal of
treatment
Systemic lupus Hydralazine, procainamide, • Symptoms include arthralgias,
erythematosus (SLE) or beta-blockers, carbamazepine, myalgias, malaise, fever, pleurisy and
lupus like syndrome chlorpromazine, disopyramide, pericarditis
isoniazid, methyldopa, • Symptoms improve within days or
nitrofurantoin, penicillamine, weeks of cessation of suspected drug
phenytoin, quinidine, • Usually occurs after several months
sulphasalazine, sulphonamides, or years of continued therapy
tetracycline’s (minocycline, • Presentation of drug-induced SLE
particularly young patients) differs from SLE
thiazides, thiouracil. • Leucopenia, thrombocytopenia,
anemia, elevated ESR and
"HIPPP MCQ" antinuclear antibodies may be
present.
• Increased risk in slow acetylators

ADRs affecting GI system

Adverse GI effects Causative drugs Comments
Taste disturbance ACEi, CCB, etidronate, Usually resolves on cessation of treatment but
(dysguisea) griseofulvin, isotretinoin, may take for months.
levodopa, losartan,
penicillamine, terbinafine Zopiclone: Bitter taste
Metallic taste Allopurinol, gold, lithium,
metformin, metronidazole,
penicillamine, zopiclone
Gingival Phenytoin, dihydropyridine Usually occurs within 3 months of starting
overgrowth CCBs, cyclosporine treatment. Good oral hygiene minimizes risk of
gingival hyperplasia.
Pigmentation of Tetracycline’s Rare and particularly minocycline
the oral mucosa

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Dental Tetracycline’s Avoid tetracycline in children under 12 years old

discoloration
Dry mouth Anticholinergic effects, May cause weight loss, candidiasis, dental caries,
(xerostomia) antihistamine, TCAs, CNS poor adherence to drug regimens, reduced
stimulants, phenothiazines efficacy of sublingual drug administration (e.g.
nitroglycerin).
Saliva secretion Cholinergic agonist (e.g. Risk of choking at night
(Ptyalism) pilocarpine, clozapine)
Stomatitis and Aspirin, barbiturates, Usually resolve quickly when drug is stopped.
Mouth ulcers captopril, griseofulvin,
isoniazid, nicorandil,
NSAIDs, proguanil,
sulphasalazine
Esophageal Ascorbic acid, ASA, Usually occurs within hours to days of taking
disorders bisphosphonates, causative drug. Most cases heal within days or
clindamycin, doxycycline, weeks of treatment cessation.
ferrous sulfate, NSAIDs,
potassium salts, quinidine,
tetracycline, and
theophylline.
Acid reflux or CCB, opioids, nitrates, and Due to relaxation of the lower esophageal
heartburn anticholinergics. sphincter.
Nausea and Many but often occurs with Symptoms may resolve with continued use or
Vomiting anticancer drugs, occasionally by taking the drug after food. It may
emergency contraception indicate toxicity of digoxin or theophylline.
(Plan B), levodopa, opioids,
SSRIs, iron salts,
bromocriptine,
erythromycin, estrogens
Gastro toxicity NSAIDs, corticosteroids, Increased risk when coprescribing with NSAIDs
CCB, SSRIs, clopidogrel.
Duodenal NSAIDs, less often It may be difficult to diagnosed at early stages, as
ulceration and corticosteroids, but likely if the inflammation is asymptomatic. This may be a
perforation taken with NSAIDs. cause of “unexplained bleeding”. Complications
include iron-deficiency anemia due to blood loss,
hypoalbuminemia due to protein loss, ulceration
and stricture formation (results from
postprandial colicky pain). Associated with
alcohol abuse. Diagnosis may follow the
detection of iron-deficiency anemia, usually after
long-term treatment, hypoalbuminemia
(associated with peripheral edema and other
signs of fluid retention due to protein loss from
damage intestinal mucosa). Blood loss is not
often sufficient for detection in fecal occult blood
test (FOBT)

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Paralytic ileus and Acarbose, CCB, clozapine, Physical obstruction or anticholinergic effects
pseudoobstruction bulk forming laxatives, inhibiting smooth-muscle activity, particularly if
loperamide, opioids, more than one anticholinergic agent is prescribed
phenothiazines, potassium
salts, TCAs
Malabsorption Cholestyramine, colestipol, Supplements of fat-soluble vitamins may be
from the orlistat, liquid paraffin, required.
duodenum metformin Serum vitamin B 12 may be reduced in patients
taking metformin but clinical significance appears
to be small
Diarrhea Many but most common Clindamycin-induce diarrhea may be the result of
are, antibiotics (most Pseudomembranous colitis. Treatment should be
commonly clindamycin), stopped.
acarbose, metformin, bile Severe diarrhea may lead to treatment cessation
salts, colchicine, cytotoxics, of diarrhea causing drugs
dipyridamole, gold, iron
salts, laxatives,
magnesium-containing
antacids, NSAIDs
(mefenamic acid), orlistat,
ticlopidine, misoprostol,
olsalazine
Colitis Amphetamines, cocaine, Presents as sudden onset of severe abdominal
digoxin, ergot amine, pain, nausea, vomiting, diarrhea, and abdominal
sumatriptan, distension. Tachycardia, pyrexia, leucocytosis,
methotrexate, methyldopa, and bloody stools may be present.
methysergide, NSAIDs,
estrogen, salicylates
Constipation Many but most common Risk factors include polypharmacy, dehydration,
are, anticholinergics, immobility, advance age and low-fibre diet.
opioids (codeine, morphine Opioids induced constipation is treated by
etc), iron slats, verapamil, stimulants laxative (Senna or bisacodyl).
TCAs, antihistamines,
clozapine, MAOIs,
peppermint oil,
phenothiazines, sucralfate,
and diuretics.
Al and Calcium antacids.

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Dark stools Iron slats, bismuth salts, You must counsel the patient rare but mild if
pancreatitis aminosalicylates, ACEi, causative agent is stopped risk factors may
azathioprine, furosemide, include gallstones, alcohol consumption,
H 2 receptor antagonist, hyperlipidemia, hypercalcemia
metronidazole, estrogen, Presents as sudden onset of upper abdominal
propofol, sodium pain, vomiting, tachycardia, fever, jaundice and
valproate, sulindac, rigid tender abdomen. Serum amylase is raised
thiazide diuretics.

ADRs involving the KIDNEY

Renal disorder Causative drugs Comments
Prerenal failure Diuretics, laxatives Due to reduced renal perfusion
Intrarenal failure NSAIDs (especially when volume is Due to effects on mechanisms
(changes to GFR) depleted), ACEi, and diuretics. controlling the tone of renal arterioles.
Increased risk in patients with bilateral
renal disease. Monitoring is essential in
at-risk patients.
Intrarenal failure NSAIDs, beta-lactam antibiotics, Hypersensitive, inflammatory reaction
(acute interstitial furosemide (furosemide), leading to damage of renal tubules.
nephritis AIN). allopurinol, azathioprine, captopril, Diagnosed by biopsy presents as acute
cimetidine, cotrimoxazole, renal failure. Dialysis may be required
phenytoin, rifampin, Thiazides, and but most patients recover up to several
sulphonamides. months after causative agent is
withdrawn.
Intermittent rifampin therapy should
be avoided due to immunological
response.
Re-exposure to rifampin should be
monitored closely.
Intrarenal failure Amphotericin, cyclosporin. A common direct toxic effect
(acute tubular Ciprofloxacin, gentamicin,
necrosis) methotrexate, radiological contrast
agents, rifampicin.
Intrarenal failure Gold, penicillamine, NSAIDs Bilateral, immunologically mediated
(glomerulonephritis: hydralazine (acetylator status damage to glomeruli
membranous, important), procainamide Presents as proteinuria, which may
minimal change, progress to edema and
lupus nephritis) hypoalbuminemia (nephritic
syndrome).
Postrenal failure Chemotherapy, acyclovir (IV), Due to urinary tract obstruction
methotrexate, and sulphonamides. may also follow drug-induced
rhabdomyolysis.
Chronic renal failure Chronic use of NSAIDs especially A problem particularly associated with
salicylates compound analgesic preparations
including combinations of
acetaminophen with salicylates,
codeine or caffeine.

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Nephrogenic Lithium Does not respond to desmopressin

diabetes insipidus Serum lithium and creatinine levels
should be monitored regularly
Hemolytic uremic Cyclosporine, mitomycin C, oral Hemolysis leading to obstruction of
syndrome contraceptives, metronidazole (in renal arterioles. Also causes anemia,
children), and quinine Thrombocytopenia with risk of severe
hemorrhage
Discoloration of Rifampicin, dopaminergic This may be alarming and therefore
urine antiparkinson drugs, patients should be warned before
metronidazole, phenazopyridine, starting the treatment.
triamterine, bismuth subsalicylate,
pyrantel pamoate

ADRs affecting sexual function

Sexual dysfunction Causative drugs Comments
Primary infertility Cytotoxics (alkylating agents), • May include a toxic effect on
anabolic steroids, colchicine, the gonads or altered secretion
diethylstilbestrol, methotrexate, of gonadotropin hormones by
NSAIDs (females), sulfasalazine pituitary gland
(males)
Anovulation and Anabolic steroids, danazol, • May result from drug-induced
Amenorrhea isoniazid, metoclopramide, hyperprolactinemia
cimetidine, NSAIDs, SSRIs, • NSAIDs may inhibit ovulation
estrogens, risperidone, and should preferably be
spironolactone avoided around the time of
ovulation in women trying to
conceive
Erectile Antiandrogens (finasteride), • Other factors include smoking,
dysfunction anabolic steroids, anticholinergic, alcohol, diabetes, heart
(impotence) antidepressants, antipsychotics, disease, hypertension,
benzodiazepines, beta blockers peripheral vascular disease,
(carbamazepine, gabapentin, spinal cord injury.
phenytoin) digoxin, methyldopa, • SSRIs, TCAs may be used to
metoclopramide, omeprazole, treat premature ejaculation
prazosin, spironolactone, thiazide
diuretics.
Priapism (painful Anticoagulants, alprostadil, • Immediate treatment is
erection over 4 sildenafil, vardenafil, tadalafil required to prevent fibrosis or
hours). antipsychotics (includes atypical), gangrene
hydralazine, nifedipine, prazosin,
trazodone.
Female orgasm Antidepressants, • Patients prescribed fluoxetine
dysfunction, libido benzodiazepines, cimetidine, or clomipramine have reported
changes, reduced clonidine, methyldopa, estrogen, spontaneous orgasm
vaginal lubrication propranolol, spironolactone,
thiazide diuretics, trazodone

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Reduced libido Spironolactone, cimetidine, oral • Libido may be increased rarely

(reduce sexual contraceptives, propranolol, by trazodone, moclobemide or
desire) thiazide diuretics, levodopa
antidepressants (particularly
SSRIs)
Gynecomastia Cimetidine and spironolactone,
ketoconazole, anabolic steroids

Tips
1. rapid infusion of 2. Clindamycin 3. ASA
vancomycin
4. Clozapine 5. Methimazole 6. Propylthiouracil (PTU)
7. CK-MM 8. Halothane 9. abrupt discontinuation of
antipsychotic
10. hypertensive crisis 11. decrease renal 12. alpha blockers
perfusion
13. Carvedilol 14. Labetalol 15. Ticlopidine
16. Sympathomimetics/ps 17. Clindamycin 18. Mg antacids
eudoephedrine
19. statins 20. Metformin 21. Orlistat
22. anticholinergics 23. opioids 24. antihistamine
25. AlOH 26. Verapamil 27. Calciun
28. Iron 29. TCA 30. Nitroprussides
31. Nitroglycerin 32. vasodilators 33. Hydralazine
34. CCB 35. Amiodarone 36. Bromocriptine
37. Bleomycin 38. Phenytoin 39. inhibit levodopa conversion to
catecholamine in brain
40. nausea & vomiting 41. digitalis toxicity 42. low blood perfusion
• Malignant hyperthermia is caused by? ( )
• Pre-renal failure may cause due to? ( )
• Syncope is caused by? ( )
• MAO inhibitors with pseudoephedrine (sympathomimetics) gives? ( )
• Neuroleptic malignant syndrome is caused? ( )
• Nitroglycerin gives? ( )
• What creatine kinase indicates myopathy? ( )
• Gray baby syndrome caused by? ( )
• Red man syndrome caused by? ( )
• Reye syndrome is caused by? ( )
• Pseudomembranous colitis is mainly caused? ( )
• Agranulocytosis is caused by? ( )
• Hypokalemia + digoxin gives? ( )
• Levodopa + pyridoxine gives? ( )
• Levodopa + Tolcapone ( )
• Gingival hyperplasia caused by? ( )
• Pulmonary fibrosis is caused by? ( )
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• Headache is side effect of? ( )

• What drugs do venous pooling? ( )
• What antiplatelets drug gives neutropenia side effect? ( )
• constipation is a side effect of? ( )
• Diarrhea is side effect of? ( )
• Glaucoma is a side effect of? ( )
• Spironolactone side effect? ( )
• Choose a beta blocker with vasodilator action ( )

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 www.pharmacyprep.com Drug Interactions

66
Drug Interactions
Questions Alerts!
Common questions in pharmacy exam is to ask!
• DI with antacids, Ca, and Fe supplements, sucralfate, with tetracycline,
bisphosphonates, levothyroxine, and quinolones.
• CYP 3A4 inhibitors. Erythromycin and clarithromycin, itraconazole, ketoconazole,
protease inhibitors grapefruit juice and cimetidine
• CYP 3A4 inducers. phenytoin, phenobarbital, carbamazepine, barbiturates
• DI with OCP phenytoin, carbamazepine, topiramate.
• Warfarin DI. vitamin K, NSAIDs, antiplatelets, antibiotics, dark green veg.
• Theophylline DI. age, smoking, high protein diet.
• Lithium DI. Diuretics, ACEi, renal diseases
• Receptor & Receptor. Beta blockers and Beta agonist
• Digitalis toxicity: hypokalemia drugs, quinidine, verapamil, tetracycline

Pharmacokinetics, pharmacodynamics and pharmaceutical interactions.

Pharmacokinetic interactions (Absorption, Distribution, Metabolism and Excretion)

Absorption.
Alteration of GI flora
Alteration of Antibiotics (e.g. Digoxin has better bioavailability after erythromycin.
intestinal tetracycline’s, Erythromycin administration reduces bacterial inactivation of
flora. penicillin, digoxin.
Pseudomemb erythromycin) Clindamycin may cause severe P. colitis
ranous
colitis. Anticoagulants and Cotrimoxazole increase INR in warfarin
antibiotics

Alteration of pH
Alteration of H 2 blockers and Both H 2 blockers and antacids increase gastric pH. The
gastric pH antacids dissolution of drugs like Ketoconazole and PPIs omeprazole are
reduced, causing decreased drug absorption.
Bisacodyl and Bisacodyl and antacids should not taken together
antacids

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Complexation and adsorption

Calcium, magnesium, or Quinolones complexes with divalent cations, causing a decreased
Complexation/chelation

aluminium and iron bioavailability. Tetracycline (must avoid with dairy products),
salts. complex with divalent and trivalent cation.
Bisphosphonates (alendronate) take empty stomach. Levothyroxine
should separate from iron supplements.

Sodium polystyrene Cation in antacids bind to sodium polystyrene sulphonate, causing

sulphonate (Kayoxylate) reduced renal clearance of bicarbonate, resulting in systemic
acidosis.
Cholestyramine and Reduce absorption of all drugs, thus all drugs should be separated
colestipol for 2 to 4 hrs.
Penicillamine and Al and
iron
Charcoal Adsorb with other drugs. Higher surface area the higher adsorption.
The more pure, the higher adsorption.

Alteration of motility/Rate of gastric emptying time

Increased GI Laxatives, cathartics Increased GI motility decreases bioavailability of drugs that
motility are absorbed slowly. May also affect the bioavailability of
drugs from controlled-release products.
Decreased GI Anticholinergic Propantheline decreases the gastric emptying of
motility agents acetaminophen, delaying acetaminophen absorption from
the small intestine.

Alteration of metabolism in GI tract

Inhibition of MAOIs: MAOis inhibit metabolism of tyramine containing foods in the intestine,
drug Phenelzine leading to hypertension caused by high tyramine levels. (Hypertensive
metabolism Tranycypra crisis).
in intestinal mine Levodopa converts into dopamine leads to peripheral side effects such
cells as nausea and vomiting.
Grapefruit Inhibit the metabolism of drugs substrate with CYP3A4
juice Avoid grapefruit juice with atorvastatin, lovastatin and simvastatin
(ALS), DHP-CCB, amiodarone, and carbamazepine.
Distribution. Plasma protein binding and displacement

Alteration of distribution. Phenytoin and valproic acid.

Valproic acid displaces phenytoin from plasma protein binding and decreases hepatic metabolism of
phenytoin clearance by inhibiting the livers metabolism of phenytoin.

ASA reduces protein binding and inhibits the metabolism of valporate.

Tissue cellular and drug interactions. Digitalis toxicity can be enhanced by combination of digoxin and
quinidine. (ventricular arrhythmias)

Metabolism (CYP450 substrates, inhibitors and inducers) (details in Chapter metabolism)

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Stimulation of metabolism
Warfarin and phenobarbital
Warfarin and carbamazepine. Carbamazepine increase clearance of warfarin.
• Oral contraceptives and phenobarbital, CBZ, phenytoin and rifampin
• Smoking induces CYP1A2
• Pyridoxine induce metabolism of levodopa.

Metabolism inhibitors.
Theophylline and macrolide. Macrolides such as erythromycin, clarithromycin inhibit CYP3A4.
Phenytoin and folic acid. Phenytoin enhances folic acid metabolism can cause megaloblastic anemia.

Mercaptopurines 6-MP (azathioprine) and allopurinol. Allopurinol inhibit xanthine oxidase enzyme.
This enzyme is essential for the metabolism of azathioprine. Thus increase concentration of
azathioprine, and this can lead to azathioprine toxicity. Reduce 1/3 or 1/4 dose of azathioprine in
patient who are using allopurinol.

Pharmacodynamic interaction. Drugs having opposing pharmacological effects.

Diuretics and insulin gives hyperglycemia whereas insulin gives hypoglycemia.

Drugs having similar pharmacological effects

Sedative and alcohol. Benzodiazepine and alcohol.

Anticholinergic drugs. Anticholinergic drugs with sedatives.

Antihypertensive drugs (sildenafil, tadalafil, vardenafil and nitrates). Combination of PDE 5 inhibitors
with nitrates gives severe hypotension.

NSAIDs. Two NSAIDs should not be combined.

Alteration of electrolyte interaction. Digoxin and diuretics hydrochlorothiazide and furosemide cause
hypokalemia, thus if its combine with digoxin can give digitalis toxicity.

ACEi and potassium sparing diuretics. Both ACEi with potassium diuretics cause hyperkalemia.

Lithium and diuretics. Diuretics gives side effect of hyponatremia (↓Na), thus this increase lithium
levels, and it can lead to lithium toxicity.

Interaction at receptor site. MAOi and sympathomimetics (pseudoephedrine, xylometazoline). MAOi

and sympathomimetics such as pseudoephedrine, and xylometazoline combination can lead to
hypertension crisis.

MAOi and TCAs combination can give serotonergic syndrome.

MAOi and SSRIs combination can give serotonergic syndrome.
TCA + SSRI
SSRI + venlafaxine

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Alcohol and drug interactions

Must avoid alcohol
• Metronidazole gives disulfiram like reaction
• Disulfiram gives disulfiram reaction
• Chlorpropamide (sulfonylureas) gives disulfiram like reaction
• Metformin gives lactic acidosis
• Phenothiazines (antipsychotic) gives sedation
• Benzodiazepine, opioids gives sedation
• Antihistamines gives sedation

Drug that can lead to complication if combined with alcohol.

• Cimetidine may increase ethanol blood concentration (cimetidine increases alcohol absorption in
GI, and reduce activity of alcohol dehydrogenase enzyme).
• Methadone may increase sedation.
• Acetaminophen can cause liver toxicity
• Aspirin may cause increase GI bleeding
• Methotrexate may increase hepatotoxicity
• Insulin may increase hypoglycemia
• Glyburide prolong hypoglycemia, and disulfiram like reactions.
• Glipizide prolong hypoglycemia, and disulfiram like reactions.
• Ketoconazole may results in disulfiram reaction (flushing, vomiting, increased respiratory rate,
tachycardia)
• Nitroglycerinmay result in hypotension
• Paroxetinemay result in increase risk of impairment of motor and mental skills.
• Sertraline may result in increase risk of impairment of motor and mental skills.
• Venlafaxinemay result in increase risk of CNS effects.
• Warfarin increase INR or PT (acute alcohol) or decrease (chronic) INR or PT
• Zaleplon may result in impaired psychomotor function
• Zolpidem may result in increase sedation
• Phenytoin decrease phenytoin serum concentration; increase seizure potential, and additive
CNS depressant effect.
• Morphine may result in increased sedation (during withdrawal period, alcohol may Accelerate
withdrawal effect of medication)
• Bupropion may increase risk of seizures.
• Cefotetan (2nd gen) disulfiram like reaction
• Cefometazole(2nd gen) disulfiram like reaction
• Cefoperazone—(3rd gen) disulfiram like reaction.

Food drug interactions

• Food can increase, decrease, or not affect the absorption of drugs.
• Food can influence the bioavailability of a drug from a modified-release dosage form (e.g.,
controlled release, delayed released (enteric coated) rather than from an immediate-release
dosage form.
• Complexation and adsorption of the drug in the GI tract with another food element is a common
drug interaction that reduce the extent of drug absorption. For example, quinolone antibiotics
and tetracycline complex with calcium (found in milk products).

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• Food can be metabolized by the same liver enzymes that metabolize drugs, causing enzyme
inhibition or induction, and resulting in toxic or sub therapeutic drug levels. For example,
grapefruit and valencia oranges inhibit the CYP3A4 isoenzyme system, causing increased levels of
substrate drugs such as saquinavir, indinavir, midazolam, nifedipine, lovastatin, cyclosporine,
carbamazepine, and verapamil.
• Food can pharmacodynamically antagonize the effect of some drugs. For example, spinach and
broccoli provide dietary sources of vitamin K, which antagonizes the effect of warfarin.

Tips
1. Bupropion 2. Venlafaxine 3. Fluvastatin
4. Lovastatin 5. Simvastatin 6. Atorvastatin
7. Carbamazepine 8. gives disulfiram 9. Severe orthostatic
increase clearance of reaction hypotension
warfarin
10. hypertension crisis 11. MAOI + TCA 12. MAOI + SSRI
13. MAOI + MAOI 14. Nitrates 15. alpha blockers
16. Lactic acidosis
• Sildenafil cannot be combined with prazosin because it cause? ( )
• MAOI, tranycypromine & tyramine gives? ( )
• Serotoninergic syndrome is caused by? ( )
• A patient using sildenafil should avoid? ( )
• Sildenafil + nitroglycerin can cause? ( )
• What statins should be avoided taking with grapefruit juice? ( )
• What antidepressant can be used with MAOI? ( )
• What statins should be taken with food? ( )
• Warfarin + carbamazepine ( )
• Metronidazole + alcohol ( )
• Metformin + alcohol ( )

List of drug that should be taken empty stomach

Tetracycline
Ampicillin
Zafirlukast
Alendronate, Etidronate
Cloxacillin
Penicillin V
PPIs, levothyroxine
Iron supplement
Norfloxacin

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67
Clinical Biochemistry
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Renal Function Tests (RFT)CrCl, BUN
• Liver Function Tests (LFT)LDH, AST, ALT, ALP, bilirubin
• Cardiac Enzymes  Troponin I
• Creatinine Kinase? enzyme add phosphate group to proteins.
• Creatinine kinase? CK-MM (myalgia), CKMB (MI)
• Urine Analysis  Ketone bodies, pH, specific gravity
• Blood works (hematological) CBC
• Anticoagulants.INR (International normalized ratio), warfarin (INR 2 to 3), heparin (aPTT),
and LMWH (no Test necessary).
• Thyroids Tests. Serum TSH (0.5 to 5 mU/L), TT4, FT4, TT3 and FT3

This chapter reviews basics of clinical biochemistry such as liver function tests, renal function
tests, hematology, acid base disorders, anemia and its application in laboratory tests to
monitor diseases and monitor drug adverse reactions.

Common tests. Renal function test, liver function test (LFT), urinalysis, common enzyme serum test,
and hematological test (blood works).
• Renal Function Tests (RFT)CrCl, BUN
• Liver Function Tests (LFT)LDH, AST, ALT, ALP
• Cardiac Enzymes  Troponins I, Creatinine Kinase (CK)
• Urine Analysis  Ketone bodies, pH, specific gravity
• Blood works (hematological) CBC
• Anticoagulants  INR (International normalized ratio), warfarin (INR 2 to 3), heparin (aPTT), and
LMWH (no monitoring)

Renal Function Test. Can be measured by blood urea nitrogen (BUN), serum creatinine and creatinine
clearance (CrCl) or estimated glomerular filtration rate (eGFR).

Blood urea nitrogen. Urea is an end product of protein metabolism. It is produced in liver and excreted
by the kidneys. In normal conditions, urea clearance is equal 60 % GFR. BUN increase indicates renal
disease.

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Normal values for BUN range 8 mg/dL to 18 mg/dL (3 to 6.5 mmol/L). The concentration of BUN
reflects renal function, because the urea nitrogen in blood is filtered completely at the glomeruli of the
kidney, then reabsorbed and tubular secreted within nephron.

Increase in BUN indicates an acute renal failure. The BUN decrease may indicate terminal stages of
liver disease, because liver produces solely BUN. Increase BUN indicator of azotemia or uremia.

Serum Creatinine. The creatinine is a metabolic product of muscle creatinine phosphate. More
sensitive indicator for renal damage than BUN levels.

Normal values for serum creatinine range from 0.6 to 1.2 mg/dL (80 to 120 mmol/L).
Generally serum creatinine values doubles with each 50% decrease in GFR. If a patient normal serum
creatinine is 1 mg/dL represents 100% renal function, 2 mg/dL represents 50% function and 4 mg/dL
represents 25% function. Serum creatinine solely filtered by glomerular filtration (GFR). Thereby
decrease GFR, may lead to increase in serum creatinine (SrCr). This indicates renal disease.

Serum creatinine decreased in elderly. As a person gets older muscle mass represents a small
proportion of total weight and creatinine production is decreased. In females the serum creatinine
concentration in females patient is generally 0.2 to 0.4 mg/dL less than males, because females have
relatively small kidneys.

Creatinine Clearance (eGFR). The rate at which creatinine is removed from the blood by the kidney,
roughly equal to GFR. Normal values for men range from 80 mL/min to 120 mL/min If it is less than
<50 ml/min, it is categorised as renal disease. Creatinine clearance reflects the GFR.

Calculation for creatinine clearance: Cl cr = C U V/C Cr

C U = concentration of creatinine in urine
V = urine volume (millilitres per minute or urine formed over collection period).
C cr serum creatinine concentration.

To measure creatinine clearance using Cockcroft and Gault formula, require serum creatinine, age,
body weight and gender.
for males (mL/min)= [(140-Age)x(body weight in Kg)]/(SrCr)X 72
for female, the above formula must be multiplied by 85%

Liver Function Test (LFT). There are 4 liver enzymes, which are indicators of liver dysfunction. Levels of
LDH, ALP, AST and ALT increase with liver dysfunction. Increase levels of these enzymes indicate liver
has been damaged.
LDH = Lactate dehydrogenase, ALP = Alkaline phosphate, AST = Aspartate aminotransferase; ALT =
Alanin aminotransferase
.

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LFT

LDH ALP Transaminases (AST and ALT)

LDH1, & LDH2 LDH3 LDH4, and LDH5

(Heart) (Lungs) (Liver, skeletal muscle)

• Lactate dehydrogenase (LDH). The glycolytic enzyme LD (100 to 190 units/L) catalyzes the
interconversion of lactate and pyruvate and present in most tissues. LDH is present in high
concentration in the heart, kidney, liver, lungs, and skeletal muscles.
• The liver will liberate LDH quickly when damaged by physical trauma, infection or ischemia. LDH
therefore useful in diagnosing myocardial infarction, hepatic disease and lung disease.
• Alkaline phosphatase (ALP). It is produced from the liver and bones. This is sensitive to mild or
partial biliary obstruction.

Transaminases (AST and ALT)

• Aspartate aminotransferase (AST). Previously known as serum glutamic oxalocacetic transaminase
(SGOT), primarily found in heart, liver tissues, and lesser extent is found in skeletal muscles, renal
tissues, and pancreatic tissues. AST is sensitive to damage to heart, such as MI, CHF, and acute
hepatitis.

• Alanin aminotransferase (ALT). It is previously known as serum glutamic pyruvic transaminase

(SGPT). It is primarily found in liver, and lesser amount in heart, skeletal muscles, and kidney. ALT
is sensitive to cell damage, and less sensitive than AST.

Serum Bilirubin (Bile)

• It is primary breakdown product of haemoglobin and is formed in reticulosites into stream blood.
Where it is almost completely bound to serum albumin. When bilirubin arrives at the liver at
sinosidal surface of liver cells, the free fraction is rapidly taken up by liver and converted to
bilrubin diglucorinide and monoglucorinide, referred to as conjugated bilirubin. The conjugated
bilirubin then secrete into bile, appears in intestine, where bacterial converts bilirubin to
urobilinogen. Most of urobilinogen is destroyed in feces, but some fraction reabsorbed in blood
and liver.
• Effective bilirubin conjugation and excretion depends on RBC turnover and hepatobilary function.
Normal values of total bilirubin are 0.1 to 1 mg/dL (2 to 18 mmol/L). Direct bilirubin. 0.0 to 0.2
mg/dL (0 to 4 mmol/L).
• Increase of serum bilirubin indicates jaundice, it occurs from bilirubin deposition in the tissues.

Causes of increased bilirubin. Hepatocellular damage (liver cirrhosis), cholestasis (post hepatic),
hemolysis (prehepatic). There are 3 major reasons for increase bilirubin.
• Increase hemolysis (urine color not changed).
• Biliary obstruction (biliary stones), dark urine and bile in urine, chlorpromazine gives intra hepatic
cholestasis). Liver cell necrosis (viral hepatitis), dark urine color and bile in urine.
• Liver cell necrosis occurs in viral hepatitis.

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What lab test is used to determine liver cirrhosis?

Serum Protein (blood proteins)

• Primary serum proteins. Albumin and globulins (alpha, beta, gamma). Albumin is the major protein
of the blood, it constitutes 55% of serum proteins. Acidic drugs bind to albumin. It is primarily
produced from liver. Albumin (40 to 60 g/L) liver disease decrease albumin.
• Albumin is produced by the liver and contributes approximately 80% of serum colloid osmotic
pressure. Therefore hypoalbuminemia associated with edema and transudation of extracellular
fluid.

Hypoalbuminemia
• Decrease in essential amino acids due to malnutrition can lead to hypoalbuminemia.
• Albumin can be lost directly from blood because of hemorrhage, and burns.

Hyperalbuminemia.
• Increase in albumin can cause shock or volume depletion. Plasma proteins concentration that
changes with some conditions.
Conditions Albumin Alpha –1- acid
glycoprotein
Renal failure ↓ ↑
Hepatic failure ↓ ↑
Arthritis - ↑
Burns ↓ -
Pregnancy ↓ -
Stress/Trauma ↓ ↑
Globulins. There are several types of globulins such as alpha, beta, gamma, etc.
• The gamma globulins are the same as immunoglobulin (Ig).
• Globulins 23 to 35 g/L. Decrease in albumin levels results in compensatory increase of globulins.

Alpha-Fetoprotein (AFP)
The alpha-Fetoprotein is a glycoprotein synthesized by the fetal yolk sac, fetal liver. It is primarily
produced in fetal liver and AFP test is considered as marker for diagnosis of fetal liver cancer in
pregnancy.

Cardiac Enzymes
Cardiac Troponins (Tn)
• Troponin T, C and I is complex of proteins that mediate the calcium-mediated interactions of actin
and myosin with muscles.
• Troponin T is in cardiac and skeletal muscle cells.
• Troponin I is present only in cardiac muscle.
• Troponin C is present in two distinct isoforms that are present in skeletal and cardiac muscles.
• Troponin T and I is more specific and sensitive indicator of myocardial injury.
• Troponin is a relatively new method to identify myocardial cell injury and thus assist in the
diagnosis of acute MI.
• The use of troponin as primary diagnostic tests for acute MI is widely accepted.

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Serum Enzymes.
Creatine kinase (CK), previously known as creatine phosphokinase (CPK). It is primarily found in heart
muscle, skeletal muscle and brain tissue.
Creatin kinase catalyzes the transfer of high-energy phosphate group in tissues that consume large
amount of energy. Therefore total CK can increase in exercise, IM injections of drugs that are irritating
to tissue (diazepam, phenytoin), acute psychosis episodes, and myocardial injury.

CK

CK-MM. In skeletal muscle CK-BB. In brain tissue CK-MB. Sensitive indicator of myocardial necrosis

CK isoenzyme. Creatin kinase helps to diagnose of acute myocardial (CK-MB) or skeletal muscle (CK-
MM) damage diagnostic tests. Deep intramuscularly injection can increase CK levels.

• CK-MM is found in skeletal muscle.

• CK-BB is found in brain tissue.
• CK-MB is found in heart muscle

Urinalysis. Provides basic information regarding renal function, urinary tract disease, and presence of
certain systemic diseases.
Urine colors: Normal urine color is clear, pale yellow, and deep gold.
• Red color may be blood, drugs such as pyruvinium pamoate, phenolphthalein (used as laxative).
• Brownish-yellow: conjugated bilirubin, jaundice
• Orange red: rifampin
• Dark urine: metronidazole, metformin
• Blue color: Triamterene
• Pyuria and bacturia is symptoms of urinary tract infection
• pH: Urine pH is around 5 to 9.
• Specific gravity (SG). Normal SG is 1.003 to 1.035
• Increase SG indicates excessive blood sugars or proteins in urine.
• Decreased SG indicates diabetes insipidus.
• Fixed SG at 1.003 indicates, kidney lost its ability to concentrate or dilute urine.

Urine Stools Body fluid Lens

Rifampin Orange * * * *
red
Metronidazole Dark *
Nitrofurontoin Dark *
Bismuth Dark *
subsalicylate
Triamterene Blue *

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Proteins in urine. Normal values 50 to 80 mg/24 hours. Excessive proteins in urine (proteinuria),
caused by UTI, renal disease, fever, and venous congestion.
• Albuminuria indicates glomerular permeability.
• Microalbuminuria presence of albumin in urine at the level of higher than normal but lower than
the limits that are detected by standard test. Microalbuminuria indicates nephropathy.
• Glucose does not normally appear in urine. Glycosuria indicates diabetes.

Ketones. Ketones does NOT normally appear in urine. If there is No glucose stores, fats stores begins
to metabolize to ketones. Ketonuria indicates uncontrolled DM, or starvation, and zero or low
carbohydrate diets.

Components of urinalysis:
• Urine pH 4.5 to 9.0
• Protein levels 50 to 80 mg/24 hours
• Glucose levels 180 mg/dL
• Ketone levels do not appear in urine.

Hematological Laboratory Tests (Blood work). Complete blood counts (CBC). The CBC is one of the
most commonly ordered clinical laboratory test. It is package of the following laboratory tests and CBC
measures.
• Hemoglobin (Hgb)
• Hematocrit (Hct) or packed cell volume (PCV)
• Total white blood cells (WBC)
• Red blood cells (RBC)
• Mean cell volume (MCV)
• Mean cell hemoglobin concentration (MCHC)
Some CBC may or may not include:
• Platelets count
• Reticulocytes counts
• Leukocyte differential count

The reticulocyte count provide measure of immature RBCs. This test provides an index of bone
marrow production of mature RBCs.

ESR (Erythrocyte sedimentation rate) measures the rate of RBC settling of whole, uncoagulated blood
overtime and it primarily reflect plasma composition.

ESR is indicator of inflammation. E.g. RA

ESR values used to follow, the clinical course of disease, and demonstrate the presence of occult
organic disease and differentiate conditions similar symptoms (like angina ESR normal and MI ESR↑).

Hematocrit (Hct). The percentage of red blood cells to the blood volume is the Hct. (Packed cell
volume). The decrease in (↓Hct) result from anemia, bleeding, bone marrow depression by drugs,
chronic diseases, genetic anemia (sickle cell anemia), and hemolysis. An increase in Hct may result in
increase RBC and cause of polycythemia.

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WBCs (leukocytes) also referred to white cell count.

• Normal levels of WBC 4,000 to 11,000 WBC/mm3.
• WBC signals infection (leukocytosis) and inflammation.
• WBC indicates bone marrow depression this indicates (leukopenia).
Normal Indicator
Neutrophils 55% to 75% Bacterial infection
Lymphocytes 20% to 40% Viral infection
Monocytes 0% to 7% Tuberculosis
Eosinophils 0% to 5% Parasites infection
Basophils 0% to 1% Inflammation, Allergies, Asthma,
• Bacterial infections generally increase neutrophil to 80% and decrease lymphocytes to 10%.
• Viral infections increase lymphocytes (lymphocytosis).
• Allergic reactions, such as asthma, allergic rhinitis, parasite infections, and drug allergies increase
eosinophils and basophils.
• COPD increase neutrophils
• Immunodeficiency, AIDS decrease T lymphocytes or WBCs (lymphopenia), or cluster differential
(CD 4 count).
• Tuberculosis infection increase monocytes (monocytosis).

Measuring blood coagulation

Warfarin Heparin Low Molecular Weight Heparins (LMWH)
Oral anticoagulant iv or sc Sc or iv
PT and INR aPTT Not monitored because predictable response. However
monitor rash, bleeding, and heparin assay.
• Warfarin monitoring: International normalized ratio (INR 2 to 3), and prothrombin time.
• Heparin monitoring. Activated partial thromboplastin time (aPTT) and PT.

Prothrombin Time (PT). Prothrombin is synthesized in the liver and is converted to thrombin during
blood clotting process.
• Thrombin formation is the critical event in the hemostatic process because thrombin creates fibrin
monomers that form a network of clot and thrombin activates platelets.
• Clotting time.
• Measures deficiencies in factor II, VII, IX, X (2, 7, 9 and 10)
• Not specific for liver diseases
• Normal values 10 to 13 seconds

Increase in PT (INR)
• Can occur due to inadequate vitamin K in the diet or drugs that increase PT. Warfarin, heparins,
low molecular weight heparins (LMWH), high dose of salicylates, and antibiotics. The higher the
PT, the greater the risk of bleeding.

Decrease in PT (INR)
• Increase in vitamin K supplements or diet that contains vitamin K such as dark green vegetables,
broccoli, avocado, spinach, and lettuce. Thereby increase in risk of blood clot.

Activated Partial Thromboplastin Time (aPTT)

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• The aPTT measures the intrinsic clotting system, which depends on factors.
• Measures intrinsic clotting system factors VIII, IX, XI, XII and XIII as well as common pathway
factors II, V, and X.
• Monitored for heparin therapy
• Normal values 21 to 45 sec

Increase in aPTT
Caused by
• Severe liver dysfunction
• Inadequate vitamin K intake (deficiency of vitamin K)
• Poor or inadequate nutrition
• Increase in aPTT increase the risk of bleeding

International normalized ratio (INR). The INR is the PT ratio that would result if world health
organizations (WHO) international reference thromboplastin were used to test the patient sample.
Normal INR is 2 to 3 in patient using warfarin. Increase in INR is an indication of blood thinning where
as decrease in INR is an indication of blood thickening.

Increase in INR (>3): Indicate blood thinning, overdose of drugs such as Warfarin, Heparins, LMWH,
ASA/NSAID, Acetaminophen > 2 g can cause increase in INR.
Decrease in INR (<2). Indicate blood thickening
• Vitamin K supplements
• Green vegetable (avocado, broccoli and spinach)
• Oral contraceptives

Normal lipoproteins levels

• Low density (LDL) cholesterol (serum) <2.2 mmol/L or <125 mg/dL
Triglycerides <3.6 mmol/L or <160 mg/dL
• High density (HDL) cholesterol (serum)>0.9 mmol/L >35 mg/dL.
• Cholesterol/HDL ratio is 5 mmol/L.

High risk group with coronary artery disease, the LDL levels should be <2 mmol/L.

• Apolipoprotein B <0.8 g/L (Apo-B). This protein found on the surface

of LDL particle. Each LDL particle only has one copy of apo-B.
This also found on all beta-lipoprotein surface such as chilomicrons,
LDL, and VLDL. This is used to predict CVD risk.

Thyroid function tests

Normal Hypothyroidism Hyperthyroidism
Serum TSH. 0.3 mU/L > 6 mU/L <0.3 mU/L
to 6 mU/L
Subclinical hypothyroidism >10
Serum TSH Serum TSH

Decrease Free T 4 and T 3 Increase Free T 4 and T 3

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Thyroid stimulating hormone (TSH) 0.3 to 6 mU/L, 0.3 to 6 μU/mL.

Free thyroxine (free T 4 ) 10 to 36 pmol/L, 0.8–2.8 ng/dL
Total serum thyroxine (T 4 ) 51 to 142 nmol/L, 4–11 μg/dL
Total serum triiodothyroxine (T 3 ) 1.2 to 3 nmol/L 78 to 195 ng/dL

Thyroid disease diagnosis tests Free T 4 and Serum TSH

• Replacement therapy for hypothyroidism. Serum TSH, free thyroxin index (FTI), resin
triiodothyronine uptake RT 3 U, Total thyroxin TT 4 .

Free T 3 and T 4
• The FT 4 is the most reliable diagnostic test for evaluation of hypothyroidism and hyperthyroidism
when thyroid hormone binding abnormality exists. In contrast measurement of
• FT 3 is expensive.
• Total T 3 and T 4 (TT 3 and TT 4 ):
• The TT 3 and TT 4 measures both free and bound (total serum T 3 and T 4 ).
• TT 3 is particularly helpful in diagnosis of Graves’s disease.
• TT 3 is not good indicator of hypothyroidism.

Thyroid stimulating hormone:

• The serum TSH is the most sensitive test to evaluate thyroid function.
• The TSH is elevated in hypothyroidism

Dehydration symptoms.
In dehydration
• Mild: normal BUN/Creatinine
• Moderate: ↑ BUN/Creatinine
• Severe : ↑ BUN/Creatinine, ↑ Hb, Low sucrose.

Neoplasm screening
Prostate specific antigen (PSA). For prostate cancer
Pap (papancolaou) smear. Cervical cancer
Mammogram. Breast cancer
Biopsy. Sampling of cell or tissue for examination

GI Track tests
Fecal Occult blood. Invisible traces of blood
Shilling’s test. To determine vitamin B 12 absorption.
Barium enema. To test large intestine (lower GI)

Infectious disease/Rheumatologic/immunological.
Western blot. To detect specific protein (analysis of individual proteins in protein mixture). Separated
by size and charge.
CD 4+ T cell count: HIV
Erythrocyte Sedimentation Rate (ESR): measure inflammation
ELISA test. HIV

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Tips
1 80-120 ml/min 2 bleeding 3 bilirubin
4 does not change 5 parathyroid hormone 6 3.5 to 5 mEq/L
7 2 to 3 8 troponin 9 aPTT
10 AST>ALT 11 Creatinine kinase CK-MB 12 Stop warfarin, monitor INR and give oral Vit
K
13 No monitoring
required

• Normal range of serum potassium levels? ( )

• Hypothyroidism can be monitored by? ( )
• What is normal INR level in patient taking warfarin? ( )
• Increase INR indicated the risk of? ( )
• Normal levels range of creatinine clearance ( )
• What substance levels are increased in jaundice? ( )
• What enzyme ration increases in alcoholic hepatitis? ( )
• What is monitored in patient taking LMWH? ( )
• If INR is more than 5 indicates ( )
• What is monitored by heparin? ( )
• Name the enzyme most likely to increase in levels suggesting a myocardial infarction? ( )
• What cardiac enzyme exclusively elevated after MI? ( )
• Osteoporosis can change calcium level by? ( )
• Calcitonin opposes action of? ( )

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68
Therapeutic Drug Monitoring
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Anticoagulants: Warfarin (PT, INR) , Heparin (aPTT) and LMWH (No monitoring).
• Thyroid hormones: Serum TSH, TT4, FT4, TT3
• Antipsychotic drugs: Clozapine, CBC, and weight gain, blood glucose.
• Lithium: serum levels <1.5 mEq/L
• Statins: regularly LFT and CK-MM for myopathies
• Amiodarone: chest x-ray, eye exam, serum TSH
• Ticlopidine therapy monitored for CBC or WBC because it cause neutropenia
• Methotrexate therapy monitored for lung function test, eye exam, LFT, folic acid
• Vancomycin. Renal function Test
• Isotretinoin baseline test: TG, LFT
• Ifiximab: Chest X ray

Laboratory test Therapeutic ranges Monitoring guidelines

Drug

monitored of test

Serum amikacin peak 20-25 mcg/ml Wait until the administration of the third dose to
trough 5-10mcg/ml check drug levels. Obtain blood for peak level 30
Amino glycosides

Serum minutes after IV. infusion or 60 minutes after I.M.

gentamicin/tobramycin 4-8 mcg/ml administration. For trough levels, draw blood just
peak trough Serum 1-2mcg/ml 0.6 - 1.3 before the next dose. Dosage may need to be
creatinine mg/dl adjusted accordingly. Recheck after three doses.
Monitor creatinine clearance and BUN levels and
urine output for signs of decreasing renal function
Serum creatinine 0.6-1.3 mg/dl Monitor serum creatinine, BUN, and serum
BUN 5-20 mg/dl electrolyte levels at least weekly during therapy.
Serum electrolytes Potassium: 3.5-5 Also regularly monitor blood counts and liver
(especially potassium mEq/L function test values during therapy.
and magnesium) Magnesium: 1.5-
Amphotericin B

2.5 mEq/L
Liver function tests Sodium: 135-145
CBC w/ differential and mEq/L
platelets Chloride: 98-106
mEq/L

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antibiotics WBC with differential Specimen cultures and sensitivities will determine
cultures and ***** the cause of the infection and the best treatment.
sensitivities Monitor WBC count with differential weekly during
therapy.
Serum creatinine FBSL. 5 to 6 mmol/L Check renal function & hematologic parameters
Fasting serum glucose before initiating therapy and at least annually
Glycosylated HbA1C. 5.5% to thereafter if patient has impaired renal function,
hemoglobin (HbA1C) 6.5% of total don’t use metformin because it may cause lactic
(metformin)
biguanides

CBC hemoglobin acidosis. Monitor response to therapy by

Test shows past 3 periodically evaluating fasting glucose and
mo BSL. Test q6 mo glycosylated hemoglobin levels. A patient’s home
for patient on monitoring of blood glucose levels helps monitor
insulin. Test q1yr compliance and response. Decrease mortality
for type II DM.
WBC with differential agranulocytosis Obtain WBC count with differential before
Cloza

or CBC initiating therapy, weekly, during therapy, and 4

pine

weeks after discontinuing the drug.

Serum digoxin 0.8 to 2 mg/ml Check serum digoxin levels at least 12 hours, but
Serum electrolytes Potassium. 3.5 to 5 preferably 24 hours, after the last dose is
(especially potassium, mEq/L administered. To monitor maintenance therapy,
magnesium, and Magnesium. 1.7 to check drug levels at least 1 to 2 weeks after therapy
calcium 2.1 mEq/L is initiated or changed. Make any adjustments in
digoxin

Serum creatinine Sodium: 135 to145 therapy based on entire clinical picture, not solely
mEq/L on drug levels. Also, check electrolyte levels, renal
Chloride: 98 to 106 function periodically during therapy.
mEq/L
Calcium: 8.6 to 10
mg/dl
0.6 to1.3 mg/dl
Serum electrolytes Potassium: 3.5 to 5 To monitor fluid and electrolyte balance, perform
Serum creatinine mEq/L baseline and periodic determinations of serum
BUN Magnesium. 1.7-2.1 electrolyte, serum calcium, BUN, uric acid, & serum
Uric acid mEq/L glucose levels.
Fasting serum glucose Sodium: 135-145
Muscle pain mEq/L
diuretics

Chloride: 98-106
mEq/L
Calcium: 8.6-10
mg/dL
0.6-1.3 mg/dl
5-20 mg/dl
2-7 mg/dl
70-110 mg/dl
Hematocrit Women. 36% to After therapy is initiated or changed, monitor the
erythropole

48% hematocrit twice weekly for 2 to 6 weeks until

Men: 42% to 52% stabilized in the target range and a maintenance
dose determined. Monitor hematocrit regularly
tin

thereafter.

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Serum ethosuximide 4 to 100 mcg/ml Check drug level 8 to 10 days after therapy is
initiated or changed
ethosuximide

Laboratory test Therapeutic ranges of test Monitoring guidelines

monitored
Drug

Serum lipids Total cholesterol < 5 Therapy is usually withdrawn after 3 months
mmol/L if response is inadequate. Patient must be
Gemfibrozil LDL <2.2 mmol/L fasting to measure triglycerides level.
(Fibrates) HDL women: >0.9 mmol/L
Triglycerides: <3.2 mmol/L

Increase BSL

Niacin Glucose

Activated partial 1 to 2 times control When drug is given by continuous IV infusion,

thromboplastin time check aPTT q4 hours in the early stages of
(aPTT) therapy when drug is given by deep SC.
injection, check aPTT 4 to 6 hours after
injection

1) Warfarin? INR & PT

2) Heparin? aPTT
3) LMWH? No
Heparin

4) Dabigatran? aPTT (antidote is

idarucizumab)

Serum lipids CK-MM is indicator of Perform liver function tests at baseline, 6 to

Liver function tests myopathies 12 weeks after therapy is initiated or
(LFT) changed, and periodically thereafter. If
HMG-CoA
reductase
inhibitors

and creatine kinase adequate response isn’t achieved within 6

(CK) weeks consider changing the therapy

Fasting serum Optimal blood sugar Monitor response to therapy by evaluating

glucose levels. serum glucose and glycosylated hemoglobin
Glycosylated Fasting. 4-7 mmol levels. It is a good measure of long-term
hemoglobin (HbA1 C ). HbA1C <7% control. A patient’s home monitoring of blood
Insulin

Post prandial. 5-10 mmol glucose levels help measure compliance and
response.

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Serum lithium Serum levels. 0.8 to 1.5 Checking blood lithium levels is crucial to the
Serum creatinine mEq/l safe use of the drug. Obtain serum lithium
CBC levels immediately before next dose. Monitor
Serum electrolytes K: 3.5 to 5 mEq/l levels twice weekly until stable. Once at
(eg. K and Na) Mg: 1.7 to 2.1 mEq/l steady state, levels should be checked
Lithium

Fasting serum Na: 135-145 mEq/l weekly; when the patient is on the
glucose Cl: 98 to 106 mEq/l appropriate maintenance dose, levels should
Thyroid function 70-110 mg/dl be checked every 2-3 months. Monitor serum
tests TSH: 0.5-5.4 micro U/ml creatinin, serum electrolyte and fasting serum
T 3 : 80 to 200 ng/dl glucose levels. CBC and thyroid function test
T 4 : 5.4 to 11.5 mcg/dl before therapy is initiated and periodically
during therapy.
Serum methotrexate Normal elimination: Monitor methotrexate levels according to
CBC with differential <10 micromol 24 hours dosing protocol. Monitor CBC differential,
Platelet count, post dose platelet count and liver and renal function
Methotrexate

liver function tests <1 micromol 48 hours tests more frequently when therapy is
Serum creatinine postdose initiated or changed and when methotrexate
Chest x-ray <0.2 micromol 72 hours levels may be elevated such as when the
post dose patient is dehydrated.
150 to 450 x 103/mm2
0.6 to 1.3 mg/dl
Serum phenytoin 10 to 20 mcg/ml Monitor serum phenytoin levels immediately
CBC before next dose and 2 to 4 weeks after
therapy is initiated or changed. Obtain a CBC
Phenytoin

at baseline and monthly early in therapy.

Watch for toxic effects at therapeutic levels.
Adjust the measured level for
hypoalbuminemia or renal impairment, which
can increase free drug levels.
Serum potassium 3.5 to 5mEq/L Check level weekly after oral replacement
Potassium

therapy is initiated until stable and every 3 to

chloride

6 months thereafter

Serum procainamide 4-8mcg/ml (procainamide) Measure procainamide levels 6-12 hours after
5-30mcg/ml (combined a continuous infusion is started or
Serum N- procainamide and NAPA) immediately before the next oral dose
Procainamide

acetylprocainamide **** combined (procainamide and NAPA) levels

can be used as an index of toxicity when renal
CBC impairment exists. Obtain CBC periodically
during long-term therapy.
Serum quinidine 2-6mcg/ml Obtain levels immediately before the next
CBC **** oral dose and 30-35 hours after therapy is
Liver function tests * initiated or changed periodically obtain blood
Serum creatinine 0.6-1.3mg/dl counts, liver and kidney function tests values
Serum electrolytes K:3.5-5 mEq/L and serum electrolyte levels
(esp K) Mg: 1.7-2.1mEq/L
Quinidine

Na:135-145mEq/L
Cl: 98-106mEq/L

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Sulfonylure Fasting serum 70-110mg/dl Monitor response to therapy by periodically

glucose 5.5-8.5% of total evaluating fasting glucose and glycosalated
Glycosylated hemoglobin hemoglobin levels, patient’s home
hemoglobin monitoring of blood glucose levels helps
as

measure compliance and response.

Serum theophylline 10 to 20 mcg/ml Obtain serum theophylline immediately
Theophyll

before next dose of sustained-release oral

product and at least days after therapy is
ine

initiated or changed.

Thyroid function Serum TSH: 0.3 to 6 Monitor thyroid function tests every 2-3
tests microU/ml weeks until appropriate maintenance dose is
hormone
Thyroid

T 3 : 80 to 200 ng/dl determined.

T 4 : 5.4 to 11.5 mcg/dl

Serum vancomycin 20-35 mcg/ml (peak) Serum vancomycin levels may be checked
5-10 mcg/ml (trough) with the third dose administered, at the
earliest. Draw peak levels half hour after the
IV infusion is completed. Draw trough levels
Serum creatinine immediately before the next dose is
0.6-1.3 mg/dl administered. Renal function can be used to
adjust dosing and intervals.
Vancomycin

For an acute MI, atrial Check INR daily beginning from 3 days after
fibrillation, treatment of therapy is initiated continue checking it until
pulmonary embolism, therapeutic goal is achieved and monitor it
prevention of systemic periodically thereafter. Also, check levels 7
PT and embolism, tissue heart days after any change in warfarin dose or
INR 2 to 3 valves, valvular heart concomitant, potentially interacting therapy.
Warfarin

disease, or prophylaxis or
treatment of venous
thrombosis.
2 to 3 for mechanical
prosthetic valves or
recurrent systemic
embolism 2.5-3.5.

Note: ***** For those areas marked with asterisks, * For those areas marked with one asterisk
the following values can be used: the following values can be used:
Hemoglobin: Women: 12-16 g/dl Differential: Neutrophil: ALT: 7-56 units/L
Men: 14-18 g/dl Bands: 0%-8% AST: 5-40 units/L
Hematocrit: Women: 37%-48% Lymphocytes: 16%-45% Alkaline phosphatase:17-142 units/L
Men: 42%-52% Monocytes: 4%-10% LDH: 6-220 units/L
RBCs: 4-5.5 x 106/mm3 Eosinophills: 0%-7% GGT: <40 units/L
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WBCs:5-10 x 103mm3 Basophills: 0%-2% Total bilirubin: 0.2-1 mg/dl

Tips
1. LFT & CK 2. shows BSL for past 3 3. serum TSH
months
4. CHF 5. liver and renal diseases 6. lactic acidosis
7. blood work 8. renal function 9. WBC
10. CBC 11. 0.8 to 1.5 meq/L 12. PT & INR
13. 10 to 20 mcg/ml 14. increase CL=smoking age 1 to 9 15. oliguria, CrCl<50
ml/min, increase BUN
16. Post dose antibiotic 17. Require low dose for 18. Have no oral dosage
effect UTI form
19. Treatment of anemia 20. Folic acid 21. CK-MM
in chronic renal failure

• Lithium normal serum levels ( )

• Warfarin monitoring ( )
• Statin monitoring ( )
• Serum levels of phenytoin ( )
• Factors that affect theophylline clearance ( )
• HbA1C test monitoring ( )
• Symptoms of renal disease ( )
• Monitoring hypothyroidism ( )
• What laboratory tests indicates myopathies? ( )
• What supplements recommended with phenytoin therapy? ( )
• Amino glycosides have? ( )
• Metformin is contraindicated in? ( )
• What is true about erythropoietin's? ( )
• Clozapine mechanism & monitoring ( )
• Propylthiouracil (PTU) and methimazole should be monitored for? ( )
• Vancomycin is monitored for? ( )

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PharmacyPrep.com OTC and Prescription drugs for Dermatological Conditions

69
OTC and Prescription Drugs
for Dermatological
Conditions
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Head lice mode of transmission and treatment
• Acne and rosacea symptoms and treatments
• Dermatitis, diaper rash self care, uncomplicated and complicated therapy.
• Psoriasis symptoms (red scaly patches) and treatment

Head lice
Drugs to treat head lice (parasites) and scabies
Generic Name Brand Name Generic Name Brand Name
Permethrin 1% Nix Permethrin
Lindane 1% (shampoo) Isopropyl mersteate Resultz
Sulphur 6% in Pyrethrins
petrolatum
• Hair to hair contact, commonly shared items such as combs, brushes, hats and stuffs
toys. It does not fly.
• Lice live on the skin with short or long hair. Scalp and back & sides.
• Female lay eggs daily, these nits hatch after 7 to 10 days.
• Hygiene is not criteria of head lice transmission.
• All physical contact should be treated, if head lice or nits are found.

Non-pharmacological
• Infected fomites, soak combs/brushes in hot water for 5 to 10 min (1:4 vinegar in water) or
wash in pediculicide shampoo.
• Store unwashable items in plastic bags for 10 to 14 days.
• After treatment with pediculicide shampoo remove nits using fine toothcomb.

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Treatment. Treat all contacts if you notice head lice. Treat infected contact after close
examination.
• Inform daycare but still go.
• Eggs hatch after 7 to 10 days. Once hatch nyphs must have access to the human host within
12 to 24 hr period to survive.

Pharmacological.
Neurotoxic drugs. Permethrin, and Lindane.

Drug of choice permethrin 1%.

• Wet hair with water. Use fine teeth comb to remove nits.
• Apply drug to wet hair. Leave on for 10 min. Wash with water and repeat removal nits by
fine teeth comb. Permethrin 1% applied day 1 and day 7 may be effective for cases resistant
to all topical pediculosides.
• Best ovicidal activity among all treatment with 70 to 80% efficacy.
• Re treatment after 7 to 10 days.

Lindane (shampoo) 1%
• Contraindicated in seizures.
• Caution in under 2 year age and nursing mothers, pregnancy and elderly, inflamed skin.
• Apply for 4 minutes to dry hair.

Non neurotoxic products. Isopropyl mersteate IPM (Resultz)

Scabies
• Infestation of the skin with human mites. Highly contagious of the skin. Human mite
Sarcoptes scabiei var hominis.
• Clothes/linens should be cleaned with soap and hot water or stored in bags for 5 to 7 days
(separate from host die in 2 to 3 days).
• Vacuum all surfaces (rugs, carpets, furniture).
• Avoid contact with others.
• All close contacts should be treated. It is a hygienic problem.

Treatment
Treat infested individuals and all close physical contact with topical scabicides Permethrin
5%.
• Drug of choice in adults and children >2 month old.
• Less than 2 months require prescription (medical supervision).
• Effective 96 to 100%. Low systemic absorption.
• Caution individual with ragweed chrysanthemum allergy.
• Applied to entire body neck down to toes (include toes, nails, genital areas), except in eyes,
mouth. In children head down to toes. Must be washed off after 12 hours. Retreat after 7 to
14 days to prevent ping-pong effect.

Sulphur 6% in petrolatum
• DOC in pregnancy, lactation, and children under 2 months
• Apply bid for 10 days
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• Unpleasant odor and local irritation

How to use. Massage into all skin areas, from the neck down to the soles of the feet; every bit of
the skin must be treated, including the fingernails, waist, and genitalia; leave on for 8 to 14 h,
then wash off (shower may be the best way).
Lindane cannot be used by children <10 yrs old, elderly, pregnancy and lactation, seizure
disorders.
• Patients with extensively excoriated skin, elderly & children may be enhanced percutaneous
absorption and increased potential toxicity
• 10% systemic absorption & accumulates with repeated exposures
• Killing time 6 h can repeat treatment in 7 to 10 days
• Sulfur 5 to 10% ointment is used in small children and pregnant woman.

Acne
Generic Name Dosage Generic Name Dosage form
Benzoyl peroxide, gel, lotion topical Tetracycline oral
Salicylic acid 2% topical Minocycline Oral
Clindamycin (solution) topical Doxycycline oral
Erythromycin (gel, lotion, solution, Oral & Tretinoin Topical
pads) topical
Isotretinoin Oral

Steps in Acne pathogenesis.

• Increase sebum production (microcomedone)
• 2)Pore orifice remains close (close comedone) (Proliferation of Propionibacterium acne,
gram +ve anaerobic)
• 3) Antibody to P.acne develops and inflammation rupture follicule wall.
• 4)Papule (Pore orefice remains close)
• 5) Nodule or Cyst (foreign body response)
• 6) The other name of P. acne is Corynebacterium parvum.

Increase sebum (sebacious gland) sebum+keratinocytes  Microcomedone 

(inflammatory lesions Propionibacterium acne) or papule, pustule, nodule --> [(white head
pimples are closed comedone] --> [Open comedone (blackhead)].

Acne is due to
• Increased follicular keratinization.
• Increased sebum production
• Propioni bacterium acne or Corynebacterium parvum. Increased (bacterial) lipolysis of
sebum triglycerides to free fatty acids.
• Inflammation
• Acne is not caused by dust
Nonpharmacological
• Squeezing pimples may increase risk of scarring, avoid excessive cosmetic use and use
only non-comedogenic water-based products. Washing; not more than twice daily with
mild soap.
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• For shaving use safety razors (soften with soap)

• Comedone extractionWash with hot water and place extractor on acne.
• Ultravoilet light currently not recommended
• Shampoo hair regularly keep from falling on to face. Reduce hair spray
• Keep nails short and clean
• Balanced diet is good for overall health, but there is no evidence that acne is caused by
specific food. Food does not aggravate acne.

Treatment:
Topical acne preparations:
• Benzoyl peroxide (Exofoliant and antibacterial).Populopustular acne
• Cream, Alcohol or acetone Gel, lotion, foams, paste and washes.
• Is a peeling agent that also has some antibacterial action, mainly used in
papulopustular acne.
• Apply at bedtime
• Topical Retinoids (Tretinoin 0.01%, 0.025%, 0.05%, 0.1%)
• Cream, Gel, solution. Apply at HS
• Used in comedogenic acne, not used in pregnancy
• Antibiotics
• Erythromycin 1.2%, 2% (gel, lotion, solution, pads), and clindamycin 1% (solution, gel).
• Used to decrease colonization of skin mainly in papulopustular acne.

• Salicylic acid 2%
• Available without prescription.

Systemic Antibiotics and drugs. (Tetracycline, minocycline, Erythromycin, isotretinoin)

Tetracycline
• The most commonly prescribed oral agent.
• Reduce the number of acnes and may exert an anti-inflammatory effect by inhibiting
leukocyte chemotaxis.
• Contraindicated in pregnancy.
• SEs. GI effects, photosensitivity, may exacerbate azotemia in patients with pre-existing renal
disease.
• DI. GI absorption of tetracycline may be impaired by iron, bismuth, aluminum, calcium,
magnesium in drugs and foods (e.g. dairy products) separate doses by 2 hours.

Minocycline
• Once daily
• Can be given with food or milk
• SE: dizziness, vertigo, ataxia, abnormal cutaneous pigments

Doxycycline
• Contraindicated in pregnancy and child < 8 years of age
Erythromycin
• Alternative to tetracycline due to its excellent safety.
• SEs: nausea, vomiting, epigastric distress, diarrhea.
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• DIs: may increase blood levels of theophylline, cyclosporine, carbamazepine, warfarin,

digitalis, ergotamine, methyl prednisone.
• Concurrent use with Terfenadine or cisapride is contraindicated.

Retinoids (Tretinoin and Isotretinoin)

Tretinoin. Topical
Isotretinoin. oral
• SEs. Teratogenicity, dry skin, lips, ocular effects (conjunctivitis, might decrease vision),
increase TG level, increase cholesterol level, increase liver function, reversible hair loss.
• DIs. No adverse reaction known between retinoids and oral contraceptives. Avoid taking
vitamin A supplements.
• CI. Completely contraindicated in pregnancy and planning to be pregnant.

Hormonal Therapy
• Used for women with moderate acne
• Used for several months to see improvement

Rosacea or Acne rosacea

Caused by Pityrosis R
Symptoms. Erythematic (redness)
Treatment. Metronidazole 0.75% gel or cream or 1% cream

Rosacea
1. Papulopustular lesions and eye involvement with or without flushing.
2. Telangiectasia or facial edema or rhinophyma (refer to dermatologist).

Dermatitis
Drugs to treat dermatitis
Generic Name Generic Name Brand Name
Hydrocortisone 0.5% Hydrocortisone 1%
(Topical) (Topical)
Zinc oxide 40%
Zinc oxide 15 to 20%

Three different forms of dermatitis.

• Atopic dermatitis or eczema
• Contact dermatitis (e.g. poison ivy)
• Diaper dermatitis (diaper rash)

Atopic dermatitis or eczema is chronic inflammatory pruritic dermatosis associated with

personal or family history of allergic disease.
• Affects up to 1% of population
• Common in young people
• Flare-ups initiated with emotional stress, irritants such as soaps or chemicals, environmental
factors such as heat or humidity, trauma or food allergies
• Prone to viral, bacterial and fungal skin infections.
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Signs and symptoms

• Pruritus
• Lesions due to scratching
• Weeping erosions, vesicles and excoriated, reddened, scaling papules or plaques
• Skin may be thickened with pigmentation changes

Differential diagnosis
• Contact dermatitis – pattern of lesions, distribution, identification of allergic, chemical or
physical cause can differentiate it from atopic dermatitis.

Nonpharmacological treatment
• Minimize use of bath soaps and solvents
• Reduce laundry soap residue in clothing
• Avoid bleach and fabric softener
• Use cool air humidifiers to reduce room dryness
• Avoid wool, nylon or rough fabrics
• UV lights may be helpful

Pharmacological treatment
• Topical hydrocortisone is mainstay therapy
• Oral antihistamine
• Coal tar
• Burrow’s solution for weeping lesions. Compress for 2 to 3 days for astringent and
antibacterial effects
• No antibiotics

Pharmaceutical agents
Bath products; soothing to itchy, irritated skin

Emollients
• Cover tiny fissures in skin
• Provide soothing protective film

Topical hydrocortisone 0.5% - relieve the itching associated with atopic dermatitis
• Most common local side effects: contact dermatitis, allergic reactions, pain and pruritus

Oral antihistamines
• Older sedative types may help relieve itching associated with dry skin
• May cause drowsiness, gastrointestinal disturbances, paradoxical excitability,
• Nervousness and difficulty in sleeping
• Contraindicated in patients with angle-closure glaucoma, kidney or liver disease,
prostatic hypertrophy, pregnant or breast-feeding women

Coal tar – best applied under an emollient due to their drying properties
• Often messy, had unpleasant odour, stains hair, skin and clothing
• May cause folliculitis, tar acne, contact dermatitis and photosensitivity
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How to manage atopic dermatitis

Possible causes:
• Stress
• Skin irritants such as soaps or chemicals
• Environmental factors such as high heat or humidity.
• Foods, molds or pollens to which the person may be allergic

Allergic Contact Dermatitis

• Allergic contact dermatitis is an itchy skin condition caused by an allergic reaction to
material in contact with the skin.
• It arises some hours after contact with the responsible material, and settles down over
some days providing the skin is no longer in contact with it.
• Contact dermatitis should be distinguished from contact urticaria, in which a rash
appears within minutes of exposure and fades away within minutes to hours. The
allergic reaction to latex is the best-known example of allergic contact urticaria.
• Olive oil after bathing or oat meal bath can help.

Active dermatitis is usually treated with the following:

• Emollient creams
• Topical steroids
• Topical or oral antibiotics for secondary infection
• Oral steroids, usually short courses, for severe cases
• Photochemotherapy.
• Azathioprine, cyclosporin or other immunosuppressive agent.
• Tacrolimus ointment and pimecrolimus cream are immune modulating drugs

Diaper Dermatitis: Synonyms. Diaper rash, napkin rash.

Non-pharmacological treatment. Use warm water to clean diaper area and air dry diapering
(NOT alcohol wipes).
• Change diaper frequently.
• Maintain hygienic conditions.
• Discontinue aggravating factors.
• Allow air-drying. Avoid powders as barriers (NO cornstarch, talc, and baking soda).
• Gentle cleansing with mild soap and water. (Avoid baby wipes & acid pH cleanser).
• Avoid food that increases urinary output and fecal pH (high protein diet, caffeine, citrus
juices).

Uncomplicated
• Zinc oxide 15 to 20% or silicone. Zinc oxide 40% for treatment and 15% for prevention. Use
lanolin-free protectant barrier with each diaper change.
 Reapply every few hours in a thick layer. Remove with mineral oil or water.
Complicated
Confluent tomato red plaques, white scaly border. Anti yeast agents miconozole, clotrimazole,
nystatin for 7 to 10 days.
• Anti yeast agent. Clotrimazole, miconozole (imidazole).
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• Nystatin. Effective only against Candida.

• C. albicans likely cause if condition present >3 days.
• Should be discontinued once inflammation has subsided.
• Anti-inflammatory agents (hydrocortisone 0.5% to 1%). Should not be used >1 wk.
• Use 1% hydrocortisone only under physician for under 2 year age.

Urticaria: Urticaria refers to a group of disorders in which swelling occurs in the skin. The
release of chemicals such as histamine causes small blood vessels to leak and results in tissue
swelling. Acute urticaria is sometimes due to allergy. Allergy depends on previous exposure to
the material, and the development of an immune reaction to it. A protein called IgE is involved.

Treatment:
• Oral antihistamines control wealing and itching for the majority of patients with urticaria.
• Non-sedating antihistamines (loratidine, fexofenadine, terfenadine, cetrizine, and
astemizole) are less likely to cause drowsiness than the less expensive conventional
antihistamines.
• Oral steroids (prednisone) – useful for severe acute urticaria but unsuitable long term.
• If you have generalized urticaria, ask your doctor if a medicine could be the cause. Avoid
Aspirin and codeine, and reduce your intake of acidic fruits

Dry, Scaly Skin

Dry skin – due to dehydration of stratum corneum
• Also called xerosis
• May be present with other dermatoses such as atopic dermatitis, in normal skin due to
aging, illness or environmental factors
• Causes: low humidity, exposure to cold winds in winter, mechanical abrasion and repeated
exposure to solvents, soaps and disinfectants that remove lipids from skin

Signs and symptoms

• Roughness, flaking, scaling and chapping in front of lower legs, back of hands and forearms
• With inflammation, pruritus and fissuring

Differential diagnosis
• Atopic, contact and seborrheic dermatitis
• Dandruff
• Psoriasis

Nonpharmacological treatment
• Bathe once a week and sponge on other times
• Use emollients or protectants to maintain hydration
• Increase water intake

Pharmacological treatment
• Bath products and skin moisturizers that contain lactic acid, phospholipids or urea
• Oral antihistamines to help relieve itching
• Topical hydrocortisone preparations to reduce inflammation

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Pharmaceutical agents
Bath products -Contains oil such as mineral oil or lanolin, salts such as sodium bicarbonate or
colloidal solids such as oatmeal may not enhance hydration but may sooth itchy, irritated skin
Cleansing products – soaps made from saponification of animal and/or vegetable fats or soap-
like synthetic detergent cleansers
• Both emulsify fats with water to remove oil and dirt from skin
• Any type of skin cleanser can aggravate skin dryness depending on its pH, cleansing
ability, composition and additives
Emollients – bland oleaginous substances applied to skin by rubbing
• Used to replace natural skin oils, cover tiny fissures in the skin and provide a soothing
protective film
• Don’t hydrate skin, they slow evaporation of moisture from skin
• Maintain hydration if applied immediately after bathing
• Common emollients: petrolatum, glycerin, urea, lactic acid, mineral oil, lanolin and fatty
acids
Topical hydrocortisone 0.5% - to relieve minor itching and inflammation associated with dry
skin
• Most common local side effects: contact dermatitis, allergic reactions, pain and pruritus
Oral antihistamines – relieve itching associated with dry skin
• May cause drowsiness, gastrointestinal disturbances, paradoxical excitability,
nervousness and difficulty sleeping Contraindicated in patients with glaucoma, kidney
and liver disease, prostatic hypertrophy, pregnant and breast-feeding women

How to prevent dry skin

• Use a humidifier on forced-air heating systems
• Keep the room temperature at the lowest comfortable level in the winter and use a
humidifier
• Avoid air conditioning when possible
• Use a mild or superfatted soap; if dry skin continues, use soaps to cleanse only the groin,
underarms and feet
• Avoid wool and rough clothing that will irritate skin
• Protect skin from wind, extreme cold and sun

How to treat dry skin

• Add a bath oil to the water in the last 5 minutes of your bath; adding it earlier will not allow
water to get into your skin
• Add baking soda or oatmeal to your bath if skin is itchy
• Rub an ointment into your skin after your bath to help skin hold in the moisture
• Rub a moisturizer into your skin often during the day and at bedtime; special dry skin
creams can be tried if regular moisturizers are not helpful
• Oral antihistamines can help relieve itching especially at bedtime
• To correct a dry skin tendency from any cause reduce contact with soap and water and
apply a moisturizer or emollient

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Hydrocortisone cream 0.5% can help relieve itching and red skin that may occur with some cases
of dry skin. It will not cure dry skin. Hydrocortisone should not be used for long term control of
dry skin. If the itching and redness do not improve after 7-10 days of treatment, see your doctor

• Reduce washing to every second day, or less often, although the body folds may be sponged
daily if desired.
• Baths or showers should be kept as brief as possible.
• Water should be lukewarm.
• Minimize the use of soap. Reduce the need for bathing by keeping as clean as possible both
at home and at work.

Moisturizers and emollients . The terms 'moisturizer' (to add moisture) and 'emollient' (to
soften) are interchangeable as they describe different effects of these agents on the skin.
Basically they have two actions.

• Occlusives, which provide a layer of oil on the surface of the skin to slow water loss and thus
increase the moisture content of the stratum corneum.
• Humectants, which are substances introduced into the stratum corneum to increase its
water holding capacity.

Some moisturizers contain both occlusives and humectants. The humectants, agents adding
water to the stratum corneum, include glycerine and urea.

Alpha hydroxy acids such as lactic acid or glycolic acid. At higher concentrations these also have
a descaling or keratolytic action by thinning the stratum corneum, they are often known as
peeling agents.

Psoriasis
Psoriasis is a disorder of the skin that typically consists of red scaly patches covered by silvery
white scales. Psoriasis is very common. Approximately 2% of adults have psoriasis.

• Sunshine. Sunshine may help to clear psoriasis, in many people it improves dramatically
during sunny holidays.

• Baths. Soaking in warm water with a bath oil or tar solution can soften the psoriasis and lift
the scale. Bland soaps or soap substitutes are useful and detergents and antiseptics are not
necessary and may irritate.

• Emollients. The psoriasis should be kept soft with moisturizing creams to prevent it cracking
and becoming sore. Vaseline, emulsifying ointment and sorolens cream are among suitable
preparations.

• PUVA = psoralens + UVA (ultraviolet light inhibit epidermal mitosis) and psoralens is
photosensitizer.

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• Occlusive dressings patches of psoriasis which are limited in extent may improve with
occlusive dressings i.e. waterproof adhesive dressings. Occlusion with plastic wrap, plastic
baggies or thin plastic gloves, covered with fabric, a sock or cotton gloves can also be used.

Hydrogel/hydrocolloids are occlusive interactive dressings. Hydrogel contain high content of

water.

Crude coal tar. Coal tar in the 'Goeckerman' regime in hospital, it is applied twice daily to the
patches after exposure to ultraviolet light. The psoriasis clears in 4 to 6 weeks and may stay
away for months.

Topical steroids anti-inflammatory inhibit epidermal proliferation and alter immune reactions.
Hydrocortisone 0.5% is only anti-inflammatory lacks the antiproliferative effect. Instead
moderate potency clobetasone 17-butyrate 0.5% is used.

Oral medications include methotrexate. Methotrexate tablets are taken once a week. salicylic
acid and Anthralin.

Dandruff and Seborrhea

Dandruff and seborrhea. Scaly dermatoses occurring in area of high sebaceous gland
concentration
• Dandruff affects most adult
• Seborrhea occur most often in infants less than 3 months of age (cradle cap) and adults 30
to 60 years of age
• 2-5% of population is affected with more men than women.
• Exacerbated with stress. Low humidity and temperature
• Worse in winter
• Skin irritation, bacterial and yeast infections have been implicated

Signs and symptoms

Dandruff characterized by excessive scaling and itching of the scalp, dry, white, grayish scales
spread uniformly in scalp. Dry white scale scattered. (Scalp)

Seborrhea is excessive scaling and itching but found in the axilla, back, chest, ears, face and
groin. Greasy, yellowish scale over erythmatous patches. (scalp, facial, groin)
• it is an inflammatory dermatosis
• Lesion is a patchy areas of yellowish scales with slight to moderate redness of underlying
skin.
• Cradle cap in infants is seborrheic dermatitis but not itchy

Nonpharmacological treatment
• Regular cleansing of the scalp or other affected areas with non medicated shampoo
• Should shampoo and massage scalp at least 3 times a week to control the condition

Pharmacological treatment
Cytostatic/antifungal shampoo with selenium sulfide, zinc pyrithione or ketoconazole

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• Keratolytics useful to soften and detach flakes

• Coal tar relieves itching and lower population of bacteria or yeast on the scalp

Pharmaceutical agents
Antiseptics: (benzalkonium, chlorhexidine, povidone iodine
• Kill bacteria or fungi

Coal tar have astringent, keratolytic, antipruritic and antiseptic effects

• Available in ointments, lotions, gels, shampoos and bath preparations
• Tar often messy, unpleasant odour, stain skin, hair and clothing.
• May cause folliculitis, tar acne, contact dermatitis and photosensitivity.

Ketoconazole. Cytostatic effect that slows cell turnover and antifungal effect against
Pityrosporum ovale.
• Not be used within 2 weeks of treatment with topical corticosteroids.

Salicylic acid (2-3%). keratolytic effect

• Useful in resistant cases of dandruff and seborrhea.
• Not be used more than twice a week

Selenium sulfide. cytostatic and antifungal effect

• Remove all jewelry before use and wash hands thoroughly. Not to be used within 2 days of
applying hair tints or perm solution.
• Excessive use causes oily hair and hair loss. May stain blond or grey hair
• Don’t apply to inflamed or damaged hair. Only used twice a week.

Sulfur (3 to 5%). keratolytic effect

• Useful for dandruff but not proven to be effective
• Used twice a week
• Odor or stinks

Zinc pyrithione: cytostatic and antifungal effects

• More effective than others
• Can be used daily to control dandruff and seborrhea

Antiperspirants (anti body odour)

• Aluminum salts. Aluminum chloride , Al-chlorhydrate.
• Aluminum acetate (used in excessive sweating or hyperhidrosis).
• Zinc oxide corn starch
• potassium alum and ammonium alum

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Foot Conditions

Fig 69.1

Athlete’s Foot: Dermatophytes initiate the infection by invading and disrupting the horny layer
of the skin.

Athlete’s foot (Tinea pedis) is common cutaneous fungal infection. Secondary bacterial infection
may cause inflammation and additional maceration.
Prevent transmission to other by no going bare foot around home or in public area.

Signs and symptoms

• Itching, peeling, scaling, vesiculation, patchy hyperkeratinization and inflammation occurs
between the toes are the main clinical signs.
• Malodor may be present.
• The acute form is characterized by fissuring, scaling and peeling and the skin between toes
appears white, macerated and soggy.

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• Chronic form is characterized by hyperkeratotic, scaly eruptions on weight bearing surfaces

of feet, heels, soles and borders of the feet.

Differential diagnosis
• Should be differentiated from contact dermatitis, pustular psoriasis and drug eruptions
• Patients failing to respond to non prescription antifungal preparations used correctly for
several weeks should be referred to a physician.
• Nail involvement requires prescription treatment

Athlete's foot occurs between toe

• Antiperspirant or absorbent powder (talcum or aluminum chloride) CAN be applied to feet
to decrease sweating.
• Patient with history of athletes foot may dust an antifungal (e.g. tolnaftate) powder on their
feet to prevent further reoccurrence.
• Antifungal powder should NOT be placed in shoes, as coagulation of powder and moisture
create an unfavorable environment.
• Drug of choice to treat athlete's foot? Clotrimazole 1% cream
• Cochrane review concluded that "Tea tree oil" has NO evidence of effect for T. pedis.
• Athletes foot is transmittable to other.

Nonpharmacological treatment
• Counsel patients on proper foot hygiene.
• Bathe daily and dry feet well between the toes. Wear absorbent socks (cotton 60% less
blend with synthetic fiber, nylon) changed daily or twice daily if the patient is susceptible to
hyperhidrosis (sweating).
• Wear shoes that “breathe” (sandals, if possible).
• Change shoes daily and wear different shoes for sports.
• Dust with talcum powder or cornstarch, especially between the toes.

Pharmacological Treatment
• Expose feet to the air to dry them and suppress bacterial proliferation.
• Soak feet with an astringent or dust with a medicated powder (talcum powder)
• Use a topical antifungal agent such as clotrimazole, miconazole, tioconazole, tolnaftate or
undecylenic acid.
• Clotrimazole, miconazole or tioconazole are the preferred agents since they have both
bacterial and antifungal activity and there is less chance of recurrence.
• Use a topical antifungal agent such as clotrimazole, miconazole, tioconazole, tolnaftate or
undecylenic acid.
• Clinical improvement should be apparent within 2 weeks

Pharmaceutical agents
Clotrimazole 1% cream, Miconazole 2% cream, spray powder, oxiconazole and tioconazol,
imidazole antifungal agents. Tolnaftate 1% cream, gel, aerosol, topical powder, topical solution.
• Have some antibacterial activity.
• Adverse reactions are infrequent like mild skin irritation, burning, stinging and erythema.
• Sensitivity reactions occurs rarely.

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Naftifine and butenafine; effective antifungal but no antibacterial activity

• Mild burning or stinging, dryness, redness, itching or local irritation may occur.

Tolnaftate; effective antifungal agent, no antibacterial activity

• Recurrence and treatment failure is common
• Rarely cause irritation or hypersensitivity reaction

Undecylenic acid; oldest antifungal agents

• Can be as effective as tolnaftate, but characteristic odour is objectionable
• Hypersensitivity reactions and skin irritation are rare

How to prevent athlete’s foot

Athlete’s foot fungi prefer moist, warm places, they thrive on the feet and between the toes of
people whose feet are often hot and sweaty.

Individuals with history of athlete's foot may regularly dust an antifungal powder such as
tolnaftate once or twice daily on their feet to prevent further reoccurrences. Antifungal powder
should NOT be placed in shoes, as coagulation of powder or moisture create unfavorable
environment.
All antifungal preps apply to affected areas once or twice daily.

This can be prevented by few simple measures:

• Wash the feet once or twice a day with soap and water and dry them thoroughly, especially
between toes
• Wear sandals or shoes and socks that allow adequate ventilation
• Avoid socks made of synthetic fibers as they retain heat and moisture. Light cotton socks are
best.
• Do not wear occlusive footwear such as rubber boots or athletic shoes for any longer than
necessary
• Change shoes daily to allow them to dry inside
• Change socks regularly and wash them thoroughly in hot water
• Dust the feet, especially between the toes, with a foot powder to aid drying

Viral skin infection. Common warts and flat wart.

Common wart caused by HPV 2, 4, 27 and 29 (knee, hands, fingers, around nail.) Warts found on
sole of the feet are called plantar warts (verrucae plantaris)

Flat wart caused by HPV 3, 10, 28 and 49. (face or neck)

Tips
1. sebaceous gland 2. Diane & Alesse 3 Erythromycin or Clindamycin
4. cool humidifiers, 5. petroleum jelly, ZnO 6 cleaning w/ alcohol wipes
moisturizer cream
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7. it transmits by head to 8. Permethrin 1% 9 avoid sharing combs,

head contact or common brushes, hats & pillows
shared items
10 gives blisters, hot 11 full thickness, painless 12 superficial, sunburn
H 2 O, flame oil leathery, flame & hot metal
13 UVB 14 SPF 15 UVA
16 coal tar 17 sulfur 18 anthralin
19 UV light 20 salicylic acid 21 corticosteroids
22 Methotrexate 23 antifungal + ZnO 24 petroleum jelly, ZnO
25 Propioni bacterium 25 Second application after 7 to
acne 10 days of 1st application
• How do the head lice transmit? ( )
• What is correct self care measure for head lice? ( )
• Drug of choice for head lice? ( )
• How often head lice treatment should be applied? ( )
• What bacteria cause acne? ( )
• What gland secretions can cause acne? ( )
• What is pharmacological therapy for acne in pregnancy? ( )
• What oral contraceptives can be used for acne treatment? ( )
• What is self care measure should be recommended for dermatitis? ( )
• What is the treatment for uncomplicated diaper rash? ( )
• What is pharmacotherapy for complicated diaper rash? ( )
• What self care measure is not recommended for diaper rash? ( )
• What is pharmacotherapy for psoriasis? ( )
• What topical dermatological agent that gives stains? ( )
• What topical dermatological agent gives odor? ( )
• 1st degree burn examples ( )
• 2nd degree burn examples ( )
• 3rd degree burn examples ( )
• Photo toxicity, photoaging, immunosuppressant & skin cancer can cause ( )
• Sunburn, immunosuppression & skin cancer ( )
• Sun protection factor (SPF) 15, 30 or 50 ( )

Select True or False Statements

• Clouds, snow, beach gives high sun burn (True)
• High altitude have high sunburn (True/False)
• Water, beach areas, snow have high sunburn (True/False)
• Atopic dermatitis or eczema. Olive oil is applied directly to rehydrated skin after bath.
• Colloidal oatmeal bath, Soaps are made from animal or vegetable (glycerine soaps
(transparent soaps).
• Treatment of atopic dermatitis Burrows solutions (aluminum acetate), Hydrocortisone 0.5%
and Tacrolimus cream

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70
Ophthalmic, Otic and Mouth
Conditions
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Ophthalmic preparations to treat red or pink eye, and dry eye.
• Eyelid conditions. Hordeolum, chalazion and blepharitis.
• When to refer? pain and vision changes, diabetic dry eye, foreign object.
• Prescription directions of ophthalmic (OU, OD, OS), otic drops (AU, AD, AS).
• Hard and soft lenses and lens solutions.
• Vertigo or Menerie disease treatment.
• Mouth conditions like canker sores, and cold sores therapy.

Fig 70.1

Eye problem: Mild blepharitis, single hordeolum (stye), conjunctivitis and dry eye.

Blepharitis: Inflammation of the eyelid margin

• Burning, irritation, itching and hyperemia along lid margins

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• Crusting and scaling around eyelashes may be present hordeolum. Acute inflammation
in the eyelash follicle or eyelid gland
• Tenderness, edema and redness
• Pus may appear along the eyelid margin in a few days

Pharmacological treatment
• Blepharitis and hordeolum
• Commercial eyelid cleanser useful for blepharitis
• Indiscriminate use of nonprescription ophthalmic anti-invectives should be avoided
• Thorough cleansing sufficient for self-limited disorders

Conjunctivitis (red or pink eye). Inflammatory condition of the membrane that lines the inside
of the eyelids and covers the exposed surface of the sclera. Conjunctivitis can be allergic,
bacterial, and viral.

Conjunctivitis diffuse redness in both eyes

• Redness is more marked in the outer aspects of the eye and less around the cornea
• Muco purulent discharges is more common with bacterial conjunctivitis
• Clear discharge in viral or allergic conjunctivitis
• Intense itching occurs with allergic conjunctivitis

Bacterial or viral Allergic

Symptoms Abrupt onset, purulent or mucopurulent Burning sensation, itchy eyes watery
discharge, lids endomatus +/- stuck AM. discharge, mild redness +/- lid swelling.
Self resolved in 7 to 10 days, chronic if >2
wks. Minimal itching.
Non-Rx Clean gauze compresses avoid cleanser and Allergen avoidance, cold compresses
avoid eye patches. over the eyes, water irrigation BID, and
Polymyxin B/gramicidin (eye drops), avoid contact lenses.
polymixin B/bacitracin (ointment).
Rx Trimethoprim/polymyxin B (drops), Artificial tears 4 to 6 times a day,
erythromycin or bacitracin (ointment), ophthalmic antihistamine, oral
sulfacetamide 10% solution antihistamine, mast cell stabilizers, and
for chronic corticosteroids

Bacterial conjunctivitis: Common causes are S. aureus, S. pneumonia (most common in

children), H. influenza (most common in children).
Symptoms: Abrupt onset, purulent or mucopurulent discharge, lids endomatus +/- stuck AM.
Self resolved in 7 to 10 days, chronic if > 2wks. Minimal itching.

Non-prescription therapy: Clean gauze compresses, avoid cleanser and avoid eye patches.
Polymyxin B/gramicidin (eye drops), polymixin B/bacitracin (ointment).

Rx therapy: Trimethoprim/polymyxin B (drops), erythromycin or bacitracin (ointment),

Sulfacetamide 10% solution

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Viral conjunctivitis
Common cause: Adenovirus, herpes simplex virus
Symptoms: Itchiness is minimal, redness is generalized. Discharge is profuse, serous

Non-pharmacological: Give warm or cold compress to increase comfort.

NonRx therapy: Ocular decongestants and/or lubricants may be useful.
Rx therapy: Trifluridine (topical), Acyclovir, Famciclovir, and Valacyclovir (oral).

Allergic conjunctivitis
Common cause: ragweed, Grass pollen, Itchiness is severe
Symptoms: Burning sensation, itchy eyes watery discharge, mild redness +/- lid swelling

Non Pharmacologic therapy: Allergen avoidance, Cold compress over the eyes, water irrigation
BID, and avoid contact lenses.

Rx therapy: artificial tears 4 to 6 times a day, ophthalmic antihistamine, oral antihistamine, mast
cell stabilizers, and for chronic corticosteroids

Levocabastine; emedastine (H1 antagonist) for itchy and watery eye, Olopatadine (antihistamine
and mast cell stabilzer), Nedocromil, Iodoxamide (mast
cell stabilizing agent) alleviates. Ketorolac (Nonsteroidal Drugs that cause dry eye
anti-inflammatory eyedrop) for itching & redness. • Anticholinergics: Antimuscarinic
Other types of Conjunctivitis include: Chlamydial drugs
Conjunctivitis: Trachomatis Fungal conjunctivitis: In rare • First generation antihistamines
cases: Rickettsial conjunctivitis: Rare: Parasitic • B-blockers: propranolol, timolol
conjunctivitis: Rare • Diuretics: hydrochlorothiazide,
indapamide
Dry eye • Isotretinoin
• Niacin (in hyperlipidemia)
Symptoms: Dry eye, sandy, gritty sensation, • Phenothiazine antipsychotics (e.g.
photosensitivity and difficulty moving the eyelids Chlorpromazine)
• TCA’s (amitriptyline)
• Etiology: Aqueous deficiency. Decrease lachrymal
gland secretion.
• Mucin deficiency: Damage or inflammation of goblet
cells can be cause by condition erythema multiforme.

• Lipid deficiency: decrease lipid layer is common in patients with blepharitis.

• Epitheliopathies: defects in the corneal epithelium that can impair tear film stability.

Nonpharmacologic treatment
• Cleanse eyes thoroughly
• Blepharitis and hordeolum benefit from warm, moist compresses applied for up to 15
minutes, 3 to 4 times a day
• Cool, moist compresses have a soothing effect for conjunctivitis and dry eye.

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Treatment

Nonprescription Therapy: Artificial tear solutions: An ideal tear replacement product would
posse:
• Electrolytes in concentration similar to that normal tear.
• An osmolality of 2000 to 280 mOsm
• Viscosity of less than 20 centipoise
• No cytotoxic
• Preservative free.

Pharmacotherapy: Substituted cellulose ethers (Carboxymethylcellulose 1%): Polyvinyl Polymers

(Polyvinyl alcohol 1.4% and sodium hyaluronate)
• Ointments: Petrolatum and carbomer
• Artificial tear inserts – hydroxypropylcellulose
• Pilocarpine, Acetylcysteine, Methylprednisolone
• Instillation of artificial tears every 1-6 hours for a trial period of 48 hours
• Emollients can cause blurring of vision and are better suited at night

Any eye irritation that fails to respond to nonprescription therapy within 48 hours should be
referred to an eye care professional for proper diagnosis

Pharmaceutical agents
Antihistamines – may cause photophobia or allergic reactions
• Antazoline, pheniramine, pyrilamine
Anti-invectives – polymyxin B combined with bacitracin or gramicidin
Artificial tears – chemically inert and coat the eyes
• Help them retain moisture
• Protect from irritation
• Slow turnover of tears
• Examples dextran, methylcellulose, and hydroxypropyl methylcellulose,
• Polyethylene glycol, polyvinyl alcohol and sodium carboxymethylcellulose
Astringents – not to be used for hordeolum or allergic conjunctivitis
• Zinc sulfates a mild astringent that clears eye secretions.
Decongestants – can cause rebound hyperemia if overused
• Contraindicated in patients with glaucoma
• Examples naphazoline, oxymetazoline, phenylephrine, tetrahydrozoline,
xylometazoline.
• Emollients, soften eye tissue and protect it from drying such as Lanolin, mineral oil,
petrolatum

How to administer eye drops

• Wash hands thoroughly.
• Tilt the head back or lie down.
• With eyes open, gently pull the lower lid below the eyelashes away from the eye to form a
pouch.
• Approach the eye from the side and hold the container near the lid (at least 2 cm away). Do
not touch the lid or lashes.
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• Look toward the ceiling. Looking up moves the center of the eye away from the instillation
site, minimizing the blink reflex.
• Instill one drop into the pouch. Hold this position to let the drop fall as deep as possible into
the pouch.
• Look down for several seconds and then slowly release the lower lid. Looking down brings
the cornea into maximum contact with the drop.
• Gently close (don’t squeeze) the eyes for 1 to 2 minutes while applying gentle pressure to
the bridge of the nose for 30 to 60 seconds. Gentle pressure prevents the drops from being
drained from the eye.
• A tissue may be used to blot around the eye, but do not rub. Closing the eye helps prevent
loss of solution caused by blinking. If the eye is closed too tightly, the medication may be
expelled.
• Don’t rub the eye. Try not to blink.
• To apply several drops, wait 3-5 minutes after the instillation of each drop
• Never contaminate the dropper tip or the top o the container by allowing it to touch the
eye, eyelid, eyelashes, fingers or counter surface.

Eye care products

Contact Lenses
Types of contact lenses
• Hard (rigid) gas permeable lenses or Rigid gas permeable (RGP) and hydrophobic. Silicone,
fluorosilicone acrylate, polymethyl methacrylate (PMMA).

• Soft lenses are hydrophilic. Hydroxyethyl-methacrylate (HEMA).

RGP (hard lens) Soft lenses (most commonly use)

PMMA HEMA
HYDROPHOBIC HYDROPHILIC
LIFE 5 YEAR UNTIL LOST 1 DAY TO 1 YEAR
DAILY WEAR TIME <12 HR DAILY WEAR TIME >12 HR
RISK OF MICROBIAL CONTAMINATION IS HIGH
LOW
STRONG FRAGILE
Disposable are opened for each day. No regular
solution requires.

Contact lens solutions (cleaning solutions)

Two types. Surfactants remove loose debris and protein cleaners. In other words remove
proteins from soft lens.

Surfactants. Disinfect and remove contaminants.

Protein cleaners or enzyme cleaners contain papain, pancreatin, or subtilism. Remove protein
deposits by catalysing the natural breakdown of debris into simple compounds.

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Wetting and rewetting solutions. Produce cushioning and lubricant effect between lens and
eyelid, between eye and cornea (removes dryness).

Drugs interaction with contact lens

• Oral contraceptive alters tear composition results decrease lubrication.
• Antihistamine, Hypnotics, Sedative decrease blink rate (blink increases hydration).
• Anticholinergics, antihistamines, TCA’s decrease tear volume
• Isotretinoin may cause itching and decrease wear time in soft lens users.
• ASA may cause ocular irritation, redness in soften wearers.
• Disinfecting solutions kills bacteria
• Preservative; maintain sterility of solution
• Saline solution preservative minimize the risk of contamination
• Wetting and rewetting solutions provide wetting, lubrication and cushioning functions.
• Contact lens should be stored in disinfecting solutions.
• Drying out is the major (75%) problem for soft lens users.

Drugs cause discoloration of soft lens.

Dopamine Nitrofurantoin Sulfasalazine
Tetracycline Phenazopyridine Phenolphthalein
Rifampin Pyrantel pamoate

Mouth Ulcers (aphthous ulcer)

Non-prescription Medications
• Local anesthetics (topical). Benzocaine, lidocaine.
• Oral analgesics: Acetaminophen, ASA, and NSAIDs
• Protectant: hydroxycellulose; base agent (Zilactin, Oractane).

Prescription Medications
• Corticosteroids, Fluocinonide, Clobetasole and Triamcinolone.

Dental Abscess: accumulation of puss in dental cavities.

Drug of Choice: Pen V or Amoxicillin or Erythromycin (base for adults and estolate for children)

Cold Sores
Cold sores sign and symptoms begins with prodromal symptoms of mild burning or itching on
the lips.
• Small vesicles filled with clear fluid which eventually ruptures and crust over
• Last for 3 to 10 days.
• Cankers and cold sores are diseases that improve without treatment.

Oral herpes infection also called fever blisters is caused by herpes simplex virus 1 (HSV 1 ).
Transmitted through direct contact. Usually appears on the lips also on hard palate or gums.

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Cold sores also known as recurrent herpes labialis.

Tingling sensation progressing to tiny painful grouped blister on lips, then crust.
• Usually caused by activation of latent herpes simplex virus type I.
• Primary infection occurs between 6 and 36 months of age.
• 15% of adults have primary infection. Recurrent infection occurs in 20 to 45% of
previously infected people.
• Mostly get first infection with herpes when they are infant. Virus remains in the body
and spread through physical contact.
• Abreva (docasanol) is used for treatment of recurrent cold sores.
• Acyclovir ointment.

Nonprescription medications
Pharmacotherapy
Topical anesthetics
• Ester type: Benzocaine, tetracaine; contact sensitizers
• Benzocaine: most common topical anesthetic used to relieve pain associated with canker
and cold sores.

External analgesics
• Camphor, menthol, and benzyl alcohol
• Counterirritants commonly found in cold sore balms
Astringent: Burrow’s solution or cold compresses with tap water applied 3 to 4 times daily is
helpful for cold sores
• Sunscreen with SPF 15; recommended to prevent cold sores in those with recurrence after
exposure to sun.
Protectants
• Petrolatum, ZnO, cocoa butter, allantoin, and calamine
• Prevent drying of lesions from cracking or fissuring
Heparin sodium and zinc sulfate (lipactin) – reduces pain duration
• Shorten time required for lesions to heal

Prescription medication. Antivirals like acyclovir

CANKER SORES
Recurrent aphthous stomatitis usually appear on the cheeks, tongue, soft palate floor of the
mouth.

Canker sores. visible manifestation of recurrent aphthous stomatitis

• Streptococcus sanguis partly the cause
• Autoimmune mechanism is also implicated
• At least 20% is affected
• Women twice as susceptible as men
• Susceptibility appears to be inherited

Canker sores sign and symptom. Painful, recurrent ulcers in the oral mucosa
• 3-10 mm shallow lesions
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• Round with white center and red halo

• Persist for 7-14 days

Treatment
Topical anesthetics
• Ester type. Benzocaine (contain up to 20% benzocaine), and tetracaine; contact
sensitizers.
• Applied to only small areas of the mouth to prevent a “cotton-mouth” feeling and
loss of oral sensation.
Protectants
• Petrolatum, ZnO, cocoa butter, allantoin
• Emollient mixtures or denture adhesives can alleviate pain
Chlorhexidine gluconate mouthwashes. help resolve cankers

Oral thrush
Also known as Candidiasis caused by fungus Candida albicans.
Drugs that commonly cause oral thrush are inhaled corticosteroids.
Patient self care. Rinse mouth with water after inhalation corticosteroids spray

Xerostomia (dry mouth). Xerostomia is a dry mouth conditions in which there are no salivary
secretions and also caused by improper functioning of the salivary gland (Sjogren’s syndrome).

Nonprescription medication: Ice chips, artificial saliva, and sugarless candies.

Treatment. Artificial saliva

Teething pain
Nonpharmacological
• Hard, smooth and clean products may be given to the child to bite and chew on such as
frozen face cloth.
• Safe teethers cooled in refrigerator before use can be helpful.
• The Canadian dental association recommends rubbing the back of a small, cold spoon on the
gum.
Non-prescription medication
Oral analgesic. Acetaminophen and ibuprofen
Topical anesthetic. Benzocaine 7.5% and 10% gel

Treatment of eruption cysts

• In general cysts rupture spontaneously.
• Rare cases surgically removed, if significant discomfort or interferes with feeding occurs.

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Dental Caries. Destruction of calcified tissue resulting from an infection. Dental caries most
commonly caused by Streptococcus mutans. This bacteria produce acids that demineralized
the enamel.
Treatment
1. Tooth paste contains
• Detergents (sodium laurel sulfate, sodium N-lauryl sarcosinate)
• Humectants (glycerin, propylene glycol)
• Whitener (peroxides; sodium triphosphate)
• Fluorides – reduce caries formation
2. Mouth wash contains
• Cetylpyridinium chloride may cause staining of teeth
• Chlorhexidine; may cause stains, taste change, discoloration of tongue
3. Triclosan
• Antiplaque
• Antimicrobial agent that helps prevents gingivitis, plaque cavities and tartar.

Trench mouth. This can cause acute necrotizing ulcerative gingivitis (ANUG) is caused by
overgrowth of spirochete and fusiform microorganism.

Gingivitis/periodontitis

The infection of gingival tissue is gingivitis. Gingivitis mouth rinse

• Chlorhexidine mouth rinse
Non-prescription
• Mouth hygiene
• Anesthetics; Benzocaine, and eugenol
• Analgesic; Acetaminophen.

Endocarditis
Caused by S. viridan and S. aureus.

Prophylaxis
• Amoxicillin 1 g before (1 hr) surgery, followed by 500 mg TID for 3 days.
• Azithromycin 1 g/day followed by 500 mg OD x 2 to 3 days (for patients
allergic to betalactam).
• Clindamycin 600 mg followed by 300 mg QID x 3 days (for patients allergic to
betalactam).
Reference. Canadian Pharmaceutical Specialties

Otic disorders

Excessive/impacted earwax
• Overactive ceremonious glands
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• Narrowed ear canal

• Large amount of hair in the canal occurs often in elderly.
• Ineffective or insufficient chewing or talking, especially in elderly.
• Improper removal methods.

Earwax softening agents

• Carbamide peroxides the only approved as safe and effective agent for earwax removal.
• To prevent vertigo, medication in the vial should be warmed in the hands and put 5-10
drops in the ear BID for 4 days.
• Do not use if ear drainage, discharges, pain, and irritation or rash occurs.
• Do not use if there is injury of perforation of eardrum.
• If the patient feels pain or severe fullness upon instilling the drops, this might be an
indication of ruptured tympanic membrane.

Altitude and ear pressure:

• This is caused by not functioning the Eustachian tube properly
• Pain can be reduced or prevented through: Swallowing (chewing gum or eating candies) to
activates the muscle that pull open the Eustachian tubes and helps to unblock the ear.
Giving a bottle of milk or juice to the baby may reduced or prevent ear pain among babies.
• Yawning is effective in opening Eustachian tubes.
• Pinching the nostrils using the cheek and throat muscles, and forcing air back of the nose,
may help in unblocking the ear.
• Decongestant may be a great help either an oral agent (Sudafel) taken an hour before
descent, or topical agent (oxymetazoline) should be administered 10-15 minutes before
descent.

Otitis Externa (swimmer ear)

• It is the inflammation of ear canal. This is commonly known as swimmer’s ear or hot
weather ear. Most often it occurs during summer.
• 50% of this is cause by Pseudomonas aeruginosa, other common microbes include Staph,
Bacillus, and Proteous organisms.
• Symptoms includes itching, moving pain in air, a fluid discharge from canal in severe cases,
decrease or loss of hearing

Non-pharmacological
• Hot compresses; pain, discontinue sticking
• Cold compresses; swelling, itch
• Avoid using shampoos
• Do not manipulate with swabs
• Removal earwax
• Use blow drier after shower. Bath not shower

OTC. Aluminum acetate 0.5% (Burosol), Benzothenium chloride 0.03% and Acetic acid 2%

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Prescriptions
• Gentamycin otic solution (amino glycosides active against gram –ve, (Pseudomonas),
and S. aureus (side effect: ototoxicity).
• Ciprofloxacin ophthalmic solution (no ototoxicity)

Otitis Media (OM)

• Otitis media is the infection of middle ear. Symptoms. Pain in the ear, and fever
• Acute otitis media (most common cause S. pneumonia, H. influenza, and M. catarrhalis).
However the types of OM chronic suppurative otitis media Otitis media with effusion.
• Drug of choice. Amoxicillin or +/- clavulanate

Vertigo and dizziness

Dizziness is refers to variety sensations such as light-headedness, fainting, spinning, and
giddiness.

Vertigo is defined as sensation of motion in response given bodily movement. Nausea and
vomiting, pallor, and perspiration accompany vertigo. It is vestibular disease as result of lesions
or disturbances in inner ear. e.g. Meniere's disease.
Meniere's disease prophylaxis. Diuretics (HCTZ, Triamterene), Betahistine (histamine agonist)
is commonly used. Diet salt restrictions and avoid coffee, and smoking.

Boils. Infected hair follicles in the ear canal that usually cause by S. aureus. This is self-limiting
and is best treated by application of warm compress.

Tips
1. 1 gtt OU 2 1 gtt AU 3 Carbamide peroxide
4. otitis externa 5 cold sores 6 wax removal
7. antibiotics & 8 inflammation of the eyelid 9 HSV 1
corticosteroids margin
10. HSV2 11 CMV 12 Epstein barr virus
13. VZV 14 pain in eye 15 blurred vision
16. blepharitis 17 dry eye 18 diabetes
19. polyvinyl alcohol 20 hydroxypropylmethylcellulose 21 Thimerosal
(HPMC)
22. 0.01% 23 sterile & isotonic 24 Tropicamide
25. emollients, anesthetics, 26 Acyclovir 27 cerumenous gland
astringents and Acyclovir

• What ophthalmic conditions require referral to doctor? ( )

• What is added in ophthalmic preparation to increase eye contact? ( )
• the most allergic ophthalmic preservative? ( )
• Benzalkonium chloride concentration as preservative in ophthalmic drops? ( )
• Ophthalmic preparation should be? ( )
• What eye drops that are used in eye exams? ( )
• Cold sores are caused by? ( )
• What is treatment of cold sores? ( )
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• What is not a treatment cold sores? ( )

• Both eyes is directed as? ( )
• Both ear is directed as? ( )
• Earwax removal is? ( )
• Swimmer’s ear is? ( )
• Abreva is used for? ( )
• What is active drug of valacyclovir? ( )
• Ear wax glands are also known as? ( )
• Mineral oil in ear is used as? ( )
• Acyclovir is effective against? ( )
• Blepharitis is? ( )
• An autoimmune disease characterized by destruction of the lacrimal and salivary glands
resulting in the inability to produce saliva and tears. ( )
• Stye (hordeolum) require warm compress where as blepharitis require cold compress

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71
OTC Drugs, Antihistamine,
Decongestants,
Antitussives, and
Expectorant
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Topical xylometazoline and oral decongestant pseudoephedrine, phenylephrine
precautions and contraindications.
• Antitussives like dextromethorphan, codeine DIs with MAOi can cause serotonin
syndrome.
• What OTC drugs have abuse potential? Dextromethorphan, pseudoephedrine,
diphenhydramine, and Tylenol # 1.

Pharmaceutical Agents
1. Analgesics/antipyretics; acetaminophen, ASA or ibuprofen
• Treat pain and fever.
• Don’t administer ASA to infants, children, teenagers or young adults because of Reye’s
syndrome.

Antihistamines. Relieve rhinorrhea, sneezing and watery eyes associated with cold
• Often cause drowsiness and drinking alcohol or taking other antihistamines or sedatives
can increase effect.
• Paradoxical excitability, nervousness and difficulty sleeping sometimes occur in children.
• Contraindicated in patients with glaucoma, kidney or liver disease, prostatic
hypertrophy and pregnant or breast-feeding.
•
1st gen 2nd gen
Rapid onset and short duration Slow onset and long duration
Highly lipophilic Less lipophilic
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Diphenhydramine Q6-8h Cetrizine Q24h

Fexofenadine Q12h 60 mg, SR Q24 120mg
No decongestant Desloratadine is approved for relief of
nasal decongestant.
Drug of choice to allergic rhinitis.

Antitussives. Dextromethorphan indicated only for dry, unproductive coughs when congestion is
not present.
• Contraindicated in patients with chronic, persistent cough, patients with lung disease
and in women who are pregnant or breast-feeding

4. Decongestants: pseudoephedrine, phenylephrine

• Oral agents are more effective but caution in patients with heart disease,
hypertension, thyroid disease, diabetes, glaucoma and prostatic hypertrophy, patients
taking antidepressants, and women who are pregnant and breast feeding.
• Topical agents can cause rebound congestion if used for more than 3 to 5 days.
• Oral decongestant should avoid in first trimester of pregnancy.

5. Expectorant. Guaifenesin is the only one available in Canada

• Adverse effects are rare.
• Overdose can cause nausea and vomiting
• Contraindicated in patients with chronic, persistent cough, patients with lung disease
and in women who are pregnant or breast feeding.

Antihistamine: To treat Allergies, Allergic rhinitis, Insomnia, Motion sickness, Nausea and
vomiting.
Precaution. driving, operating machine, anticholinergic side effect, and constipation.
Diphenhydramine or dimenhydrinate is the drug of choice for motion sickness.
Meclizine have long half-life is the drug of choice in pilots and navigator.

Decongestants. pseudoephedrine, xylometazoline, saline drops

• Congestions and cough, shortness of breathe.
• Caution. Uncontrolled blood pressure, uncontrolled diabetes, glaucoma.
• DI. MAOi is not taken with oral decongestants.

Antitussives. dextromethorphan, codeine used to treat cough or dry cough.

• DI: MAOi can cause serotonin syndrome.

Expectorants: Guifenesine used to treat productive cough (cough with sputum).

The Common cold

Common cold: self-limiting viral infection

• Involves mainly the nose, throat and chest
• Transmitted from person-to-person through sneezing, coughing, hand-to-hand contact
and contact with objects handled by a person with cold
• No cure for the common cold
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• Available treatments lessen the severity of symptoms

Most frequently caused by:

• Rhinovirus (30-50%) and coronavirus (10-20%)

Less frequently caused by:

• Respiratory syncytial virus (RSV), Adenovirus, Para influenza, Enterovirus

Infection is transmitted by:

• Hand to hand (Virus contact nasal mucosa) and via aerosol particle.
Signs And Symptoms
• First sign is usually sore throat, described often as dry or scratchy sensation
• Rhinorrhea and nasal congestion follow the sore throat.
• Fever is common in children, but not in adults
Prevention:
• Wash hands often
• Cover mouth while coughing

Avoid direct contact with contaminated objects

Treating the common cold
• No cure for common cold. Remedies that may help relieve some of the discomfort
• Stay at home if possible and rest in bed
• Drink plenty of fluids (up to 8 glasses of water or other fluid a day). Hot liquids are
particularly helpful for a stuffed up nose
• Keep the air around you well humidified to make breathing easier

Pharmacological Treatment
• Salt water gargles and throat lozenges – soothing to a sore throat
• First generation antihistamines – relieves rhinorrhea and watery eyes
• Topical and oral nasal decongestants – relieves stuffy nose and sinuses
• Oral decongestants more effective than topical but produces more adverse systemic
effects
• Expectorant, guaifenesin – treats productive cough with chest congestion
• Dextromethorphan – to suppress dry, unproductive cough
• Analgesic/antipyretic – for body aches and fever in adults
• Zinc – controversial but zinc gluconate lozenges may reduce some symptoms of
common cold but may cause nausea and impart bad taste

Recognizing A Common Cold

Typical signs and symptoms:

• Sore throat: often dry, scratchy feeling rather than a painful feeling
• Runny or stuffed up nose: appears just after sore throat. Nasal discharge is clear and
watery at first and become thicker as cold progresses
• Watery eyes: common in early stages of cold
• Headache and sinus pain: discomfort usually arises from inflammation of the sinuses
• Dry cough: usually follows the nasal congestion. Becomes watery as the cold progresses
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Fever
Fever. Body temperature, which is above the normal range (37 oC) resulting from an elevated
thermoregulatory set point in the anterior hypothalamus.

Signs and symptoms.

• Mild fever can cause chills, dehydration, headache, and loss of appetite, nausea and
vomiting.
• High fever in children can cause convulsions (febrile seizures) while in adults can cause
confusion or even delirium. Neurological damage can occur at body temperatures of 41.7 ᴑC
(107 ᴑF) and greater.

Differential diagnosis. Hyperthermia, increase in body temperature without an increase in the

thermoregulatory set point.

Nonpharmacological treatment
• Sponging with tepid water may soothe but wont reset the hypothalamic set point
• Alcohol sponge is not recommended
• Remove all excess clothing and bedding to allow for heat dissipation
• Give fluids to ensure adequate hydration

Pharmacological treatment
• Antipyretics – reduce body temperature by reducing the hypothalamic set point to normal
• Don’t administer ASA in infants, child or teenager because it can cause Reye’s syndrome
Pharmaceutical agents
1. Acetaminophen – effective antipyretic
• Treatment of choice for fever in infants, children and teenagers
• Patients with liver disease or who consume 3 or more alcohol containing drinks per day
should consult a physician before taking acetaminophen

2. Acetylsalicylic acid (ASA) – useful antipyretic in adults

• Can cause stomach irritation leading to heartburn, bleeding and ulcers
• Has marked antiplatelet effect
• Patients with asthma or kidney disease or taking other medications should consult a
physician before taking ASA

3. Ibuprofen – fever in adults, children and infants

• Can cause stomach irritation, leading to heartburn, bleeding and ulcers

Allergic Rhinitis (Hay fever)

• Acute inflammation of the mucous membrane of the nose usually accompanies the common
cold
• Hypersensitivity response to airborne allergens mediated by immunoglobulin IgE. (Mediated
by Ig E)
• Allergic rhinitis can be seasonal or perennial
• Seasonal allergic rhinitis begins in spring and ends in fall.
• Perennial allergic rhinitis is caused by allergens present year-round, such as house dust,
mites, animal dander, cockroaches, and indoor molds.
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Allergens Pollens, molds, house dust mites, cockroaches, and insect allergies stimulate the
release of chemical mediators such as:
 Histamine Allergic rhinitis Symptoms
 Leukotrienes LTC 4 , LTD 4 and LTE 4 , Runny nose, Pruritis of eye ear and
 Prostaglandins D 2 , throat, Sneezing, Cough
 Kinins No fever and no sore throat
Watery eyes, Fatigue
Risk factors:
• Gender, childhood, male, age before 20 years
(80%), family history of atopy increases risk for rhinitis, asthma and eczema

Environmental control: Pollens, Molds, House dust mites, Animals and Insect allergies

Treatment:
• Antihistamines; sneezing, itching of eyes, ears, nose, and throat, runny nose, tearing.
• Decongestant; desloratadine relieves nasal congestion.
• Corticosteroids
• Mast cell stabilizer
Others: Anticholinergics, Antileukotrienes, Mast cell stabilizers, Sodium cromoglycate (side
effects: sneezing, nasal stinging, irritation, bad taste in the mouth

Influenza (Flu)
• Caused by viral infection. Two types of virus cause serious infections Influenza A (most
common and more severe) and Influenza B. Effects are on the superficial epithelium of the
airway tract.
Symptoms. Dry cough, sore throat, nasal discharge. Chills and fever (immune response), and
sweat, muscle pains, weakness/fatigue.
Flu vaccine contraindications
Flu mist nasal spray can be used in children.
• Less than 6 mo age
Persons at high risk of flu • Allergies to eggs
• Persons over 65 years age. • Person with flu symptoms
• Any resident of nursing home or other care facilities regardless of age.
• Adults and children with chronic cardiac or pulmonary disorders sever enough to
require regular medical condition.
• Adults with chronic condition such as asthma, COPD, diabetes mellitus, cancer,
immunodeficiency or immunosuppression, renal disease, anemia or
hemoglobinopathy.
• Children over 6 months of age to 2 years.
• Pregnancy

Treatment
• Nasal decongestants
• Antihistamines
• Antitussive
• Expectorants
Flu shot are given annually

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• Influenza season between October through April

• Immunization season from October through November

Sinusitis
 Inflammation of sinus in response to infection or allergy and may be influenced by
anatomical abnormalities.
 Sinusitis is more common in children.

Caused by (70%): S. pneumonia, Influenza, Catarrhalis

Symptoms persist more than three months consider as chronic sinusitis: Caused by
• H. influenza (50%, S. aureu, P. aeruginosa, Fungi (diabetic patient)
Treatment:
• Nasal decongestants, Antihistamines, Antitussives, Expectorants and Analgesic
Drug of choice:
• Acute sinusitis: Amoxicillin
• If allergic to β-lactamsTrimethoprim/Sulfmethoxazole (TMP/SMX)
• Ref: Formulary for general practice drug of choice, p.104, 1998

Pharyngitis

Inflammation of pharynx. (Part of other illnesses cause by infections)

Viral pharyngitis: Epstein-bar infection, Influenza, Common cold, Measles, Vericella
• Allergic rhinitis, Sinusitis, Or allergies.

Bacterial pharyngitis: Beta hemolytic streptococcus (Group A Strep-GAS) (15-30%)-during winter

or early spring.

Symptoms:
• Sore throat
• Fever, headache
• Swollen lymph nodes, usually in neck
• Runny nose

Medications: Nasal decongestants,Antihistamines, Antitussives, Expectorants, Analgesic

Treatment:
• Bacterial pharyngitisPenicillin V
• If allergic to –Erythromycin
  lactams base (adults), erythromycin estolate (children)
• Ref: Formulary for general practice drug of choice, p.98, 1998

Cough
Symptoms of many respiratory diseases. Can result from many chemical or mechanical effects.
Common causes of cough are: Asthma, Chronic bronchitis, Congestive Heart Failure (CHF), Drugs
(eg. ACE inhibitor), Emphysema, Foreign body, GERD, Post nasal drip, Upper/lower Respiratory
Tract infection.
Treatment: antitussive such as: Dextromethorphan, expectorants:
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Antitussives (for cough): Non-narcotics antitussive: Dextromethorphan, Diphenhydramine

Narcotic antitussive: Codeine and hydrocodon

a) Dextromethorphan
Widely used in OTC cold remedies to suppress non-productive cough
P.O onset 15- 30 min
Duration 3 to 6 hours
Side effects: Nausea, Drowsiness, Dizziness
Contraindications: CNS depression will increase if drug used with: Alcohol, Narcotics, Sedatives-
hypnotics, Barbiturates, Depressants

Narcotics Antitussive:
Codeine: 15-30 mg of dextromethorphan = 8 -15 mg of codeine
Side effect: Drowsiness, Sedation, Constipation (Stimulant laxative bisacodyl or senna), nausea,
and vomiting

Expectorants
 Gauifenesen (extract of tar)
 Ammonium chloride
Expectorants reduce sputum viscosity and allow more effective removal of secretions from the
respiratory tract.

Gauifenesen (extract of tar)

Mechanism:
• Increase ciliary action
• Fluid from the respiratory tract less viscous
• Facilitate the removal of mucus
• High doses cause emesis

Side effects. Rare (drowsiness, nauseas, vomiting)

Ammonium chloride:
Mechanism: Irritant to stomach, Causes reflex increase in airway mucus secretions.
High doses will cause acidosis in individuals with renal failure

Decongestant
Topical decongestants. Oxymetazoline and Xylometazoline
• Decrease nasal airway resistance and nasal blood flow, but usually do not cause
systemic sympathomimetic action.
• Act rapidly within 10 min
• Lead to rebound nasal decongestion (rhinitis medicamentosa) which usually occurs 5-10
days of treatment.
• Short term treatment, 2-3 days
• Topical: Onset of action 5-10 min.
• Phenylephrine, Naphazoline, and Xylometazoline

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Side effects. Local burning sensation, Sneezing, Dryness of the nasal mucosa. Bradycardia,
Tachycardia, Hypertension

Nasal decongestants. Phenylephrine, and Propylhexedrine

Systemic decongestants:
• Pseudoephridine, Epinephrine, Phenylephrine and Phenylpropamine
• Cause nasal vasoconstriction and decreased nasal edema within 30 minutes and
continues for 6 hours (regular formulation)
• Oral (onset of action 30 min)
• Caution with patient, Hypertension, heart disease, hyperthyroidism, diabetes, narrow
angle glaucoma, BPH.

Side effects. CNS stimulation (mild), Insomnia, Headache, Irritation, Tachycardia or palpitation,
Increase of BP in hypertensive patient. Affects blood sugar levels in diabetics.

Contraindication. Uncontrolled hypertension, Severe coronary artery disease, MAOI, Glaucoma,

BPH

Tips
1. glaucoma 2. hypertension crisis 3. runny nose
4. uncontrolled BP 5. diabetes 6. sore throat
7. BPH 8. watery eyes 9. sneezing
10. low grade fever 11 self-limiting viral infections of 12 malaise
rhinovirus (30 to 50%) & corona virus
(10 to 20%)
• Common cold is caused by? (self-limiting viral infections of rhinovirus (30 to 50%) & corona
virus ( )
• Common cold symptoms(runny nose, sore throat, watery eyes, sneezing, low grade fever &
malaise) ( )
• Contraindications of oral decongestants ( )
• MAOI + sympathomimetics like pseudoephedrine give --> ( )
• Echinacea purpurea probably can be effective in the prevention and treatment of common
colds in adults.
• Expectorants examples are? 
• Topical antihistamine examples 
• High risk groups for flu vaccine 
• Who should NOT take flu vaccine 
• Flu vaccine is taken every 
• When is the flu season in Canada 
• Flu immunization season 
• Contraindications of antihistamines 
• Cautions of oral decongestants 
• Nonpharmacological treatment common cold? Bed rest, Drinking plenty of fluids and
Humidifying the air

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72
OTC drugs for Nausea,
Vomiting, Diarrhea
Constipation, and
Hemorrhoids
NAUSEA & VOMITING
Non-prescription anti emetic drugs
• Dimenhydrinate is used for all types of nausea and vomiting (N&V) (except post
chemotherapy N&V). Given 30 min before exposure
• Meclizine is used for all types of N & V
• Promethazine
• Diphenhydramine is alternative for dimenhydrinate
• Pyridoxine (vit. B 6 ) used only for pregnancy induced N&V (PANV)
• Scopolamine: used only for motion sickness
• Ginger root
Sedation is common side effects of non-prescription antiemetic drugs (except pyridoxine). If
alertness is required, scopolamine or promethazine + ephedrine or dexamphetamine (used by
airline pilots).

Pregnancy associated nausea and vomiting also known as “Morning Sickness”.

Self care measure

Alter diet emphasize on small & frequent meals, avoid fatty or spicy foods.
• Eat at all times of the day when nausea is less severe.
• Eat before getting up from bed (in the morning).
• Discontinue iron supplements (temporarily) because this causes nausea and vomiting.
• Ginger root 250 mg qid may reduce nausea and vomiting.

Nonprescription
• Dimenhydrinate use only for 2 to 3 days refer to physician if ineffective.
• Pyridoxine (vitamin B 6 ) can be used alone. No side effects & drug interactions.
Prescription
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• Drug of choice Diclectin (pyridoxine 10 mg + doxylamine).

Opioid induced nausea and vomiting (OINV)

Alter administration schedule (make sure nausea does not interfere with meal).
• If pain does not decrease, attempt an increase in opioid dosage (pain could be caused by
nausea and vomiting).
• Switch to another narcotic drug
• Use other anti-emetic. Metoclopramide (drug of choice), and perchlorperazine,
diphenhydramine, dimenhydrinate, ondansetron, haloperidol.

Post chemotherapy nausea and vomiting (PCNV)

Alter diet (emphasize on small & frequent meals. Avoid fatty or spicy foods).
Non-prescription medicines are not useful. Prescription medicines are metoclopramide,
dronabinol and perchlorperazine.

• Low emitogenic drugs

• Treatment start with dexamethasone as needed.
• Delayed nausea and vomiting
• The drug of choice for moderate emitogenic is dexamethasone
• Drug of choice for acute emitogenic is 5HT 3 antagonist ondansetron+ dexamethasone.
• High emitogenic drugs
• The drug of choice for high nausea and vomiting is dexamethasone.
• Anticipatory nausea and vomiting.
• The drug of choice is benzodiazepine (lorazepam).

Motion sickness
Self care measures
• Avoid eating large meal within 3 hours of travel.
• Avoid dairy products or food high in protein content, high-calories, or high in sodium before
travel.
• Avoid alcohol, smoking and bad smells.
Treatment
For short duration of exposure, dimenhydrinate is effective for most patients. Diphenhydramine
is an alternative. Take oral medication at least 60 min in advance. Because motion induces gut
stasis. The second dose can be used after 6 hrs.
Scopolamine trans dermal patch.
• Placed behind ears. 1 patch every 72 h, can be removed and reused within 72 h but should
rotate site of application.
• Side effects include constipation, dry mouth, blurred vision, skin rash, disorientation,
delirium.
• Should not be used in children.

DIARRHEA
Management
• Rehydration and maintain electrolyte balance can reduce diarrhea symptoms
• Children: Continue breastfeeding & oral rehydration solution (ORS) should be offered;
otherwise, discontinue all food and drinks and give ORS.
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• Give ORS as soon as diarrhea begins until diarrhea is less frequent

• Rapid re-feeding should immediately follow rehydration
• If diarrhea with vomiting, give ORS 15 ml every 10 to 15 minutes (using a spoon).
• Oral rehydration therapy (ORT) is the most effective treatment for children with acute
diarrhea.
• Pregnant. Maintain fluid intake. Loperamide is safe in pregnancy.
• Elderly. Prompt rehydration is essential.
• Fruit juice pop, or tea with sugar are not suitable due to high carbohydrate content.

Symptoms of dehydration. Dry mouth (increased thirst), crying without tear, sunken eyes, less
or low frequency or decreased urination and skin turger. Sunken soft spot in infants. Feeling
weak and lightheadedness.
Sweating or frequent urination is NOT a dehydration symptom.

Treatment
Nonprescription
Loperamide (Imodium).
• Not given to children under 2 years old also in children less than 12 years old without
doctor’s advice.
• Not recommended for acute dysentery/infections diarrhea (bloody stool with fever).
• SEs include abdominal cramps, drowsiness, dry mouth, and skin rash.
• Maximum dose is 16 mg/day (4 mg start then 2 mg after each loose bowel movement).

Attapulgite (Kaopectate) may be used for drug-induced (mild to moderate) diarrhea. Not to be
used for less than 2 days.

Bismuth Subsalicylate
• The bismuth subsalicylate (BSS) should be avoided in patients taking anticoagulants,
salicylates, probenecid, or methotrexate.
• Avoid in NSAIDs or ASA allergies
• Not for children less than 2 years old due to Reye’s syndrome
• Used in chronic diarrhea, for travelers diarrhea & H. pylori management
• SEs. include black tongue and stools, and tinnitus

Psyllium (Metamucil)
• Should be taken within 2 hours of other medications because it reduces absorption of other
medicines
• Should be taken with at least 250mL water to prevent fecal impaction and/or esophageal
obstruction
Prescription
• Cholestyramine – for treatment of bile acid induced diarrhea
• Codeine – for patients who do not respond to non-prescription medicines
• Clonidine – for diarrhea associated with opioid withdrawal and diabetic neuropathy
• Diphenoxylate with atropine (Lomotil) less effective than loperamide
• Octreotide – for chemotherapy-induced and AIDS-associated diarrhea
• Herbal and other Remedies:
• Herbal – chamomile, carob, marshmallow, slippery elm, bayberry
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• Probiotics – live microorganism (bacteria and yeast)

• Refer to physician if diarrhea does not improve in 48 hours with high fever, blood in feces,
severe pain in belly, children less than 6 months old, with vomiting for more than 4 to 6
hours with sign of rehydration; more than 6 BM in one day.

Most cases, diarrhea in children is self-limiting and non life threatening.

Focus on dehydration with ORT.
Breast feeding should be continued during episodes of diarrhea.
If not breast feeding appropriate food should be continued (avoid BRAT diet. is complex
carbohydrate diet). After 24 hr normal condition can resume normal diet. take 7-10 days to
become stools completely formed.

If child vomiting and diarrhea does not stop in 4-7 hr should receive medical attention.

NONINFECTIOUS diarrhea. Drug induced diarrhea could be caused by:

• Antibiotics
• Chemotherapeutic agents
• Anti-inflammatory agents (NSAIDs, Colchicine)
• Anti-arrhythmics (Quinidine)
• Anti-hypertensive (Beta-blockers, ACE inhibitors)
• Antacids (Mg-containing antacids, ranitidine, omeprazole)
• Miscellaneous. Misoprostol and theophylline

TRAVELLERS DIARRHEA caused mainly by E. coli, Shigella sp and Compylobacter jejuni

Prevention.
• Hot and cooked meals, cooked vegetables (no salad or no fresh salad).
• Peeled fruits, boiled/bottled water, carbonated beverages without ice cubes, pasteurized
milk (properly stored).
• Bismuth sub salicylates as prophylactic agent.
• Typhoid vaccine recommended for travelers
• Cholera vaccine for healthcare workers in endemic areas.

Nonpharmacological therapy
Children and elderly should use oral rehydration solution. Adults maintain hydration with
canned juices, purified water, clear salty soup, carbonated soft drinks.
Pharmacotherapy. Prior to departure, travelers should see physician for appropriate antibiotics.

Treatment (prescription)
• Drug of choice is ciprofloxacin 500 mg BID X 3 days
• Alternative azithromycin, cefixime.
• Cotrimoxazole of limited use due to widespread resistance

CONSTIPATION
Self care measures
• High-fiber diet (for children less than 2 years old should have dietary levels of fiber equal to
or greater than their age + 5 g/day, 25 to 30 g intake for adults).
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• Minimum fluid intake of 1500 ml daily. Moderate physical activity.

• Regular toilet routine (children should be encouraged to defecate 5 to 15 min after meal).
• Heed the urge to defecate, weight loss for overweight patients.
• Prune and other juices with sorbitol may also help.

Drug inducing constipation.

• Anticholinergic agents: antidepressants, antipsychotics, antiparkinson's (levodopa).
• Cation containing agents aluminum containing antacids, sucralfate, CaCO 3 , and Ca
supplements, bismuth, and iron supplements.
• Other drugs. Verapamil, clonidine, diuretics, cholestyramine, NSAIDs, opiates, vinca
alkaloids, sympathomimetics agents, and ganglion blockers.

Pharmacological treatment: laxatives

Bulk-forming (psyllium, bran, and methylcellulose)
• Adsorb water to soften the stool and increase the bulk, which stimulates peristalsis.
• Should be taken with at least 250 mL water to prevent esophageal obstruction and/or fecal
impaction.
• Side effects include flatulence, bloating. Safe to use in pregnancy.
• Contraindication in patients with fluid restriction and mechanical obstruction of the GIT.
• Not to be taken within 2 hours with other medications because it reduces drug absorption.

Osmotic laxatives. (Lactulose, and glycerin)

• MOA. Retains water and allow the stool to pass easier through the bowel.
• Lactulose not tolerated by most patients because of too much sweetness in taste.
Can be used by diabetic patients.
• Side effects include flatulence, abdominal cramps, and N&V.
• Contraindicated in patients on galactose free diet.
• Taken with fruit juice or milk only to improve palatability.
• Lactulose is the drug of choice for hepatic encephalopathies, because it absorbs
ammonia.
• Glycerine. Softens the stool and lubricates the bowel by increasing water retention
(osmotic properties) in the intestinal lumen. Also stimulates rectal contractions. SEs
rectal irritation.

Saline laxatives (Mg hydroxide, and Mg sulfate)

• MOA. Same mechanism of action as osmotic laxatives.
• Mg hydroxide (Milk of magnesia).
• SEs. Diarrhea, dehydration and electrolyte imbalance, hypermagnesemia
• CIs. Patients with cardiac or renal disease
• Chilled before administration to increase palatability
• Mg sulfate (Epsom salt)
• Na phosphate (Fleet enemas)
• Best administered on an empty stomach, 30 min AC or HS
• SEs. includes hyperphosphatemia, hypocalcemia, hypokalemia, hypernatremia
• CIs. for pregnant and lactating women.
• Enemas

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• It is not recommended in children <2 y and caution in children below 2-5 y.

• Not recommended in Na restricted patients
• Use with caution in patients with renal or cardiac disease

Stimulant laxatives
• MOA. Increase the secretions of water and ions into the lumen and stimulate the
bowel wall to contract. (produces rhythmic muscle contractions in intestine).
Recommended if osmotic laxative are fail or not tolerated.
• SEs. is abdominal cramping. Can cause dependency.
• Senna
• May discolor the urine from red to pink or brown to black, excreted into breast
milk.
• The drug of choice for opioids induced constipation
• Faster onset of action than bulk laxatives.
• Bisacodyl
• Preferred stimulant laxative for long term use in patients on H 2 antagonist and
should not be taken within 1 h of antacids.
• Tablets should not be crushed, or broken, or chewed (swallowed whole).
• Cascara sagrada (“sacred bark”)
• CI: In children
• Excreted in breast milk
• May discolor urine red to pink or brown to black
• Castor oil
• Not recommended in children <2 yrs
• CIs. in pregnancy due to purgative action
• Used in emergency procedures

• Stool softener. (Docusate sodium)

• Soften hard stools
• Used in combination with bulk laxatives
• Primary rule is in prevention of constipation
• SE: include abdominal cramps, diarrhea, nausea, and rash.

• Lubricant/Emollient, mineral oil. not recommended in children < 1 y old

• Warning: Can decrease absorption of fat-soluble vitamin (ADEK)
• Increase anticoagulant effect due to decrease absorption of vitamin K
• Risk of lipid pneumonitis
• Can lead to hepatotoxicity
• Can cause anal seepage and perianal discomfort
• Should be taken on empty stomach

** Best Laxatives for:

Infants:
• NOT recommended: enemas, mineral oil, stimulant laxative
• Recommended: glycerin supplement, lactulose or sorbitol (as stool softener)
Children:

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• Mg hydroxide, mineral oil, lactulose and sorbitol, polyethylene glycol.

Pregnancy:
• Bulk-forming agents, stool softener, osmotic, or Mg laxatives
• Avoid: stimulant laxative, mineral oil, castor oil
Breastfeeding
• Bulk forming and osmotic laxatives (1st line therapy),
• Mg Sulfate, cascara and senna (2nd line therapy)
Cancer patients:
• Stimulant laxatives with enemas intermittently; avoid bulk laxatives
Elderly patients:
• Lactulose or glycerine supplements (initial treatment)
• Bulk laxatives for prevention; stool softener
• Avoid stimulant and saline laxatives
Long-term use (in opioid patients)
• Bisacodyl (with physician supervision)
** See physician if no BM for 7 days, pain or bleeding in rectum, fever, pain in belly, and
feeling of vomiting.

Flatulence (Gas) and Cramps

Non-prescription treatment
• α-D-galactosidase is taken with 1st bite of food
• Lactase; taken with or before ingestion of lactose
• Simethicone acts by preventing bubbling of liquids in the stomach. Does not absorb
from GIT. Does not have significant side effects.
• Peppermint, garlic, ginger are alternative therapy.
**Refer to physician if symptoms persist for more than 1 to 2 weeks or non-prescription therapy
is ineffective.

Hemorrhoids (Pile). Abnormally swollen veins in the rectum and anus, caused by too much
pressure in the rectum forcing the blood to stretch and bulge the walls of the veins, and
sometimes rupturing them.

Treatment.
• Anti-inflammatory agents. Hydrocortisone 0.5% (should not be used > 7 days).
• Astringent. ZnO (relieves irritation and burning sensation), calamine (5 to 25%). Hamamelis
water (witch hazel) 50% gel available as pads or wipes.
• Local anesthetic. Dibucaine 0.5 to 1% ointment/cream, Pramoxine 1% ointment
• Antiseptics. Domiphen (0.05% cream/ointment).
• Protectants. Glycerine, white petrolatum and ZnO.
• Vasoconstrictor. phenylephrine 0.25% gel.
• Wound healing. Shark liver oil 3% ointment/cream 66 mg supp. yeast 1% ointment
• Pregnancy. Correct constipation and taking sitz bath.
• Analgesic. Menthol, and camphor.
Prevention.
• Avoid constipation
• Increase fiber diet, fluids, and physical exercise
• Regularize stool habits and minimize strain and time on seat
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Intestinal worms. (Pinworm, ascariasis, and whipworm)

PINWORM
Nonpharmacological measure
• Take shower every morning.
• Regular cleaning or bedding, nightclothes, under wear and hand towels.
• Hand wash, and nail cleaning mainly before meals.
• During week the following treatment, all family members should wear cotton underpants.
(washed in soap water). Worn day and night change twice daily.
• Cleaning of floors of sleeping place.
• Clean bedroom articles, curtains where high concentration of eggs.
• Avoid shaking linens, curtains before wash.
• Avoid thumb sucking in children.
• Not effective. Cleaning or vacuuming entire house or washing sheets every day is probably
not effective to prevent re-infection.
• Avoid sharing dishes.
• Avoid sharing undergarments

All close contacts should be treated. Avoid in pregnancy.

Prevention. Proper hygiene

Treatment
Drug of choice pyrantel pamoate
• SEs. Nausea, vomiting, dizziness, headache, and anorexia
• Avoid in pregnant and with liver disease
• Liquid should be shake well before use.

Pyrivinium pamoate
• SEs. Nausea, vomiting, abdominal pain, photosensitivity
• Tablets should be swallowed whole to avoid staining the teeth
• Will color stool red for 24 to 48h after dose; also stain vomitus and clothes

Piperazine adipate
• Can be used in pregnancy
Prescription.
Mebendazole
• Drug of choice (100 mg single dose, repeated after 1-2 weeks)
• For adults and children >2 y
• SEs. abdominal pain and diarrhea
• Taken with meal

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Tips
1 Psyllium 2 Diclectin Vit B6 + 3 Docusate sodium + senna or
Doxylamine bisacodyl
4 Dexamethasone 5 Ciprofloxacin 6 Benzodiazepines
7 Bismuth subsalicylate 8 uncooked food 9 contaminated water
10 ice cubes 11 fresh salads 12 dry mouth
3 sunken eyes 14 less frequent urine 15 loss of skin turger
16 crying without tears
• DOC for pregnancy induced nausea and vomiting ( )
• DOC for low emitogenic chemotherapy induced N& V( )
• DOC for delayed chemotherapy induced N&V( )
• DOC for anticipated nausea and vomiting( )
• symptoms of dehydration( )
• traveler’s diarrhea mainly caused by? ( )
• black stools and tongue is side effect of? ( )
• DOC for traveler’s diarrhea( )
• DOC in pregnancy for constipation( )
• DOC for opioids induced constipation( )
• What is the drug of choice for pregnancy induced nausea and vomiting 
• What are the self care measures recommended for N&V associated with PCNV
• DOC for low emitogenic chemotherapy induced N&V 
• DOC for delayed chemotherapy induced N&V 
• DOC for anticipated nausea and vomiting 
• Symptoms of dehydration
• Traveler’s diarrhea mainly caused by 
• Black stools and tongue is side effect of 
• What type of food should be avoided by travelers to prevent infectious diarrhea 
• Drug of choice for travelers diarrhea 
• What are the most important self care measure is recommended relieve constipation?
• Drug of choice in pregnancy for constipation?
• Drug of choice for opioids induced constipation
• What are the self care measures to relieve hemorrhoids

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www.pharmacyprep.com Analgesics and Topical Pain Relievers

73
Analgesics, and Topical Pain Relievers

Questions Alerts!
Common questions in pharmacy exam is to ask!
• NSAIDs side effect and maximum dose
• Triptans mechanism and onset of actions (sc is fastest)
• Migraine prophylaxis. Amitriptyline, propranolol, verapamil, and nortriptyline.

Three types of pain

Neuropathic pain. Due to damage or dysfunction nerve, spine or brain.
Nociceptive pain. Caused by injury to body tissue. Aching, sharp, throbbing.
Psychogenic pain. Related psychological factor.

Headache. Generally headache is characterized as tension, cluster and migraine.

Tension. Associated with stress, tension etc. No nausea and vomiting.

Migraine
• Unilateral headache (throbbing pain), often associated with nausea and vomiting.
Decrease quality of life by interrupting activities.
• Associated with nausea and vomiting, triggers by light, smell, noise, and food etc.

Migraine Therapeutic Plan

• Mild migraine attacks. ASA, ibuprofen, adjunctive dimenhydrinate, metoclopramide, and
acetaminophen (weak evidence).

• Moderate attacks. NSAID, triptans, dihydroxy ergotamine (DHE) (weak evidence).

Combination drugs acetaminophen + codeine, ASA + codeine + caffeine + ASA + butalbital +
caffeine.

• Severe and ultra severe attacks. Butraphanol, chlorpromazine, dexamethasone, ketorolac,

meperidine, metoclopramide, prochlorparazine, and sumatriptan.

Mild Migraine attacks

• ASA. Dose” 650 to 1300 mg q4h buffered or soluble tablets (not enteric coated)
• Ibuprofen: Dose 400 to 800 mg q6h, rapid dissolving tablets available
• Acetaminophen: Weak evidence of benefit. Monitor AST/ALT.

Moderate to severe migraine attacks

• NSAIDs (ibuprofen, naproxen, mefenemic acid).
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• 5HT 1b/d agonists. Sumatriptan, rizatriptan, zolmitriptan, and naratriptan.

Sumatriptan SEs chest tightness. CIs: pregnancy.
• Oral 25 to 50 mg, MR q2h (max 200 mg/24 h).
• Intranasal 5 to 20 mg, 1 spray in 1 nostril per dose.
• MR in 2 hours (max 40 mg/day). Do not shake and prime.
• SC 6 mg, MR 1 hr/max 12 mg/24 hr.
• Take at first sign of headache or at aura.
• If NO relief first dose, DO NOT use second use. If it relieved, and second attack, use only
after 2 hours. Avoid other triptans use with 24 hours.

Dosage forms
Tab. All triptans
SC. sumatriptan
Oral disintegrating tablets (wafers), rizatriptan and zolmitriptan
Internasal. sumatriptan and zolmitriptan.

Combination analgesics
• Acetaminophen 300 mg + codeine 8 mg + caffeine 15 mg (Tylenol #1)
• ASA+ codeine + caffeine (222)
• ASA+ butalbutal + caffeine (Fiorinal). Regulated as control drug part 2.

Migraine prophylaxis
Propranolol, atenolol, metoprolol, nadolol, verapamil, amitriptyline, nortriptyline, topiramate,
valproic acid, divalproex sodium and carbamazepine. Venlafaxine and pizotifen (serotonin
antagonist) and lithium.

Low Back Pain

• Avoid unnecessary bed rest for uncomplicated back pain. As well as premature physical
therapy.
• For acute uncomplicated low back pain, NSAIDs are effective for pain relief particularly
during the first few weeks.
• For back pain and chronic soft tissue pain, tricyclic or other types of antidepressants have
equivocal efficacy, but may be useful for their antidepressant effect.

Pharmacological treatment
• Acetaminophen
• NSAIDs. ASA
• Skeletal muscle relaxant (chlozoxazone, methocarbanol)

Sports Injuries
Goals of therapy.
• To reduce acute symptoms (pain, inflammation) and recurrences
• To correct contributing factors (e.g. malalignment, muscle weakness)
• To return the athlete’s weight-bearing capability, flexibility, range of motion, strength and
proprioception to normal
• To enable that athlete to participate comfortably and fully in all pre-injury activities

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General approach
• R – Rest the injured part
• I – Ice application to the injured part for 15 to 20 minute ≥4 x/day for the 48 hours or longer.
• C – Compress the injured part with elastic bandage if there is swelling.
• E – Elevation
• Other injuries requiring immediate medical attention eye, head, and nosebleed.
• Along with the R-I-C-E therapy ASA or NSAIDs could be used for short period for pain and
swelling.
• Note. A patient with DVT and injury should not follow the full “RICE Therapy” because ice
and compression could lead to stasis hence rests and elevation of limb would be options for
such kind of patient.

Pressure Ulcers. Also known as decubitus ulcers (rectal ulcer)

Ulcer care.
• Wound debridement, wound cleansing and dressing of wound.
• Note that for wound cleansing, antiseptic agents/hydrogen peroxide and other wound
cleaners may be toxic to the wound and should be avoided.
• Cleansing or irrigation of wound should be done with normal saline.

Multiple sclerosis
Immunomodulators. Glatiramer, interferon beta1a, interferon beta 1b, fingolimod (spingosine-
1-phosphate receptor agonist), dimethyl fumerate.
Adhesion molecule inh. Natalizumab
Anti-CD52 monocolonal antibody. Alemtuzumab

Tips
1. Propranolol 2 NSAIDS or 3 Triptans, alternatively
Acetaminophen ergot alkaloids
Avoid prolong bed 5. Throbbing pain; feels 6 Unilateral
4. rest hitting w/ a hammer headache
7 Nausea & vomiting 8. 5HT1 b/1d agonist 9 R-I-C-E
10 Amitriptyline 11 Valproic acid 12 Verapamil

• What are the symptoms of migraine headache

• What is drug of choice for acute migraine attack
• What are the drugs used to treat migraine prophylaxis -->
• What is prophylaxis is recommended for migraine in-patient experiencing 3 to 4 migraine
attacks every month and having constipation 
• What is mechanism of action of triptans 
• General approach for sports injuries ( )
• What drugs are used for migraine prophylaxis? ( )
• What are recommended self measures for back pain? ( )
• What is the treatment for back pain? ( )
• Migraine pain is? ( )
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• Pressure ulcers also known as 

• Mechanism of muscle relaxants 
• Drugs used in multiple sclerosis 

Select True or False statements

• A 45 yo man diagnosed with benign prostatic hyperplasia, and migraine prophylaxis.
Propranolol appropriate therapy for migraine prophylaxis?
• after taking sumatriptan migraine headache does not relieve than double the dose of
sumatriptan
• after taking sumatriptan migraine headache does not relieve than decrease the dose of
sumatriptan
• after taking sumatriptan migraine headache does not relieve than do not use sumatriptan

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74
Asthma and COPD

Questions Alerts!
Common questions in pharmacy exam is to ask!
• Asthma triggers
• Mild, Moderate and Severe asthma therapy
• Theophylline drug interaction
• Predniosone side effects and dose tapering
Asthma. Chronic inflammatory disorder of the airways, ↑ airways responsiveness, causes
reversible obstruction. In asthma esinophils, mast cells and T lymphocytes plays significant role.
Sensitivity, and hypersensitive of airways to specific and non specific stimuli, such as air, odour,
allergens, virus etc.

Fig 72.1

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Diagnosis.
Spirometer (preferable method of diagnosis).
Peak flow meter (home monitoring)
bronchoprovocation challege test, using methanacholine or histamine if diagnosis is in doubt.

Sequence of asthma therapy SABA prn  ICS  LABA  LTRA PO CTS  iv CTS.

Beta 2 Adrenergic Agonist

MOA: beta 2 stimulation causes increase camp in smooth muscle leading to bronchodilation

Short acting beta 2 agonist (SABA)

• Inhaled: Albuterol (salbutamol), terbutaline, isoproterenol
• Onset within 5 min
• TU: relieve branchoconstriction, the acute symptoms of cough, wheezing and chest
tightness, asthma emergencies and exercise induced asthma.
• SE: Tremors, nervousness, weakness, flushing of face or skin, nausea and vomiting
• Regular use can lead to decline in lung function.
Oral Beta 2 agonist: Albuterol (salbutamol), and Terbutaline
More SE and less bronchodilation effect than inhaled preparations

Long acting beta2 agonist (LABA)

• Inhaled: Formoterol (full B 2 agonist), salmeterol (partial agonist)
• Onset: 14 min and duration upto 24 hours. Regular BID treatment
• TU: Maintenance therapy and exercise induced asthma NOT for acute. Used in patients
already taking corticosteroids
• Formoterol can be used for acute and maintenance

Anticholinergic: Ipratropium bromide: useful as alternative for patients who are already
susceptible to tremors or tachycardia from B 2 agonist
Tiotropium is long acting anticholinergic once daily, it is administered by handihaler

Corticosteroids
• ICS: Benefit ↑ lung function, ↓ airway hyperreponsiveness, ↓ symptoms of excerbations
• Max clinical effects in 2 to 4 wks. Fluticasone in few days
• Given 2 to 4 pf BID
• SE: oral pharangeal candidiasis, dysphonea from vocal cord myopathy, and cough
• Mouth rinsing and using spacer can minimize SE,

Oral corticosteroids (Po CST)

TU: Severe asthma with intensive airway inflammation

Leukotriene antagonist. Montelukast and Zafirlukast

• Only oral available
• TU: Asthma maintenance (steroid sparing agents), and ASA induced asthma

Chronic Obstructive Pulmonary Diseases

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COPD: Chronic obstructive pulmonary diseases; COPD is due to chronic obstruction of the
airway. There are two types of COPD.
• Emphysema (high altitude sickness)
• Chronic bronchitis.

Emphysema is a disease in which the small air exchange sacs (alveoli) in the lungs become
permanently enlarged and damaged (alveoli walls destroyed) thus decreasing oxygen absorption
and resulting in shortness of breathe.

Chronic bronchitis is an inflammation of the airways that causes lungs to produce excessive
amounts of mucus (phlegm), associated with chronic productive cough. This reduces the flow of
air to the lungs. Onset age 45 years.
Risk factors that cause COPD:
• Smoking (80 to 90%)
• Family history
• Occupational exposures to certain ducts and fumes
• Air pollution
• Second hand smoking
• Asthma

Diagnosis. spirometer, peak flow meter, bronchoprovocation.

alpha1-antitrypsin level - for family history of COPD
Chest X-ray
pulse oximetry+/- arterial blood gas

Recommend: flu vaccine (annually) and Pneumococcal vaccine

Treatment sequence for COPD?

SABD --> LABD --> Theophylline --> oral steroids or antibiotics

Drug used for the treatment of COPD

o Anticholinergics: Ipratropium (Atrovent) and tiotropium (Spiriva). It is a
muscarinic blocker and acts as bronchodilator
• Beta adrenergic agonists
• Corticosteroids
• Theophylline
• Antibiotics. Doxycyclin, azithromycin, and amoxicillin

References. Allergens, Asthma Information Association (www.aaia.ca)

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Tips
1. Salbutamol 2. short acting beta2 agonist 3. Terbutaline
4. Corticosteroids 5. 5Prednisone/ 6. Zafirlukast
Prednisolone
7. Theophylline 8. Diphenhydramine 9. Codeine
10. Ephedrine 11 Cromolyn sodium 12 Ipratropium bromide
13. Exercise 14 Emotional stress 15 Cold air
16. montelukast

• Triggers of asthma ( ), not: air conditioner, hot air.

• Rescue medications or treatment of acute exacerbations and prevention of exercise-induced
asthma ( )
• It relieves the symptoms of asthma, chronic bronchitis and emphysema ( )
• It may interact with MAOIs and cause a dangerous rise in blood pressure ( )
• Rinsing mouth and using spacer can minimize the side effect of this drug ( )
• It is use for the treatment of skin diseases, rheumatic disorders and certain blood disorders (
)
• It is the drug of choice for Aspirin induced asthma ( )
• This drug should be use with caution in patients with peptic ulcer and seizure diseases ( )
• It is a non narcotic antitussive ( )
• What narcotic antitussive that causes addiction and tolerance ( )
• What causes slight increase in blood pressure and has both alpha and beta effects ( )
• What is use for prophylactic treatment and not used for acute asthma attack ( )
• What is the drug of choice for chronic obstructive pulmonary disease ( )
• Indications of short acting beta 2 agonists include 
• Indications of long acting beta 2 agonist include 
• Sequence of asthma therapy: SABA prn 
• When LABA are initiated in asthma patient? 
• What are asthma triggers? 
• What is NOT a trigger? 
• Leukotrienea are
• Theophylline clearance in 3 year old? 
• Omalizumab is? 

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www.pharmacyprep.com Smoking cessation

75
Smoking Cessation
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Nicotine withdrawal and overdose symptoms
• Bupropion mechanism and side effects
• Varenicline (Champix) mechanism and side effects.

Pharmacological aids to smoking cessation

Nicotine Replacement Therapy (NRT) Other Therapy

Nicotine gum Nicotine patch Bupropion Varenicline

Nicorette Nicoderm or (Zyban) (Champix)
Nicorette plus Habitrol
Nicotine inhaler

Nicotine withdrawal symptoms. Severe craving, anxiety or irritability, restlessness, nervousness,

difficulty with concentration. Sleep disturbance, headaches, increase appetite (weight gain) or eating
habit and constipation.

Nicotine overdose symptoms. Palpitation (heart racing), difficulty in breathing, nausea, vomiting, and
diarrhea.

Drug of choice
• Bupropion could be used with or without nicotine replacement therapy.
• Nicotine inhaler is contraindicated if allergy to nicotine or menthol. Use with caution in
patients with bronchospastic disease.
• If patient has CVS disease, weight less than 45 kg, or smokes less than ½ pack/day begin with
17 to 24 for 6 weeks then decrease to 7 mg/24h for 2 weeks.

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• NICOTINE BASED: Nicotine patch or gun; Stop smoking completely.

• NON-NICOTINE BASE: Bupropion (Zyban); Can smoke for first two weeks of treatment.

Nicotine replacement therapy

• Almost every smoker can benefit from using nicotine replacement therapy. In pregnancy and
heart or blood vessel problems, its use requires precaution.
• The nicotine replacement therapy available in patch, gum, nasal spray and inhaler forms.

Nicotine Patch
• Most smokers should start using a full-strength patch (15 to 22 mg of nicotine) every day for 4
weeks and then a weaker patch (5 to 14 mg of nicotine) for another 4 weeks.
• Directions for use. At the start of each day, place a new patch on a part of your body between
the neck and the waist. Put the patch on a new spot each day to lessen skin irritation.
• Treatment period. The patch is usually used for up to 8 weeks.
• Side effects. Some people who use the patch get a rash on their body where the patch is
placed. Skin rashes are usually mild and easily treated. Moving the patch to another area of
the body helps.

Nicotine Gum
• Start using the 2 mg dose. However, start with 4 mg gum if you smoke more than 20 cigarettes a
day.
• Use gum if you smoke as soon as you wake up in the morning.
• Have severe withdrawal symptoms when you don't smoke.
• Have tried to quit on a lower dose and failed.
• If you are a very light smoker (less than 10 to 15 cigarettes a day)

Directions for use.

• The gum must be chewed in a special way to make it work. Chew it slowly until you feel a
"peppery" taste. Then stop chewing and move the nicotine gum between your cheek and your
gum. Each piece of nicotine gum should be kept in your mouth for about 30 minutes.

Treatment period.
• A regular schedule (at least one piece of nicotine gum every 1 to 2 hours for 1 to 3 months)
may give the best results. Some people don't chew enough pieces of gum a day and or they
don't chew the gum for 8 weeks. They might not get the most benefit from nicotine gum.
• Maximum 6 months
Side effects: mild side effects such as hiccups, stomach upset or sore jaws. Most of these side
effects disappear if the gum is used correctly.
Nicotine Nasal Spray
• Directions for use: Apply one spray in each nostril. Use the spray one to two times each hour
while you are awake. Use the spray at least 8 times a day. Don't use it more than 40 times a
day.
Side Effects:
• The nasal spray may cause nasal irritation, diarrhea and a fast heart rate. If you have hay fever
or sinus infection.

Nicotine inhaler
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• Directions for use: Inhale from a cartridge when you have a desire for a cigarette. Use no more
than 16 cartridges a day for up to 12 weeks.
Side Effects:
• You might have irritation of throat and mouth when you first start to use the inhaler. It might
make you cough. You should get over this after a while.

Nicotine lozenges: available

Bupropion (Zyban)
• 150 mg daily x 3 days than 150 mg BID for 7 to 12 weeks.
• Begin 1 to 2 weeks before the selected quid date.
• Monitor in hypertensive patients
Contraindicated in:
• Pregnancy
• History of seizure
• Anorexia nervosa
• Bulimia nervosa
• Precaution in taking MAOi’s
Side effects
• More common. Dry mouth, and insomnia. Less common, hypertension, myalgia, arthralgia,
dizziness, tremor, somnolence, bronchitis, pruritus, rash, and taste prevention

Varenicline (Champix)
• Mechanism of action. Act on nicotinic receptors.
• It is partial agonist that binds selectively to alpha4, beta 2, nicotinic acetylcholine receptors with a
greater affinity than nicotine .

• Used in combination with quit smoking and education.

• Helps to relieve the craving and withdrawal symptoms associated with stopping smoking.
• This drug works by affecting nicotine receptors (acts like a weaker version of nicotine receptors
and also blocks nicotine receptors.
• Starting dose is 0.5 mg once daily for the first 3 days, then 0.5 mg bid for next 3 days and then 1
mg bid daily thereafter. Treatment for 12 weeks. Stop smoking in 1 to 2 weeks of starting this med.
• SEs. Dizziness, drowsiness, dry mouth, flatulence (passing gas), gingivitis, headache, N&V, rash,
insomnia, unusual weakness and constipation.
• CI. Pregnancy, breastfeeding, and children.
DI. Insulin, NRT, warfarin, and theophylline. Contact doctor if constipation, abdominal pain, appetite
changes.
Symptoms to be monitored in case of nicotine withdrawal are:
• Severe craving
• Anxiety or irritability
• Restless, nervousness, difficulty with concentration
• Sleep disturbance, headaches,
• GI symptoms, Increase appetite or eating behavior
• Symptoms are peak after 24 to 72 hours of last cigarette
• Smoking is single most common preventable cause of death and disability in Canada
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Tips
1. Severe craving 2. Anxiety or irritability 3. Dry mouth
4. Insomnia 5. Restlessness 6. Nervousness
7. Difficulty with 8. Sleep disturbance 9. Headaches
concentration
10. Nicotine gum 11. Nicorette 12. Nicorette plus
13. Nicotine patch 14. Nicoderm or habitrol 15. Champix
16. Increase appetite or 17. Bupropion 18. Room temperature
eating behavior

• What drugs are used for smoking cessation? ( )

• How nicotine patches are stored? ( )
• What is incorrect about nicotine patch? ( )
• The types of nicotine dosage forms? ( )
• Nicotine replacement therapy products ( )
• NRT used in combination with quit smoking education (True/False)
• Nicotine withdrawal symptoms ( )
• This could be used with or without nicotine replacement therapy ( )
• More common side effect of bupropion ( )
• Varenicline mechanism of action ( )
• Bupropion side effects include?
• Bupropion contraindications?

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www.pharmacyprep.com Sleep Related Disorders

76
Sleep Related Disorders
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Insomnia self care (avoid exercise before bedtime)
• Benzodiazepine classification and side effects

Some examples of primary sleep related disorders:

• Insomnia (10-30%)
• Restless Leg Syndrome (2 -15%)
• Sleep Apnea (4-8%)

Insomnia Non-pharmacological Sleep hygiene

• Sleep hygiene • Keep regular sleep wake schedule for 7 days/wk.
• Relaxation exercises • Restrict sleep time to average sleep time.
• Sleep restriction and • Avoid extensive horizontal rest or daytime napping
stimulus control • Get regular exercise every day (avoid exercise before
• Aerobic exercise. decreases bedtime).
daytime rest and increase • Avoid heavy meals just before bedtime.
exercise • Do something which is boring before bedtime Avoid before
bedtime; Caffeine, alcohol, heavy meals, hungry. Minimize
noise and light, high temperatures. Minimize drinking
fluids. Avoid vigorous exercise 2-3 hours before bed.

Non prescription therapy Prescription therapy

• Diphenhydramine • Benzodiazepines
• Valerian • Barbiturates
• Melatonin • Antidepressants (TCA’s)
• Chloral hydrate

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Restless leg syndrome: Desire to move limbs (creepy crawly sensation, itchy, aching feeling, crampy
and painful) with motor restlessness, worse at rest, temporary relief by activity, and worse at night.
Diagnosis based on periodic limb movement (PLMS). Rule out; iron deficiency, peripheral neurapthy,
Akathisia (drug induced or positional): peripheral neuropathy, nocturnal leg cramps.
Treatment:
Dopamine agonist; ropinirole (D 2 agonist) 0.5-3 mg; pramipexole (D 2 and D 3 agonist) 0.12 -0.15 mg.
Bromocriptine 5 to 20 mg
Levodopa-carbidopa 25 to 400 mg
Opioids, benzodiazepines, gabapentin, carbamazepine, clonidine, beclofen, Vitamin B12 and folate.

Sleep apnea: Cessation of breathing lasting at least 10 seconds with desaturations and arousals.
Symptoms are snoring, gasping for air, stopping breathing at night, memory complaints, irritability,
depression, morning headaches, sexual problems, restless sleep, and sedation or tiredness during the
day.
Treatment: CPAP
Tips
1 Temazepam 2. Short acting 3 Lorazepam
4 Midazolam 5. Zopiclone 6 Oxazepam
7 Diazepam 8. Triazolam 9 Exercise before bed

• What benzodiazepine is indicated for initiating sleep? ( )

• What drug may cause less rebound on withdrawal? ( )
• What is inappropriate self care measure ( )

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www.pharmacyprep.com Eating Disorders

77
Eating Disorders
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Definitions of bulimia (loves to eat then purge) and anorexia (fear of eating) nervosa.
• Drug related problems orlistat

Anorexia Nervosa. It is characterized by deliberate loss of weight (to <85% of expected weight), refusal
to maintain normal body weight, fear of weight gain and amenorrhea.
There are 2 sub types. Restricting, non purging, excessive exercise or fasting.
Drug of choice is domperidone, metoclopramide reduce the feeling of fullness.

Bulimia Nervosa. It is characterized by repeated episodes of binge eating followed by inappropriate

compensatory behavior such as self-induced vomiting, misuse of laxatives, diuretics, emetics, other
medication, long time fasting, or excessive exercise.
There are two subtypes. Purging by using laxatives, or emetics. DOC is SSRI, and venlafaxine

Medications. Appetite suppressant. Diethyl propion , Bupropion .

Satiety enhancers
• Sibutramine (Meridia). Serotonin and norepinephrine reuptake inhibitor (SNRI)
• Lipase inhibitor. Orlistat (Xenical): Gastric lipase inhibitor reduces 30% fat absorption

Cannabinoid type 1 receptor antagonist.

• Rimonabant: Blocks the central and peripheral effects of the endocannabinoid system mediated by
cannabinoid (CB)-1 receptors.
Drugs that are used for weight loss Drugs that give anorexia (loss of appetite)
therapy
Orlistat Metformin
Sibutramine Amiodarone
Bupropion CNS stimulants (amphetamine and
Topiramate methylphenidate)
Drugs that increase appetite Drugs that cause weight gain
TCAs Insulin
Corticosteroids TCAs
Oral contraceptives MAOI
Sulfonylurea's Antipsychotics
Sulfonylurea's
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Meglitinides

Tips
1. Domperidone 2. Metoclopramide 3. Orlistat
4. Anorexia nervosa 5. Bulimia nervosa 6. Purging
7. Non purging 8. Loves to eat 9. Fear of eating

• It is characterized by deliberate loss of weight ( )

• Excessive exercise or fasting ( )
• Reduce the feeling of fullness ( )
• It is characterized by repeated episodes of binge eating ( )
• Intestinal lipase inhibitor ( )
• Using laxatives or emetics ( )
• What type of eating disorder patient use purging? ( )
• Bulimia nervosa =
• Anorexia nervosa =

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www.PharmacyPrep.Com GERD, Ulcers, IBD, and IBS

78
GERD, Ulcers, Inflammatory
Bowel Disease, Irritable Bowel
Syndrome
Questions Alerts!
Common questions in pharmacy exam is to ask!
• GERD symptoms and heart burn management
• Ulcers: causes and triple therapy to treat H.pylori ulcer
• Ulcerative colitis and Crohns disease treatement
• Irritable bowel syndrome symptoms

This chapter review the symptoms and therapy of gastroesophageal reflux disease (GERD),
ulcers, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD).

Gastroesophageal Reflux Disease. It is defined as (heart burn, regurgitation) chronic symptoms

or mucosal damage produced by the abnormal reflux of gastric content into the esophagus.

Risk factors. High fat meal, carbonated drinks, pregnancy, obesity and increase age.

Symptoms. Heartburn (pyrosis), it is a substernal burning or pain that may radiate to the neck,
back, or throat. Symptoms occur shortly after meals or when reclining after meals, or upon lying
down at bedtime. Often symptoms may awaken one’s sleep. Symptoms are exacerbated by
eating a large meal (high fat meals), and bending over.

Nonpharmacological measures
• Quit smoking & reduce alcohol and caffeine intake
• Take smaller, more frequent meals (avoid high fat and spicy foods)
• Avoid exercising/bending on full stomach
• Avoid tight fitting clothes around the waist
• Elevate head of bed 10 cm high
• Avoid lying down after meal
**Refer to the physician if symptoms are more than 2 weeks
Avoid smoking and limit alcohol and caffeine intake.

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Gastroesophageal reflux disease is categorized into mild and severe.

• Mild GERD, relief of symptoms is with antacids, alginates or non-prescription strength H 2 RA.
• Severe GERD PPI are the drug of choice. Use PPI for 2 to 4 weeks
• The goal is to raise the intragastric pH 4 during periods when reflux is likely to occur.

Pharmacologic treatment. Symptom control for minor or intermittent symptoms use antacid
alginic acid, or H 2 RA. Moderate to severe GERD use PPI, H 2 RA, or metoclopramide.
• Food induced GERD, drug of choice is H 2 RA
• Special populations: Pediatric. Non prescription H2 RA are CI. in children <12 yrs old
• Pregnant can be used antacids, except sodium bicarbonate
• Elderly. Can use antacids and non prescription H 2 RA

Antacids: Al hydroxide, Ca carbonate, and Mg hydroxide and Na bicarbonate

• Al hydroxide SEs constipation and hypophosphatemia (in prolonged use)
• Ca carbonate SEs constipation, milk alkali syndrome (hypercalcemia); causes rebound
hyperacidity.
• Mg hydroxide SEs diarrhea and hypermagnesia (in renal failure)
• Shake or chew well; quick acting with cathartic effect. Should be avoided in renal failure and
limited use in elderly due to risk of hypermanesemia.
• Al-Mg combination products, SE; diarrhea (in long term use)
• Na bicarbonate: Not often used because of sodium can be hypertensive.
• All antacids have drug interactions with quinolones, tetracycline, digoxin separate dosing by
2 hours.

Alginic acid: It works as foaming agent. Tablets must be chewed with full glass of water taken
when patient is in upright position. Should not be taken at bedtime.

Prokinetic agent: Metoclopramide and domperidone

H 2 - receptor antagonists (H 2 RA): cimetidine, ranitidine (Zantac), famotidine (Pepcid), nizatidine

(Axid)
• equally effective: usually effective in mild GERD, BID
• the efficacy is limited by the rapid development of tachyphylaxis & the inability to properly
suppress meal-related acid secretion.
• Step-down therapy: H 2 RAs are instituted after symptomatic relief has been achieved with
PPIs
• SE: diarrhea, constipation, headache
• Cimetidine SE: gynecomastia, impotence (rare)
• Famotidine; potent
• DI: Ranitidine: decrease clearance of theophylline, phenytoin and warfarin Cimetidine;
CYP450 inhibitors,
• Use H 2 RAs to reduce the “night-time awakening” caused by GERD

Proton pump inhibitors (PPI): omeprazole (Losex capsules, MUPS, tablets), esomeprazole
(Nexium), lansoprazole (Prevacid), pantoprazole (Pantoloc), rabeprazole (Pariet)
• Drug of choice in the most GERD patients
• Side effects: abdominal pain, diarrhea and headach.
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• take ½ hour before meals: the most effective acid suppression, once daily
• acid rebound occurs with discontinuation (tachyphylaxis is not a problem)
• At equivalent doses, available PPIs offer similar efficacy and safety
• DI: ↓ efficacy of drugs requiring an acid medium for absorption (ex. Itraconazole,
atazanavir, indinavir)
• Omeprazole: DI; Omeprazole may decrease metabolism of warfarin, diazepam and
phenytoin (require dosage adjustment), and clopidogrel
• Esomeprazole; may confer a modest advantage over other agents for severe erosive
esophagitis
• Pantoprazole; rapid onset
• Rabeprazole; ↑digoxin level

Ulcers. or dyspepsia (pain and discomfort in the upper abdomen) GI bleeding.

Ulcers are categorized based on their of ulcers such as:
Peptic ulcers
• Gastric ulcers. Due to reflux since it has weak pyloric sphincter
• Duodenal ulcers. Excessive acid secretion from parietal cells
• Acute stress ulcers (Curling’s ulcer). Tumors.
• Pathologic acid-hypersecretory states (Zollinger-Ellison syndrome).
• Chronic peptic ulcer disease is the most commonly caused by H. pylori.

Symptoms. Epigastric pain occurring 1 to 3 hours after meals that is relieved by ingestion of food
or antacids is classic symptoms of peptic ulcer disease. Pain can occur and episodes lasting from
weeks to months and may be followed by variable periods of spontaneous remission and
reuccarence.
Diagnostic for gastric ulcer, or duodenal ulcer is EGD (esophagogastroduodenoscopy)

Treatment of peptic ulcers

• For neutralization of gastric acid use antacids
• To reduction of gastric secretion use H 2 receptor blocker, and proton pump inhibitors
• For cytoprotection use sucralfate. For ASA/NSAIDs use prevention with PPI or misoprostol

Treatment of peptic ulcer disease due to H.pylori infection.

H.pylori confirmation test is urea breath test (UBT)

• To eradicate Helicobacter pylori use triple therapy of 2 antibiotics + PPI

• Triple therapy 2 antibiotics + 1 PPI
• Losec 1-2-3 A. Clarithromycin 500 mg bid + omeprazole +amoxicillin
• Losec 1-2-3 M. Clarithromycin 250 mg bid+ omeprazole + metronidazole
• Quadruple therapy. Tetracycline+ metronidazole + bismuth subsalicylate + Omeprazole
Choose the alternative: Omeprazole + metronidazole + clarithromycinLosec 1-2-3M
• If patient is allergic to amoxicillin or if patient is having diarrhea or if patient is more prone
to having anaerobic infection

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Gastritis. The gastric ulcers are associated with a corpus predominant (diffuse predominant)
gastritis. This pattern gastritis is associated with low acid output, gastric atropy, and
adenocarcinoma.

Inflammatory Bowel Disease. Consist of two conditions ulcerative colitis and Crohn’s. The
ulcerative colitis mainly colon and chrons disease in all over GI tract.

Causes of inflamatory bowel disease:

• Infection with Mycobacterium and other pathogens
• Genetic factors
• Environmental conditions
• Non-pathogenic intestinal flora

Crohn’s disease. Inflammation is present from the esophagus to the anus but predominantly in
the small bowel or colon. Obstruction of the bowel abscess formation.

Drug of choice to treat mild Crohn's disease 5ASA or oral budosenide.

Drug of choice moderate oral budosenide and severe iv steroid
Drug of choice to treat fistula? Azathioprine or 6-MP

Drug of choice to treat NO remission (not cured) from initial therapy? AZA, 6MP, or MTX and in
severe biologics (infliximab, adalimumab, cetrolizumab).

The prednisone dose is tapered once stabilized on oral prednisone (12-16 wks).

Ulcerative colitis. Relapsing inflammatory condition in the colon with symptoms of bleeding,
urgency, diarrhea and tenesmus.
• Erosion and ulceration of the mucosa
• Decrease in the number of goblet cells
• Frequent infection secondary to fever and anemia
• Drug of choice in mild to moderate is 5-ASA
• Drug of choice in severe ulcers is oral prednisone

Aminosalicylates. Sulfasalazine and 5-ASA.

• Sulfasalazine metabolized to sulfapyridine + 5-ASA (mesalamine)
• Sulfpyridine has systemic absorption and is responsible for SE’s N/V, headache, anorexia,
and folate malabsorption.
• Sulfa free compounds. Mesalamine (5-ASA), olsalazine (two molecules of 5-ASA linked to
diazo bond).
• The side effects experienced with mesalazine and olsalazine are less then sulfasalazine

Irritable Bowel Syndrome. It is defined as abdominal discomfort associated with altered bowel
habits. It is characterized by symptoms of abdominal discomfort, bloating, cramping,
constipation or diarrhea.

Non pharmacological therapy

• Regulating dietary fibre and lactose intake.

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• Stress management.
• Probiotics may help.

Pharmacological treatment
• Dicyclomine. It has anticholinergic side effects
• Loperamide: Used for diarrhea
• Magnesium hydroxide: Used for heartburn
• Lactulose. Used for constipation
• Psyllium.Bulk laxative
• Cholestyramine: For patients with bile salts malabsorption

Tips
1. High fat meal/ 2. pregnancy 3. increase age
carbonated drinks
4. obesity 5. Al antacids 6. Mg antacids
7. Ca antacids 8. Alginic acid 9. Sucralfate
10. Famotidine 11. Cimetidine 12. Omeprazole
13. Esomeprazole 14. Lansoprazole 15. Pantoprazole, Rabeprazole
16. Misoprostol 17. GERD 18. IBS
19. H. pylori 20. Ulcerative colitis 21. Chrons
22. 5-ASA 23. Prednisone 24. Infliximab
25. Ulcers 26. Colon 27. Simethicone

• Triggers of heartburn or GERD ( )

• Symptoms are heartburn, epigastric pain ( )
• It is defined as abdominal discomfort associated with altered bowel habits. It is
characterized by symptoms of abdominal discomfort, bloating, cramping, constipation or
diarrhea. ( )
• Symptoms are relapsing inflammatory condition in the colon with signs of bleeding, urgency,
diarrhea and tenesmus. ( )
• Symptoms of inflammation is present from the esophagus to the anus but predominantly in
the small bowel or colon. Obstruction of the bowel abscess formation. ( )
• Takes ½ hour before meals; the most effective acid suppression, once daily ( )
• Gram negative bacteria that cause gastric ulcer ( )
• Active metabolite of sulfasalazine ( )
• What is an antiflatulence agent ( )
• What antacids may gives the side effect of diarrhea (Mg = must go) ( )
• Gives the side effect of constipation ( )
• Isomer of omeprazole ( )
• Gives rare side effects as gynecomastia, impotence ( )
• Do not take with ciprofloxacin, tetracycline, biphosphonates and thyroxin ( )
• Has rapid onset proton pump inhibitors ( )
• Decrease efficacy of drugs requiring an acid medium for absorption ( )
• Usually effective in mild GERD, as BID ( )

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• Step down therapy; are instituted after symptomatic relief has been achieved with PPIs (
)
• Lactulose is used in what type of chronic liver disorder 
• An example of ecosanide is ( )
• Misoprostol is analogue of 
• Type of pain in GERD is
• Increase in bilirubin causes 
• What are the side effects of aluminum salts 
• What are the side effects magnesium antacids 
• H. pylori will cause 
• What type of hepatitis is chronic 
• What is treatment of hepatitis B, or C? 
• NSAIDs induced ulcers can be treated by
• Independent risk factors for peptic ulcers are: H.pylori and NSAIDs (True/False)
• Epsom salt is? 
• Ulcerative colitis occurs at? 
• Antiflatulance agent? 
• What vaccine can be used for traveler’s diarrhea (E.coli, cholera)? 
• Symptoms of ulcers?
• Symptoms of irritable bowel syndrome (IBS)? 
• Symptoms of ulcerative colitis? 
• Symptoms of Crohn’s disease? 

Select TRUE OR FALSE Statement

• Na bicarbonate is contraindicated in patient with hypertension, CHF, severe renal disease,
and edema. This also contraindicated in ulcers. (True/False)
• CaCO 3 antacids have rebound acidity due to stimulation of acid secretion. (True/False)
• CaCO 3 antacids should be avoided in hypercalcemia patients. (True/False)
• Hypophosphetemia and osteomalacia can occur with long-term use of aluminum containing
antacids. (True/False)
• Antacids bind with tetracyclins, and fluroquinolone and reduce their absorption.
• Antacids may destroy coating of enteric-coated drugs. (True/False)
• Mg antacids can cause cathartic side effects. (True/False)
• Zollinger-Ellison syndrome: Gastric hypersecretory states in systemic mastocytosis which is a
rare disorder with increase number of mast cells systematically and in skin.
• H. pylori: bacteria that cause gastric ulcer (True/False)

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79
Insulin and Antidiabetic Drugs
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Long actin Insulin (glargine)
• Insulin dose management
• Long acting sulfanyl ureas such glyburide, gliclazide and glimepride.
• Metformin side effects like stomach upset and rare SEs lactic acidosis
• Sitagliptine and saxigliptine is DPP4-inhibitor
• Rosiglitazone cardiovascular side effects
• Incretin hormone analogs like Liraglutide
• Acarbose mechanism

This chapter review of insulin therapy for diabetes mellitus and antidiabetic drug for the
treatment of type II diabetes.

Diabetes mellitis, type I and type II.

Type I. Insulin dependent DM (IDDM) 5 to10% Type II. Non-insulin dependent DM (NIDDM) >90%
Juvenile onset Adult onset (40 yrs)
Destruction of beta-cells in pancreas Milder form
No production of insulin associated with Very strong genetic predisposition
treatment is by diet and insulin. Inability of beta cells to produce adequate insulin
Ketoacidosis occurs and doesn’t meet the body’s requirements.
Mainly due insulin resistance
Family history related or genetic

Normal Blood Sugar Levels (BSL)

• Fasting BSL 5 to 6 mmol/L
• Random BSL <11.1 mmol/L
• Post prandial <11.0 mmol/L
• HbA1C is 4 to 6%
• Measures past three months blood sugar levels
• Used to determine antidiabetic drugs compliance of patient

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Types of Insulin

Ultra rapid Rapid Intermediate Long-acting

Insulin lispro Regular NPH Glargine

Detemir

Types of insulin are categorized by their onset of action, and these relative positions hold true
for their effectiveness and their duration of action as well.
Insulin Duration Onset Peak (hours) Duration of
(hours) Action (hours)
Humalog (H) (lispro) Very short 5-10 30-40 min 2-3 h
synthetic (Fastest) min
SC or iv form
Clear solution
Regular (R) Rapid (short) ½ -1 h 1-3 h 5-7 (dose-
(suitable for iv dose). Both SC or iv (in dependent;
human and animal source emergencies) may be longer)
clear solution
NPH (N) Isophane Intermediate 2-4 h 6-10 h 14-18 h
Amorphous precipitate of Semilente (30%) not suitable for
insulin with zinc ion acetate iv dose
buffer
Ultralente Long (70%) 4-5 h - 18-28 h
Zinc suspension crystals in Slowest onset of
acetate buffer contain large action but Longest
particles that are slow hypoglycemic
dissolve effect.
Glargine Longest acting Should not be
Detemir Single daily dose mixed with
other insulins.

Insulin SE: Weight gain and hypoglycemia, lipohypertrophy at site of injections.

Very Rapid-acting Insulin Analogues: clear

• insulin aspart (NovoRapid)
• insulin glulisine (Apidra)
• insulin lispro (Humalog)

Rapid-acting Human Insulin-clear

• insulin regular (HumulinR, Novoline ge Toronto)
Intermediate-acting Human Insulin– cloudy
• insulin NPH (Humulin N, Novoin ge NPH)

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Long-acting Insulin Analogues: clear

• Clear, don’t mix with other insulins, duration 24 hr (no discernible peak)
• insulin detemir (Levemir)
• Insulin glargine (Lantus); acidic solution (pH4), microprecipitates form (slowly released), NO
im or iv.
Mixed (regular/NPH) Human Insulin– cloudy
• insulin regular/insulin NPH (Humulin 20/80, 30/70), Novolin qe 10/90, 20/80, 30/70,
40/60,50/50)

Mixed Insulin Analogues– cloudy

• insulin lispro/lispro protamine (Humalog Mix25)

Insulin storage conditions

• Should be stored in refrigerator
• Can be stored at room temperature 28 days (1 month)
• Do not shake vigorously
• If you notice turbidity or vapors or precipitation, do not use, discard it
•
Oral antidiabetic drugs

Sulfonylureas; Chlorpropamide, gliclazide (Diamicron), gliclazide long-acting (Diamicron MR),

glimepiride (Amaryl), glyburide (Diabeta), tolbutamide
• MOA: Stimulate release of endogenous insulin thus increase insulin secretions.
• SE: hypoglycemia and weight gain avoid obese or over weight patients
• Avoid in sulfa allergies
• CI: pregnancy
• SEs : hypoglycaemia, weight ↑
• Chlorpropamide; dose adjustment in real impairment, once daily long half life
Associated with disulfiram reaction with alcohol may give nausea, vomiting, headache,
flushing upon ingestion of alcohol. SIADH (Syndrome of Inappropiate antidiuretic hormone)
this leads to edema.
• SE: alcohol-associated flushing, and ↓Na.
• gliclazide – produce an earlier insulin release than others.
• gliclazide long-acting – once daily
• glimepiride (Amaryl) – once daily
• glyburide (Diabeta) - dose adjustment in real impairment, lowest risk of cardiovascular
events and high hypoglycemia.

Meglitinides: Nateglinide (Starlix), repaglinide (GlucoNorm)

• MOA: Increase insulin secretions, Decrease post prandial blood glucose levels
• SE: hypoglycemia and weight gain, hypoglycaemia (esp. if not take meal). CI: pregnancy
• May be taken prior to meals (skip dose if you miss meals)  take at first bite of meals
• take 0 to 30min before meal → lowering postprandial glucose levels
• Repaglinide – DI: gemifibrozil (↑repaglinide conc. - avoid)

Biguanides: metformin (Glucophage)

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• MOA: Reduce gluconeogenesis, and increase glucose utilization, Increase glucose uptake
into cells
• SE: Less common but more serious SE is lactic acidosis. No hypoglycemia, can give weight
loss. To avoid GI SEs, start low & titrate up q2-4wk.
• Dose adjustment in real impairment, SE: lactic acidosis, diarrhea (most), VB 12 ↓
• ONLY oral, NO weight↑ → good for obese patient, NO hypoglycaemia on its own. Take with
food or after food
• DI: alcohol (potentiates hypoglycemic effect)
• CI: hepatic impairment, renal impairment, CHF, hypoxemic states patient
• Caution if CrCl 60 ml/min
• Decrease mortality
• Does not cause sulfa allergy

Alpha-glucosidase Inhibitors: acarbose (Glucobay)

• MOA: Inhibit alpha glycosidase intestinal enzymes
• Decrease absorption of starch and sucrose (do not stop absorption of glucose)
• Decreases the postprandial plasma glucose level
• SEs: It causes bloating and flatulence and diarrhea
• With meal, not used as monotherapy.
• Meal-time dosing; may take several weeks for maximum effect. Taken with the first bite of
food.
• Maximal effect takes weeks↑ dose q4-8wks
• Sulphanilureas + acarbose
• Does not by itself cause hypoglycemia
• GI intolerance: flatulence >41%, diarrhea >28%, sucrose not absorbed.

Thiazolidinediones (TZDs). Pioglitazone (Actos), and rosiglitazone (Avandia)

rosiglitazone/glimepiride (Avandaryl), metformin (Avandamet)
• MOA. PPAR-γ receptors agonist. Increase peripheral insulin sensitivity, and reduce
gluconeogenesis.
• Effective in lowering HbA1C
• CIs. Liver disease, and CHF
• SE: Wt↑(most), fluid retention edema 4.8% (HF; HTN). ↑Weight, anemia ~1% mild
↑ HDL, NO hypoglycaemia on its own.
• DI: gemifibrozil (↑repaglinide conc. avoid). CI. CHF pts, can use renal impairment pts
• ↑ risk of pregnancy if adequate contraception not used (ovulation resumes)
• NO use with insulin (not approved by health Canada)
• Pioglitazone. ↓ TG, have more +ve lipid effect. More DI than roziglitazone
• Mon: If baseline ALT is elevated (>2.5 times normal), do not use glitazones
• Rosiglitazone. ↑ LDL Decrease TG, Increase HDL, Once daily with or without food
• Monitor liver function (ALT) when indicated;
• Delayed action… Onset ~2-4wks Max effect in 8-16 wks.
• Rosiglitazone / metformin – associated with overall lower glucose & HbA1c

Dipeptidyl peptidase-4 Inhibitors (DPP-4). Sitagliptin (Januvia), and saxigliptine

MOA. Inhibitor of dipeptidyl peptidase enzyme (DPP-4) that enhances the incretin hormone
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• SEs. Nasopharyngitis DIs. low potential (do not inhibit CYP450), can cause hypoglycemia
with sulfonyl ureas.
• Take with metformin, with or without food, do NOT potentiate hypoglycaemia.
• 100 mg once daily taken with or without food.
• Not used in type I diabetes, there is no clinical studies.

Incretin analogs. Glucagon Like-Peptide 1 (GLP1) agonist.

Liraglutide (Victoza). Exenatide.

Canagliflozin (Invokana). 100 mg qd, Sodium Glucose Co-transporter 2 (SGLT2) inhibitor.

SGLT2 is enzyme in the renal tubule that causes glucose reaborption back into the blood.
Therefore canagliflozin reduces the reabsorption of glucose from renal tubule leading to more
excretion of glucose in urine.

Intestinal Lipase Inhibitors. Orlistat (Xenical)

• SE: Diarrhea, steatorrhea, abdominal discomfort, and oily leakage.
• Take with food, impair absorption of fat soluble vitamins (A, D, E, K).

Tips
Tips format 002: Find answers from the table
1. FBG >7.1 mmol/L 2. HbA1c > 7.0% 3. Random >11.0
4. Polyurea 5. Polydipsea 6. weight in Kg/(height in m)2
7. Weight loss 8. Sweating 9. Palpitation
10. Rapid acting Insulin 11. Insulin regular 12. Intermediate (NPH)
13. Long acting insulin 14. Premixed insulin 15. Sulfonyl ureas 1st gen
16. Sulfonyl ureas 2nd gen 17. Meglitinides 18. Metformin
19. Thiozolidinediones 20. Acarbose 21. Incretin enhancers (DPP-4
Inhibitor)
22. Diabetic complications 23. Insulin 24. Intestinal lipase inhibitors
25. Waist line >102 cm 26. Waist line >86 cm 27. Confusion

• Act on cell membrane receptors to increase glucose uptake ( )

• Blood sugar levels if a person is diabetic ( )
• Symptoms of hyperglycemia ( )
• Symptoms of hypoglycemia ( )
• All insulins are clear solutions, except ( )
• Sitagliptine and saxigliptine are ( )
• What drug may give lactic acidosis if taken with alcohol and renal diseases, liver disease
( )
• Diabetic complications are retinopathy, nephropathy, cardiovascular diseases, and foot
amputation, except: hepatic cirrhosis ( )
• Waist line that have risk of diabetes in men ( )
• Waist line that have risk of diabetes in women ( )
• Drugs increase glucose uptake ( )
• Drugs increase insulin secretion ( )
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• Drugs that should be taken with first bite of meals ( )

• Drugs that are withdrawn due to heart failure side effects ( )
• Drug used for weight loss therapy ( )

Select True or False Statements

• A 65 yo uncontrolled diabetic patient have got foot ulcers. Patient wants to know
diabetic foot care. The pharmacist should refer this patient to Podiatrist ? (True)
• premixed insulins Used for stable lifestyle patients (True)
• premixed insulins Can be self adminstered by patient (True)
• premixed insulins Cartridges cannot be exchanged with different mixture of insulins
(True)
• premixed insulins is an expensive than insulin (True)
• premixed insulins Require insulin pen to adminster (True)

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80
Thyroid Disorders
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Symptoms of hypothyroidism and hyperthyroidism
• Monitoring of thyroxine. Serum TSH, FT3, FT4
• DI's of thyroid hormone with antacids, Ca, Fe supplements

Hypothyroidism. Symptoms that are caused by deficient thyroid hormone production, thus
resulting into slowing down of all body metabolic functions.

Types of hypothyroidism
• Primary hypothyroidism caused by thyroid gland failure.
• Hoshimoto disease. It is an autoimmune disease resulting from cell and antibody mediated
thyroid injury.
• The hyposecretion of the thyroid hormone causes myxedema, goiter and cretinism.
• Symptoms. Sensitivity to cold, constipation, bradycardia, and weight gain
• Signs. Dry flaky skin, coarse hair, slurred speech, puffy face, hands, feet, and hearing loss.
Decreased libido, slow return of deep tendon reflexes, if untreated myxedema and coma
will develop.
• Diagnosis. Initial test is serum TSH assay and TSH levels are elevated in primary
hypothyroidism and low serum free T 4 .

Pharmacotherapy. Levothyroxin (Eltroxin, Synthroid) or dessicated thyroid hormone

Thyroid hormones
• levothyroxine. T 4 dosage, 1.6 µg/kg/day (adults), 12.5 to 25 µg/day (patient with coronary
artery disease or elderly).
• Pregnancy. Dose↑ (thyroid binding globulins↑), check TSH each trimester & 4 to 6 wk after
any dosage adjustment.
• It takes 6 weeks to attain a new steady state
• Take empty stomach. Taken in morning. SEs. exacerbation of angina.

• DI. Absorption↓ by Fe, Ca, Al, Mg, sucralfate separate 2 h, cholestyramine, colestipol
(separate administration by 6 hours).
• Blood sugar control may decline with initial therapy (dosage adjustment of
antihyperglycemic agents) liothyronine, triiodothyronine (T 3 )

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• Use for short-term management of patients with thyroid cancer undergoing withdrawal of
levothyroxine (T 4 ).
• In the elderly (because of age) or in patients with coronary artery disease, start with a dose
as low as 12.5 mcg/day as tolerated and titrated every four weeks. TSH levels changes after
6 to 8 weeks.
• Iron salts, clacium and sucralfate decrease absorption of levothyroxine thus separate 2
hours. Resins like cholestyramine, cholestipol separate 6 hours. Do not take aluminium
compounds with thyroid preparations. Dessicated thyroid hormone may contain pork
proteins.

Hyperthyroidism. The hypersecretion of the thyroid hormone may cause thyrotoxicosis or

Grave’s disease and Plummer’s disease.

• Type of hyperthyroidism. The hyperthyroidism normaly is divided into two categories:

Grave’s disease or diffuse toxic goiter and toxic nodular goiter.
• Grave’s disease. The most common form of hyperthyroidism. It is an organ specific
autoimmune disorder in which antibodies produced against autoantigens stimulates the
secretion of the thyroid hormone. It may cause protrusion of the eyeballs. Hasimoto’s
disease is completely opposite, as the resultant antibodies due to autoantigens inhibit the
secretion of the thyroid hormone.
• Symptoms. Intolerance to heat, and weight loss, weakness and anxiety. Signs. heart
palpitation, nervousness, diarrhea, and tachycardia.
• Diagnosis. ↓serum TSH, (sensitive TSH) and ↑T 4 and T 3

Pharmacotherapy. Anti thyroid drugs (methimazole, propylthiouracil), and lugol solution (KI +
I 2 ).
Antithyroid Agents
• Methimazole. MMI, propylthiouracil PTU
• Stop about 5 days prior to a thyroid scan, RAIU or treatment with 131I.
• SEs. allergy, rash, agranulocytosis, hepatotoxicity and nephrotoxicity (rare)
• Stop if rash, fever, sore throat (agranulocytosis) or jaundice develop.
• PTU. daily, block theconversion of T 4 to T 3 , DOC. pregnant & lactation women
• MMI – TID
• Anti thyroid drugs (methimazole, propylthiouracil). Both cross the placental barrier and can
accumulate in the thyroid gland of the fetus.
• Methimazole. Monitor TSH sensitivity test. Side effects are cough, fever and agranulocytosis.
• Propylthiouracil is preferred in pregnancy.
• More agranulocytosis seen than that of methimazole. Rapid absorption after oral
administration. Drug choice in pregnancy. Monitor complete blood count
• Lugol solution (KI + I 2 ). Given as oral drops, and it may cause stains

Iodine
• oral Lugol’s solution, iv sodium iodide

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• Blocks thyroid hormone production, use in the acute management of severe

hyperthyroidism.
• Administer 1 h after PTU or MMI; blocks radioactive iodine uptake
• iv sodium iodide used for thyroid storm
• Lugol’s solution used for thyroid storm & prior to thyroidectomy (2 to 6 drops TID 7d
preceding operation), 6.3 mg iodide/drop

Iodine, radioactive
• sodium iodide 131I (Iodotope)
• SE: hypothyroidism, CI : pregnancy, in patients with significant ophthalmopathy – with
caution or steroids
• Use to ablate thyroid tissue in patients with Graves’ disease, toxic autonomous nodules and
toxic multinodular goitres
• Giving as single oral dose(usually only one dose required)

Beta 1 -blocker, nonselective: propranolol

Selective
• atenolol, metoprolol
• use adjunctively in the management of Graves’ disease or toxic nodules
• CI: asthma patients
• Propranolol; ↓ the conversion of T 4 to T 3
• Selective Beta1 -blocker; foster onset of action than propranolol

Corticosteroids, systemic
• dexamethasone, hydrocortisone sodium succinate
• Use adjuvant therapy in treatment-resistant cases for hyperthyroidism
• dexamethasone used for thyroid storm
• hydrocortisone used for Myxedema coma

Tips
Tips format 002: Find answers from the table:
1. Bradycardia 2 Hypotension 3 Constipation
4. Diarrhea 5 Dry skin 6 Sensitive to heat
7. Weight loss 8 Weight gain 9 Sensitive to cold
10. TSH < 0.5 11. TSH > 5.5 12 Graves disease
13. Hashimoto disease 14. Thyroxin 15 Methimazole
16. Propylthiouracil 17. Lugol solution 18
• Symptoms of hypothyroidism ( )
• Symptoms of hyperthyroidism ( )
• Hyperthyroidism ( )
• Hypothyroidism ( )
• What is the drug of choice for hypothyroidism ( )

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• What is the drug of choice for hyperthyroidism ( )

• What is the drug of choice for hyperthyroidism in pregnancy ( )
• What drug that are taken empty stomach ( )
• Drug absorption is decreased if taken with calcium supp or dairy products, iron, antacids
( )
• What drugs that stain ( )
• Severe fever, sore throat and agranulocytosis are the side effects of ( )
• Calcitonin is stimulated by
• TSH is secreted from 
• In treatment of hypothyroidism with T 4 have effect on 
• Hypothyroidism is monitored by 
• T 4 metabolized to T 3 by deiodinase enzyme in -->
• Sweating is symptom of 
• Lugol solution is an oral drops of? 
• Thyroxine absorption is decreased by 

Select True or False Statements

• Hyperthyroidism in pregnancy: PTU is drug of choice, with the lowest possible doses
used to maintain the maternal T4 level in the high normal range. (True)
• A 55 yo women using levothyroxin 75 mcg to treat hypothroidism. She is experiencing
sweating, heat sensitive and diarrhea. Indicates overdose. (True)
• levothyroxin take in the morning empty stomach(True)
• levothyroxin take with full glass of milk (False)
• Lugol solution used to treat thyrotoxicosis, (Graves disease) (True)
• hypothyroidism, Total T 4 decrease(True)
• hypothyroidism, Free T 4 decrease(True)
• hypothyroidism, Total T 3 decrease(True)
• hypothyroidism, Serum TSH decrease(False)
• hypothyroidism, Free Thyroxine index decrease(True)
• FT4, TT4, TT3 and FTI decrease in hypothyrodism, only serum TSH increase. For
hyperthyroidism, exactly opposite changes. (True)
• Myxedema; In this disease, the patient may have slow speech, a puffy face, slow pulse,
low BMR and scanty hair. (True)
• Cretinism: The growth and height of the child is stunted. The patient has low BMR and
a bloated face. The patient is also mentally retarded. (True)
• Goitre: It is also known as simple or non-toxic goiter. A dietary deficiency of iodine may
be responsible for this. The neck of the patient is swollen. (True)
• Toxic nodular goiter: It is due to benign neoplasm or adenoma or may be because of
long standing normal goiter. (True)
• Hoshimoto thyroiditis: It leads to hypothyroidism(True)
• Discontinue antithyroid if patient notice even a single rash (Pruritis Maculopapular
rashesh associated with vasculitis)
• Why is it beneficial to add propranolol to a drug regimen of a patient diagnosed with
hyperthyroidism? decrease heart rate, anxiety, tremors, and heat intolerance

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81
Contraception
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Side effects of oral contraceptive pills
• OCP DIs with phenytoin, carbamazepine, topiramate, rifampin, antibiotics.
• OCP CI's. coronary artery disease, DVT, PE and liver diseases.
• What if patient miss one pill? What to do?
• Emergency contraception like plan B side effects (N&V)

Barrier methods: condoms. Male (latex, polyurethane, lambskin)

• Protect against STIs including HIV (latex condoms only).
• Lambskin: no protection against STIs.
• Latex SEs: hypersensitivity in either partner, use water lubricants (oil-based ↓ integrity).

Condoms. female
• Not to be used with male condoms, shelf-life of up to 5 years.
• inserted up to 8 h prior to intercourse & removed immediately after

Diaphragm
• SEs. Toxic shock syndrome
• Use with spermicidal, can be inserted 6 h before intercourse & used in breastfeeding women.
• Use silicone diaphragm (allergy to latex).

Sponge
• SEs. Toxic shock syndrome, spermicidal is released in a sustained fashion for 10 to 12h
• Do not use during menstruation

Cervical cap
• SEs. Toxic shock syndrome, can be left in place for up to 48h for multiple acts of intercourse.
• Can be used in breastfeeding women, not to be used within 6wk of delivery

Spermicides: nonoxynol-9 (Vaginal Contraceptive Film)

Not effective against HIV or STI

Intrauterine devices (IUD). copper-T IUD (Nova-T, Flexi-T)

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Contraceptives, oral combination

• Avoid in lactating women during the first 6 wk postpartum, with caution in the first 6mo
postpartum
• SE: chloasma, hypertension, breakthrough bleeding or spotting, N/V, breast tenderness, and
mood changes.
• DI. rifampin & griseofulvin – use backup barrier method during therapy
• Obesity affects metabolism to compromise contraceptive efficacy. May decrease the effectiveness
of contraceptive.
• "ACHES" danger signals Abdominal pain/Chest pain/Headaches/Eye problems/Severe leg pain

Diane-35 (EE 35 µg / cyproterone 2 mg)

• Drug of choice in severe acne (Not for birth control)
• Discontinue 3 to 4 mo after signs of acne have completely resolved

Contraceptives, transdermal. EE/norelgestromin (Evra)

• Apply a new patch once a wk on the same day of the wk for 3 w
• If off for >24 h start new patch & use backup method for 7 days
• OCPs→ patch. The first patch on the first day of withdrawal bleeding
• If later than the first day of withdrawal bleeding, use backup method for 7 days
• Depot MPA→ patch, start on day of scheduled injection.
• Not effective. Weight 90 kg or more
• Do not apply on chest

Contraceptives vaginal ring . EE/etonorgestrel (NuvaRing)

• CI. <6 wk postpartum if breastfeeding
• Do not use diaphragm or cervical cap as backup, vaginal tampons (ok: after removing vaginal ring)
• Can be left at room temperature for 4 mo, 3 wk inside vagina then removed for a 1wk for
menstrual periods.
• Left out longer than 3h → efficacy ↓, use backup method for 7 days.

Contraceptives, progestin only oral: norethindrone (Micronor).

• Inhibits cervical sperm penetration by thickening the cervical mucus
• Can use 1)over 35 years old smoker, 2) intolerate ethenyl estradiol, 3)have unwanted SE with COCs
4) breastfeeding, 5)migraine with neurologic symptoms
• SEs. ectopic pregnancy, irregular bleeding, DOC. Lactating women, contraindication to EE
• Contains 28 tablets of active drugs

Contraceptives. Progestin only injectable. Medroxyprogesterone acetate (Depo-Provera)

• Depot injection, can use in the postabortal state (5 days postpartum), during lactation (6wk
postpartum).
• Can use over 35 years old smoker, and intolerate ethenyl estradiol
• CIs. Pregnancy, breast cancer, SEs. Wt↑, BMD↓ (long-term)
• Injected within first 5days of onset of menses, interval between injections must not exceed 13 wk
• Ovulation & regular menstrual periods may not resume for up to a year after the last injection.

Contraceptives, progestin only intrauterine system (IUS) levonorgestrel (Mirena)

• Inserted within 7 days of onset of menses, remains in place for 5 y.
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• Highly efficacious ( ≤ 0.2%).

Emergency contraceptive methods

• EE 50µg+levonorgestrel 0.25mg/dose (Ovral)
• levonorgestrel 0.75 mg/dose (Plan B). SEs. N &V, dizziness, fatigue
• single dose of 1.5mg used within 24hr (prevent 95%) can take up to 5 days after unprotected
intercourse
• copper-T IUD (Nova-T) consider up to 7 days after unprotected intercourse

Contraception and breast feeding

• Oral contraception should be avoided in postpartum women and breast-feeding until 6 weeks
after delivery. Barrier contraceptives can be used.
• IUDs should be avoided with 4 to 6 weeks postpartum (until ovulation occurs)
• Progestin contraceptives can only be used during lactation (without increase of thromboembolic
events). Low dose combination of OC’s may be used once the milk supply is well established
(progesterone unlike estrogens do not inhibit the binding of prolactin to its receptors hence no
decrease in breast milk, therefore Progestin is preferred.

Starting OC’s
• 1st tablet either on the day of menses (eliminates the need for alternate means of contraception)
or take 1st tablet on the first Sunday after beginning of menses and use and use extra
contraception method for 1st 7 days of OC’s
• Oral contraceptives are best taken in the evening (before bedtime, to decrease the side effects
such as nausea, breast tenderness, chloasma (exacerbated by sunlight when estrogen
concentration are high and can be prevented by the use of sunscreen wide hats).

Missed pills
• If 1 pill, then take as soon as you remember and next pill as per schedule (no need for extra
contraception method).
• If 2 pills missed, in a row 1st/2nd week take 2 pills when remember and 2 pills the next day, and use
alternative method of contraception for 7 days from the day missed.
• If 2 pills missed in 3rd week, discard pack and start new pack or continue a pill everyday till Sunday
and then start a new pack and use alternate method for 7 days.
• The same applies for 3 pills in a row for any week.

Emergency contraception.
Plan B, is effective up to 3 days after unprotected sex.

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Tips
Find answers from the table
1. Ovral 2. Plan B 3. Condoms
4. Nonoxynol-9 5. Pregnancy 6. Breast cancer
7. Deep vein thrombosis 8. Vaginal bleeding 9. Alesse
10. Dian 25 11. Nausea and vomiting 12. Dimenhydrinate
13. Chloasma 14. Breast tenderness 15. Chest pain
16. Headache 17. Eye problems 18. Severe leg pain
19. Tampons 20. Evra patch 21. Nuva ring
22. IUDs 23. Depo provera 24. Abdominal pain

• Spermicidal: Vaginal contraceptive film ( )

• Contraception method may protect STIs and HIV ( )
• Contraindications of oral contraceptive pills ( )
• Oral contraceptives approved to treat acne ( )
• What is the common side effect of plan B ( )
• What is used as treatment for nausea and vomiting for contraceptives ( )
• What contraceptive methods and hygiene product that can cause toxic shock syndrome ( )
• Contraceptive method that applied for once a week, ( )
• The side effects of oral contraceptive pills ( )
• The danger signals of oral contraceptive pills ( )
• Emergency contraceptive methods ( )
• Emergency contraception plan B side effects ( )
• If missed one pill, what should be done ( )
• Contraceptive method that used once a month (removed after 21 days) ( )

Select True or False Statements

• Non contraceptive health benefits of OCs include decrease endometrial cancer, ovarian cyst,
endometriosis pain, fibroids, dysmenorrhea, and pelvic inflammatory disease. (True/False)
• Oil based lubricants should not be used for latex condoms (male), diaphragms, cervical caps.
(True/False)
• Diaphragm and cervical caps do not require a prescription but need a trained health professional
to insert. (True/False)
• Spermatocides are used along with condoms, diaphragm, and cervical cap. (diaphragm requires
spermicidal for every intercourse where cervical cap does not require extra spermicidal for
subsequent intercourse. (True/False)
• STI are only prevented transdermal patch contraceptives. (False)
• STI are only prevented subdermal progesterone implants (False)
• STI are only prevented by condoms contraceptive methods (True)
• Transdermal contraceptive Evra patch should be applied to the abdomen, buttocks upper torso,
and upper arm at the beginning of menstrual cycle (True)

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www.pharmacyprep.com Gynaecological and genitourinary conditions

82
Gynaecological and Genitourinary
Conditions
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Risks associated with endometriosis
• Menopause symptoms
• Toxic shock syndrome infection is caused by? S. aureus
• Drugs to treat erectile dysfunction like sildenafil, tadalafil and vardenafil DI with nitroglycerin

Dysmenorrhea
• Painful menstruation is referred to as dysmenorrhea
• Increase levels of prostaglandin during ovulation cycles, in endometrium it gives cramps, this leads
to menstrual pains. Thus problem can be treated by prostaglandin inhibitors.
• Drug of choice is mefenemic acid or diclofenac.

Endometriosis
• Endrometriosis can cause pelvic pain, dysmenorrhea and infertility.
• Treatment for pain. NSAIDs, oral contraceptives, progesterone only oral contraceptives, androgen
agonist. Danazole and gonadotropic releasing hormone (GnRH) analogs
• Treatment of fertility clomiphene.

Male sexual dysfunction

• Erectile dysfunction treatment. PDE 5 inhibitors Sildenafil, vardenafil, and tadalafil.
• Side effects. Headache, flushing, dyspepsia, nasal congestion, transient visual disturbance,
dizziness, and skin rash. Rarely priapism, and permanent visual loss.
• Drug interactions. Nitrates, alpha blockers, CYP3A4 inhibitors, grapefruit juice, and erythromycin.
• PDE 5 inhibitors. sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)
• CI. Nitrates (seek emergency care if chest pain present within 24 to 48 hr of taking PDE 5 inhibitors,
or use for 5 days after stopping long-acting nitrates).
• Non selective α-blockers, CYP3A4 inhibitors
• SEs. Headache (15%), flushing (10%), dyspepsia (5%), nasal congestion (5%), transient visual
disturbances (2%) and Priapism.
• Sildenafil is used 30 to 60 min before sexual activity.
• Dose adjustment. Hepatic or renal disease (<30 ml/min) & in the elderly.
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• SEs. Priapism & permanent vision loss (go to see a doctor).

• Up to 12 hr duration of effect
• Vardenafil. 30-60 min before sexual activity
• Dose adjustment. In moderate hepatic or renal disease & in the elderly
• SEs. Priapism & permanent vision loss (go to see a doctor)
• Up to 12 hr duration of effect, take empty stomach
• Tadalafil – at least 60 min before sexual activity
• Dose adjustment: No need in the elderly
• SE: visual disturbances & permanent vision loss (go to see a Dr)
• Up to 35hr duration of effect – no more frequently than every 2nd day
• CI : sever hepatic impairment

• PGE 1 analogues: alprostadil; intracavernosal injection (Caverject), intraurethral pellet (MUSE)

• Use to Pts with taking nitrates or α-blockers
• Injection – not use more than once daily or 3times /wk, at least 24hr between each dose
• Pellet - not use more than once per 24hr period, MO: BP (detect asymptomatic hypotension)

Menopause
• Cessation of menstrual periods is referred as menopause.
• The average age of menopause in Canada is 51 years.
• Symptoms. Hot flushes, night sweats, sleep disturbances, lethargy, depression, vaginal dryness,
dyspareunia (painful sexual intercourse).
• These symptoms are mainly due to the depletion of estrogens and progesterone.

Menopause symptoms treatment.

Hormone replacement therapy. Estrogen, (vaginal suppositories), estrogen patch, progestin.

Hysterectomy. Removal of uterus.

Hysterectomy patient use estrogen only. Progestin are not used.

Toxic shock syndrome (TSS)

• It is a infection resulting from toxin producing strains of S. aureus.
• TSS is a severe life threatening condition, can evolve clinically in rapid fashion becoming severe ill
in less than 12 hours.
• TSS is associated with use of tampons, reservoir types of contraceptives such as sponges, IUD, and
cervical caps. However condoms are not associated with TSS.

Benign prostatic hyperplasia (BPH)

• It is a condition where a male prostate becomes enlarged to the point that it causes discomfort.
There are two categories of symptoms:

• Obstructive symptoms. Weak urinary stream, difficulty initiating stream, stream starts and stops,
inability to terminate, post void dripping, urinary retention, sensation of incomplete empty
bladder.
• Irritative symptoms: Urinary frequency, nocturia, pain during urination, urinary urgency
• Treatment: finasteride and dutasteride (5α reductase inhibitor) and  1 adrenergic antagonist
tamsulosin, prazosin, doxazosin, and terazosin.
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• 5 α reductase enzyme catalyzes testosterone to dihydrotestosterone.

Pre-menstrual symptoms (PMS)

• Cyclic re occurrence of physical, behavioral, and psychological symptoms during the luteal phase
of menstrual cycle (after ovulation).
• PMS symptoms occur 1 to 2 days before periods may be due ↓ progesterone, or estrogen

A sever PMS include, and mood changes.

• Luteal phase of menstrual cycle
• All women have no PMS.
• There is no treatment for PMS
• Evening prime rose oil is used for PMS.

Vaginitis or vaginosis
• Infection of vagina caused by vaginal microorganisms or overproduction.
• Bacterial vaginosis
• Creamy and fishy odor discharge (yellow/grey)
• Most common form of vaginitis
• Sexually transmitted disease thus partner requires treatment
• Vaginal candidiasis
• Severe pruritus, with white cottage cheese discharge (only recommended for self treatment).
• It is not sexually transmitted disease thus partner does not require treatment.
• Over the counter antifungals miconazole, clotrimazole, nystatin are drug of choice.
• Trichomoniasis
• Frothy, wet discharge
• It protozoa infection.
• It is a sexually transmitted disease thus partner require treatment.
Atrophy
• Vaginal discharge, spotting, and soreness, burning.
• Drug of choice is metronidazole

Urinary incontinence in adults

• Bladder symptoms involve the leakage of moderate to large amount of urine due to hyperactivity,
stress, and over distended bladder.
• Stress incontinence. loss of urine due to an increase in intra-abdominal pressure. Examples cough,
and exercise.
• Urge incontinence. symptoms of overactive bladder which caused by inability delay voiding when
urge is perceived. Examples CNS condition, like Parkinson's disease and stroke.
• Overflow incontinence. Involves the leakage of urine due to an over distended bladder, commonly
resulting from outlet abstractions. Examples such as BPH or neurogenic causes such as diabetic
neuropathy or multiple sclerosis.
• Functional incontinence; loss of urine caused by the inability to get to toilet. Example physical
disabilities, difficulty removing clothing, cognitive factors such as dementia, depression, or
environmental factor such as distance to toilet, and positioning.
• Drug of choice is oxybutynin (Ditropan) and is an anticholinergic drug act M 3 receptors.

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• Drug that should be avoided in urinary incontinence diuretics (furosemide), glucocorticoids,

thiazolidinediones.

Enuresis in children (bed wetting)

• Drug of choice is antidiuretic hormone derivatives desmopressin (DDAVP)
• Smooth muscle relaxant, oxybutynin and imipramine

Tips
Find answers from table:
1. Mood changes (swing) 2. Flushing 3. Night sweat
4. Vagina dryness 5. PDE 5 inhibitors 6. oxybutynin
7 Luteal phase 8. Urinary incontinence 9. Benign prostatic hyperplasia
(BPH)
10 Premenstrual syndrome 11. dysmenorrhea 12. Jet urination
(PMS)
13. Difficulty in urination 14. Finasteride 15. Dutasteride
16. Prazosin 17. Tamsulosin 18. irritation
19. Saw palmetto 20. Pelvic pain before periods 21. S. aureaus
22. Contraceptive sponges 23. IUD 24. Cervical caps
25. Sildenafil

• Symptoms of dysmenorrhea 
• Symptoms of endometriosis 
• What microorganism cause toxic shock syndrome 
• What contraceptive methods can cause TSS 
• What drugs are inhibitors of PDE 5 enzyme 
• Nitrates + sildenafil should not take together because 
• Menopause symptoms 
• Benign prostatic hyperplasia symptoms include all except 
• What phase of menstrual cycle does PMS symptoms occur 
• What drugs should be avoided in urinary incontinence 
• What is the drug of choice enuresis in children 
• Symptoms of menopause ( )
• Sildenafil, tadalafil, vardenafil are ( )
• The drug of choice of urinary incontinence ( )
• Occurs in premenstrual syndrome (PMS) ( )
• Symptoms of benign prostatic hyperplasia ( )
• The drug of choice for BPH ( )
• The drugs that used to relieve the symptoms of BPH ( )
• What is not symptoms of BPH ( )
• What anticholinergic drug that acts on M 3 receptors ( )
• Herbal product that is used to treat prostatic hyperplasia ( )

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Select True or False Statement

• A customer of your pharmacy presents with symptoms of vaginal discharge, yellow and fishy
odour. Refer to doctor is appropriate? (True)
• Color discharge and fishy odour is indicator of bacterial infection, thus refer to doctor.
• If a patient is not treated for asymptomatic sexually transmitted infections. Can cause pelvic
inflammatory disease and infertility (True)
• pre menstrual symptoms occur during luteal phase. (True)
• toxic shock syndrome caused by infections of S. aureus. (True)
• toxic shock syndrome can cause by tampon use. (True)
• toxic shock syndrome Can cause by condom use (False)
• toxic shock syndrome can cause by candida infections. (True)
• toxic shock syndrome Can cause cervical cap contraceptives. (True)
• patients experienced priapism condition avoid using sildenafil? (True)
• patient have reported visual disturbances condition avoid using sildenafil? (True)
• patient using nitrates condition avoid using sildenafil? (True)

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PharmacyPrep.Com Osteoarthritis, Rheumatoid arthritis and Gout arthritis

83
Osteoarthritis, Rheumatoid
Arthritis and Gout Arthritis
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Osteoarthritis therapy acetaminophen 650 mg q4-6h
• Rheumatoid arthritis therapy methotrexate and Infliximab
• Methotrexate dose to treat rheumatoid arthritis max 25 mg/wk
• Acute gout attack therapy Indomethacin, colchicine and prednisone.
• Acute gout risk factors, high protein diet, low dose ASA.

Osteoarthritis and Rheumatoid Arthritis

Osteoarthritis (OA) is a degenerative joint disease caused by a breakdown of the cartilage
between bones.

Rheumatoid arthritis (RA). Inflammation of joints with frequent acute attacks.

Rheumatoid arthritis occurs when body’s immune system attacks the tissue lining and
results in the joints causing cartilage to erode. Weight bearing and non weight bearing
joints. Soft tissue effected.
Causes:
• RA. Autoimmune
• OA. Aging of cartilage and trauma
Sex distribution
• RA. More common in females
• OA. Equal in both sex
Symptoms
• RA. Joint stiffness in the morning, painful and swollen joints
• OA. Painful joints, restricted joint movements
Diagnosis
• RA. Rheumatoid factor, erythrocyte sedimentation rate (ESR), x-ray, antinuclear
antibody, and c-reactive protein (CRP)
• OA. X-ray only

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Treatment
Rheumatoid arthritis  NSAID’s, and DMARD’s
Osteoarthritis  NSAID’s

Symptoms Osteoarthritis Rheumatoid arthritis

Stiffness Morning or after inactivity (last 30 min) In the morning (last 1 hour)
Limited affected joints.
Localized Worsens with activity or after prolong use, Not localized
Pain (weight bearing activity). Worsened with prolonged inactivity. (usually
Generally weight bearing joints. improves with activity).
Affects on weight bearing and non weight
bearing joints
Inflammation Uncommon Common
Risk factor > 65 years Autoimmune

Osteoarthritis
A degenerative joint disease caused by a breakdown of the cartilage of the bones or degradation
of articular cartilage in synovial joints.

Non-prescription
• Acetaminophen is initial drug of choice for symptom relief. Maximum therapeutic dose
should be tried for 2 to 3 weeks
• Acetaminophen 650 mg 4 to 6 times a day
• ASA/NSAIDs/Ibuprofen is 2nd line therapy
• Acetaminophen + caffeine + codeine
• Glucosamine/Chondroitin
• Topical counter-irritants (Methyl salicylate/Menthol/Capsaicin)

Prescription Medication:
• COX-2 inhibitors (Celecoxib) as effective as NSAIDs but lower incidence of GI side effects.
• Intraarticular corticosteroids (3 to 4 injections year)
• Hyalunon injections only for those who failed other therapies
• Narcotic analgesics

Rheumatoid arthritis
A chronic systemic, autoimmune inflammatory condition. Symmetric synovitis affecting similar
joints bilaterally.
• It is non organ specific autoimmune disease
• Type III hypersensitive reaction
• Blood contain rheumatoid factor
• Stiffness occurs in the morning
• Large areas of joints are effects
• Not associated with frequent of use of joints
• It effects on weight bearing and non-weight bearing joints.

Pharmacological Choices
Disease modifying anti-rheumatic drugs (DMARDs)
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• Methotrexate is the gold standard for the treatment of RA

• Should be started within 3 months of disease onset (max effect in 3 to 6 months)
• Initial dose of 20 to 25 mg po/wk, do not exceed >25 mg/wk
• Minor SEs oral ulcers can be reduced by concurrent use of folic acid
• Should be avoided in patients with hepatitis B and C, renal insufficiency, or lung disease,
serious SEs are cytopenia, and hepatic toxicity.
• Hydroxychloroquine; SE corneal and retinal deposition
• Sulfasalazine
• Leflunomide: Can be used in combination with methotrexate (CI in pregnancy) or in place of
it for patients who have failed or have contraindications to methotrexate.
• Should be stopped in both males and females at least 3 months before attempting
conception (patient must undergo drug elimination by taking cholestyramine 8 g TID for 11
days.
• Azathioprine a purine analog immunosuppressive agent
• Cyclosporine
• Minocycline
• Penicillamine
• Gold sodium thiomalate

NSAIDs
Glucocorticoids. Prednisone/Triamcinolone – safest therapy during pregnancy and
lactation
Biological response modifier. Infliximab, etanercept, adalimumab

Infliximab
• Biological response modifier act as TNF α inhibitor. It is monoclonal antibody.
• Only available as iv. Stored in refrigerator.
• Approved for ulcerative colitis
• It is always used with methotrexate.
• SEs. The most common SEs are headache, fever, chills, fatigue, diarrhea, pharyngitis upper
respiratory tract and UTIs.

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Gout Arthritis
Gout is a disease in which monosodium urate monohydrate (MSU) crystal are deposited in
joints, soft tissues such as cartilage, tendon and bursa or renal tissues such as glomeruli,
interstitium tubules. Gout arthritis involves 4 stages Asymptomatic hyperuricemia (female >360
µmol/L, men >420 µmol/L), Acute gouty attacks, Intercritical gout, Tophaceous gout.

Risk factors. Protein diet, purine foods, meat, beer and male gender, low dose of ASA, obesity,
sea food.

Drug that cause hyperuricemia. Thiazides, low dose ASA, niacin, alcohol, levodopa, iv
nitroglycerine, ethambutol, pyrazinamide.

Asymptomatic hyperuricemia
• Normal serum urate levels. Woman 360 micromol/L and men 420 mol/ L. More comm
men over 40 year of age
• Hereditary metabolic disease that is a form of acute arthritis and is marked by inflammation
of the joints.
• Gout is associated with increased body stores of uric acid.
• Acute attacks involve joint inflammation caused by precipitation of uric acid crystals.
• Hyperuricemia  Urate crystal in joints  inflammatory response

Acute gout (attack) arthritis

• Abrupt onset of excruciating pain and inflammation of joint at night or early morning.
• Patient cannot tolerate even light pressure such as a bed sheet on the affected joint.
• Attacks often resolve spontaneously over 3 to 10 days.
• 1st line treatment is NSAIDS like indomethacin, colchicines (if NSAIDS contraindicated) and
corticosteroids (if colchicine is contraindicated)

NSAIDS. Indomethacin
• It is prostaglandin type I NSAIDS
• It has the highest anti inflammatory action in all NSAIDs
• It has high GI irritation SE (add gastroprotection with PPI for patient with risk increases for
GI bleed).
• It does not decrease uric acid

Colchicine
• It is anti-inflammatory drugs
• It has no analgesic action
• The most common SE is GI irritation
• CIs. in severe renal diseases (CrCl <50 ml/min)

Corticosteroids
• Given intra-articular injections for monoarticular pain
• Given oral for polyarticular pain

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Treatment of hyperuricemia. Antihyperuricemic agents as allopurinol, sulfinpyrazone and

probenecid

Allopurinol
• Inhibit xanthine oxidase (XO)
• Allopurinol and azathioprine drug interactions is due to which enzyme XO
• SEs. Rash is the most common, can form urate crystal in kidney. Take with plenty of fluids
• DIs: Half life of azathioprine and 6 mercaptopurine increased by allopurinol so this may
increase toxicity from increased plasma concentration of these drugs.
• Oxypurinol is metabolite of allopurinol

Febuxostat. Can be used in allopurinol allergy patient.

Sulfinpyrazone
• Increase uric acid excretion
• SE: can from kidney stones
• Drink plenty of fluids

Probenecid
• Increase uric acid excretion
• SE. Can from kidney stones
• Drink plenty of fluids

Tips
1. Acetaminophen 2. Methotrexate 3. Minocycline
4. Hydroxychloroquine 5. Infliximab 6. Allopurinol
7. Sulfinpyrazone 8. Colchicine 9. Indomethacin
10. Weight bearing joints 11. Non weight bearing joints 12. Obesity
13. Family history 14. Inadequate Ca & Vitamin D 15. Deficiency of
estrogen
16. Hyaluronic acid 17. Intra articular 18. Probenecid
19. RA 20. Osteoarthritis 21. Gout
22. 25 mg/WK 23. TNF alpha blocker

• Morning stiffness is symptoms of 

• Rheumatoid arthritis can occur on 
• Examples of DMARDs 
• Biological response modifiers 
• TNF-alpha blockers 
• Biological modifier that blocker IL-1 
• Methotrexate maximum dose for rheumatoid arthritis treatment is 
• Infliximab is a 
• Acetaminophen have least activity as 
• Probenecid, sulfinpyrazone and allopurinol should be taken with 
• This may cause renal damage or bone marrow depression ( )

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• The drug of choice against osteoarthritis ( )

• An anticancer drug used for the treatment of rheumatoid arthritis ( )
• Drug that used to treat rheumatoid arthritis and malaria ( )
• A broad spectrum antibiotic used in the treatment of rheumatoid arthritis ( )
• Drug used for rheumatoid arthritis and Crohn’s disease treatment ( )
• A suicide inhibitor of xanthine oxidase (XO) ( )
• Drugs that promotes uric acid excretion in urine ( )
• Drugs used to treat acute gout attacks ( )
• Long term use acetaminophen is associated with -->

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84
Osteoporosis
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Risk factors of osteoporosis age, menopause, family history, thin and small build.
• Calcium and vitamin D supplements dose and DI's.
• Bisphosphonates like alendronate, residronate, etidronate and zolendranoic acid
• Bisphosphonates doses

Osteoporosis. Overall reduction of bone mass (osteopenia), resulting in thin, fragile bones that is
prone to fracture.
There are 4 common sites of fracture in osteoporosis. wrist, shoulder, hip and spine.
Spine fracture also know "vertebral compression fractures" results due to falls, sneezing,
coughing, reaching, lifting or carrying.

Paget’s disease. Bone remodeling disorder, resulting in excessive bone resorption followed by
disorganized.
Risk Factors
Non Modifiable Modifiable
• Age >65 y • Low calcium intake (<1000 mg elemental
• Vertebral compression fractures calcium per day)
• Postmenopausal woman (not on estrogen • Inadequate sun exposure.
therapy). • Cigarette smoking
• Premature menopause (<45 years) • Excessive alcohol intake
• Gender (Female) • Caffeine containing beverages.
• Family history • Sedentary life style
• Thin and small boned • Excessive heparin therapy
• Hypogonadism • Oral corticosteroid therapy
• Race. Caucasians, Asians
• Hyperparathyroidism
• Hypocalcemia

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Nutritional Supplements: Ensure

adequate intake of both Calcium and
vitamin D of these nutrients when
prescribing pharmacologic therapy
• Ca - Premenopausal women:
1000 mg/day, menopausal
women & men > 50 y 1500
mg/day
• SE : constipation & nausea
Calcium Salts
Calcium carbonate (40% elemental calcium)
• Tricalcium phosphate (calcium phosphate, tribasic) 39%
• Calcium chloride 27%
• Calcium citrate (21%) good choice for seniors
• Calcium lactate (13%)
• Calcium gluconate (9.3%) least elemental calcium

Vitamin D
• Vitamin D. <50 y 400 IU/day, >50 y 800IU/day
• SEs. hypercalcemia, hypercalciuria, renal calcification, renal stones (usually at very high
doses)
• Vitamin D 3 (cholecalciferol) is preferred over vitamin D 2 (ergocalciferol).

Diagnosis.
Bone density measurements by Dual energy X-ray Absortiometry (DEXA).
T-score -2.5 or lower is osteoporosis.

Non pharmacologic
Reduce risk of falling
Adequate dietary calcium
Stop smoking, reduce alcohol <2drink/day, caffeine 2 cups.

Pharmacotherapy:
DOC for osteoporosis is bisphosphonates.
Bisphosphonates. Antiresorptive agents. Etindronate (Didronel, Didrocal: packaged with calcium
in 3 month kit).
• Alendronate (Fozamax), alendronate/VD (Fosavance)
• risedronate(Actonel), risedronate/Ca (Actonel Plus Ca)
• Safety in impaired renal function (ClCr <35 mL/min) is unknown.
• SEs. GI symptoms, muscle pain, osteonecrosis of the jaw (ONJ)
• Take on an empty stomach and only with water, very poor intestinal absorption
• Etindronate. Cyclic use 14 days Q3M, then calcium alone
• Take at bedtime, at least 2 h before or after eating
• Ca supplements should be separated by at least 2 h before or after.

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• Alendronate. Prevention. 5 mg/day, 35 mg/wk, Treatment, 10 mg/day or 70 mg once

weekly.
• Take at least 30 min before the first food, beverage, or medication
• SEs. Esophageal ulceration. Do NOT lie down for 30 min after taking.
• Risedronate 5 mg/day or 35 mg once weekly, 150 mg/once month
• Take at least 30 min before the first food, beverage, or medication. NOT lie down for 30
min after taking.
• SE: esophageal ulceration
• Alendronate/VD once weekly
• risedronate/Ca – Ca day 2-7

Selective Estrogen Receptor Modulators: raloxifene (Evista)

• Prevent postmenopausal bone loss, estrogen antagonist, NO ↑cardiovascular risk
• absence of hip fracture prevention data – consider after bisphosphonate therapy
• SE: Leg cramps, hot flashes (not be started until menopause is established)
• Venous thromboembolism risk similar to estrogen.

Calcitonin Peptides: calcitonin salmon, intranasal (Miacalcin NS) & sc (Calcimar, Caltine)
• Second line therapy, reduces pain associated with acute vertebral fractures
• Nasal spray prevent vertebral fractures

Anabolic Agents. Teriparatide (Forteo)

• SE: orthostatic hypotension (in a supine or sitting position for administration)
• parathyroid hormone (PTH) analogue
• sc for 18' lifetime exposure in Canada (2 years in the USA), due to occurrence of osteogenic
sarcoma
• Consider for severe cases characterized by more than one fragility fracture and a very low
BMD.

Tips
1. Alendronate 2. Calcium carbonate 3. Risedronate
4. Raloxifene 5. Calcium citrate 6. Calcitonin
7. Family history 8. Inadequate Ca & Vit D 9. Deficiency of estrogen
10. Swimming 11. Weight bearing 12. Obesity or overweight

• Risk factors of osteoporosis ( )

• Approved for prevention and treatment of postmenopausal bone loss, treatment of
established osteoporosis and glucocorticoid-induced osteoporosis ( )
• 40% elemental calcium; provides the most calcium ( )
• Selective estrogen receptor modulator (SERM), estrogen like action on bone and lipid
metabolism ( )
• A hormone secreted from thyroid gland ( )
• Calcium supplement recommended in elderly ( )
• this drug should be taken first thing in the morning on an empty stomach ( )

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• What is NOT risk factor of osteroporosis 

• Bone remodeling occurs, which is present
• Osteoporosis is caused by 
• Androgen deficiency cause 
• Recommended daily allowance of vitamin D over 50 year old is 
• Elderly may absorb calcium poorly due to 
• Paget disease
• Calcium carbonate (40% elemental calcium)
• What excercise is the least beneficial for osteoporosis -->

Select True or False Statements

• Inadequate Ca and vitamin D can cause osteoporosis (True)
• Smoking increase risk of osteoporosis? (True)
• Physical activity like weight bearing excercises like stair climbing, walking, and jogging
decrease risk of osteoporosis. (True)
• Increase in dietary soy intake decrease risk of osteoporosis. (True)
• Increase intake of broccoli decrease risk of osteoporosis. (True)
• A 35 yo women get the prescription of 50,000/wk unit of vitamin D. What to do? talk to
doctor and dispense. (True)
• protein diet like dietary are plant derived phyoestrogen present in soy proteins. (True)
• Drugs that cause osteoporosis: Corticosteroid, prednisone, levothyroxine. (True)
• anticonvulsants, phenytoin, heparin (long term use), and Al-containing antacid (True)

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85
Hypertension
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Cardiovascular risk factors.
• Clinical practice guidelines of hypertension monitoring
• Drug of choices to treat high blood pressure in patient with diabetes, renal, and coronary
artery disease, stroke patients.

Hypertension is defined as a systolic blood pressure >140 mm Hg, a diastolic blood pressure >90 mm
Hg. Diagnosis criteria from joint national committee (JNC-7) report recommendations for follow up in
adults.
• <130/85  Recheck in 2 yrs
• 130-139/85-89  Recheck in 1 yr
• 140-159/90-99  Confirm within 2 months
• 160-179/100-109  Evaluate or refer to source of care within 1 month
• >/-180/110  Evaluate or refer to source of care immediately or within 1 week depending clinical
evaluation
Maintain BP below
• 140/90 uncomplicated hypertension
• 140/90 with target organ damage or CV disease
• Isolate systolic hypertension >140/<90
• Diabetic or renal impairment <130/<80
• <125/75 with proteinuria >1 g/24 hrs

BP Measurement
• Patient should avoid smoking or caffeine for 30 min prior
to BP measurement
• Rest 5 min before BP measurement
• Position arm (bronchial artery) at heart level
• Uncover arm, do not put cuff over cloths
• Position cuff 1 inch above antecubital crease
• Ask patient about previous reading. Inflate cuff rapidly to
approximately 30 mm Hg above previous readings.
• Deflate cuff slowly, and completely. Measure pressure in
both arms.

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• Wait 1 to 2 min before repeating, and take average of 2 reading. If second reading differ by >5
mm, additional reading should be performed.

1st line therapy

Thiazide ACEi ARBs Calcium Beta

>60 yrs DOC for DM Channel Blockers
and renal Blockers <60 yrs
disease

Combining antihypertensive: Preferably combine from type 1 and type 2

Type 1 Type 2
ACE Inhibitors Thiazide
ARBs Beta blockers
Alpha blockers
K sparing CCB

Thiazide Diuretics
• Thiazide Diuretics. Hydrochlorothiazide, chlorthalidone, indapamide, metolazone and
combinations.
• MOA: Direct arteriole dilation, inhibit Na reabsorption in the distal tubule.
• SE: HYPERGLUC
• Increased lipid (cholesterol); increased LDL and increased TG.
• Increased uric acid; Hyperuricemia
• Increased glucose; Hyperglycemia (Mon: BSL)
• Increased Ca2+ = Hypercalcemia
• Decreased K+ = Hypokalemia
• Decreased Na+, Cl- = metabolic alkalosis

Beta blockers (BBs)

• non-selective BBs  Nadolol, propranolol, and timolol
• Cardio selective BBs are  Esmolol, Metaprolol, atenolol, acebutolol (selective beta blockers).
• Cardioselective BBs with ISA  Acebutolol, pindolol (non selective)
• Beta and alpha1 blockers  labetalol and carvedilol
• MOA: ↓ Cardiac contractility  ↓ CO
• ↓ HR  ↓ CO
• ↓ central sympathetic output
• Block rennin secretion
• SE: Increase LDL and TG
• CI: Peripheral vascular diseases (Reynaud's and claudication), prinzmetal angina (vasospastic
angina)

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• DOC: stable angina, hypertension (<60yr), post MI (STEMI), CHF (pulmonary edema) in general
avoid CHF because of bradycardia.
• Beta blockers  DOC: stable angina, hypertension (<60yr), post MI (STEMI), CHF (pulmonary
edema) in general avoid CHF because of bradycardia.
• Propranolol (Inderal LA) indicated for Social anxieties (stage fear) migraine prophylaxis, and
hyperthyroidism
• Beta blockers precaution and CI Peripheral vascular diseases (Reynaud's and claudication),
prinzmetal angina (vasospastic angina)
• The most beta 1 selective BBs that has been studied in lung dysfunction  Bisoprolol

Angiotensin converting enzyme inhibitors (ACE I)

Benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril,
trandolapril
• MOA: Inhibit conversion of ACEI to ACEII thereby ↑ peripheral vasodilation
• and ↓ fluid volume
• SE: angioedema, dry cough treat by switching to other class of drug. It has NO effect on LDL, TG
and HDL, gives hyperkalemia (do not combine K sparing)
• CI: in pregnancy, initially increase serum Cr up to 30% is OK, if more discontinue ACE I
• MON: K+ level should not exceed 5 mEq/mL
• TU: BP, CHF, posts MI, diabetic nephropathy, (microalbuminurea > 1 g), intermittent claudication.
• Captopril and fosinopril are NOT prodrug
• ACEI  Inhibit conversion of AT 1 to AT 2 thereby ↑ peripheral vasodilatation
• and ↓ fluid volume
• Captopril  Taken Q8H, All ACE I daily single dose, except captopril
• Take on an empty stomach, 1h a.c.
• Enalapril  is 3 time more potent used once daily and NO sulfhydril group

Angiotensin receptor blockers (ARBs)

ARBs: Candesartan, eprosartan, irbesartan, losartan telmisartan, and valsartan
• Direct Renin Inhibitors Aliskiren (Rasilez)
• Alpha 1 blockers  doxazosin, prazosin and terazosin
• Why is bedtime the best time to dose terazosin? syncope
• Alpha 1 blockers  avoid with PDE 5 inh. (Sildenafil, vardenafil, tadalafil)

Calcium channel blockers (CCBs)

• DHPs  amlodipine, felodipine, nifedipine XL. SEs. Ankle edema, flushing, headache, and
palpitation (reflex tachycardia)
• NDHP  diltiazem, verapamil. SEs. Headache, dizziness, bradycardia, 2nd and 3rd degree heart
block, new onset or worsening of heart failure and constipation.
• Amlodipine  Long acting DHP
• Verapamil  SEs. Constipation and take with or after meals
• Felodipine  DOC Reynaud phenomenon
• Non dihydropyridines  Additive effects with beta blockers (bradycardia), digoxin, amiodarone,
• Diltiazem SEs. stomach irritation. Take regular tab before meals and SR: with or without food.
• Dihydropyridines  SEs. reflex tachycardia, headache and ankle edema

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Alpha 2 agonist
• Methyldopa and clonidine
• MOA: ↑ alpha2 action and ↓ sympathetic outflow to heart
• Methyldopa Drug of choice for pregnancy
• SE: hemolytic anemia Mon: CBC

Tips
1 Propranolol 2. Thiazide diuretics 3. Clonidine
4 Hydrochlorothiazide 5. Methyldopa 6. Triamterene
7 Captopril 8. Furosemide 9. Enalapril
10. Minoxidil 11. Sodium Nitroprusside 12. Hydralazine
13. Felodipine 14. Terazosin 15 Losartan
16. BP >160/80 17. Ramipril
• What is the recommended sodium intake for a patient diagnosed with hypertension?( )
• The drug of choice against uncomplicated hypertension age over 65 yo is ( )
• The drug of choice against uncomplicated hypertension age less than 65 yo is ( )
• The drug of choice for hypertension in pregnancy ( )
• Use in non complicated hypertension and also indicated in opioids and benzodiazepine withdrawal
symptoms ( )
• Decrease BP in both supine & standing position, especially in elderly ( )
• Diuretics that gives ototoxicity, hypokalemia, dehydration, allergy, nephritis and gout ( )
• What drug turns urine into blue color ( )
• What antihypertensive drug should be taken 1 hour before meals ( )
• it is 3x more potent and used once daily and no sulfonil group ( )
• it is use for hypertension and alopecia treatment ( )
• The drug of choice for hypertensive crisis ( )
• It causes salt and water retention which may lead to CHF ( )
• The drug of choice for Reynaud phenomenon ( )
• This drug may cause a sudden drop in blood pressure that can result in loss of consciousness ( )
• Drugs may increase the effects of potassium supplements, potassium sparing diuretics,
cyclosporine, leading to raise of potassium in the blood ( )
• Hypertension with diabetes drug of choice is 
• Hypertension with renal disease drug of choice is 
• Isolated systolic hypertension which drugs should not use
• Cardio selective beta blockers are 
• The most beta 1 selective blockers that has been studied in lung dysfunction; 
• Name the cation most prevalent in the extracellular fluid of the body.
• Why is bedtime the best time to dose terazosin?
• It is an antihypertensive drug which is also used prophylaxis migraine ( )

Select True/False Statements

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A customer of your pharmacy checked two times blood pressure in your pharmacy blood pressure
monitor and found to have average 190/95. What is appropriate to do? talk to him first and refer to
doctor

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86
Coronary Artery Diseases
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Atherosclerosis and plaques
• Examples of coronary artery diseases angina, and myocardial infarction
• Risk factors and investigations (biochemical marker CK-MB, Troponin-i, ECG)
• Treatment of NSTEMI (Non ST segment elevated MI). ASA, BB
• Treatment of STEMI (ST segment elevated MI). Alteplase, ASA

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Types of angina

Stable/Exercise induced angina Prinzmetal/Varian/ Vasospastic Unstable/Crusendo angina

Due to coronary partial blood angina
clot Acute with platelet aggregations.
↓ coronary blood flow. Due to non-occlusive thrombus in
↓ ST segment (subendothelial) an area of coronary
↑ ST segment (transmural) atherosclerosis / or disrupted
Due to vasospasm effect of TXA2 plaques

Definition. Angina is those symptoms of myocardial ischemia that occur when myocardial oxygen
availability is insufficient to meet myocardial oxygen demand.
Symptoms. discomfort or pain in the chest, arm, shoulder, back or jaw. Frequently worsened by
physical exertion or emotional stress.

Diagnosis. ECG. and exercise test

Stable angina
• Caused ↓ O 2 supply due to ↓ blood flow
• Symptoms. Pain located over sternum and may radiate to left shoulder or arm, right arm or neck,
or jaw. Duration 0.5 to 30 min.
• Patient description of symptoms pressure or heavy weight on chest, burning, tightness, deep,
suffocating, squeezing, aching, and crushing.
• Precipitating factors exercise, cold weather, sexual activity and emotional stress.
• Approximately 75% of ischemic episodes are silent and not detected especially in diabetes.
• Symptoms occurring for weeks without worsening consider stable angina.
• Usually relieved by rest or nitroglycerin SL.
• Treatment. NTG-SL,  All BBs, or NTG-LA or CCBs,  ASA, or clopidogrel,  ACEi (in DM).

Prinzmetal angina (vasospastic)

• Caused by spasm, do not increase MVO 2
• Mainly due to atherosclerosis
• Symptoms. Pain usually occurs at rest awakens from sleep
• Characterized by recurrent, prolong attacks of severe ischemia.
• Treatment. NTG-SL  CCBs (nifedipine, amlodipine)

Acute coronary syndrome (ACS).Term describes the symptoms that may lead to acute myocardial
infarction (acute MI). Acute MI further characterized as STEMI and NSTEMI and as well as unstable
angina.

Diagnosis:
• Chest pain. Generally lasting for >30 min
• 12-lead ECG. ST segment elevation
• Cardiac isoenzymes. CK-MB elevated and cardiac troponin T or I elevated.
• If indicated an echocardiogram to identify the site and severity of wall motion abnormalities.
• Patient presentation. Diaphoresis (sweating), nausea, vomiting, weakness, and shortness of
breath, arm tingling, and syncope. May confuse as heartburn symptoms.
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Acute Coronary Syndrome (ACS)

NSTEMI. Partial blockade of coronary blood STEMI Completely occlusive thrombus

flow Effect entire thickness of myocardial wall. Cause
Involves only subendocardial myocardium myocardial necrosis.
ST depression or NO ST elevation on ECG ST segment elevation on ECG
Positive: CK-MB and Troponin-I More extensive damage
Positive. CK-MB and Troponin I
Tx. Antiplatelets (ASA or/and clopidogrel and
GPIs are used Tx. Thrombolytic (Alteplase) or
angioplasty
UA: Unstable angina, STEMI: ST segment elevated myocardial infarction, NSTEMI: Non ST segmented
elevated Myocardial infarction, GPI; Glycoprotein IIb/IIIa receptor antagonists.

NSTEMI
• Caused by disruption of an atherosclerotic plaque or formation of platelet aggregation thrombus.
• Symptoms: Crushing chest pain that can radiate to neck, back, shoulders, arms and jaw. Pain is
similar to angina but more severe. May occur at rest and may be caused by less exertions.
• Pain is NOT relieved by NTG
• Diagnosis: Chest pain is NOT relieved by NTG and persist longer than 5 min.
• Treatment: MONA therapy: Morphine  Oxygen  Nitrates  ASA; BBs without ISA or CCBs 
Heparin or LMWH

STEMI
• The most common type MI (85%) is due to thrombus formation caused by precipitated by
atherosclerosis plaque rupture. This propagated thrombus leads to occlusive thrombus.
• The complete blockade due to occlusive thrombus results in persistent ischemia that clinically
manifest as STEMI. If this is not treated, occlusion of coronary arteries can lead to sudden cardiac
death.
• Symptoms: similar to UA/NSTEMI, however it is common in women, elderly, and DM.

Tips
1. Nitroglycerin 2. Amlodipine 3. Ca channel blockers
4. Nitrates 5. Nitrites (Na Nitroprusside) 6. ASA
7. Heparin 8. Dihydropyridine 9. Clopidogrel
10 LDL > 2.2 11 Beta blockers 12 Thrombolytics
13 Diltiazem 14 verapamil
• These drugs may cause hypotension with sildenafil ( )
• The drug of choice for hypertensive crisis ( )
• This can be safely used by asthmatic and non-insulin dependent diabetics ( )
• It is effective for acute and chronic angina ( )
• These are the treatment of choice in patients with coronary arterial spasm ( )
• It is use for STEMI treatment (ST-segment elevation MI) ( )
• It is use for NSTEMI treatment (Non ST-segment elevation MI) ( )
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• It acts on peripheral vascular system that causes reflex tachycardia ( )

• It is appropriate drug for those who cannot take ASA ( )
• Symptoms of stable angina 
• The drug of choice for stable angina  ( )
• Prinzmetal angina is due to 
• The drug of choice for prinzmetal angina is 
• Neutropenia is side effect of 
• A patient is intolerant or allergic ASA, should get alternate drug of prophylaxis for vascular
diseases 
• Nitroglycerin act as smooth muscle vascular dilator due to 
• Venous pooling effect is caused by 
• Nitroglycerin storage conditions 
• The drug of choice for STEMI 
• What are the examples of LMWH 
• Mechanism action of LMWH 
• What laboratory test is used for monitoring LMWH 
• Headache is side effect of 
• Protamine sulphate is antagonist of heparin, which react by 

Select True or False statements:

• Symptom of coronary artery diseases? chest pain, sweating, shortness of breath (True)
• IV dosage of form of nitroglycerin is the fastest acting or have rapid onset of action? (True)
• Nitroglycerin onset of iv ( 1 to 2 min), SL ( 1 to 5 min), oral (40 min), ointment (20- to 60), patch (
40 to 60) (True)
• Alteplase is least likely used after myocardial infarction after 6 hr of acute attack? (True)
• Nitroglycerin SL spray is used to relieve angina symptoms (True)
• nitroglycerin SL spray should spray on or under the tongue(True)
• nitroglycerin SL spray should store at room temperature(True)
• nitroglycerin SL spray do NOT require shaking before use(True)
• nitroglycerin SL spray relieve angina symptoms(True)
• nitroglycerin iv is faster acting than nitroglycerin SL (True)
• LMWH have predictable response thus no monitoring required(True)
• Heparin is the drug choice anticoagulant in pregnancy(True)
• Warfarin is monitored by PT and INR(True)
• warfarin should not be taken with vitamin K supplements(True)
• Protamine sulphate is antidote of heparin(True)
• With isoniazid take vitB 6 , with levodopa avoid vitamin B 6 , with warfarin avoid vit. K. (True)
• Isotretinoin and tretinoin avoid vitamin A because analogs of vitamin A and Phenytoin &
methotrexate take folic acid(True)
• Coumarin derivatives anticoagulants is used as rat poisoning? (True)
• Angina, MI, transient ischemic stroke medical conditions are associated with ischemia.
• Omega 3 polyunsaturated fatty acids are abundant in fish oils? (True)
• Ecosapentanoic acid (EPA) and docosahexanoic acid (DHA) are derived from Omega 3(True)

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87
Stroke
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Symptoms of stroke sudden dizziness, headache, confusion, blurred vision, and fainting
• Stroke risk factors. coronary artery disease, DVT, high cholesterol, and age.
• Transient Ischemic attack ASA.
• Acute stroke therapy. Alteplase or anticoagulant
• Thrombolytic inclusion and exclusion criteria

Stroke symptoms. Headache, dizziness, blurred vision, confusion, and incoherent speech.

Primary prevention of vascular diseases.

Early recognition and management of modifiable risk factor such as poor diet, sedentary
lifestyle, obesity, high BP, cholesterol, DM and smoking.

Secondary prevention of vascular disease (Transient ischemic attack)

Management of risk factors after patient has suffered vascular event.

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Drug of choice for the transient ischemic attack? ASA 81-325 mg

Lab tests. CT brain scan (to rule out hemorrhagic process).

ESR (to test hypercoagulable state)
ECG (exclude atrial fibrillation)
MRI to confirm the diagnosis.

Pharmacotherapy
Anti-platelets. ASA, Clopidogrel, Ticlopidine, Dipyridamole/ASA
DOC: 2nd prevention of Noncardioembolic ischemic strokes
ASA. initial therapy (50-325 mg/day for prevention)
Clopidogrel – 75mg/daily, alternative agent, somewhat more effective < ASA alone Avoid
grapefruit juice

ASA + Clopidogrel; should NOT be used for long-term secondary prevention of ischemic events
(↑bleeding)
Ticlopidine ; 250mg bid , SE: diarrhea, skin rash, neutropenia (need monitoring). Not routine use
Dipyridamole SR/ASA; 200/25g bid, ↓ risk of stroke (mostly for ischemic stroke)

Anticoagulants; Warfarin, nicoumalone

DOC : 2nd prevention of Cardioembolic ischemic strokes prevent cerebral and systemic emboli in
patients with acute MI, valvular and nonvalvular AF and prosthetic cardiac valves. Nonvalvular
AF and prior TIA/stroke → require INR of 3.0 instead of 2.5.

Warfarin: INR 2 to 3 (cerebrovascular indications), 2.5 to 3.5 (with mechanical heart valves)
INR3-5 & NO significant bleeding, lower dose or omit dose and monitor
INR>5 to <9 & NO bleeding: skip dose
INR>5 to <9 & bleeding: skip dose & give VK orally (<5mg)
INR>9 & NO bleeding: hold WF & give high dose of VK orally
INR>9 & bleeding. hold WF & give VK infusion

Drug of choice for stroke prevention? ASA

Drug of choice to treat acute stroke? Thrombolytic (alteplase)

Tips
Tips format 002: Stroke
1. Headache 2. Dizziness 3. Blurred vision
4. Confusion 5. Incoherent speech 6. Warfarin
7. ASA 8. Clopidogrel 9. Ticlopidine
10 Alteplase 11. BP >140/90 12 LDL >2.6 mmol/L
13 Seizure
• Symptoms of stroke ( )
• What is the initial symptoms of stroke ( )
• What are the drugs of choice for long term prevention of atherothrombotic events ( )
• Risk factors for stroke ( )
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• What is the drug of choice for transient ischemic attack (TIA) ( )

• What is the initial therapy for stroke prevention ( )
• Combination of drugs increases the risk of bleeding ( )
• What drug gives neutropenia infrequently but is potentially serious and require monitoring
of CBC (every 1 to 2 wks) ( )
• What is not recommended routine protection of stroke. ( )
• What drug prevents cerebral and systemic emboli in patient with acute MI ( )
• Drugs that are used in within 3 hrs of acute ischemic stroke ( )
• What is not a stroke symptoms. ( )

Select True or False Statements

• Dizziness and head ache are the initial symptoms of stroke. (True)
• Pathophysiologic of cerebral ischemia are associated with carotid atherosclerosis that can
result into stroke. (True)
• ASA is the drug of choice for transient ischemic attack (TIA)? (True)
• Migraine headache is least documented risk factor of stroke? (True)
• Thrombolytics like alteplase should be used within 3 hours of stroke
• Seizures is not a symptoms of stroke? (True)

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88
Congestive Heart Failure
Questions Alerts!
Common questions in pharmacy exam is to ask!
• CHF symptoms dyspnea, fatigue, edema, weight gain
• CHF Treatment. ACEi. furosemide, digoxin
• Digoxin mechanism. + ve inotropic, -ve chronotropic and vagomimetic
• Digitalis toxicity. Quinidine, thiazides, loop, erythromycin, tetracycline, verapamil
• Digoxin CI's. Ventricular arrhythmias
• Digitalis toxicity symptoms: severe nausea vomiting, anorexia, muscular weakness,
bradycardia, and ventricular premature contractions. Severe toxic symptoms include:
blurred vision, disorientation, diarrhea, ventricular tachycardia, AV blockade which
progress to ventricular fibrillation.

Symptoms. Typical symptom of CHF include dyspnea, fatigue and fluid retention.
The primary manifestation of heart failure are dyspnea and fatigue that may limit exercise tolerance,
and fluid retention the may lead to pulmonary or peripheral edema. Other symptoms may include
paroxysmal nocturnal dyspnea, orthopnea (shortness of breath that prevents lying down), tachypnea
(rapid breathing), cough, ascites and nocturia.

Other symptoms include jugular venous distention, hepatojugular reflux, hepatomegaly (enlarged
liver), bibasilar rales, pleural effusion (increase in fluid in pleural surfaces), tachycardia, pallor (pale
skin) and S 3 gallop. Symptoms of advanced heart failure are the same but more severe.

Causes of CHF. In 65% of patients coronary artery disease is the cause of heart failure, other causes
include nonischemic cardiomyopathy example hypertension, thyroid disease or valvular disease. These
patients usually have reduced left ventricular dysfunction; usually ejection fraction is <40%.
Nearly 20 to 50% of patient with heart failure is secondary to diastolic dysfunction. This is often seen
in elderly.

Diagnostic tests
• The echocardiogram is one of the most useful diagnostic tests in CHF.
• B-type natriuretic peptide (BNP) is often in acute care at emergencies. The test is useful in
differentiating CHF exacerbations and other causes of dyspnea such as COPD, asthma or
infections. Patient dyspnea secondary to CHF will have elevated plasma BNP concentrations.

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• The most common type of CHF is left ventricular ejection fraction <40% is indicates systolic
dysfunction.

CO BP Renal Blood Flow Renin

&
Angiotensin II

CHF
Venous Aldosterone
Pressure

Capillary Na/H2O retension

Filtration
EDEMA

Pharmacotherapy.
Diuretics (hydrochlorothiazide, metolazone, furosemide, bumetanide, and ethacrinic acid,
spironolactone)
• MOA: ↓ Na/H 2 O retention by inhibiting reabsorption of Na in loop of henle
• SE: hypotension, hypokalemia and hypo magnesia
• DI.Take empty stomach, food ↓ bioavailability

ACE Inhibitors (captopril, enalapril, lisinopril, ramipril, and trandopril)

• MOA: Inhibit potent vasoconstrictor ACEII, reduce mortality 20 to30%, ↑ CO, ↓BP and HR
• TU: all patient with left ventricular systolic dysfunction should receive.
• CI: Pregnancy, and lactation

ARBs (Candesartan, and valsartan). Same as ACEi

Beta blockers (Bisoprolol and carvedilol, labetalol, Metoprolol)

• MOA. Antagonize sympathetic activity. Negative inotropic effect is a disadvantage.
• Therapy. Bisoprolol and metaprolol b 1 selective and carvedilol a 1 , a 2 and b 1 receptor inhibitor
are effective.

CCBs, Only dihydropyridine CCBs are used

Digoxin
• Does not improve mortality only produces symptomatic relief.
• MOA: Inhibits Na+K+ATPase pump. ↑ +ve inotropic effect, and vagomimetic effect.
• SE: bradycardia, cardiac arrhythmias, and heart blockade
• DI: verapamil, amiodarone, tetracycline, erythromycin, quinidine, and hypokalemic drug loop and
thiazides gives digitalis toxicity

CCBs (amlodipine, felodipine)

• Verapamil and diltiazem are not used because –ve inotropic effect
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Vasodilators. Hydralazine, isosorbide dinitrate, nitroglycerine, and nitropruside

Inotropic agents (digoxin, milrinone, and dobutamine).

Tips
1. Digoxin 2. Digifab 3. Loop diuretics
4. Captopril 5. Verapamil 6. Thiazides
7. Dyspnea, fatigue 8. Impaired left ventricular (LV) 9. Fluid retention
function and reduce LV reserve
10 Systolic HF 11 Edema

• Symptoms of congestive heart failure ( )

• Characterized as congestive heart failure ( )
• Initial CHF symptoms include  ( )
• What is the common type CHF characterized by decreased pump function, dilatation of LV, and
decreased LV ejection fraction ( )
• What is the most widely used cardiac glycoside ( )
• What drug should be avoided in ventricular arrhythmias ( )
• What it is the antidote for digoxin toxicity ( )
• What drugs that increase digoxin levels ( )
• Decrease Na/H 2 O retention by inhibiting reabsorption of Na in loop of henle ( )
• What drugs has the most common side effect of this drug is cough ( )
• Drugs that decrease K levels ( )
• +ve inotropic agents 
• -ve inotropic agents 
• The drug of choice for CHF ( )
• The drug of choice for CHF 

Select True or False Statements

• Symptoms of left ventricular heart failure cause  pulmonary edema (True)
• Symptoms of right ventricular heart failure cause peripheral edema
• Weight loss is NOT a symptoms of congestive heart failure? (True)
• ACEI, furosemide, and digoxin are the drug of choice for CHF? (True)
• A patient while discharging from hospital emergency doctor has prescribed atenolol and ramipril.
Patients comes to home and calls your pharmacy to know he was using digoxin before hospital
admission. If he should continue digoxin or discontinue. Pharmacist calling doctor is better
response. (True)
• In the above patient scenario, medication reconciliation, could have prevent this confusion?
• Academic detailing educational programs conducted by pharmacy with doctor to enhance
prescription practices. Medication reconciliation is counselling to patient at the point of hospital
admittance and discharge. ISMP gather information about medication incidents.

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• Advanced legal directives = a type "will" that describes in the event if patient is in coma or dead.
(True)
• Beta blockers are NOT a positive inotropic drug? (True)
• Digoxin, beta agonist and phosphodiesterase inhibitors

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www.PharmacyPrep.Com Antiarrhythmic drugs

89
Arrhythmias

Questions Alerts!
Common questions in pharmacy exam is to ask!
• Mechanism of Class Ia, Ib, Ic, II, and III drugs
• Examples of Class Ia, Ib, Ic, II, and III drugs
• Atrial fibrillation is an irregularly, irregulary supraventricular rhythm with consistant atrial
activity (P Wave). Atrial flutter is regular supraventricular rhythm with characterisitic of
flutter wate (saw tooth wave).
• Treatment of atrial fibrillation (P Wave) and atrial flutter
• Amiodarone SEs and Monitoring

Symptoms. It is mainly related to poor cardiac output i.e. dizziness, syncope, chest pain, fatigue,
comfusion and exacerbation of heart failure.
• Tachyarrhythmias. May have palpitation.
• Atrial fibrillation/flutter. May experience signs and symptoms of transient ischemic attack or
stroke.
• Ventricular tachycardia and ventricular fibrillation may be asymptomatic.

ECG, holter monitor or loop monitor.

Echocardiography to assess left ventricular function, and left atrial size valvular status.

Types of arrhythmias

Supraventricular (atrial) SVA Ventricular arrhythmias (VA)

• Premature atrial contraction Premature ventricular contraction (PVC)
• Atrial flutter Ventricular tachycardia (VT)
• Atrial fibrillation Ventricular fibrillation (VF)
• Paroxysmal supraventricular tachycardia (PSVT)
• Sinus tachycardia
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• Sinus bradycardia

Supraventricular (atrial) SVA treatment. Rate control drugs

• Cardiac glycoside (digoxin), Beta blockers (Propranalol, atenolol, metoprolol, nadolol), CCBs
(verapamil and diltiazem), Antiarrhythmic class 1C: flecainide, propafenone; Antiarrhythmic
Class III: Sotalol, Amiodarone, and dofetilide

Ventricular tachycardia treatment

• Class 1A (quinidine, procainamide); Class 1B (mexiletine); Class 1C (flecainide, propafenone);
Class III (sotalol, Amiodarone); Beta blockers (metoprolol)

Antiarrhythmic Drugs Classification

Class I Class II Class III

Ia-Na+ channel β-blockers K+ channel Class IV
blockers Esmolol inhibitors Ca2+ channel
Quinidine Propranolol Amiodarone blockers
Procainamide Timolol Bretylium Verapamil
Disopyramide Atenolol Dofetilide Diltiazem
Metoprolol Sotolol Nifedipine Miscellaneous
Ib: Lidocaine Nadolol Adenosine
Mexiletine Magnesium
Tocainide
Ic: Flecainide
Propafenone
Class 1a drugs are Na+ channel blocker slows phase 0 depolarization (Qunidine)
Class 1b drugs are Na+ channel blocker shortens phase 3 repolarization (Lidocaine)
Class 1c Na+ channel blocker significantly slow phase 0 depolarization (Flecainide)
Class II beta blockers decrease phase 4 depolarization (Beta blockers)
Class III K+ channel blockers prolong phase 3 repolarization (Amiodarone)
Class IV Ca2+ channel shortens action potential (verapamil and diltiazem)

Quinidine
Mechanism • Binds to sodium activated channels, Inhibits ectopic arrhythmias, VA
Therapeutic use • Atrial, AV junctional, and ventricular tachycardia.
• Maintain sinus rhythm after direct atrial flutter or fibrillation.
Drug-Drug • Antihypertensive, Anticoagulant – Quinidine may increase the effects of these
interaction drugs.
• Phenobarbital and Phenytoin – reduce the effect of quinidine
• Digoxin-Quinidine increases the effects of digoxin (decrease 50% digoxin
dose).

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Side Effects • SA and AV block or asystole, nausea, vomiting, diarrhea (cinchonism-large

doses-blurred vision, tinnitus, headache, disorientation and psychosis. Torsos
De pointes (VA)
• Toxic level—induce ventricular tachycardia.
• Increases steady state conc. Of digoxin by displacing PPB

Procainamide
Mechanism • Binds to sodium activated channels
Side Effects • Chronic use: lupus like syndrome (25-30%), toxic levels—asystole or induction
of VA.
• GI intolerance is less than quinidine.
• CNS. Depression, hallucinations and psychosis.

Amiodarone

Therapeutic use Amiodarone is structurally related to thyroxine, and it contains iodine.

DOC antiarrhythmic & recommended in more severe LVD & if CI with / BB
IV amiodarone is effective in terminating VT, more so in preventing recurrence.
Most effective for treatment in electrical storm.
Usually used as an empiric therapy
Side effects (4P) Respiratory. Pulmonary, including intererstitial pneumonitis; Respiratory
muscle impairment.
GI: nausea, anorexia, constipation, hepatitis and cirrhosis.
Hypothyroidism. Amiodarone inhibit peripheral conversion of T 4 to T 3
Blue skin color (pigmentation), corneal deposits, hepatic toxicity, optic neuritis,
erectile dysfunction, photophobia.
Counseling Avoid exposure to sunlight, use sunscreen and grapefruit juice

Digoxin
Therapeutic use Atrial arrhythmias
Contraindicated Ventricular fibrillation and hypokalemic patients
Counseling May be taken with or without food
Meals w/ bran fiber, antacids may reduce amt of drug absorbed
Store between15-25 deg. C in a tight container and protect from light

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Tips
Find answers from the table:
1. Quinidine 2. Amiodarone
3. Propranolol 4. Lidocaine
5. Procainamide 6. K Channel blockers
7. phase 1 to 3 8. Phase 3

• Slows phase 0 depolarization ( )

• What class drugs prolong phase 3 repolarization (increase refractory period) ( )
• What drugs is used to treat cardioversion related arrhythmias ( )
• Competitively block catecholamine induced stimulation of beta receptor thereby suppress
phase IV depolarization ( )
• Chronic use of this drug may cause lupus like syndrome( )
• When taking this medication grapefruit juice should be avoided ( )
• Drugs that cause QT prolongation (torse des pointes) ( )
• What phases of action potential curve have no effect of stimuli  ( )
• What is relative refractory period is  ( )
• Phase I action potential is 40 (+ve) due to 
• What drug causes QT prolongation (torse des pointes) ( )
• Digoxin is contraindicated in what type of arrhthmias
• Class Ia drugs act on 
• Proarrhythmic drugs are 

1a Quinidine, procainamide Slows phase 0 depolarization

disopyramide
1b Lidocaine Shortens phase 3 repolarization (shortens duration of
refractory period)
1c Flecanide, propafenone Significantly slow phase 0 depolarization (slow
conduction)
II Propranolol Decrease phase 4 depolarization (beta 1 blocker action)
III Amiodarone and sotalol Prolong phase 3 repolarization (increase refractory
period)
IV Verapamil Shortens action potential (increase refractory period AV
node)

Select True or False Statements

• Amiodorone side effects are: Photosensitive reactions, skin pigmentation, blurred vision,
pulmonary toxicity, and pneumonitis. (True/False)

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90
Peripheral Vascular Disorders
Questions Alerts!
Common questions in pharmacy exam is to ask!
DVT risk factors. Immobility, age >50 y, history of DVT, obesity, major surgeries, paralysis (after
stroke), CHF, CAD, deficiency of protein C and S and smoking.
• Deep vein thrombosis symptoms and treatment.
• Reynaud's phenomenon treatment.
• Drug should avoid in peripheral vascular disorders and BBs, ergot alkaloids

Fig 90.1
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Peripheral vascular disease occurs in arteries and veins of periphery, other than heart and brain.

Peripheral Vascular Diseases

Disease of Veins Disease of Arteries

Venous blood clots Arterial blockage
Pulmonary embolism Aortic aneurysms
Phlebitis Buerger’s disease
Varicose veins Reynaud's phenomenon
Intermittent claudication

Venous Thromboembolism (Fig 90.1)

Deep vein thrombosis (DVT) is obstruction of vein by blood clot. It is most common within the deep
veins of calf muscles of the leg. The affected leg may become swollen and tender. The main risk is that
the clot may become detached and give rise to pulmonary embolism.
DVT symptom can cause pain in poplietal area.
Regular exercise of leg and anticoagulant therapy are used for prevention and treatment.
Drug of choice for prevention of DVT? LMWH
Treatment. LMWH (enoxaparin, dalteparin, tinzaparin, nadroparin), specific factor Xa inhibitors
(fondaparinaux) and unfractionated heparin (heparin) and warfarin.
LMWH are approved for prophylaxis and treatment of DVT.
heparin is prophylaxis only.
Warfarin is to target INR 2-3.

Prophylaxis Drugs (LMWH & UFH). Graduated compression stockings and intermittent pneumatic
compression devices, and caval interruption by filters

Treatment For treatment of established DVT and/or PE start oral warfarin together with sc
LMWH, or iv UHF. The LMWH or UHF is continued for minimum of 5 days or until the
INR is therapeutic for at least 2 days. The duration of oral anticoagulant is dependent
on the risk of recurrence of VTE.
LMWH In most analysis of treatment of VTE, LMWH use has typically more effective and less
costly overall compared to unfractionated heparin.

During UFH is the anticoagulant of choice during pregnancy. Injection sc twice a day to
Pregnancy achieve the therapeutic levels. Warfarin or UFH may be used for about 6 weeks after
delivery for secondary prevention.

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Arterial Thromboembolism
Acute Heparinized (80 u/kg) followed by thromboembolectomy (thrombolytic treatment in
therapy all patients).

Chronic Warfarin (maintain INR 2-3 for cardiac source; 2.5-3.5 for prosthetic mechanical
therapy valve). If the risk of recurrence become high (e.g. cardiac source, significant vascular
disease or abnormality of coagulation cascade) we can consider ASA in combination
with warfarin
Combination of glycoprotein IIb/IIIa receptor inhibitors with thrombolytic therapy
may improve outcomes for arterial thrombosis

Intermittent Claudication (Fig 90.1)

Intermittent claudication is a cramping pain, induced by exercise and relieved by rest, that is caused by
inadequate supply of blood to the affected muscles. It is most often seen in the calf and leg arteries.
The pulses are absent and feet may be cold.

Antiplatelets Antiplatelets agents reduce vascular death in high-risk patients about 25% and are
agents equally effective in those with coronary artery disease and PAD.

Clopidogrel Clopidogrel may be more effective than ASA in patients with PVD but is usually
reserved for those who cannot tolerate ASA or continue to have events while on
ASA

ACE inhibitors ACEi reduce the risk of ischemic events beyond that expected from lowering blood
pressure in patients with (PAD).

Ramipril Ramipril demonstrated similar effects in patients with or without PAD.

Contraindicatio Beta blockers (TC page 374 Use cautiously in sever disease with hypertension).
ns
Rheologic modifiers  pentoxifyline

Reynaud's Phenomenon

Reynaud's phenomenon is a condition in which arteries of the fingers become spastic (vasospastic).
This may result from atherosclerosis, connective tissue disease, ingestion of ergot alkaloids, or
frequent use of vibrating tools.
RP is due to result of over sensitive blood vessels in the body extremities. It is characterized by a pale
to blue to red sequence of color changes in extremities.

Non-Pharmacological Choices. Minimize cold exposure, and use warm gloves

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Therapy. CCBs (nifedipine XL, felodipine, amlodipine) and diltiazem

• Alpha blocker  prazosin
• PGI 2 analog  iloprost
• Peripheral vasodilator may relieve this condition.
CI. Avoid prescribing medications with vasoconstrictive potential: ergot derivatives, methyl sergide and
beta-blockers.

Medication taken daily (as opposed to PRN) during the winter will increase
tolerance to side effects (headache).
CCB of DOC is CCBs
dihydropyridine CCB of dihydropyridine class (e.g. nifedipine XL 30 mg or felodipine 5 to 10 mg)
should be used 60 minutes before cold exposure.
PGI 2 analog i.v. iloprost (PGI 2 analog) may be useful for short term use; oral iloprost is less
effective
CI Ergot alkaloids, methysergide and beta blockers?

Tips
Find answers from the table
1. Smoking 2. Obesity 3. Increase age
4. Immobility 5. Severe pain in legs 6. Pale finger tips
7. Effects extremities 8. Plaques 9. iv heparin
10 sc LMWH 11 Warfarin 12 fondaparinux
13 Embolism 14 Pulmonary embolism 15

• Risk factors of venous thrombosis ( )

• Symptoms of deep vein thrombosis ( )
• Symptoms of Reynaud's phenomenon ( )
• What is not a cause of Reynaud's phenomenon ( )
• What is the initial treatment of established DVT or PE ( )
• What is the first of a new class of antithrombotic agents, the specific factor Xa inhibitors. ( )
• Examples of vascular diseases 
• Symptoms of deep vein thrombosis 
• What is the pharmacotherapy for deep vein thrombosis 
• Intermittent claudication symptoms 
• Reynaud's phenomenon symptoms 
• What is the drug of choice in Reynaud's phenomenon 
• What drugs should be avoided in Reynaud's phenomenon 

Select True or False Statements:

• LMWH is the most important drug is used to prevent peripheral vascular diseases? (True/False)
• Anticoagulants like warfarin is commonly used to treat acute peripheral embolic disorders.
(True/False)
• Beta blocker are least likely used to treat peripheral vascular diseases? (True/False)

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• beta blocker cause vascular constriction thus it is contraindicated in peripheral vascular diseases
(True/False)
• Reynaud phenomenon symptoms occurs in limb extremities (True/False)
• Calcium channel blockers are the drug of choice (True/False)
• Reynaud phenomenon can be trigger cold exposure (True/False)
• Reynaud phenomenon is may occur in old age (True/False)
• arterial plaques is risk factor intermittent claudication (True/False)
• estrogen/progesterone have risk of blood clots in peripheral vascular system(True/False)
• LMWHs like enoxaparin, dalteparin, tinzaparin, and nadroparin are approved for both prophylaxis
and treatment of venous thromboembolism (VTE) (True/False)

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 91
Anticoagulants
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Intrinsic (01972)and extrinsic blood clot factors
• Warfarin, Heparin, and LMWH mechanism
• Warfarin DIs and Monitoring
• Dabigatran (Pradoxa) factor IIa (thrombin) inhibitor and Rivaroxiban, apixaban is selective
Factor Xa inhibitors
• Antidotes of warfarin, heparin and LMWH
• Safe anticoagulants in renal disease? warfarin
• Safe anticoagulants in pregnancy? LMWH and heparin

MOA Increase rate of thrombin (IIa) and LMWH preps are insufficient length to
antithrombin (factor Xa) reaction at least a catalytic inhibition of thrombin produce an
1000 fold by serving as catalytic template to anticoagulation effect mainly through
which both inhibitor + protease bind inhibition of Xa by antithrombin. (anti
thrombin Xa activity).

PK t 1/2 depends on amount. Heparin has LMWH have predictable pharmacokinetics

immediate action when iv. (within minutes), and have Longer t 1/2 than heparin. Takes 4
SC takes 1 to 2 hours Q8 to 12h dosage hours for action.

Dose is based on body weight Once or twice daily SC

Absorbed more uniformly

Monitoring aPTT No monitoring (predictable response)

Antidote Protamine sulfate Protamine sulfate

Bioavailability 20% 90%

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Pregnancy yes LMWH are the drug of choice in pregnancy.

Side effects Bleeding is more common Bleeding is less common. HIT is less common

Heparin induced thrombocytopenia (HIT)

Mucopolysaccharide Fractionated mucopolysaccharide

LWWH. Factor IIa and Xa inh.

Fondaparinux is (indirect) non specific factor Xa inh.
Rivaroxiban and apixiban are direct selective factor Xa inh.
Dabigatran is direct factor IIa or thrombin inh.
Antidote for dabigatran is idarucimab

Tips
Find answers from the table:

1. Heparin 2. iv & sc

3. Protamine Sulfate 4. Warfarin

5. LMWH 6. Vit K

7. Enoxaparin 8. ASA

9. Alteplase

• What drug interacts with warfarin because of its antiplatelets action ( )

• The major thrombolytic drug for DVT and pulmonary embolism ( )
• Drug catalyzes the factor (thrombin activation factor) 2a, 9a, 10a, 11a, 12a,&13a ( )
• Drug used to prevention of DVT or PE, NSTEMI and unstable angina ( )
• it acts longer and do not require close blood monitoring ( )
• What anticoagulant used to prevent blood clots, mainly in areas where blood flow is peripheral (
)
• PT & INR should be monitored when taking this drug ( )
• it is the antidote for warfarin ( )
• What it is the safest anticoagulant used in pregnancy ( )
• What it is the antidote for heparin and it act by neutralization ( )

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www.Pharmacyprep.com Anxiety Disorders

92
Anxiety Disorders
Questions Alerts!
• Common questions in pharmacy exam is to ask!
• Antidepressants mechanism and DI with MAOi
• Benzodiazepine classifications (intermediate acting BZDs daily) for max 2 to 4 wks.

• Anxiety is a normal response to fear, threat, or psychological stress and is experienced

occasionally by every one.
• Anxiety disorder involves a state of distressing chronic but fluctuating nervousness that is
inappropriate in certain circumstances.
• Anxiety disorder can be categorized into several types, such as panic attack, social anxiety
disorder, social phobia, obsessive-compulsive disorder, generalized anxiety disorder etc.
• Panic attack and panic attack with or without agoraphobia
• Panic is acute, short lived, extreme anxiety with some physical symptoms. This could occur
any anxiety disorder person with any specific situations. For example, a person with phobic
of snake may panic when encounter with snake.
• Patient may actively avoid situations in which panic attacks are predicted to occur
• Intolerance of physical symptoms of anxiety
• Social anxiety disorder (SAD) and (or) social phobia
• Excessive or unrealistic fear of social or performance situations
• Intolerance of embarrassment or scrutiny by others
• Specific phobia
• Excessive or unreasonable fear of a circumscribed object or situation usually associated with
avoidance of the feared object (for example, an animal, blood, injections, heights, storms,
driving, flying, or enclosed places).
• Obsessive compulsive disorder (OCD)
• Presence of obsessions. Recurrent, unwanted, and intrusive thoughts, images, or urges that
cause marked anxiety (for example, thoughts about contamination, doubts about actions,
distressing religious, aggressive, or sexual thoughts).
• Compulsions. repetitive behaviors or mental acts that are performed to reduce the anxiety
generated by the obsessions (for example, checking, washing, counting, or repeating).
• The drug of choice is SSRIs.
• Generalized anxiety disorder (GAD)
• Uncontrollable and excessive worry occurring more days than not, about a number of
everyday, ordinary experiences or activities. Often accompanied by physical symptoms (for
example, headaches or upset stomach).

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• Intolerance of uncertainty.
• Post traumatic stress disorder (PTSD)
• Occurs after a traumatic event to which patient responds with intense fear, helplessness, or
horror; patients relive the event in memory, avoid reminders of the event, and experience
emotional numbing and symptoms of increased arousal. Nightmare. (prazosin)
• Intolerance of experiencing trauma.
DSM-5. Diagnostic and statistical manual of mental disorder 5th ed.

Anxiety PD SAD OCD GAD PTSD

disorders
SSRIs
Fluoxetine (Prozac) Y
Fluvoxamine (Luvox) Y
Paroxetine (Paxil) Y Y Y Y Y
Paroxetine (Paxil CR) Y Y Y
Sertraline (Zoloft) Y Y
Dual action antidepressant
Venlafaxine (Effexor XR) Y Y Y
Azapirones
Buspirone (BuSpar) Y
5HT1a agonist
Benzodiazepines Y
Propranolol Y (stage ear)

Reference:
Can J Psychiatry, Vol 51, Suppl 2, July 2006
The Merck Manual of medical information
Treatment choices are modified from data from Compendium of Pharmaceuticals and
Specialties 2016

Tips
Find answers from the table:
1 Benzodiazepines 2. Flumazenil 3 Fluoxetine
4 Sertraline 5. Paroxetine (Paxil) 6 Fluvoxamine
7 Venlafaxine 8 Paroxetine (Paxil CR) 9 Buspirone

• What are minor tranquilizers used to treat insomnia and anxiety ( )

• What it is the antidote for benzodiazepine ( )
• What drugs that are use for Obsessive-Compulsive Disorder (OCD) ( )
• What drugs that are use for Post Traumatic Stress Disorder (PTSD) ( )
• What drugs that are use for Generalized Anxiety Disorder (GAD) ( )
• What drugs that are use for Social Anxiety Disorder (SAD) & social phobia ( )
• Paroxetine is indicated for 
• Obsession is 
• Compulsion is 

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93
Depression
Questions Alerts!
Common questions in pharmacy exam is to ask!
• Antidepressants first line SSRI, Bupropion, venlafaxine, Mirtazepine, mocolbamide .
• Serotonin syndrome. DIs with MAOi gives serotonin syndrome
• Dual acting antidepressants like venlafaxine, bupropion, mirtazepine
• MAOi drugs interactions with sympathomimetics and antidepressants
• SE's of TCAs like amitryptiline

Depression is a feeling of intense sadness. It may follow a recent loss or other sad event but is
out of proportion to that event and persists beyond an appropriate length of time.
Signs and symptoms. Sadness, tearfulness, dejection, self-criticism, loss of ability to experience
pleasure, loss of appetite, inability to sleep and loss of libido.
Depression can be categorized into major depression, and bipolar depression

The drug of choice for the treatment of major depression is SSRIs, dual acting, mirtazepine and
moclobemide.

The drug of choice for the treatment depression and anxiety? Fluoxetine

SSRIs. Fluoxetine, Sertraline , Paroxetine, Citalopram, Escitalopram, Fluvoxamine.

• SEs. Sexual dysfunction, GI, CNS. Nausea is the common.
• Discontinuation: taper slowly over four to 6 weeks.(particularly important for Paroxetine
and venlafaxine).
• Fluoxetine can be used in children & adolescents & pregnancy. SEs: insomnia, potent
CYP2D6 inhibitor
• Sertraline; least DI, Take with food, breastfeeding, SE : diarrhea
• Citalopram; least DI, breastfeed patient
• Paroxetine; breast-feed
• Escitalopram: isomer of citalopram

SNRIs - Venlafaxine
• SE: BP↑(If dose >225 mg/day)

Dual action: Bupropion, mirtazepine, trazadone

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Bupropion: NE&DA reuptake inhibitor

• DOC: depression & smoking cessation
• CI: anorexia or bulimia nervosa, head trauma or prior seizure.
• SE: insomnia, sexual dysfunction (low rate)

Mirtazepine act on NE (directly) & serotonin (indirectly), alpha2 antagonist

SEs. sadation, weight gain (GI & sexual dysfunction is less)

Trazadone. 5HT 2 antagonist with some serotonin reuptake inhibitory properties

• Excessive sadation (300 to 400 mg daily) →as a hypnotic (50-100mg)
• With other antidepressants
• SEs. drowsiness, priapism

TCAs. Desipramine, Nortriptyline, Amitriptyline, Imipramine, Clomipramine, Doxepin,

Trimipramine
• 2nd or 3rd line agent
• SEs. Anticholinergic
• Clomipramine. obsessive-compulsive disorder
• Amitriptyline - chronic pain
• Nortriptyline – elderly depressed patients

Tetracyclic antidepressants – Maprotiline

• Higher risk of seizures than the others

MAOIs;
Reversible: Moclobemide
• Dietary precautions are NOT required at standard doses
• SE: nausea, insomnia (persist)
• DI: Avoid sympathomimetics (pseudoephedrine, ephedrine), meperidine.
• Caution with opioids, antihypertensives, antipsychotics, SSRIs,
• Selegiline, excessive tyramine, alcohol. Reduce dose with cimetidine.

Irreversible: Phenelzine, Tranylcypromine

• Reserved for the treatment of resistant depression
• Food and drug cautions must be followed during treatment and for 2 weeks
• After the last dose of the MAOI
• DI: Sympathomimetics may ↑ BP
• Meperidine may cause agitation, hyperpyrexia, circulatory collapse
• SSRIs, TCAs, levodopa may ↑ effects and side effects
• Tyramine containing food may cause hypertensive crisis.

Washout period
Generally there is no need for a washout period, and a crossover technique can be applied (i.e.,
tapering one agent while titrating the other).
• Exception
• Irreversible MAOI (phenelzine/tranylcypromine)→ other antidepressants 2 weeks
• Moclobemide → other antidepressants 5 days
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• Fluoxetine → an irreversible MAOI 5 weeks

• Caution: when starting other antidepressants after fluoxetine discontinuation.

Serotonin syndrome is an acute condition due to increase serotonin levels and develops within
minutes to hours (typically within 6 hours) after starting a medication, increasing the dose of a
medication, or overdosing.

Signs and symptoms of Serotonin syndrome

Neurobehavioral confusion, agitation, coma, seizures
Autonomic Hyperthermia (fever), diaphoresis (sweating), tachycardia,
hypertension, diarrhea
Neuromuscular myoclonus, rigidity, tremor (shivering), ataxia, shivering, nystagmus

Most cases are mild and resolve spontaneously within 24 to 72 hours. Cardiac arrest, coma, and
multiorgan system failure have been reported as consequences of serotonin syndrome.

Serotonin syndrome occurs with the following agents. Serotonin Syndrome

All SSRIs Miztazapine T =tremor
Venlafaxin Moclobemide H = hyperpyrexia
Non selective MAOi e = excessive muscle tone
Dextromethorphan S = shivering, seizure
Linezolide H = hypertension
A = agitation
The syndrome is possible when these agents are combined with.
N = neuromuscular pain
-each other
-MAOIs C = coma
-lithium, meperidine, pentazocine, and dextromethorphan D = Death
Discontinued symptoms. Fatigue, nausea, dizziness, and lightheadedness, tremors, chills,
insomnia, anxiety and diaphoresis are the most common effects of abrupt discontinuation of
SSRIs.

Trazodone. potent postsynaptic serotonin (5HT 2 ) receptor antagonist, with weak serotonin
reuptake inh.

SNRI. Venlafaxine, duloxetine and desvenlafaxine.

Desvenlafaxine is active metabolite of venlafaxine.

Tips
Find answers from the table:
1. Phenelzine 2. Moclobemide
3. Mirtazepine 4. Venlafaxine
5. Bupropion 6. Lithium
7. Trazodone 8. Fluoxetine
9. Amitriptyline 10. SSRI
11 TCAs 12. MAOInh.

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• Drugs selectively blocks the prejunctional neuronal reuptake pumps in the CNS ( )
• What is the most anticholinergic and sedative TCA ( )
• What drug is used to treat depression with insomnia, what is therapy ( )
• What antidepressant requires 5 weeks washout period ( )
• Antidepressant also used for smoking cessation ( )
• What drug is used to treat depression in sexual dysfunction, what is the best therapy ( )
• An example of an irreversible non selective MAO ( )
• it is the only reversible & selective inhibitor of MAO that is currently available( )
• Drugs acts directly on noradrenergic system & has low rate of GI and sexual side effects but
is associated with sedation and weight gain ( )
• Antidepressant also use for generalized anxiety disorder (GAD) ( )
• Its is used in prophilactically in treating manic-depressive patient, treat manic episodes &
bipolar depression ( )
• What drug serum level should not exceed 1.5 mEq/L (6)
• SSRI onset of action is 
• Fluoxetine washout period 
• Drug of choice in depression with sexual dysfunction 
• Depression with insomnia 
• Depression with diabetes 
• Depression with diabetes, the drug of choice for major depression
• Higher dose of venlafaxine (225mg/day) have effect on 
• A patient on antidepressants and shows with dilated pupil, may be due to
• TCA onset of action is 
• A substance found commonly in fermented foods which can be toxic when MAO inhibitors
are used
• MAO is classified as 
• SSRI like fluoxetine inhibit cytochrome CYP2D6 (True/False)
• Mirtazepine may cause higher weight gain (True/False)
• Avoid cheese with 
• Milk + MAOI 
• St. John wort has antidepressant effect (True/False)
• Serotonergic symptoms
• The drug of choice against bipolar disorders and manic depression -->
• Lithium toxicity symptoms -->
• What antidepressant is used as pharmacotherapy for smoking cessation 
• Paroxetine therapeutic use -->
• What antidepressants are NOT used to treat bulemia and anorexia nervosa -- 

Select TRUE OR FALSE Statements

• Buprapion, trazadone and mirtazepine have least sexual dysfunction (True/False)
• Take SSRI in the morning and TCAs in evening or bedtime (True/False)
• Normal blood levels of lithium in adult should not exceed is 1.5 mEq/L (T/F)
• Lithium concentration varies with Na+ ions (True/False)

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• Li+ conc. increases with decrease Na+ and Li+ conc. decreases with Increase in Na+ (T/F)
• ACEI, NSAID, Thiazides, decreased renal perfusion  increase Li toxicity
• Fluoxetine (SSRI), dehydration and renal dysfunction increase Li+ toxicity(T/F)

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Pharmacyprep.com Antipsychotic Drugs

94
Anti Psychotic Drugs
Symptoms. The schizophrenic individual is out of touch with reality, hallucinates, hears voices
and exhibits bizarre behaviour. These symptoms are only one aspect of schizophrenia. Other
symptoms are social withdrawal, and an inability to communicate or to concentrate.

Positive Symptoms Negative Symptoms

Reality distortions. Delusions persecution Blunted affect: Lack of expressed emotion,
Grandiosity, thought broadcasting, thought Poor eye contact and inattentiveness, and
insertion, loose associations, gestures, mind- Reduced spontaneity.
reading, and being controlled.
Alogia: Lack of spontaneity of conversation and
Hallucinations. Auditory (most common) poor ability to concentrate
Olfactory, somatic, and visual.
Avolation/apathy: Lack of interest in activities, no
Disorganizations. Disorganized speech motivation, social withdrawal and poor hygiene.
Incoherent speech, Tangentiality and Loose
association Anhedonia: Loss of pleasure and Few recreational
activates
Disorganized behavior. Agitation, Hostility
Assaultiveness, Uncooperativeness, Attentional impairment. Lack of ability to
Inappropriate sexual/social behavior, concentrate on tasks or conversation
Inappropriate dress and catatonia.
Treatment. 2nd generation
st nd
Treatment. 1 & 2 genereration
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Antipsychotics side effects are associated

extrapyramidal symptoms. Parkinsons like symptoms
(tremors), akthisia (motor restlessness), tardive Parkinson's Symptoms
dyskinesia (inappropriate postures of neck, trunk and T = Tremor
limbs), and dystonia. R = Rigidity
Parkinson’s symptoms include T = Tremor, R = A = Akinisia
Rigidity, A = Akithisia, P = Postural instability P = Postural unstability
• 1st gen (haloperidol, loxapine, chlorpromazine,
thioridazine) is effective in positive schizophrenic Extrapyramidal symptoms
symptoms. However, 2nd gen (clozapine, P = Parkinson's symptoms
risperidone, olanzapine, quetiapine) covers
A = akthisia
negative schizophrenic symptoms. Olanzapine,
not effective for the treatment of resistance, and D = dystonia
risperidone works for negative and positive T = Tardive dyskinesia
symptoms.
• Orthostatic hypotension is SEs of 2nd generation
antipsychotics (can cause additive effects with other antihypertensive drugs).

1nd generation Antipsychotics

Low potency
• Chlorpromazine. SEs. QT c prolongation
• Methotrimeprazine

Intermediate potency
• Loxapine, Perphenazine
• Zuclopenthixol –injectable FGA , long T 1/2, Do not use in antipsychotic-naïve patients

High potency
• Fluphenazine, Flupenthixol
• Haloperidol: with Lorazepam im for acute phase. SE: QT c prolongation
• Pimozide; SE : QT c prolongation with dose > 8mg/day (avoid use with sertraline)
• Thiothixene and Trifluoperazine

2ndgeneration Antipsychotics (SGAs)

• Advantage in first-episode psychosis, in improving negative symptoms, mood and cognitive
deficits and in preventing relapse and rehospitalization.
• First line treatment
• Depression in the acute phase effectivity SGAs>FGAs
• SEs. ↑glucose abnormalities

Clozapine. Only antipsychotic with proven efficacy in treatment-resistant schizophrenia

• Not first-line (SEs. agranulocytosis, need for regular blood monitoring).
• MOA. Inhibit D (less), 5HT, H 1 , M and α 1
• SEs. Weight gain (greatest), hyperlipidemia, agranulocytosis > (1%), increase risk of diabetes,
dyslipidemia, orthostatic hypotension, and high weight gain
• TU: Drug of choice in resistance psychosis, -ve and +ve symptoms

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• MON: CBC q week

Risperidone: SE; hyperprolactinemia (dose-related). EPS

• Risperidone-tabs oral disintegrating – do not split
• SE: hyperprolactenemia

Olanzapine. SEs. Weight gain (greatest), hyperlipidemia, EPS (especially akathisia)

• Use for acute phase: do not combine with parenteral BDZs. (cardiac & respiratory problems)
• Olanzapine- orally disintegrating May stir into 125 mL of water, milk, coffee, orange juice or
apple juice consume immediately.
• Approved for acute treatment of mania
• SEs: no hyperprolactenemia

Quetiapine . SEs.Increase risk of diabetes, hyperlipidemia (↑TG), and ↓ thyrois hormone levels

Paliperidone is the active metabolite of risperidone.

Ziprasidone. Agonist activity at 5T 1A receptors and unlike other SGAs has antagonist activity of
5HT 1D . Must be taken with food.
Aripiprazole. Partial agonist of D 2 and 5HT 1A . and potent antagonist activity at 5HT 2A receptor.
Potential efficacy in -ve symptoms.

Extrapyramidal side effects. (EPS. dystonia, parkinsonism, akathisia, tardive dyskinesia, tardive
dystonia).
Management. Prevention, use SGAs first-line
if EPS occurs, first reduce dose, consider switch to SGA if on FGA, anticholinergics (benztropine,
procyclidine and trihexyphenidyl) should NOT be used prophylactically even with FGAs, and
should usually only be used on a short-term basis to treat parkinsonism associated with FGAs,
anticholinergics are generally not recommended with SGAs
akathisia - if dose reduction is not effective→ β-blockers (e.g., propranolol 10 to 120 mg/day);
anticholinergics are ineffective
dystonia (acute torticollis or oculogyric crisis) → IM benztropine or diphenhydramine (acute),
followed by reduction in dose or switch to SGA.

Neuroleptic malignant symptoms. Fever, muscle rigidity, Autonomic disturbance, fluctuation in

BP, Tachycardia, elevated WBC, and CK.
NMS is treated by dantrolene, or bromocriptine
Comparison of antipsychotic drug side effects
st nd
Typical (1 generation) Atypical (2 generation)
High sedation Low sedation (respiradone)
Low weight gain High weight gain (clozapine)
High tardive dyskinesis Low tardive dyskinesia – clozapine
High anticholinergic SE Low anticholinergic side effects
High Sexual Dysfuntion Low sexual dysfuntion (quitiepine)
High EPS Low EPS

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Tips
• 1st gen (haloperidol, loxapine, chlorpromazine, thioridazine) is effective in positive
schizophrenic symptoms. However, 2nd gen (clozapine, risperidone, olanzapine, quetiapine)
covers negative schizophrenic symptoms. Olanzapine, not effective for the treatment of
resistance, and resperidon works for negative and positive symptoms.
• Orthostatic hypotension is SE of  2nd generation antipsychotics (can cause additive effects
with other antihypertensive drugs)
• Mechanism of clozapine  D 2 , D 4 , 5HT, H 1 , M and 
1 blockers
• Drug of choice for acute agitation in seniors Quetiapine
• 1st generation 4 to 8 weeks no response, change to 2nd generation.
• Severe case of psychosis (schizophrenia) or bipolar disorder  add mood stabilizers
(Valproic acid, carbamazepine)
• For 1 episode of psychosis, continue for 1 to 2 yrs and for 2 episode, continue treatment for
2 to 5 yrs

1. Zuclopenthixol 2. Haloperidol 3. Chlorpromazine

4. Risperidone 5. Clozapine 6. Olanzapine
7. High EPS 8. Tardive dyskinesia 9. Weight gain
10. Agranulocytosis 11. WBC 12.
• 1st generation 4 to 8 weeks no response, change to 2nd generation.
• Severe case of psychosis (schizophrenia) or bipolar disorder 
• 2nd gen (clozapine, olanzapine) increase risk of lipids and diabetes, EXCEPT: Respiridone
• Least extra pyramidal symptoms 
• Highest EPS 
• Patient experiencing hallucination 
• Patient experiencing social withdrawal 
• 2nd generation covers
• Schizophrenia is characterized by 
• Metoclopramide 
• Chlorpromazine 
• Tardive dyskinesia is caused by 
• TD symptoms 
• For resistance schizophrenia DOC 
• Mechanism of clozapine 
• Drug of choice for acute agitation in seniors
• it is not use in antipsychotic-naïve patients ( )
• it is the only antipsychotic with proven efficacy in treatment-resistant Schizphrenia ( )
• the most widely used treatment for psychotic agitation ( )
• it is used in patients experiencing withdrawal ( )
• this can cause lupus like syndrome ( )
• this should not combine with parenteral benzodiazepines ( )
• highest extrapyrimidal symptoms ( )
• WBC should be monitored because of high agranulocytosis ( )
• act on dopamine & serotonin receptors almost equally ( )
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www.PharmacyPrep.Com Dementia

95
Dementia
Severity of dementia
• Mild dementia. Forgetting daily activities. Example taking medicines, tel.phone number,
finances, directions.
• Moderate. Forgetting personal activities. Bathing, dressing, eating (remember upon
reminders).
• Severe. Forgetting personal activities but cannot recall upon reminders.
• Terminal. Patient must be fed, immobile and mute.
• Alzheimers dementia is due to? deficiency of acetylcholine.
• Levy body dementia associated with psychosis.

Diagnosis.
MMSE. Minimental scale exam is used to assess cognitive impairment.

Amyloid plaques are found in? Alzheimers dementia.

Drug of choice of Alzheimer dementia? Donepazil

Drug of choice of Levy body dementia? Rivastigmine

Symptoms. Memory loss, disorientation, impaired executive functions, behavioural

distrubances, depression, psychotic disturbances, and inability to care for self.
Risk factors. Age, family history (genetic link), head injury, and cardivascular risk factors.

Drugs for Alzheimer’s disease

Reversible
Acetylcholinesterase inhibitor

Nonselective Selective

Galanthamine
Donepezil Rivastigmine
(relatively selective)
Tacrine. Oldest drug, it is non selective and limited used because of its hepatotoxicity.
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• Donepezil. Centrally active reversible, non competitive. It selective and have greater
affinity for AchEI in brain than periphery. Little or no hepatotoxicity.
• Rivastigmine: is centrally selective arylcarbamate AchEI, it has short half life of 2hours,
but able to inhibit AchEI upto 10 hours. Because of slow dissociation of carbamate
enzyme it is referred as pseudo-irreversible AchEI.

Donepezil
Drug of choice for Alzheimer's dementia.

Mechanism
• Centrally active reversible, non competitive. It selective and have greater
affinity for AchEi in brain than periphery. Little or no hepatotoxicity.
• Reduces the hydrolysis of acetylcholine, increasing the amount available in
the synaptic cleft.
Side effects GI effects. Nausea, vomiting and diarrhea.
DUMBLESS • CNS effects. Fatigue, insomnia, headache
• Other effects. Muscle cramps, anorexia, and difficulty in passing urine.

Dosage • Daily one dose in the morning or evening

• Initial 5 mg/day, target 10 mg/day adjust dose after 4 wk
Advantage • Toxicity may be ↑ by inhibitors of CYP2D6 or CYP3A4 (e.g. paroxetine,
erythromycin, prednisone, grapefruit juice, nefazodone).
Drug and Drug • Effectiveness may be ↓ by inducers of CYP2D6 or CYP3A4 (e.g.
Interactions carbamazepine, phenytoin, rifampin).
Monitor • Periodic checks may be performed to see benefit of drug.

Rivastigmine

Mechanism
• Inhibits non specific butyrylcholinesterase and reversible
acetylcholinesterase or centrally selective arylcarbamate AchEi,
• It has short half life of 2 hours, but able to inhibit AchEi up to 10 hours.
Because of slow dissociation of carbamate enzyme it is referred as
pseudo-irreversible AchEi.
Side effects • Weight loss due to reduced appetite. Nausea, abdominal pain.
• Depression, agitation, confusion, drowsiness, dizziness
• Weakness, trembling, sweating, malaise, convulsions (rare).
Therapeutic use • Drug of choice to treat Lewy body dementia.
• Treatment of Lewy body dementia. Avoid antipsychotics
• Acute pain such as dysmenorrhea (painful periods).
Dosage • For rivastigmine, the initial dose is 1.5 mg PO BID, and can be doubled to
3 mg PO BID after 30 days, which is the minimum effective dose.

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Galanthamine

Mechanism Selective, competitive, reversible acetylcholinesterase inhibitor and also

enhances the action of acetylcholine on nicotinic receptors.
Therapeutic Effective in Alzheimer’s and vascular dementia.
use
Side effects Nausea, vomiting, abdominal pain, diarrhea, indigestion, decreased appetite
and weight loss, headache, dizziness, tiredness, sleepiness or sleeplessness,
confusion, runny nose, urinary tract infection, and falls.
Dosage 16- 32 mg bid.

Memantine. NMDA receptor antagonist.

Tips
1 Donepezil 2 Rivastigmine
3 Galanthamine 4 Memantine
5 Tacrine 6: Mild dementia
7: moderate dementia 8: decrease Ach

• it is non selective & limited use because of its hepatotoxicity( )

• causes Alzheimer’ dementia ( )
• the drug of choice of Alzheimer’ dementia ( )
• effective in Alzheimer’s & vascular dementia( )
• effective in Lewy body dementia ( )
• drug that has anorexia side effect ( )
• it is effective for patients with dementia associated with Parkinson’s disease( )
• N-methyl D-aspartate (NMDA) blocker ( )
• forgeting instrumental activities of daily living (phone #s, keys, driving direction, finance) ( )
• forgeting daily activities (bathing, feeding, dressing), recalls upon reminders. ( )
• DOC for Alzheimers is 
• Alzheimers occurs due to 
• Donepezil and rivastigmine and galatamine all have anorexia SE.
• Delirium is 
• Amnesia is
• What are risk factors for Alzheimers disease 
• Levy body dementia 
• Galantamine is classified as 

Terminology
• Dementia is a decline in mental ability that usually progresses slowly, in which memory,
thinking, judgment, and ability to pay attention and learn are impaired, and personality may
deteriorate.

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• Delirium: Acute mental disorder, with symptoms of acute agitation, hallucination, extreme
excitement, and disorientation.
• Delirium tremens: Acute psychosis caused by alcohol withdrawal.
• Aphasia : Impaired ability to communicate
• Amnesia: short time loss of memory
• Dysarthia: difficulty of speech

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96
Epilepsy
Antiseizure drugs by mechanism of action

Reduces NMDA Affect GABA Reduce Na+ Reduce Ca2+

Receptor activation receptors conductance in current
hyperactive neurons through T-
channels

*Felbamate Phenobarbital
Primidone
Ethosuximide

Carbamazepine
Diazepam Phenytoin
Vigabatrin Fosphenytoin
Topiramate Lamotrigine
Tiagabine
Gabapentine
Valproate
Pregabalin
Valproic acid
Focal or partial seizures

Simple Partial. With NO loss of consciousness like somatosensory warning also called auras.
Complex Partial: With alteration of consciousness. The patient may have periods of memory
loss, automatism, and aberrations of behaviour.

Generalized seizures. Have loss of consciousness and involvement of both hemispheres.

Generalized seizure can be sub divided by EEG and clinical manifestation.
Partial Seizure
Comments Drug of choice
Simple Seizures begin locally 1st Carbamazepine
partial Consciousness not impaired 2nd Phenytoin
With motor symptoms jerking, lip smacking, 3rd Primidone

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chewing motions 4th Gabapentin

With autonomic symptoms. Sweating, pupil
dilation.
With behavioral symptoms
Complex Seizure begin locally Drug of choice:
partial With conscious impairment 1st Carbamazepine
Begin as simple 2nd Phenytoin
With or without automatism (automatism: picking 3rd Phenobarbital
at cloths is common may follow visual, auditory 4th Valproic acid
hallucinations)

Generalized seizures
True absence seizures (petit mal)10 to 30 seconds, causes alteration of
Absence consciousness, starts with occasional blinking (Nystagmus).
seizures Avoid phenytoin and carbamazepine use in absence seizure.
(Petit mal) Drug of choice is ethosuccimide.
Myoclonic Sudden very brief involuntary jerking of facial, limb, and trunk muscles or all
seizures body.
Tonic-clonic Tonic seizures generally occurs in children, muscle stiffening (tone)
seizure (grand Clonic seizures. Sustained muscle contraction altering with relaxation.
mal) Sudden loss of consciousness, become rigid, falls to the ground, last about 1
minute.
Single prolonged seizure lasting more than five minutes.
Status In some cases no regain of consciousness between attacks. DOC is iv
epilepticus diazepam.

Anti-Epileptic Drugs
Iminostilbene Derivatives: Carbamazepine, Oxcarbazepine
• Carbamazepine: SEs. transient neutropenia may worsen absence (petit mal) seizures
Stevens Johnson syndrome
• Oxcarbazepine: SEs: hyponatremia, skin rash cross-reaction with carbamazepine
• NO auto induction of liver enzymes.
• ↑ clearance of warfarin, OCs, TCAs and risperidone
• DOC for partial seizures, tonic clonic seizures, treat trigeminal neuralgia

Hydantoin Derivatives: Phenytoin

• Available as: Phenytoin 100% suspension & chewable. Phenytoin sodium (capsule & iv) are
phenytoin 90% sodium 10%
• SE: Skin rash, gingival hyperplasia, and nystagmus
• NOT effective for absence (Petit-Mal) seizures.
• Phenytoin suspension and chewing tablets are 100% phenytoin
• Gingival hyperplasia, recommend mouth hygiene and 0.15% chlorhexidine mouth rinse
• Space 30 min before or after food
• Swish and swirl then spit out.

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Benzodiazepines (BDZs): Clobazam, Clonazepam, Diazepam, Lorazepam, Nitrazepam

• Rapid onset, tolerance
• Regulated: Can be transferred once only
• Destroying: Can be witness by: Pharmacist, Intern and
• Inspector from a college of pharmacy
• Tolerance to therapeutic effects.
• Diazepam iv; used for status epilepticus

Succinimide Derivatives: Ethosuximide

• For absence seizures only, few DI
• Least teratogenicity

GABA Derivatives: Gabapentin, Vigabatrin

• SE: vision changes and trmors, and visual changes,
• Gabapentin: No DI, can use in liver failure, “add on”drug, TID dosing
• Vigabatrin: few DI, can use in liver failure, worsen absence seizures
• DI: No interaction with oral contraceptives
• Safe in pregnancy. Not metabolized. Can be used in liver failure.
• Gabpentin: Administration with Al/Mg, Ca antacid may ↓bioavailability.
• Gabapentin: drug of choice to treat trigeminal neuralgia, diabetic neuropathy.
• Vigabatrin: worsens absence seizure
• Pregabalin: Post herpetic neurologia (PHN) and deiabetic neuropathy (DeP)

Barbiturates: Phenobarbital, Primidone

• Used for generalized seizure
• Tolerance is common
• Phenobarbital – take at bedtime (long t1/2 )
• Primidone – metabolized to phenobarbital
• Control Drug Substance and require sales reports

Carboxylic Acid Derivatives: Valproic acid, Divalproex

• SE: teratogenicity, GI (Valproic acid > Divalproex). Very low incidence of rash
• No ↓OCs efficacy
• DOC: mixed 1° generalized seizures (generalized tonic-clonic, myoclonus, absence)
• Pregnancy Neural tube defects
• No interactions with oral contraceptives
• Low incidence of rash, Steven Johnson’s syndrome

Other Anticonvulsants – Lamotrigine, Levetiracetam, Topiramate

• Lamotrigine. SE: insomnia, rash, no enzyme induction
• Levetiracetam – No DI
• Topiramate. SEs. kidney stones, weight ↓, cognitive problems (limit use), ↓ efficacy of OC’S,
word finding difficulties. ↓ efficacy of OC’S, expensive
• Also used as weight loss drug

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Tips
1 Carbamazepine 2 iv Diazepam
3 Phenytoin 4 Gabapentin
5 Topiramate 6 Valproic acid
7 clobazam 8 phenobarbital
9 gingerval hyperplasia 10 steven jhonson syndrome
11 simple partial seizures 12 Generalised seizure
13 petit mal (absence) seizures 14 tonic clonic
15 Status epilepticus
• it has the least drug interaction with oral contraceptives ( )
• the drug of choice for status epilepticus ( )
• it is use for partial seizures and tonic clonic seizures ( )
• it causes Steven Johnson syndrome side effect ( )
• it is not effective in absence (petit mal ) seizures ( )
• the drug of choice for trigeminal neuralgia ( )
• it enhances GABA activity; antagonizes amino acid ( )
• the drug of choice for generalized seizure ( )
• it decrease the efficacy of oral contraceptives ( )
• Carbamazepine interferes with thyroid function test
• Phenobarbital and phenytoin stimulates -->
• Carbamazepine is DOC for -->
• DOC for status epilepticus is -->
• Avoid phenytoin in -->
• Phenytoin have -->
• Gingival hyperplacia associated with phenytoin is treated by mouth hygiene and
chlorohexidine mouth wash.
• Chlorhexidine is used for -->.
• Carbamazepine, phenytoin, clonazepam -->
• Gabapentin and valproic acid, lamotrigine have no interaction with oral contraceptives
• Topiramate cause 
• Gabapentin has least 
• Phenytoin available as -->.
• Carbamazepine available as -->
• Clobazam has high 
• Gabapentin and lamotrigine 
• Xerostomia 
• Sialorrhea 
• Vigabatrin + carbamazepine 
• A patient is on phenytoin but now dose is increased, when is the appropriate time to
measure steady state
• Phenytoin blood levels monitored for 
• List the monitoring parameters for phenytoin

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97
Anti-Parkinson’s Drugs

Symptoms: dysarthria, gait disorders, postural instability, cognitive

dysfunction.

Levodopa and Levodopa/carbidopa

• Decarboxylase inhibitor: carbidopa & benserazide used to minimize
acute side effects
• Motor fluctuations & dyskinesia →develop in up to 50% of patients
after 5 years
• Slow-release preparation → good for patients having “wearing-off”
• cognitive dysfunction → poorly responsive to levodopa therapy
• SE: N & V, orthostatic hypotension, dyskinesias, hallucinations,
confusion
• Avoid VB 6 supplements
• Take empty stomach preferably

Dopamine agonists: Bromocriptine, Pergolide, Pramipexole, Ropinirole

• Adjunctive therapy with levodopa → good for an advanced Pts with

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motor complications
• Initial therapy in younger patients (<70y)
LEVODOPA
add levodopa if they need
L = Levodopa is the DOC for parkinsons
• SE: GI upset, orthostatic hypotension, E = empty stomach
psychiatric reactions (hallucinations and V = Vomiting and Nausea
confusion) > levodopa O = orthostatic hypotension
• Ergot dopamine agonists (pergolide & D = dyskinesia / domeperidone for N/V
bromocriptine). SE: pulmonary fibrosis P = Protein diet interactions, so avoid
(chest X-ray before initiating therapy), A = Avoid VB6 supplements
erythromelalgia, cardiac valve fibrosis
(pergolide)
• Non-ergot dopamine D 2 selective agonists (pramipexole & ropinirole). SE: sudden sleep
attacks, better choice than ergot dopamine agonists
• bromocriptine: take with food

MAO-B I: Selegiline, Rasigline

• Good for the first year of treatment (very mild effects & don’t delay the development of
dyskinesia or fluctuations associated with L-dopa therapy)
• Potent: Rasagiline > Selegiline
• SE: insomnia
• Selegiline: may need ↓dose in women taking OCs

NMDA receptor antagonists: Amantadine

• Improves L-dopa-induced dyskinesia in the later stages of the disease
• MOA: releasing dopamine from the presynaptic terminals or by blocking its reuptake
• SE: leg edema, erythema, livedo reticularis
• Caution: patients with cognitive deficits a (↑confusion)

Anticholinergic agents: Benztropine, Ethonopropazine, Procyclidine, Trihexyphenidyl

• Effect on tremor, bradykinesia (little or no effect)
• Use as monotherapy or as adjuncts to dopaminergic therapy
• Benztropine – take with food

COMT Inhibitors: Entacapone

• COMT (catechol-O-methyl transferase), an enzyme that helps metabolize Ldopa, is found in
both the brain and in the peripheral nervous system
• MOA: prevent peripheral metabolism of Ldopa, which increases its availability to the brain
• SE: relate to ↑ dopaminergic activity in the brain (dyskinesia, confusion/hallucinations etc.)
• ↓30% dose of Ldopa with COMT inhibitor
• Tolcapone; SE: hepatotoxicity (only through the Special Access Program, Health Canada, for
use in exceptional cases)
• Entacapone; SE: diarrhea (often weeks to months after initiation), discoloration of the urine,
NO hepatotoxicity

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Tips
1 deficiency of dopamine 2 Amantadine
3 Entracapone 4 Levodopa
5 Selegiline 6 Tolcapone
7 levodopa/carbidopa 8 Bromocriptine
9 does not cross blood brain barrier 10 tardive dyskinesia
11 MAO- type B inhibitor 12

• it is a non selective dopamine agonist ( )

• it is converted to dopamine within presynaptic dopaminergic neurons ( )
• it is indicated in Parkinson’s disease and also for prevention and treatment )of Influenza A
viral infections (
• it a selective MAO type B inhibitor ( )
• it help prevent peripheral metabolism of levodopa, which increase its availability to the
brain ( )
• PD is due to decrease in 
• Levodopa does penetrate into brain ( )
• Dopamine does not penetrate into brain ( )
• Carbidopa does not penetrate into brain ( )
• Dyskinesia
• Metochlopramide an antiemetic drug should be avoided in PD patient
• All antipsychotics require caution in PD
• Levodopa/carbidopa is DOC in PD
• Selegline is a selective MAO- type B inhibitor
• Akinesia 
• Bradykinesia -->
• Over treatment of Parkinsonism drugs can result into 
• Sciatic nerve: are found in all foot branches
• Why do we add entracapone to levodopa treatment in parkinson’s -->

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98
Antimicrobials
Eye Infections

Eye Infections

Blepharitis Hordeola Conjunctivitis Keratitis

Or Stye

Hordeola (external hordeolu ‘stye’) or (internal hordeolum “acute meibomianitis)

Causative agent S. aureus
Site of infection At the edge of the eyelid or underneath it. Head and it ruptures
spontaneously within days.
Treatment Warm compresses + oral antistaphylococcal agent e.g. cloxacillin or
flucloxacillin.
Comments Incision and drainage are indicated and patient should be referred to an
ophthalmologist if the patient does not respond to the treatment above.

Conjunctivitis (pink eye or red eye)

Causative Viral, bacterial, chlamydial & noninfectious, allergy, foreign body.
agent
Treatment Chlamydial disease in adults. Oral tetracycline (doxycycline 100 mg 12 hourly) or
Erythromycin (safe in pregnancy) (500 mg 6 hourly) for 7 days, or Azithromycin
(safe in pregnancy) 1 g PO as a single dose.
Amoxicillin (safe in pregnancy). Gonococcal conjunctivitis in adults. Ceftriaxone 1 g
IM as a single dose.
Comments Purulent or mucopurulent discharge suggests a bacterial or chlamydial cause.
Symptoms Watery discharge may be associated with upper respiratory infection or
adenovirus.
Hallmarks of viral conjunctivitis are follicular reaction and preauricular
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lymphadenopathy.

Viral conjunctivitis (“pink-eye”)

Treatment Treatment is supportive
Topical corticosteroid therapy is controversial.
Comments Children are generally kept out of school for up to 2 weeks after the onset
of the infection

Bacterial Conjunctivitis
Causative agent Staphylococcus and/or Streptococcus for adults
Haemophilus influenza more common in children
Treatment Alternative agents include Gentamicin or Tobramycin eye drops (adults),
and ointment (for children), or Fusidic acid eyedrops

Conjunctivitis in newborn (ophthalmic neonatum)

Causative agent Chlamydia trachomatis or Nisseria gonorrhea
Treatment Chlamydia trachomatis. Erythromycin syrup (40 to 50 mg/kg/day) in 3
divided doses for 14 days. If needed treat parents for genital infection.
Nisseria gonorrheae.Ceftriaxone 25 to 50 mg/kg IM as a single dose. If
needed treat parents for genital infection
Comments The best form of prophylaxis is 2.5% aqueous povidone-iodine solution.

Canaliculitis
Causative agent Actinomyces, and rarely propiobacterium, nocardia or bacteroids.
Treatment Mechanical expression of the exudative or granular material from
canaliculi, combined with probing and irrigation of the nasolacrimal
system with penicillin G (100,000 U/ml) eye drop solution.
Comments Patients should be referred to an ophthalmologist for definitive treatment.

Dacrocystitis
Causative agent Streptococci including S pneumoniae or S. aureus but culture should
guide definitive therapy
Site of infection Infection of nasolacrimal sac
Treatment Acute infection:
Oral amoxicillin-clavulanate or cefuroxime
Chronic infections:
Irrigate the outflow tract with an antibiotic solution such as penicillin G
(100,000 U/ml) as a temporary measure.
Definitive surgical decompression ultimately rests with the
ophthalmologist

Keratitis
Causative agent Bacteria, Fungi, Herpes simplex virus, acanthamoeba
Site of infection Infection of the cornea
Comments It is a sight-threatening ocular emergency and requires prompt recognition
and immediately referral to an ophthalmologist.

Herpes simplex keratitis (Viral) or keratoconjuntivitis

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Causative Herpes simplex (HSV-1)

agent
Treatment Epithelial disease. Topical antiviral agents e.g. acyclovir ointment applied
to eye 5xday, continued for at least 3 days after healing.
Trifluridine (Viroptic) and idoxuridine (Herplex-D) ophthalmic drops.
Stromal disease. Complex-combination of antiviral therapy and topical
corticosteroids.

Ear, Nose, and Throat Infections. (Upper respiratory Tract Infections)

Causative agent
Common cold (acute Viruses e.g. Rhinoviruses
rhinitis)
Sinusitis Bacteria e.g. Streptococcus pneumonia
Pharyngitis Viruses e.g. Adenovirus, Bacteria S. pyogenes
(Sore throat)
Acute bronchitis Viruses e.g. Myxoviruses
Chronic bronchitis H. influenza
Pneumonia (CAP) S. pneumonia, H. influenza, M. catarrhalis,M.pneumonia
CAP DOC.in out patient. Azthromycin, Clarithromycin,
Doxycyclin.
Otitis media S. pneumonia, H. influenza, M. catarrhalis
DOC. Amoxicillin, amoxi/clav, azithromycin, clarithromycin,
cefuroxime axetil.

Skin and Soft Tissue Infections

Bacterial skin infections

Cellulites Impetigo Folluculitis Erysipelas Necrotising fascitis

Normal skin Gram (-) ve and Staphylococcus viridans, Streptococcus diphteroid

flora Propionobacterium, actinobacter and yeast.
Normal person carry 1012 bacteria on the skin, including Staphylococcus
epidermidis and Propionibacterium acnes.

Cellulitis
An acute spreading infection of the dermis. Lesion is hot, usually red and swollen,
edematous.
Causative Strep. pyogenes and/or Staphylococcus aureus
agent
Site of Dermis
infection
Treatment Cloxacillin PO/IV and amoxicillin, cephalexin 7-10d, Clindamycin and
cotrimoxazole and azithromycin and clarithromycin.

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Impetigo
Causative agents Strep. pyogenes (hemolytic group A Strep) and/or S. aureus and presents
as bullous, crusted or pustular eruption of the skin.
Site of infection Epidermis layer due to local invasion of causative agent.
Treatment Cephalexin 7–10 d, if topical fusidic acid or mupirocin 7 –10 d (only
topical, because unique mechanism (selectively bind to bacterial
isoleucyl-tRNA) and no cross resistance with antibacteria) .

Follculitis, boil (furuncles) and carbuncles

Causative agent S. aureus
Site of infection Invasion of S. aureus in the hair follicles causing minor abscess
Treatment Penicillin's or amoxicillin

Erysipelas
Erysipelas is a rapidly spreading infection of the skin (dermis)
It has weel-defined spreading erythematous inflammation, usually
accompanied by fever and other systemic manifestation
Causative agent/s Streptococcus pyogenes, Occasionally S. aureus
Site of infection Dermis of the face
Treatment Penicillin or Amoxicillin, with or without Fluoxacillin as S. aureus may
occasionally be the causative agent.
Necrotising fasciitis
Is an inflammatory response to infection of the tissue below the dermis,
spreading with alarming rapidity along the facial planes causing
disruption of the blood supply hence necrosis and gangrene
Causative agent/s Streptococcus pyogenes (B-haemolytic group A Strep)
Micro aerophilic Streptococci with anaerobic bacteria
Site of infection Soft tissue below the dermis
Treatment Benzyl penicillin, and clindamycin with or without Metronidazole, in
addition to tissue debridment

Fournier’s gangrene
A form of necrotising fasciitis occurring around the groin area
Diabetes and local trauma are the main predisposing factors
Causative agent/s Coliform (E. coli), Streptococci (Group A Strep)
Treatment Penicillin and Cephalosporin's if allergic to beta lactams use Quinolones
(ciprofloxacin)
Comments Pain, fever, and systemic toxicity are usually prominent factor of the
disease
Signs of gas formation and gangrene may also be seen

Infection of Skin by VIRUSES:

Causative agent Disease and Characteristics
Papilloma virus Common wart
Molluscum contagiosum (pox Fleshy papule
virus)
Pox virus from sheep, goats Paplovascular lesions, or skin lesions with systemic spread such
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as herpes simplex (vesicular lesions)

Infection of Skin by fungi

Causative agent Disease and characteristics
Dermatophyte (keratin- Ring worm or skin lesions can be part of systemic manifestation of the
loving fungi) disease such as Cryptococcus neoformans and Blastomyces
dermatitidis.
Tinea pedis Athlete’s foot treatment is clotrimazole 1% cream, miconozole,
tolnaftate (topical).
Where does athletes foot occurs? Between toes

Infection of the CNS

Bacterial Meningitis Disease and characteristics
(Neonatal 6 weeks) Group B Empirical treatment. Ampicillin + Gentamicin or Ampicillin
Strep, E. coli and other + Ceftriaxone
Children (>3 months) and adults: Empirical treatment. Cefataxime, Ceftriaxone or
S. pneumonia, N. meningitis, H. ampicillin or vancomycin
influenza type B (can be
prevented by vaccination)
Elderly (>50 yrs), alcoholics, Empirical treatment: Ceftriaxone or ampicillin or vancomycin.
immunocompromised, head
injuries: E. coli, S. pneumonia, L.
monocytogenes
Meningococcal Infection: Spread by respiratory route, pharyngeal colonization in 5 to
Neisseria meningitidis 10% of population.
Haemophilus influenza type B Affects 6 months to 5 year old children (can be prevented by
Hib vaccine). Spread through respiratory route
(→blood→meninges)
Pneumococcus Elderly patients: pneumonia, immunosuppressed,
haematological malignancy. Very young (<3 months): Head
injury with skull fracture. High mortality (up to 30%).

Encephalitis Virus infection of brain and CNS cells.

HSV-1 (most common), CMV, rabies, mumps, measles,
eschovirus, coxsackievirus
Polio Enterovirus, faecal-oral spread; 90-95% well; 5% viral
meningitis, 1% paralytic polio destroys motor neurons of
anterior lumen
Brain abscess Streptococcus; Staphylococcus;
Haematogenous Direct spread from middle ear, sinuses or mastoid
Usually mixed infection, anaerobes + streptococcus +
haemophilus, coliform

TB meningitis
Causative agent Meningococcus; Pneumococcus; H. influenzae
Site of infection CNS
Treatment Meningococcus: benzyl penicillin
Pneumococcus: benzyl penicillin/cefotaxime or vancomycin if resistant
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H. influenzae – cefotaxime (start with penicillin and cefotaxime)

Prophylaxis: meningococcus – Rifampicin or ciprofloxacin (whole
family/close contacts)
Respiratory infections:
Community acquired pneumonia
Causative agent S. pneumonia (most common)
Ambulatory patients 18 to 40 yr Requiring hospital admission
Mycoplasma pneumonia (24%) S. pneumonia (17%)
S. pneumonia (5%) Mycoplasma pneumonia (14%)
Chlamydia pneumonia (2%) Chlamydia pneumonia (10%)
H. influenza (1%) H. influenza (7%)
Legionella pneumophilia (1%) L. pneumophilia (1%)
Staphylococcus aureus
Treatment Emergency treatment for pneumonia
S. pneumonia. Amoxicillin or Macrolide
High level resistant. Cefotaxime, ceftriaxone, po or iv fluoroquinolones.
H influenza: 2nd and 3rd generation cephalosporins or amoxicillin +
clavalunate
Staphylococcus aureus
Methicillin susceptible - - - Cloxacillin
Methicillin resistant - - - - - Vancomycin
M. pneumonia & C. pneumonia. Doxycycline or Macrolide
Legionella sp.: Fluoroquinolones, macrolide + rifampin
E. coli (aerobic gram -ve bacilli) and proteous sp. 2nd and 3rd Gen
cephalosporins (initial therapy should be with Cefoxitin or piperacillin +
tazobactam)

Bronchitis
Viral Bronchitis Etiology based on age group
(95%) <1 year: RSV (respiratory Syncytial Virus), Parainfluenza, Corona virus
1-10yo: Parainfluenza, Enetrovirus RSV
>10 years: Influenza, RSV, Adenovirus
Bacterial Bronchitis Chlamydia pneumoniae, Mycoplasma pneumoniae
Treatment: Routine antibiotic treatment is not recommended
Antipyretic/analgesic: Acetaminophen
Antitussives: Dextromethorphan
Beta-agonist: Salbutamol

Urinary tract infection

Lower UTI Upper UTI
Urethra (urethritis) Pyelonephritis
Bladder (cystitis) Ureteritis

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Urinary Tract Infection

Causative agent The most common causative agen is E. coli.
Cystitis Cotrimoxazole 3d, Nitrofurontoin 5d, Trimethoprim 3 day or Cephalexin
7d. If ineffective or allergic use ciprofloxacin 3 d.
Urethritis Acute urethral syndrome (urea plasma and chlamydia infection).
Doxycycline. During pregnancy used erythromycin.
Pyelonephritis Bacterial infection of kidney substances.
Ciprofloxacin 7-14 d, cephalosporin's, cotrimoxazole or amino glycosides +
ampicillin (for severe).

Uncomplicated UTI Complicated UTI

Infection in healthy patient with normal GU Factors that aqcuire bacteria and decrease
Tract efficacy of therapy such as abnormal
genitourinary tract (BPH, stone, bladder
cancer, and multidrug resistance)
DOC cotrimoxazole DOC ampicillin+aminoglycoside
Ampicillin + vancomycin
Blood in urine

Sexually Transmitted Infections

Causative Nisseria gonorrhea
agents Chlamydia (in children Chlamydia neonatrum)
Syphilis
Lymphogranuloma
Trichomoniasis. vaginitis (colored discharge)
Bacterial vaginosis. vaginitis (fishy smell)
AIDS
Condylomata acuminate
Hepatitis B and C
Chancroid (syphilis)
Genital herpes
Genital warts (papilloma virus)
Comments Candida infections (Vulvovaginitis) is not STI thereby sexual partner does not
require treatment. Symptoms of candida infections are white curdy discharge. If
reoccur within 2 months, partner need treatment.

Infections of the joint and bones

Joint and bones infections

Arthritis infections Lyme disease Osteomyelitis

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Infectious arthritis
Male/female The gonococcus bacteria may cause different symptoms in women than
differences in men. Women may develop red sores on the hand feet, in addition to
severe pain in the wrist and ankles. In men, the gonococcus will
frequently attack only a single joint, most often the knee.
Treatment Arthritis due to gonococcus can be treated with oral ampicillin.
Surgery is generally not necessary or particularly helpful

Lyme disease
A tick-borne infection can cause arthritis and, in severe cases, heart
and/or CNS complications.
Causative agent Spirochete (Borelia burgdorferi) is transmitted to humans via deer
tick (a tiny insect found not only in deer but in squirrels, rabbits,
other rodents, birds, and household pets)
Comment Prevalent during July to August

Osteomyelitis
It is a bacterial infection of the bone and bone marrow
Causative Agent Staphylococcus aureus. Sequential therapy require.
Gastrointestinal Infection
Normal person carry 1014 bacteria in his GI tract, 95 to 100% of which
are anaerobic. The gut has a resident bacterial population..
Stomach Infection with Helicobacter pylori is common and is associated with
peptic ulcer disease and gastric cancer.
The large These are predominantly anaerobes (99.9%) and an apparent
intestine negligible 0.1%) of aerobes.
Anaerobes Bacteriosides, Bifidobacterium, Clostridium, anaerobic cocci
Aerobes Enterobacteriaceae, E. coli, Klebsiella, Proteus, Enterococci.
Food poisoning
Bacteria Poisoning
Shigella Dysentery (traveler’s bloody diarrhea)
Campylobacter jejuni Traveler’s diarrhea
Salmonella Eggs, poultry, meat
Clostridium difficile Pseudomembranous colitis
Escherichia coli Meat food poisoning and traveler’s diarrhea
S. aureus Meat, mayonnaise, custard
Clostridium perfringens Acute gastroenteritis, reheated dishes
Norwalk virus Diarrhea in hospitalized patient
Entomoeba Amoebiasis
Bacillus cereus (B. cereus) Reheated rice (Be Serious!!!)
Vibrio parahaemolyticus Contaminated sea food
Listeria Meat

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Drug for Pseudomonas aeurigunosa?

What bacteria is not present in CAP infections? P.aeruginosa

Tips
Steven-Johnson’s Syndrome (SJS). Rash, skin peeling, and
sores on the mucus membrane. In Steven Johnson’s SJS may cause by: SASPAN
syndrome, a person has blistering of mucus membrane, S = sulfonylureas
typically in mouth, eyes and vagina. Patchy areas of rash. SJS A = anticonvulstants
can occur in all age groups. S = sulfonamides
Due to SASPAN (sulfonylurea, anticonvulsant (phenytoin, P = penicillin
carbamazepine, valproic acid), sulphonamide, penicillin, A = Allopurinol
allopurinol and NSAIDs). Topical sulfadrugs are N = NSAIDs
contraindicated because it may cause disease like SJS, this
disease is life threatening. Treatment of SJS is cortisone

Cell wall synthesis inhibitors

1 Amoxicillin 2 Penicillins 3 Amoxicillin

4 Type 1 allergy 5 Type 2 allergy 6 Azithromycin
7 Minocycline 8 Clindamycin 9 Metronidazole
10 Doxycyclin 11 Ciprofloxacin 12 Cotrimoxazole

• Methicillin is only IV and IM

• Penicillin G benzathine has long half life
• Naficillin is mainly hepatic elimination
• Beta lactamase sensitive drugs: Pen G, Amoxi, Pen V and Ampicillin
• Endocarditis prophylaxis is (Dental extraction prophylaxis) 
• A child less than 2 y allergic penicillin, what is the drug choice for otitis media treatment
• A patient has heart diseases and underwent prostatic valve surgery. Dentist plan to tooth
extraction, what antibiotic is suitable for endocarditis prophylaxis
• Chewable antibiotics
• Beta lactams that should be taken empty stomach 
• Aminopenicillins are:
• Penicillin allergic patient, alternate drug of choice is?
• Penicillins are ineffective in treatment of bacterial infections associated with 
• MRSA infections are treated by 
• P.colitis associated diarrhea is treated by 
• Bacteria is inhabitant in GI, what location of GI tract is commonly found 
• Type of bacteria mainly present in colon is 
• Penicillin hypersensitive reactions
• If allergic penicillins the best alternate choice of antibiotics is macrolide.
• Penicillins gives what type hypersensitive reaction  Type 1 to V

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Macrolides Tips
1 Erythromycin 2 Clarithromycin 3 Azithromycin
4 Type 1 allergy 5 Type 2 allergy 6 Gastric upset
7 Room temperature 8 Refrigerator 9 H. influenza
10 Doxycyclin 11 Ciprofloxacin 12 Cotrimoxazole

• Azithromycin suspension stored at 

• Clarithromycin suspension stored at 
• Which macrolide suspension have to refrigerate after reconstitution 
• What antibiotics should caution and require monitoring in patient receiving warfarin -
• What antibiotic potentiate the effect of digoxin and can cause digitalis toxicity 
• Azithromycin is the drug of choice in traveler diarrhea for patient traveling to 

Tetracyclin Tips
1 Tetracyclin 2 Doxycyclin 3 Minocyclin
4 Photosensitive 5 Must take empty stomach 6 CC/PC
7 Room temperature 8 Refrigerator 9 H. influenza
10 Calcium supplements 11 Dairy 12 Cotrimoxazole

• Tetracyclin are contraindicated are contraindicated in pregnancy and children.

• Tetracyclin can stain teeth causing discoloration.
• Oral or topical tetracycline are drug of choice for acne treatment
• Tetracyclin MUST BE taken on empty stomach.
• Tetracyclin binds 
• GI distress (abdominal discomfort, diarrhea) are most common SE. This can be prevented by
taking with food or decreasing dose.
• Expired tetracycline can lead 
• Doxycyclin is the DOC 
• Doxycyclin should be taken 
• Minocyclin maybe taken with or without food.
• Phototoxic reactions (sever skin lesions) can develop with exposure to sunlight. Photoxicity
is the most common side effect of doxycyclin or demeclocyclin.
• Epimerization is a 
Tetracyclins = Take empty stomach
Doxycyclins = Take with or after food
Minocyclins = Regardless of food

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Clindamycin Tips
1 Clindamycin 2 Diarrhea 3 P. colitis
4 Photosensitive 5 Must take empty stomach 6 CC/PC
7 Room temperature 8 Refrigerator 9 H. influenza
10 Calcium supplements 11 Dairy 12 Cotrimoxazole

• Most common complication of clindamycin is 

• Clindamycin is active against 
• Pseudomembranous colitis symptoms include: fever, abdominal pain, bloody stools.
• Clindamycin can cause 
• Clindamycin drug associated diarrhea is treated by
• Clindamycin suspension can be stored at 
• Clindamycin should be taken 

Quinolone and fluroquinolone Tips

1 Ciprofloxacin 2 moxfloxacin 3 Nor floxacin
4 Photosensitive 5 Must take empty stomach 6 CC/PC
7 Room temperature 8 Refrigerator 9 UTI
10 Calcium supplements 11 Dairy 12 Cotrimoxazole

• Fluroquinolones are indicated for UTI, Infectious diarrhea (Travellers diarrhea), lower
respiratory tract infections, bone and joint infections (osteomylitis).
• Gatifloxacin, Moxifloxacin SE are 
• FluroquinolonesContraindicated in children, under 18 y, pregnant women due to its
• Antacids, bivalent and trivalent ions significantly decrease absorption of 
• Fluroquinolone increase INR in patient receiving warfarin, therefore monitor 
• Fluroquinolones can cause hypo or hyperglycemia, therefore monitor 
• Fluroquinolones at higher alkaline pH can cause 
• Cipro is the drug of choice in 

Metronidazole Tips
1 Metronidazole 2 Alcohol 3 Trichomonas
4 Amoeba 5 Must take empty stomach 6 CC/PC
7 Room temperature 8 Refrigerator 9 anaerobic bacteria
10 Calcium supplements 11 Dairy 12 Disulfiram like reaction

• Alcohol with metronidazole can cause 

• Metronidazole is classified as: Antiprotozoal drug
• Metronidazole is effective against 
• Metronidazole discolor urine
• Metronidazole caution in pregnancy

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Sulfadrugs Tips
1 Cotrimoxazole 2 Sulphamethoxazole 3 Minocyclin
4 Photosensitive 5 Must take empty stomach 6 PCP
7 Room temperature 8 Refrigerator 9 UTI
10 Calcium supplements 11 Dairy 12 pregnancy

• Sulfamethoxazole + trimethoprim have 

• A 22 year old patient currently using cotrimoxazole for UTI, reported sever rashes on arms,
neck and back, what are the possible reactions
• What are the folic acid synthesis inhibitors
• Patient with G6PD deficiency, takes sulfadrugs can cause 
• Hypersensitive reactions of sulfadrugs most commonly involve 
• Life threatening hepatitis caused by sulfadrug toxicity or sensitization rare SE, the signs and
symptoms include
• Sulfamethoxazole have high frequency of skin hypersensitive reaction in patient with
• If used in last trimester of pregnancy, can cause kernecterus in new born.
• Cotrimoxazole suspension stored at room temperature in amber color glass bottle.
• P. carinii pneumonia (PCP) drug of choice is Cotrimoxazole.

1 Vancomycin 2 Penicillins 3 Tetracycline

4 Clarithromycin 5 Streptomycin 6 Azithromycin
7 Minocycline 8 Clindamycin 9 Metronidazole
10 Doxycyclin 11 Ciprofloxacin 12 Cotrimoxazole

• use in gram +ve anaerobic bacteria Bacteroid fragilis (abdominal infection) ( )

• it should be stored at room temperature ( )
• it is not effective for Mycoplasma bacteria ( )
• it increase Warfarin INR, increase Digoxin & theophylline levels ( )
• it is effective for H. pylori (used along with PPIs in triple therapy ( )
• it is use in treatment of acne ( )
• drug for treating methicillin-resistant Staphylococcus aureus infections ( )
• it has the highest ototoxicity ( )
• it is more active against gram-ve H. influenza than Erythromycin ( )
• it is use for acne and rheumatoid arthritis ( )
• must avoid alcohol while on this drug because it cause disulfiram like reactions ( )
• it is use as prophylaxis in traveller’s diarrhea ( )
• the drug of choice for UTI 7 traveller’s diarrhea ( )
• it is use in chronic treatment of UTI ( )

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1. Amoxicillin 2. Cephalexin 3. Penicillin G and V

4. Cefuroxime 5. Tetracyclin 6. Ceftriaxone
7. Erythromycin 8. Clarithromycin 9. Azithromycin
10. Ciprofloxacin 11. Ofloxacin 12. Clindamycin
13. Trimethoprim- 14. Metronidazole 15. Vancomycin
sulfamethoxazole
(TMP-SMX)

• is commonly causes dose-related GI tract disturbances, including nausea, vomiting, and

diarrhea ( 7,8, )
• raises blood levels of theophylline and potentiates terfenadine in producing ventricular
arrhythmias( 7,8 )
• have enhanced activity against Haemophilus influenza (9 )
• inhibit the activity of DNA gyrase and topoisomerase IV ( 10, 11 )
• are effective in bacterial prostatitis and bacterial diarrhea except that caused by C.
difficile ( 13 )
• as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle ( 13
)
• it is used primarily for the treatment of Trichomonas, amebiasis, giardiasis and P. colitis (
14 )
• Steven-Johnsons syndrome is a severe form of erythema multiforme ( 13 )
• characterized by bullae on the oral mucosa, pharynx, anogenital region, and conjunctiva,
target like lesions, and fever (erythema multiforme major)
• antacids containing Mg or aluminum interfere with absorption if taken within 4 hours (5,
10, 11 )

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99
Anticancer Drugs and
Chemotherapy
Action of DNA

Damage DNA Inhibit synthesis or

functions

Alkylation:
Others Antimetabolites
Mechlorethamine 5-fluorouracil
Cyclophosphamide *Actinomycin D
*Etoposide Cytarabine
Ifosfamide Mercaptopurine
Chlorambucil *Teniposide
*Amsacrine Thioguanine
Melphalan Methotrexate
Busulfan
Lomustine
Carmustine Free radicals:
Streptozolin *Bleomycin
Cisplatin
Topoisomerase
Carboplatin
Dacarbazine inhibitors
Procarbazine Doxorubicin
Altretamine/ Daunorubicin
Hexamethylmelamine Topotecan
Mitomycin Irinotecan

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Definitions:
Neoplasm = New and diseased form of tissue growth
Benign neoplasms = Non cancer form of tissue growth, which can be removed by surgery. No
metastases.
Malignant neoplasms = Cancer form of tissue growth. Invasive growth of cancer.
Malignant neoplasms can be categorized as;
Bone marrow = Leukemia (cancer of cells in blood)
Connective tissue = Sarcoma
Epithelium = Carcinoma
Lymphoid tissue = Lymphoma (also named as Hodkins disease)
Myeloid stem cells = Myeloid leukemia
Endothelium = Kaposis sarcoma
Skin (melanocytes) = Malignant melanoma

Cell Cycle Phases All cells must traverse the cell cycle phases before and during cell division.
Anticancer drugs may act on specific phase. Tumor cells are more
responsive to specific drugs

G 0 phase – Resting phase

G 1 phase – Synthesis of enzymes needed for DNA synthesis
S phase –DNA replication (DNA synthesis)
G 2 phase –Synthesis of components needed for mitosis.
M phase – Mitotic tubule formation Vincristine and vinblastine
Cell cycle phase More active against cells that are specific phase of cycle:
specific drugs G 1 phase L-aspraginase and prednisone
S phase Methotrexate, 6-thioguanine, cytarabine
G 2 specific Bleomycin and etoposide
M phase Vincristine and vinblastine, peclitaxol
Cell cycle specific drug Alkylating agents, Antitumor antibiotic, Cisplatin
(phase-non specific)
Cell cycle non specific Effective whether cancer cells are in cycle or resting phase radiation,
agents nitrosoureas, mechlorethanime

Chemotherapy
The treatment of cancer with drugs is called chemotherapy. Antineoplastic drugs, also referred
to as chemotherapeutic agents, are drugs that are used to treat cancer.
Side effects of chemotherapy
Acute:
• Extravasation (effects the adjacent tissue)
• Vessicant drugs (damage to tissue/necrosis) Example: Bleomycin, cisplatin, dactinomycin,
domorubicin, vincristine, vinblastin etc.
• Thrombophlebitis (inflammation associated with thrombus). Patient with cancer can
develop thrombosis after chemotherapy. Due to activation of fibrinogen.
• Hypersensitive reactions. Example Etopiside, peclitaxol, rituximab, trastuzumab.
• Rapid tumor lysis syndrome
• Nausea and vomiting

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Chronic, organ specific:

Skinalopecia, dry skin, nail changes, pigmentation (melanoma), xerostomia

Alopecia is the loss of hair: Drug that cause alopecia is doxorubicin, daunorubicin,
cyclophosphamide, vincristine, and paclitaxel.
Vessicant agents include: dactinomycin, doxorubicin, mechlorethamine, mitomycin, vincristine,
and vinblastine.
Hair regrowth occurs after 1-2 months after stopping chemotherapy.

Xerostomia: Dry mouth is one of the most common complications associated with radiation
therapy. Reversible after 6 to 12 months of therapy.
Can be managed by: sugar free hard candy, chewing sugar free gum stimulates salivation. Ice
chips, sugarless candies, and commercially available saliva substitute or cholinergic agonist
(Pilocarpine 5mg tab).

Bone marrow depression (Myelosuppression)

• Bone marrow depressionNeutropenia, and thrombocytopenia
• Neutropenia  treated by colony stimulating factors (G-CSF and GM – CSF) Filgrastim or
pegfilgrastim
• Thrombocytopenia  for prevention use Oprelvekin (Inerleukin-11)
• Complications: Bone marrow suppression is the most dose limiting side effect of cancer
• Myelosuppression in general the onset is 7 – 10 days and peak is 10 – 14 days. Recovery
count occurs usually occurs in 2 – 3 weeks.
• Megaloblastic anemia by methotrexateFolinic acid (leucovorin, 5-formyltetrahydrofolic
acid).
• Neutropenia associated anticancer drugs can be treated by filgrastim (human granulocyte
colony stimulating factor).
• Least bone marrow depression anticancer drugs is Bleomycin
• Cancer patient with anemia  Erythropoeitins are useful

Cardiotoxicity:
• Risk of CHF, commonly seen with doxorubicin, daunorubicin, epirubicin, mitoxantrone.
• 5-FU, capecitabine. Cause coronary spasms, mimicking a myocardial infarction (avoid in
know coronary artery disease patients).
• Cardiotoxicity can prevented or lessen by using cardioprotective agent Dexrazoxane

Pulmonary toxicity:
Pneumonitis, pulmonary fibrosis commonly seen with bleomycin, carmustine,
cyclophosphamide, mitomycin, methotrexate, vinca alkaloids.
Symptoms of pulmonary toxicity include SOB, non-productive cough, and rarely low grade fever.

Neurotoxicity:
• Common with vincristine, vinblastine, Cytarabines, Methotrexate (very little), 5FU,
interferon alpha.
• Peripheral neuropathies associated with: Vincristine, peclitaxel: Peresthesia (numbness and
tingling) can occur with vincristine, which often appears within few weeks of therapy.

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• High dose of cytarabin may produce cerebllar toxicity that manifest initially as loss of eye-
hand coordination and progress to coma.
• Fludrabine cause severe neurotoxicity
• Caramustine and other alkylating agents cause little or no neurotoxicity.

GI toxicity
Mucositis or stomatitis:
Mucositis: Generalized burning, and pain on the ventral surface of tongue. Floor of tongue,
mouth looks erythromatus. Stomatitis: generalized inflammation of oral mucosa.
• Mucositis or stomatitis: Common with Doxorubicin, Methotrexate, 5-fluorouracil,
Actinomycin, Bleomycin capecitabine.
• Recommend mouth hygiene, xylocaine, viscous sucralfate, nystatin, sodium bicarbonate, for
severe cases peliformin (growth factor) can be used.
• Avoid alcohol, antihitamine, steroids, spicy food
• Mucositis treatment and prevention:
• Topical anesthetics: Viscous lidocaine, or dyclonine HCL 0.5 or 1%
• Corticosteroid provides anti-inflammatory action.
• Capscisin: Produces burning and pain and ultimately desensitizes pain.
• Sucralfate suspension may provide benefit by coating.
• For Localized effect: use benzocain in orabase.
• Mucositis prevention:
• Chlorhexidine gluconate 0.12% (Peridex, Periogard) may reduce severity and frequency
of mucositis infections.

Nausea and vomiting

• Very high emetics anticancer drugs
• Cisplatin
• Streptozocin
• Cyclophosphamide
• High emetics anticancer drugs
• Doxorubicin
• Methotrexate (250 mg to 1000 mg)
• Cytarabine
• Lowest emetic anticancer drugs
• Bleomycin
• Methotrexate (under 50 mg)
• Vincristine
• Vinblastine
• Tamoxifen

Non pharmacological therapy

• Take small and frequent meals
• Avoid high fat and heavy aroma
• Take dry, starchy foods like crackers

Management of nausea and vomiting associated with cancer chemotherapy:

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• The lowest emitogenic drugs nausea and vomiting can be treated by Dexamethasone PRN
• High and very high emitogenic drugs associated acute: nausea and vomiting can be treated
by Dexamethasone+ Ondansetrons
• DOC for delayed nausea and vomiting  Dexamethasone
• Anticipatory nausea and vomiting Benzodiazepine.

Hepatotoxicity
Hepatotoxicity monitor LFT, jaundice, or hepatitis: asparaginase, cytarabine, mercaptopurine,
and methotrexate.

Nephropathy:
• Elevate BUN and electrolyte abnormalities: methotrexate may precipitate in kidney.
Cisplatin and streptozocin. Amifostine may be used to protect the kidney from the
nephrotoxicity associated with cisplatin.

Sexual dysfunction:
Cyclophosphamide, melphalan, and procarbazine associated with significant infertility in men
and women.

Hemorrhagic cystitis
• It is a bladder toxicity that is seen most commonly after administration of cyclophosphamide
and ifosfamide.
• These drugs produce a metabolite called acrolein, which cause chemical irritation in bladder
mucosa, resulting in bleeding.
• Hemorrhagic cystitis caused by Acrolein can be prevented by excessive hydration and
subsequent frequent urination. The other method is by administering uroprotecting agent
called MESNA, which bind acroleine and prevent from contacting the bladder mucosa.

Pulmonary toxicities. The most common with bleomycin, mitomycin, and carmustine.

Rationale for combination therapy. Overcoming or preventing resistance. Cytotoxicity to resting

and dividing cells. Biochemical enhancement of effect. Beneficial drug interactions’ Rescue host
cells.
Some agents can be administered intrathecally: Methotrexate, Cytarabine’ Thiotepa
Warning: Vincristine should be labelled as Intravenous only. Intrathecally vincristine causes
death.

Metoclopramide and Prochlorpromazine are dopamine antagonist is used for management of

low emitogenic CINV.

Tips
• Examples antimetabolites include -->
• Examples of alkylating anticancer drugs -->
• Non pharmacological measures to prevent nausea and vomiting associated with caneer
chemotherapy.
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• Melonoma is 
• Metoclopramide and dexamethasone are more effective nausea related to 
• Methotrexate is used for 
• Which anticancer drugs cause pulmonary fibrosis
• Hypertropy is 
• Hyperplasia is 
• Least emetic anticancer drug is 
• Cancer patient on cancer chemotherapy, reports shortness of breath, non productive cough,
she may be using drug 
• DOC for delayed Nausea and vomiting  dexamethasone
• Mesna is 
• Doxorubicin preparation should be performed in 
• Hypertropy is 
• Hyperplasia is 
• Melatonin 
• Peclitaxel and docetaxel act on 
• Cancer estimated deaths in men: Lung cancer 31% and Prostate cancer 11%
• Cancer estimated deaths in women: Lung cancer 25% and Breast cancer 15%
• Examples antimetabolites include -->*5-fluorouracil, *Cytarabine, *Mercaptopurine,
*Thioguanine and Methotrexate

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 100
Pharmacognosy & Natural
Products
Natural Products

Natural product Classification Use

Cranberry Antioxidant, Cleanses and stops infections in the urinary tract.
Vaccinium bacteriostatic
macrocarpon effect
Dong Quai Tonic, immuno- Used to treat all symptoms of menopause as an
Angelica sinensis stimulating, anti- alternative treatment to estrogen therapy. Regulates
spasmodic the hormonal system. Overall tonic for female
reproductive system. Reduces high blood pressure
and PMS. Caution: Contra-indication in pregnancy
Echinacea Antibiotic, anti- Stimulates and boosts immune function. Has
Echinacea fungal immuno- cortisone-like activity that helps wound healing.
angustifolia/purpurea stimulating Fights bacterial and viral infections. Contra-
indication in auto-immune diseases (i.e. Multiple
Sclerosis, AIDS)
Evening Primrose Anti-spasmodic Used in treatment of multiple sclerosis and PMS.
Oenothera biennis Helps prevent heart disease and stroke and
maintains healthy skin. Excess consumption can
result in oily skin.
Feverfew Anti-inflammatory, Helps prevent migraine headaches and also useful
Tanacetum emmenagogue against swelling and arthritis. Stimulates digestion
parthenium and improves liver function. Caution: Not to be used
by lactating or pregnant women.
Garlic Antibiotic, anti- Reduces high blood pressure and blood cholesterol.
Allium sativum fungal, anti-viral Immune support for respiratory system. Anti-cancer
and digestive tonic. Caution: Not to be used by
lactating women because it can pass to the breast milk
and cause colic in infants.
Licorice Demulcent, Gastric ulcers, adrenal insufficiency hypoglycemia.
Glycyrrhiza glabra diuretic, Good for coughs and other bronchial complaints.
expectorant, Caution: Contraindicated for those with high blood
laxative pressure or if pregnant.

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Ginger Diaphoretic, Relieves indigestion and abdominal cramping. Benefit
Zingiber officinale cholagogue, in relieving motion sickness, dizziness, nausea and
carminative, colds. Ginger lowers blood clotting.
stimulant
Ginkgo Biloba Anti-asthmatic, Increases blood flow to the brain. Improves memory
Ginkgo biloba bronchodilator, loss. Alzheimer’s disease cerebral vascular
platelet activating insufficiency and inhibits blood clotting. with warfarin
factor (PAF) and Aspirin. Take with food.
inhibitor
Ginseng Tonic, stimulant, Stimulates both physical and mental activity. Anti-
Panax schin-seng demulcent, fatigue (insomnia, nervousness, poor appetite).
stomachic Enhances immune system, inhibits exhaustion of
adrenal gland and anti-stress.

• Echinacea Common cold

• Saw palmetto Prostate (BPH-Benign Prostate Hyperplacia)
• Garlic  lipid levels
• Feverfew  Migraine
• Gingko Increase memory
• St. Johns wart  antidepressant
• Bitter melon anti-diabetic
• Prime rose oil  PMS (premenstrual syndrome)
• Atropine anticholinergic
• Vincristine and vinblastinanti-cancer
• Taxol (pecli-taxol)Yew plants (himalayas)several types of cancers
• Licorice can cause hypertension

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