PHARMACOLOGY

Theory Module

GPAT | NIPER | DRUG INSPECTOR

PHARMACIST
 Contents
Sl. UNITS PAGES

1. Diuretics ............................................................................................................ 1-9

2. Antidiuretics .................................................................................................... 10-11
3. Drugs Affecting Blood and Blood Formation ......................................... 12-16
4. Drugs Affecting Coagulation and Bleeding ............................................. 17-27
5. Hypolipidaemic Drugs and plasma expanders ...................................... 28-33
6. Drugs for Peptic Ulcer and Gastroesophageal Reflux Disease .......... 34-39
7. Emetics, Antiemetics and Other GIT Drugs ........................................... 40-43
8. Drugs for Constipation and Diarrhoea ................................................... 44-46
9. Chemotherapy General Considerations .................................................. 47-53
10. Sulfonamides, Cotrimoxazole and Quinolones ...................................... 54-58
11. Beta-Lactam Antibiotics ............................................................................... 59-66
12. Tetracyclines and Chloramphenicol ......................................................... 67-71
13. Aminoglycoside Antibiotics ........................................................................ 72-74
14. Macrolide, Lincosamide, Glycopeptide and
Other Antibacterial Antibiotics, Urinary Antiseptics ......................... 75-80
15. Antitubercular Drugs ..................................................................................... 81-85
16. Antileprotic Drugs .......................................................................................... 86-87
17. Antifungal Drugs ............................................................................................ 88-93
18. Antiviral Drugs ................................................................................................ 94-99
19. Antimalarial Drugs ......................................................................................... 100-103
20. Antiamoebic Drugs ......................................................................................... 104-107
21. Antihelmintics ................................................................................................. 108-110
22. Anticancer Drugs ............................................................................................ 111-121
23. Immunosuppressant and Immunomodulators ..................................... 122-125
24. Drugs Acting on skin and Mucous Membranes ..................................... 126-127
25. Antiseptics and Disinfectants ...................................................................... 128-129
26. Chelating Agents .............................................................................................. 130-131
27. Vaccines and Sera ........................................................................................... 132-135
 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

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DIURETICS

INTRODUCTION
 Kidney serve the body as a natural filter of the blood, and removal of waste product.
 Nephron is the functional unit of kidney.
 Diuresis is condition where increase urine outflow.
 Urine formation begin with glomerular filtration.
 Volume filtered is about 180 L/day which more than 99% gets reabsorbed in the renal
tubules.
 Urine excretion is about - 1.5 L/day.
FUNCTIONS OF KIDNEY

 Regulatory - Acid-base fluid and electrolyte balance.

 Excretory - Excretion of nitrogenous waste products.
 Hormonal - Activation of vitamin D, production of renin and erythropoetin.
MECHANISM OF URINE FORMATION
It consist of the following steps
(1) Glomerular filtration.
(2) Tubular reabsorption.
(3) Active tubular secretion.

1 Glomerular 2 Tubular 3 Tubular Peritubular

Filtration Reabsorption secretion capillary

Efferent
Afferent
Glomerulus Proximal Distal
Glomerular convoluted
capsule convoluted
tubule tubule
H2 O Collecting
duct
H2 O
Reabsorption
of water

Loop of
henle

Urine Formation
Renal
pelvis

Excretion

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PARTS OF NEPHRON
Part I  Proximal Convoluted tubule (PCT)
Part II Descending loop of henle.
Part III 
Ascending loop of henle.
Part IV Distal Convoluted Tubule (DCT)
 Early Distal Convoluted Tubule
 Late Distal Convoluted Tubule
Part V  Collecting duct

PART I: PROXIMAL CONVOLUTED TUBULE

 Most of the filtered Na+ is actively reabsorbed (65-70%).

 Na+ K+ symport along with active reabsorption of glucose, amioacids, organic anions and
PO4-.
 Carbonic anhydrase plays an important role in Na+H+ exchange and helps in the reasorption
of HCO-3
 Water gets reabsorbed so tubular fluid in the PCT remains isotonic.
Site IV Early Distal Late
(~5%) Cl Convoluted Tubule Distal
-

Na
+ Convoluted
Efferent Tubule
Proximal convoluted
tubule
se BP Site I
Site IV
(1-2%)
Na
+

Afferent Glomerulus Proximal K+/H+

Carbonic NaHCO3 Convoluted (~25%)
Na+ tubule Na /K
+ +
Anhydrase
(65-70%) H2O
Inhibitors Cl
-

Thick
Loop Diuretics
Descending
Limb Site III Collecting duct
Osmotic diuretics (Permeable to Think Site V
H2O
water) Ascending
Site II Limb
(Permeable
Loof of to salt)
Henle

PART II : DESCENDING LOOP OF HENLE

 Osmotic diuretics acting on this site.

 The descending limb is impermeable to Na+ and urea and highly permeable to water.
 Hence fluid in the loop becomes hypertonic.

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PART III : ASCENDING LOOP OF HENLE

 Ascending limb is impermeable to water but highly permeable to Na+ and 2Cl- (20-25%).
 Active reabsorption of sodium and chloride occur by Na+ K+ 2Cl- Co-transporter and
Ca+2 and Mg+2 are also reabsorbed at this site.
 This is selectively blocked by loop diuretics.

PART IV : DISTAL CONVOLUTED TUBULE

Early Distal Convoluted Tubule

 It is impermeable to water but sodium and chloride are reabsorbed with the help of
Na+Cl- Symporter.
 This is blocked by thiazides.
Late Distal Convoluted Tubule
 Pottasium sparing diuretics act at this site.
 In late DCT and CD, Na + is actively reabsorbed, the cation-anion balance being
maintained partly by passive of Cl- diffusion and partly by secretion of K+ and H+.
 Absorption of Na+ at this site occurs through a specific amiloride sensitive Na+ channel
and is controlled to a large extent by aldosterone.

PART V : COLLECTING DUCT

 The collecting duct system of the kidney consists of a series of tubules and ducts that
physically connect nephrons to a minor calyx or directly to the renal pelvis.
 The collecting duct system is the last part of nephron and participates in electrolyte and
fluid balance through reabsorption and excretion, processes regulated by the hormones
aldosterone and vasopressin

MECHANISM OF ACTION

CLASSIFICATION SITE OF ACTION MECHANISM OF ACTION

Carbonic anhydrase Proximal Convoluted Tubule Inhibition of bicarbonate
inhibitor (Acetazolamide) Acting -site I reabsorption.
Osmotic diuretics Descending Loop of Henle Inhibition of water and
(Mannitol) Acting -site II Na+ reabsorption
Loop diuretics Ascending Loop of Henle Inhibits Na+ K+ 2Cl-
(Furosemide) Acting –site III co-transport
Thiazide Early distal tubule Inhibits Na+Cl- Symport
(Hydrochlorothiazide) Acting -site IV
Potassium sparing Late distal Convoluted Inhibition of Na+
Diuretics Tubule and Collecting Duct reabsorption and K+
(Spironolactone) Acting -site IV secretion.

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

CLASSIFICATION OF DRUGS

S.NO CLASS SUBCLASS DRUGS

1. High Efficacy (Loop Sulphamoyl derivatives Furosemide [GATE - 88,
Diuretics) 89, 93], Bumetanide.
(Inhibitors of
Phenoxyacetic acid Ethacrynic acid.
Na+K+2Cl-
derivatives
Co-transport)
Organomercurials Mersalyl.
2. Medium Efficacy Benzothiadiazines Hydrochlorothiazide,
Diuretics (Thiazides) Benzthiazide,
(Inhibitors of Na+Cl- Hydroflumethiazide,,
Symport) Bendroflumethiazide
Thiazide like (related Chlorthalidone,
heterocyclic) Metolazone, Xipamide,
Indapamide, Clopamide,
Chlorthiazide [GATE - 91]
3. Weak or Adjuvant Carbonic anhydrase Acetazolamide.
Diuretics inhibitors [GATE - 88, 90, 91]
Aldosterone Spironolactone
antagonist [GATE - 89, 91, 93, 97]
Potassium Eplerenone
Sparing Directly acting Triamterene
diuretics (Inhibitors of [GATE - 88, 89, 91 ]
renal epithelial Amiloride.
Na+ Channel) [GATE - 93, 95]
Osmotic diuretics Mannitol [GATE - 88, 89]
Isosorbide [GATE - 93]
Glycerol
Xanthines Theophylline

CARBONIC ANHYDRASE INHIBITORS (WEAK OR ADJUVENT DIURETIC)

 Acetazolamide is the Prototype drug of this class.

 Acetazolamide are non-competitive carbonic anhydrase inhibitor that inhibit only
luminal carbonic anhydrase enzyme [GATE-98, 99]
 Dorzolamide and Brinzolamide are used topically for glaucoma.
 Carbonic anhydrase inhibitors decrease GFR because of tubular glomerular feedback
mechanism.
Mechanism of action
 Intracellulary CA converts CO2 and H2O to carbonic acid (H2CO3) dissociates into H+ and
HCO3-
 The H+ ion exchange with luminal Na+, In the lumen the H+ ion combine with HCO3- and
form H2CO3.
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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

Proximal
Lumen urine convoluted Insterstium
tubule blood
Na+
ATP
Na+
K+
HCO3 + H
- +
H+ + HCO3-
H2CO3
H2CO3
+
CA inhibitors CA CA CA
Inhibitors
CO2+HO2
Cl-

Base

 The H2CO3 dissociates into CO2 and H2O with the help of CA.
 Drugs in this class inhibits carbonic anhydrase enzyme, prevents the formation
of H+ ion.
 Carbonic anhydrase is Na+ H+ exchange is prevented and Na+ is excreted along with in
urine and there also increase in K+ excretion they result lead to alkaline urine.
USES - [Mnemonics: GAME]
G – Glaucoma
A – To Alkaline urine in acidic drug poisoning.
M – Acute Mountain sickness.
E – Epilepsy
Contraindication for carbonic anhydrase inhibitor
 Chronic obstructive pulmonary disease
 Hepatic cirrhosis
OSMOTIC DIURETICS

 Drugs are Mannitol, Isosorbide, Glycerol and Urea

 Osmotic diuretics draw water from tissue by osmotic action. this results in increased
excretion of water and electolytes.
USED IN CONTRAINDICATED IN
Cerebral edema Pulmonary edema
Acute congestive glaucoma Acute renal failure
Prevention of cisplatin induced nephrotoxicity Active cerebral bleeding
MANNITOL
 Mannitol is used i.v. for the treatment of glaucoma and cerebral edema (DOC)
 Mannitol decreases tubular water and electrolyte reabsorption.

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

 Due to osmotic effect, fluid is retained in the lumen of PT.

 Expends extracellular fluid volume (se intravascular volume).
 Increase renal blood flow, especially to medulla.

LOOP DIURETICS (HIGH CEILING DIURETICS)

 Drugs are Furosemide, Torsemide and Bumetanide.

 Site of action of loop diuretics is thick ascending limb of loop of henle
 They are fast acting with shorter duration of action.

Thick
Ascending
Lumen urine Limb Interstitium
blood

Na
+
Na
+
Loop Na K 2Cl
+ + -

K
+
diuretic ATP
Co-transporter
2Cl
-
K
+

K
+

(+) Potential K
+

Cl
-

Mg, Ca
2+ 2+

 Furosemide has weak carbonic anhydrase inhibitory activity hence increase the
excretion of HCO3- and PO4-.
 Loop diuretics are called high-ceiling diuretics because they are highly efficacious – have
maximal Na+ excreting capacity when compared to thiazides and potassium sparing diuretics.
 Having maximum Na+ excretion capacity (Natriuretic effect)
 Furosemide decreases tubular secretion of uric acid cause hyperuricaemia.
 Loop diuretics binds to luminal side of Na+ K+ 2Cl- Cotransporter and blocks its function.
 There is increase excretion of Na+ and Cl- in urine and Ca+2 and Mg+2 excretion are
also enhanced.
 Bumetanide  40 times more potent than furosemide and less toxic ototoxic.
 Piretanide  5 times more potent than furosemide.
Mechanism of Action
Adverse Effect
 Hypokalaemia, Hypocalcaemia and Hypomagnesaemia.
 Hyperglycaemia, Hyperuricaemia and Hyperlipidaemia.
 Ototoxicity
Uses
 In renal, hepatic and cardiac edema.
 Acute pulmonary edema and cerebral edema.
 In hypercalcaemia.
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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

 In hypertension.
 In mild hyperkalaemia.
Drug interaction
 Furosemide Aminoglycoside  Increased ototoxicity.y.
 Furosemide/Thiazide  Digoxin  These diuretics causes hypokalemia which increases

 Lithium  Increased reabsoption of Na and Lithium in PCT -

the binding to Na+K+ ATPhase leading to digoxin toxicity.
 Furosemide/Thiazide +

 NSAID  Diminish effect

Lithium toxicity.
 Furosemide
Furosemide  ACE inhibitors  Balanced effect
S

 Lithium carbonate  Lithium toxicity [GATE-05]

(Hypokalemia) (Hyperkalemia)
 Hydrochlorothiazide

THIAZIDE & THIAZIDE LIKE DIURETICS (MEDIUM EFFICACY)

 Drugs are Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Bendroflumethiazide

Mechanism of action

Distal
Lumen urine Convoluted Interstitium
tubule blood

Na
+ R PTH
Na Cl
+ -
Thiazide Na
+

Symporter
Cl
-
ATP

K
+

Na
+

Ca
2+

Ca
2+

 Thiazides inhibit Na+Cl- Symport in distal Convoluted tubule and increases Na+ and Cl-
excretion.
 They decrease Ca +2 excretion, uric acid secretion and increases Mg +2 excretion.
 Chlorothiazide produce Hypokalemia, alkalosis but it is a very useful in the treatment
of volume dependent hypertension [GPAT-16]
 Diazoxide is a benzothiazide derivative and Vasodilation by activating ATP sensitive K+
channels. [GATE-07]
 There is increase delivery of Na+ to the late distal tubule, hence there is increased exchange
of Na+ K+ which results in K+ loss.
 Chlorthalidone is longest acting thiazide.
 Bendroflumethiazide has almost 100% Bioavailability.
 Thiazide are the DOC for the treatment of essential hypertension.

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

Uses -
 Hypertension, Hypercalciuria
 Edema, Diabetes insipidus
 Heart failure,
Adverse effect
 Hypokalaemia, hypomagnesaemia and hypercalcaemia
 Hyperglycaemia
 Impotence, so not preferred to young males.

THIAZIDE LIKE DIURETICS

 Chlorthalidone has long duration of action and frequently used in hypertension.

 Indapamide and metolazone are more potent.
Adverse effect

 Pulmonary edema, Headache, Tachycardia

POTASSIUM SPARING DIURETICS

 These drugs act in the late distal convoluted tubul and collecting duct.
Aldosterone Antagonist
 Drugs are – Spironolactone and Eplerenone.

Spironolactone - + Aldosterone
AL
(Antagonis) MR (Agonist)

MR - Mineralocorticoid receptor
AL - Aldosterone
m-RNA
AIP - Aldosterone Induced protein

AIP
 Aldosterone enters the cell and binds to specific receptor (MR) in the cytoplasm of late
distal tubule & collecting duct (CD)
 The MR-AL Complex enters the cell nucleus where it induces the aldosterone induced
Proteins (AIP)
 Spironolactone are competitive inhibitor of aldosterone at the receptor in the distal
tubule (GATE-99)
 The net effect of AIP is to retain sodium and potassium excretion.
 Thus inhibition of AIP by Spironolactone promotes Na+ excretion and K+ retension.
 Canrenone is the active metabolite of spironolactone.

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Adverse effect
 Hyperkalemia
 Hirsuitism
 Impotence
 Menstrual irregularities
Uses
 Spironolactone is used with thiazide/loop diuresis to compensate K+ loss.
 Edema, Hypertension, Chronic heart failure

Drug interaction :- ACE inhibitor X Spironolactone  Dangerous hyperkalemia.

Directly acting Inhibitors of renal epithilial Na+ channel

 Drugs are Amiloride and Triamternce
 Direct inhibitors of renal epithelial Na+ channel.
 Amiloride directly blocks the Na+ channels in the luminal membrane of the cell of the
late DCT and CD.
 Amiloride increase Na+ excretion and retain potassium.
 Amiloride is 10 times more potent than triamterene
 Amiloride blocks entry of Li+ through Na+ channel in the collecting duct cell and mitigates
DT induced by lithium (DOC for Li+ induced DI)
 Amilorides decreases Mg2+ and Ca2+ excretion and increase urine excretion.

POINTS TO REMEMBER
 Excessive use of diuretics can cause Hypovolemic shock. (GPAT-19)
 Metolazone is the only thiazide which is effective in severe renal failure.
 Hypokalemia - Reduction of Serum K+ level (GATE-97)
 Hyperkalemia -Increase of K+ level
 Hypercalcemia- High calcium (Ca 2+ ) level in the blood serum. The normal range is
2.1– 2.6 mmol/L with levels greater than 2.6
 Hypocalcemia-Low calcium levels in the blood serum. The normal range is
2.1–2.6 mmol/L with levels less than 2.1 mmol/l

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ANTIDIURETICS

INTRODUCTION
These are the drugs that reduces urine volume excretion without affecting salt excretion,
particularly in diabetes insipidus (DI)
CLASSIFICATION

Antidiuretic hormones Vasopressin (ADH), Desmopressin, Lypressin, Terlipressin.

Thiazide diuretics Amiloride
Miscellaneous Chlorpropamide, Carbamazepine [GPAT-15]
Other antidiuretics Thiazides, Amiloride

VASOPRESSION (ADH)
 Nonapeptide secreted by posterior, pituitary along with oxytocin.
Two main physical stimuli for ADH release are -
(1) Rise in plasma osmolarity.
(2) Decrease volume of extracellular fluid (ECF)
Hypothalamus Synthesis

Vasopressin (ADH)

Posterior pituitary Storage

ADH (Vasopressin) receptors

V1 receptor V2 receptor V3 receptor

Kidney - Increase water permeability. Release of ACTH
Blood vessel - Vasodilation.
V1a V1b
Blood vessel - Constriction Release of ACTH
Liver - Glycogenolysis from anterior pituitary.
Platelet - Aggregation
GIT - Increase peristalsis

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Mechanism of Action
Activation of V2 receptor  es cAMP formation intracellularly..

Activation of cAMP dependent protein kinase A

Excocytosis of aquaporin-2 water channel to apical membrane.

 se water permeability
y
 Vasopressin is helper hormone to corticotropic releasing hormone [GATE-07]
 Desmopressin is 12 times more potent than vasopressin.

VASOPRESSIN ANALOGUES

LYPRESSIN
 It is used in place of AVP for V1 mediated action.
TERLIPRESSIN
 Synthetic prodrug of vasopressin used for bleeding esophageal varices.
DESMOPRESSIN
 This synthetic peptide is a selective V2 agonist and 12 times more potent antidiuretic
than arginine vasopressin.
 Desmopressin is the preparation of choice for all V2 receptor related indications.
Uses
 Diabetes insipidus
 Bed wetting in children and nocturia in adults.
 Renal concentration test.
 Bleeding esophageal varices.
OTHER ANTI-DIURETICS

THIAZIDES

 These drugs used as diuretics but exerts paradoxical effect.

AMILORIDE

 It is the agent of choice for the treatment of Lithium induced DI.

 Blocking entry of Na+ in the principle cell of collecting duct

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3 DRUGS AFFECTING
BLOOD AND BLOOD
FORMATION
INTRODUCTION
 Blood is a body fluid in humans and other animals that delivers necessary substances such as
nutrients and oxygen to the cells and transports metabolic waste products away from those
same cells.

TYPES OF BLOOD CELLS

Types of blood cells

Red Blood Cells Platelets

(Erythrocytes) (Thrombocytes)
Helps in O2 and Co2 exchange Helps in blood clotting
White Blood cells
(Leukocytes)

Neutrophil Eosinophil Basophil Lymphocyte Monocyte

Fight against infection
Fig: TYPES OF BLOODS CELLS

HAEMATINICS AND ERYTHROPOIETIN

HEMOPOIESIS (HEMATOPOIESIS)
 It is the process of formation and development of the various types of blood cells and
other formed element.
 Hemopoiesis takes place in the red bone marrow found in the epiphyses of long bones
(for example, the humerus and femur),
ERYTHROPOIETIN
 Erythropoietin (EPO) is a hormone produced primarily by the kidneys. It plays a key role in
the production of red blood cells (RBCs), which carry oxygen from the lungs to the rest
of the body and process is called erythropoiesis.

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HAEMATINICS
 It is a nutrient required for the formation of blood cells in the process of hematopoiesis and
also used in the anaemia.
Haematinics

Iron Vitamin B 12 Vitamin B9

(Cyanocobalamine) (Folic acid)

IRON
 Iron is an essential element for blood production. About 70 percent of our body’s iron is
found in the red blood cells of blood called hemoglobin and in muscle cells called
myoglobin.
 Iron is stored in reticuloendothelial (RE) cells in liver, spleen and bone marrow.
 Hemoglobin is essential for transferring oxygen in blood from the lungs to the tissues.
Daily requirement :
Adult male 0.5-1 mg (13μg/kg)
Adult female 1-2 mg (21 μg/kg)
Dietary sources of iron :
 Liver, egg yolk , oyster, dry beans, dry fruits, wheat germ, yeast.
Iron is stored in reticuloendothelial (RE) cells in liver, Spleen bone marrow.

IRON ABSORPTION AND STORAGE

Dietary iron
10 - 15 mg/day

ABSORPTION BLOOD
Stomach UTILIZATION
Ferro
Iron utilization
Duodenum protein-1
Duodenal/upper and storage
Jejunal Enterocyte
Heme carrier protein-1 Hepcidin  Liver (RE cell)
 Heart
Haeme Fe
 Pancreas
2+

Fe Fe
2+

Haeme  Skeletal muscle

3+

Re
du (myoglobin)
Acid, c ti o
Reducing Fe
n
Fe2+ Fe
2+
Fe Plasma
2+ 3+

agent, Fe
3+
transferrin
Meat Divalent Ferritin Iron loss:
Metal Fe Fe
3+ 3+

(Store)  Desquamation of
Transporter Transferrin epithelial cells
Menstrual blood loss
Sloughed of mucosal cells
Fe : Ferrous iron, Fe : Ferric iron, HCP1: Haeme carrier protein 1, Hb: Haemoglobin,
2+ 3+

RE cell: Reticuloendothelial cell, Fp1: Ferroportin, Tf: Transferrin, TfR: Transferrin receptor
Fig: IRON ABSORPTION AND STORAGE

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FACTOR AFFECTING IRON ABSORPTTION

IRON INCREASE ABSORPTION IRON DECREASE ABSORPTION
Gastric HCl Alkali
Vitamin C Antacid
Alcohol Tetracycline
Low MW protein Food

PREPARATION OF IRON

CLASS DRUGS
Ferrous sulfate
Ferrous gluconate
Oral iron Ferrous fumarate
Colloidal ferric hydroxide
Carbonyl iron
Parenteral iron Iron dextran, Iron sorbitol, Citric acid.
Ferrous succinate
Iron choline citrate,
Other forms of Iron calcium complex
iron present in Ferric ammonium citrate
oral formulations Ferrous aminoate
Ferric glycerophosphate
Ferric hydroxyl polymaltose
Adverse effect of oral preparation
Constipation, Discolouration of teeth, Epigastric pain, Metallic taste.
Uses:
 Iron deficiency anaemia
 Megaloblastic anaemia
Acute Iron poisoning
 It is mostly in infants and children.
 Manifestations are vomiting, abdominal pain, Haematemesis (Vomiting of blood), Diarrhoea,
lethargy, cyanosis.
Treatment
 Antidote of acute Iron poisoning – Desferrioxamine (DOC) [GPAT -12]
 Alternative - Diethylene triamine pentaacetic acid (DTPA), Calcium edetate

VITAMIN B12 (CYANOCOBALAMINE)

 Deficiency of vitamin B12 and folic acid which are groups of vitamin B and deficiency of
these vitamin result megaloblastic anaemia and also called maturation Factor.
 Essential for normal haemopoiesis
 Vitamin B12 is a cobalt containing compound which is synthesized by the colonic bacteria
and is present in food of animal origin, such as meat, liver, egg, fish etc.

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

Dietary sources : Liver, kidney, sea fish, egg yolk, meat and cheese.
Daily requirement : 1-3 mg pregnancy and lactation 3-5 mg.
Coenzyme are : Methylcobalamin (methyl B12), Deoxyadenosylcobalmine (DAB12)
Preparation : Cyanocobalamine, Methylcobalamine and Hydroxycobalamin.
Act as a coenzyme in certain metabolic pathway
Metabolic function :
Methyl B12
Homocystine  
 Methionine
DAB12
Methylmalonyl CoA   Succinyl CoA
DAB12
Methionine   S-adenosylmethionine

VITAMIN B9 (FOLIC ACID)

 Folic acid is a combination of Pteridine nucleus + Para amino benzoic acid (PABA) +
Glutamic acid.
 Used in the treatment of megaloblastic anaemia.
 Folinic acid (Leucovorin, Citrovorum factor, 5-formyl THFA) active form of folic acid is
used to antagonize methotrexate toxicity.
 Folic acid itself is inactive, active form tertahydrofolate is essential for the biosynthesis of
amino acid, purines, pyrimidines, choline, DNA and therefore in cell division.
Preparation : Folic acid and Folinic acid
Uses :
 Megaloblastic anaemia
 Nutritional folate deficiency
 Pernicious anaemia

ERYTHROPOIETIN
 It is Sialoglycoprotein hormone produced from peritubular cell of the kidney.
 Essential for normal erythropoiesis.
 Commercially erythropoietin is produced by recombinant DNA technology.
 Darbepoetin : This is a hyperglycosylated modified preparation of EPO that has a t1/2
of 24-36 hours and is longer acting than epoetin.
Four component of erythropoisis
1. Colony forming unit erythrocyte (CFU-E)
2. Proerythroblast
3. Basophilic erythroblast
4. Reticulocyte release
Mechanism of Action
 Main effect on stem cells differentiation
 Promote Haemoglobin synthesis

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

 Promotes release of RBCs from bone marrow to peripheral circulation.

Preparation : Epoetin
Use : The primary use of epoetin is anemia of chronic renal failure.

HAEMATOPOIETIC GROWTH FACTOR

 They stimulate growth and differentiation of blood cells.
Drugs are:
(1) Erythropoietin - Epoetin.
 Epoetin ,  are recombinant human erythropoietin is administered by i.v. or s.c.
injection.
(2) Myeloid growth factor -
 Human granulocyte colony stimulating factor (G-CSF)- Filgrastim.
 Human granulocyte macrophase colony stimulating factor (Gm-CSF)-Sargramostion
(3) Thrombopoietic growth factor - Interleukin -11
(4) Megakaryocyte Growth Factors. Megakaryocyte growth factors are used to
treat chronic immune thrmbocytopenia purpurea (ITP) They work by increasing the
number of blood platelets to promote normal clotting
Drugs are : Thrombopoietin, Interleukin- II
PEGINESATIDE
 It is a new drug called erythropoiesis stimulating agent It is indicated for treatment of
anaemia due to CRF in patients on dialysis.

FUNCTION AND USES OF HAEMATOPOIETIC GROWTH FACTORS

DRUGS FUNCTIONS USES

Erythropoietin Stimulate Anticancer drugs, HIV
(Epoeitin alpha, Epoeitin erythropoiesis infection
beta and Darbopetin) (RBCs)
Myeloid growth factors Stimulate Antiretroviral drugs,
(GM-CSF, G-CSF) proliferation and Patient whose WBCs are
differentiation of suppressed by anticancer
WBCs
Thrmobopoietic growth Stimulate To treat cancer
factors (Interleukin-11, production of chemotherapy induced
Thrmbopoietin) platelets thrombocytopenia

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

4 DRUG AFFECTING
COAGULATION AND
BLEEDING
HAEMOSTATIC AGENTS
 These agents arrest bleeding either by vasoconstriction or by promoting coagulation of
blood.

CLASSIFICATION OF HAEMOSTATIC AGENTS

Astringent They precipitate proteins locally.

Thrombin Used topically to control bleeding from
Local capillaries.
Haemostatics Adrenaline It cause vasoconstriction (1) and arrest
(Styptics) bleeding.
Gelatin
Calcium alginate
Vitamin K Vitamin K1: Phytonadione [Phylloquinone],
Vitamin K2: Menaquinone
Vitamin K3:Menadione
Fibrinogen Fibrinogen fraction of human plasma control
bleeding.
Antihaemophilic Control bleed for short time, it is used to control
Systemic Factor bleedingepisodes in haemophilias.
Agents Adrenochrome Reduce capillary fragibility, control oozing
monosemicarbazone following tooth extraction, epistaxis etc.
Rutin Plant glycoside, claimed to reduce capillary
bleeding.
Ethamsylate Reduce capillary bleeding by correct abnormal
platelet adhesion and also maintains the
stability of the capillary wall.

VITAMIN K

 Vitamin K is a fat soluble vitamin which is required for synthesis of clotting factors.
 Vitamin K has basic naphthoquinone structure with or without side chain.
 Vitamin K represent a group of lipophilic and hydrophilic vitamin.

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

TYPE OF VITAMIN K SOURCE CHEMICAL NAME

Vitamin K1 Plant Phytonadione[Phylloquinone]
Vitamin K2 Bacteria Menaquinones
Vitamin K3 Synthetic Menadione
O In
CH3 K1 = Phytyl
K2 = Prenyl
R K3 = No side chain
O
Mechanism of Action

Decarboxy Prothrombin Prothrombin factor

factor VII, IX, & X VII, IX & X

Carboxylase
Oxidative
deactivation Capacity to bind with
Vitamin K Vitamin K Ca and phospholipid
+2

(Hydroquinone) (epoxide)
Vit K epoxide Essential for participation
reductase in clotting factor
Warfarin

 Vitamin K acts as a cofactor for -carboxylation of glutamic acid residue of clotting factors
VII, IX, X
 Vitamin K is involved in the activation of various clotting factors (like VII, IX & X)
 It comes out the final step in activation of  carboxylase of glutamate residue
Absorption of vitamin K
 Absorption takes place in small intestine in the presence of bile acids.
 The transportation from intestine is carried out through chylomicrons.
Function of vitamin K
 Coagulation, Bone synthesis.
 Prevention of atherosclerosis, Formation of Red blood cells.
Note
 Deficiency of vitamin K is due to liver disease, prolong antimicrobial therapy, Dietary
deficiency.
 New born have deficiency of vitamin K.
Uses
 Liver disease
 In overdose of oral anticoagulant (Vitamin K1)
 Vitamin K1 is used in salicylate poisoning with haemorrhagic complications.
 Vitamin K3 (Menadione) can cause hemolysis-contraindicated in G-6-PD deficiency and
neonates.

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

ANTICOAGULANTS -

 Anticoagulants are drugs that prevent or reduce coagulation of blood.

 It is act by indirectly by activating plasma antithrombin III.
 The heparin AT III complex then bind to clotting factor of the intrinsic and common
pathway (IIa, IXa, Xa, XIa, XIIa and XIIIa) and inactivate them but not factor VIIa
operative in the extrinsic pathway.
Mechanism of blood coagulation(anticoagulant)
1. Formation of prothrombin activator in response to rupture or damage to the blood vessels
2. Conversion of prothrombin activator to thrombin
3. The thrombin act as an enzyme to convert fibrinogen to fibrin thread that mesh platelets,
Blood cells and plasma to form the clots

CLASSIFICATION OF ANTICOAGULANT DRUGS

CLASS SUB CLASS DRUGS

Indirect thrombin Heparin (unfractionated)
Inhibitor Low molecular weight heparins
(Enoxaparin, Reviparin,
Nadroparin, Dilateparin, Parnaparin
Parenteral Ardeparin)
Anticoagulant Forndaparinux
Danaparoid
Direct thrombin Bivalirudin, Argatroban, Hirudin,
Inhibitor Lepirudin
Vit. K antagonists Bishydroxycoumarin (dicumarol)
Warfarin Sodium
Acenocoumarol (Nicoumalone)
Oral Ethyl - biscoumacetate
anticoagulants Direct factor Xa Inhibitor Revaroxaben, Apixaban
Oral direct thrombin Dabigatranetexilate
Inhibitor

PARENTERAL ANTICOAGULANTS
INDIRECT THROMBIN INHIBITOR
Heparin (Unfractionated)
 Not absorbed by oral route given by s.c. or i.m.
 These drugs act by activating plasma antithrombin III, which inhibits factor IIa and Xa.
 Heparin is mucopolysaccharide and obtained from sheep lungs.
 Heparin is the stongest organic acid present in our body.
 Commercially it is obtained from OX lung and Pig intestine.
 Heparin is not crosses placenta thus anticoagulant of choice during pregnancy.
 Heparin antagonist - Protamine sulphate (Strong base)
 Heparin in higher dose inhibit platelets aggregation and prolong bleeding time.

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

Chemistry and occurance:

 Heparin is non-uniform mixture of straight chain mucopolysacchrides.
 It consist polymer of two sulfated disaccharide units: D-glucosamine L-iduronic acid
and D-glucosamine D- glucuronic acid.
Mechanism of Action of Heparin
 Heparin binds and accelerate the activity of plasma antithrombin III.
 Heparin antithrombin III complex than inhibits activated clotting factor Xa, IIa, IXa,
XIIa and XIIIa.
 Heparin induce thrombocytopenia.
 Heparin has action both in vitro and in vivo and oral anticoagulant action only in vivo
activity.

INTRINSIC SYSTEM EXTRINSIC SYSTEM

XIIa Activated by contact

H HMW-Kininogen Tissue damage
XI XIa VIIa VII
H Ca
2+
XIIa
SLOW

XI IXa TF(III) XIa

Kallikrein

RAPID
H
VIIIa Pl. Ph Ca
2+

Ca
2+

X Xa X
H Va Pl. Ph H
Ca
2+

PROTHROMBIN (II) THROMBIN

FIBROGEN FIBRIN (soluble)

H: Heparin XIIIa Thrombin
TF: Tissue factor
Pl. Ph: Platelet phospholipid H FIBRIN (insoluble)
Fig: COAGULATION CASCADE

Adverse effect
 Bleeding due to overdose, Hypersensitivity reaction.
Side effect (Mmonics: AHOT)
A - Alopecia
H - Hyperkalemia, Haemorrhage
O - Osteoporosis
T - Thrombocytopenia

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

Contraindication (Mnemonics: TEACHER)

T - Thrombocytopenia
E - Endocarditis
A - Alcoholics
C - Cirrhosis of liver
H - Hypertension
E - pEptic ulcer
R - Renal failure

FACTORS INVOLVE IN BLOOD CLOTTING

Mnemonics : Freshers Party Tonight Come Lets Sing And Call Seniors Please Have Fun
FACTORS NAME FUNCTION
Factor I Fibrinogen Converted to fibrin
Factor II Prothrombin Converted to thrombin
Factor III Tissue thromboplastin Essential in activating in vivo coagulation
Factor IV Ca+ ions Required for coagulation factors to bind
phospholipid
Factor V Labile factor Co-factor involved in converting prothrombin to
thrombin
Factor VII Proconverting /Stable In vivo activates factor (IX)
factors
Factor VIII Antihemophilic factors Co-factor involved in activating factor X
Factor IX Plasma thromboplastin Involved in activating factor X. Deficiency will
component (PTC) cause hemophilia B
Factor X Stuart power factor Involved in converting prothrombin to
thrombin
Factor XI Plasma thromboplastin In vivo activated by thrombin and factor XII and
antecedent (PTA) important at major sites of trauma
Factor XII Hagman factors Activates factors XI and VII.
Invitro (lab test) initiates the clotting process
Factor XIII Fibrin stabilizing factor Convert fibrin polymer to stable insoluble fibrin
(Fibrinase)
Low molecular weight Heparin (LMWH)
Drugs are : Enoxaparin, Dalteparin, Tinzaparin etc are LMWH are isolated from
standard heparin by various techniques.
 Effect mainly by inhibiting factor Xa through antithrombin.
 Have longer duration of action and higher bioavailability as compared to unfractionated
heparin.
 It acts by enhancing the inhibition rate of activated clotting factors including thrombin
and factor Xa through its action on antithrombin III
 It is also inhibit platelet function. It may reduce the activity of antithrombin III at very high
doses.
 This inhibit the conversion of prothrombin to thrombin and fibrinogen to fibrin.

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

 Low molecular weight protein is obtained by either chemical or enzymatic

depolymerization of unfractionated heparin.
 Low molecular weight heparin are easily filtered from glomerular capillaries.
 Low molecular weight heparin have many advantages from unfractionated heparin:
o Lower risk of bleeding
o Longer bioavailability and more consistent
DIRECT THROMBIN INHIBITORS
 These groups includes - Hirudin, Lepirudin, Bivalirudin.
 These drugs directly inactive factor IIa (thrombin)
 All these drugs excreted by kidney therefore should be avoided in renal failure
patients.
Parenteral direct thrombin inhibitors Oral direct thrombin inhibitors
Hirudin Dabigatran (Recent)
Lepirudin Ximelagatran (Withdrawn)
Bivaluridin
 Bivalirudin has shortest half life.
 Bivalirudin are anticoagulant of choice for heparin induced thrombocytopenia.

ORAL ANTICOAGULANTS
 Among oral anticoagulants, Coumarin derivatives are commonly used.
 They act indirectly by interfering with synthesis of Vit K dependent clotting factor in
liver.
 Oral anticoagulant are contraindicated in pregnancy.
VITAMIN K ANTAGONIST
WARFARIN
 Warfarin is the most popular oral anticoagulant and cut only in vivo not in vitro.
 Warfarin contains 4 Hydroxycoumarine ring [GPAT-15]
 Warfarin inhibit synthesis of vitamin K dependent coagulation factors VII, IX, X and II and
anticoagulant protein C and its co-factor protein.
 Warfarin has 99% plasma protein binding and rapidly and completely absorbed from
intestine. Its dose should be reduced in liver disease.
 Warfarin induced skin necrosis, bleeding is most common adverse effect of oral
anticoagulant.
 The weakly acidic nature of warfarin is attributed to the presence of proton of hydroxyl
group at 4th position. [GPAT-11]
 Bishydroxycoumarin (Dicumaron) is longest acting and phenindione are the shortest
acting coumarins.
 Half life of warfarin is 36 hours.
 Ehtylbiscoumacetate is the shortest acting anticoagulant.

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

Mechanism of action:
 They are act indirectly by interffering with the synthesis of vitamin k clotting factor in liver.

Descarboxy Prothrombin
prothrombin factor VII, IX,X
factor VII, XI X
glutamyl

carboxylase
Vit K Vit K
hydroquinone epoxide
Vit K epoxide reductase

NAD NADH
Blocked by coumarin
anticoagulants

Fig: Mechanism of action of coumarin anticoagulant

FACTORS AFFECTING ENHANCING EFFECT FACTORS DECREASING EFFECT

• Debility, Malnutrition, Malabsorption, • Pregnancy
Prolong antibiotic therapy • Nephrotic syndrome, Genetic
• Liver disease and chronic alcoholism warfarin resistance
• Hyperthyroidism
• Newborns

ENHANCE ANTICOAGULANT ACTION REDUCE ANTICOAGULANT ACTION

Broad spectrum antibiotics:Reduce Barbiturate (not benzodiazepines),
Vitamin K production. Carbamazepine, Rifampin and
Cephalosporines: Cause Griseofulvin : Induce metabolism of
Hypoprothrombinaemia warfarin.
Aspirin: Inhibit platelets aggregation. Oral contraceptive: Increase blood
Sulfonamide, Phenytoin, Probenecid: level of clotting factor.
Displace warfarin from protein binding
Liquid paraffin:Reduce Vitamine K
absorption.

Drug interaction:
1. Warfarin × Aspirin : Potentiatee warfarin effect. [GPAT-13]
2 Warfarin × Tetracycline : Potentiate warfarin effect..
3. Warfarin × Cholestyramine : Reduces the absorption of warfarin from gut..
4. Warfarin × Vitamin K: Antagonistic action. [GPAT-16]

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

Therapeutic use:
1. Deep vein thrombosis
2. Myocardial infarction
3. Unstable angina
4. Atrial fibrillation
Difference between warfarin & Heparin

HEPARIN WARFARIN
Route of Parenteral Oral
Administration
Chemistry Mucopolysaccharide Synthetic
Onset of Action Rapid Delayed (1-3 days)
Source Ox lung, pig intestine Synthetic
Mechanism of Action Activate AT III and Decrease activation of
inactivates IIa,Xa II, VII, IX, X
Antagonist Protamine sulphate Vitamin K
Pregnancy Safe Teratogenic
Uses To initiate therapy For maintenance

DIRECT FACTOR Xa INHIBITORS

Drugs: Rivaroxaban and Apixaban
 It is orally active direct inhibitors of activated factor Xa.
Advantage of Direct factor Xa over Warfarin
 Rapid onset and offset effect
 Short half life
 Not laboratory monitoring required
 Antithrombtic efficacy equal to or better than warfarin
 Lower risk of bleeding compared to warfarin.
ORAL DIRECT THROMBIN INHIBITORS
Drugs: Dabigatran etexilate
 It is prodrug which after oral administration is rapidly hydrolysed to dabigatran.
 This direct thrombin inhibitors reversible block the catalytic site of thrombin and
produce a rapid anticoagulant effect..
 These are excreted by kidney therefore should be avoided in renal failure patient.

FIBRINOLYTICS (THROMBOLYTICS)
 These are drug used to lyse thrombic / clot to recanalize occluded blood vessel
(mainly coronary artery)
 Fibrinolytics promote the conversion of plasminogen ot plasmin.
 Plasmin degrades fibrin into fibrin degradation products and thus rapidly dissolve the
blood clot.
 These drug can cause bleeding as the major adverse effect.

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

Streptokinase Plasminogen
Epsilon-aminocaproic
Urokinase Fibrinolytics Antifibrinolytics acid
Alteplase Tranexamic acid
Plasmin
Fibrin Fibrin degradation Products
Fig: THE ACTIVATION OF PLASMINOGEN AND DRUGS THAT AFFECTS
 Streptokinase – Obtained from group ‘c’ -hemolytic Streptococci.
 It is antigen can cause allergic reaction.
 Streptokinase + Plasminogen  Streptokinase-Plasminogen complex  Activates 
plasminogen to plasmin  Fibrinolysis
 Urokinase - It is an enzyme isolated from human urine, has prepare from cultured human
kidney cells.
 Alteplase - Are recombinant tissue plasminogen activator (rt-PA). It is nonantigenic.
 Retaplase - It is a nonglycosylated detection of plasminogen activator produced by
recombinant technology.
Use of Fibrinolytics -
 Acute myocardial infraction
 Deep-vein thrombosis.
 Pulmonary embolism .
Contraindication of fibrinolytics [Mnemonics: BRAIN]
B-Brain tumor and aneurysms
R-Recent ischemic stroke or trauma
A-Aortic dissection
I-Intracranial hemorrhage
N-Non compressible vascular punctures

ANTIFIBRINOLYTICS
Drugs: Epsilon-Amino Caproic Acid (EACA),Tranexamic Acid
 Antifibrinolytics are medicines that promote blood clotting by preventing or slowing
down a process called fibrinolysis, which is the break down of blood clots.
 Antifibrinolytics blocks the conversion of plasminogen to plasmin and thus inhibits the
fibrinolytic activity.
Epsilon-Amino Caproic acid (EACA) & Tranexamic Acid
 It is a lysine analogue which combines with the lysine-binding sites of plasminogen
and plasmin so that the latter is not able to bind to fibrin and lyse it.
 It is is a specific antidote for firbrinolytic agents and has been used in excessive intra
vascular fibrinolysis resulting in bleeding.
 Used mainly to control bleeding due to overdose of fibrinolytics after tooth extraction
and surgery.
 Tranexamic acid is 7 times more potent than EACA

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

ANTIPLATELET DRUGS
 Drugs that inhibits platelet aggregation are called antiplatelet drugs.
Platelet mechanism
 cAMP plays a key role in platelet mechanism (Antiaggregatory or Aggregatory)
 High conc. of cAMP inhibit platelet adhesion and low conc. has on opposite action.
 cAMP is formed by the action of enzyme adenylate cyclase and degraded by phosphodi
esterase.
 Prostacyclin PGI 2 stimulate adenylate cyclase than increase cAMP conc. they show
antiaggregatory effect.
 Thromboxane A2 and ADP inhibit adenyl cyclase  decrease cAMP  platelet aggregation
and adhesion

CLASSIFICATION

Thromboxane synthesis inhibitor Aspirin

Platelet cAMP enhancer Dipyridamole
P2Y12 receptor blockers Ticlopidine, Clopidogrel [GPAT-20], Prasugrel,
Ticagrelor
GP IIb/IIIa antagonists Abciximab, Eptifibatide, Tirofiban
PGI2 analogues Epoprostenol

Mechanism of Action

Platelet adhesion to the damaged vessel wall

Platelet activation

ADP release Arachidonic acid generation

COX1 Low dose Aspirin.
PGG2, PGH2 (Unstable PG intermediate)

TXA2 Production
Ticlopidine
Activation of glycoprotein (GP) IIb/IIIa receptors on pletelets.
Clopidrogrel
Prasugrel GP IIb/IIIa receptor antagonist.
Cangrelor Binding of fibrinogen and Von willebrand factor to
GP IIa/ IIIa receptor and linkage of plateletes.

Platelet aggregation Epoprostenol (PGI2)

ASPIRIN (TXA2 SYNTHESIS INHIBITORS)

 Aspirin acetylates and inhibits the enzyme COX-1 and reduces the production of TXA2.
 Common adverse effect are gastric irritation and bleeding.

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 In higher doses, aspirin inhibit both TXA2 and PGI2, hence efficacy is reduced.
 Aspirin is first line drugs for the treatment of prophylaxis of myocardial infraction and
stroke.
 Anti-aggregation effect seen at lower dose.

DIPYRIDAMOLE(PHOSPHODIESTERASE INHIBITOR PDE3)

 It is vasodilator that was introduced for angina pectoris.
 It inhibits phosphodiesterase (PDE3) and increase the concentration of cyclic adenosine
monophosphate(cAMP) level which inhibits platelet aggregation.

TICLOPIDINE, CLOPIDOGREL, PRASUGREL (THIENOPYRIDINE DERIVATIVES)

 They inhibit adenosine diphosphate(ADP)-mediated platelet aggregation by irreversibly
blocking purinergic receptors on the platelets.
 Prasugrel has a faster onset of action and better antiplatelet effect than Ticlopidine and
Clopidogrel.

ABCIXIMAB, EPTIFIBATIDE AND TIROFIBAN(GP IIB/ IIIA RECEPTOR ANTAGONIST)

 They block GP IIb/ IIIa receptor for fibrinogen and von Willebrand’s factor on platelet surface
and thus inhibit the final step in the process of platelet aggregation.
 Abciximab – A humanized monoclonal antibody against GP IIb/ IIIa receptor.

Epoprostenol
 It cause vasodilation and inhibits platelet aggregation.
Uses of antiplatelet drugs
 Unstable angina
 Acute myocardial infarction
 Cerebrovascular disease
 Coronary bypass implants
 Venous thromboembolism
 Peripheral vascular disease

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

5 HYPOLIPEDEMIC
DRUGS AND PLASMA
EXPANDERS

INTRODUCTION
 Lipoprotein is a biochemical assembly that contains both protein and lipid, bound to the
protein which allow fats to move through the water inside and outside of cell.
 The primary purpose is to transport hydrophobic lipid (also known as fat) molecules or
cholesterol as in blood plasma or other extracellular fluids in our body.
STRUCTURE

VLDL Chylomicron Triglycerides

LDL IDL
HDL
Embedded
5-15 apolipoproteins
Diameter 8-28 25-50
Diameter Diameter 30-80 100-1000
Diameter Diameter

Diameter increase
% protein decrease Phospholipid
Density decrease
Phospholipids Triacylglycerol
Peripheral apoprotein
Cholesterol Proein
Monolayer of amphipathic
aicid (phospholipid and
TG free choliesterol)
CE Phespholipid
Free cholesterol
Core of nonpolar lipid
(cholesterol ester and
triacylglycerol)

THE PLASMA LIPOPROTEINS ARE

 Chylomicrons carry triglycerides (fat) from the intestines to the liver, to skeletal muscle, and
to adipose tissue.
 Very-low-density lipoproteins (VLDL) carry (newly synthesized) triglycerides from the liver
to adipose tissue.
 Intermediate-density lipoproteins (IDL) are intermediate between VLDL and LDL. They
are not usually detectable in the blood.
 Low-density lipoproteins (LDL) carry cholesterol from the liver to cells of the body. LDLs are
sometimes referred to as the “Bad cholesterol” lipoprotein.
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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

 High-density lipoproteins (HDL) collect cholesterol from the body’s tissues, and take it
back to the liver. HDLs are sometimes referred to as the “Good cholesterol” lipoprotein.
 HDL has fastest electrophoresis mobility and lowest TG content [GPAT-14]
 HDL increase serum level and decrease risk of atherosclerosis [GATE-03, GPAT-09,12]
NOTE- In hyperlipoproteinaemias the concentration of lipoprotein in plasma is elevated.
Class Diameter(nm) % Triacylglycerol & Cholesterol ester
Chylomicrons 100-1000 84
VLDL 30-80 50
IDL 25-50 31
LDL 8-28 8
HDL 5-15 5

HYPOLIPIDAEMIC DRGUS
 Hypolipidaemic drugs are those which lower the level of lipids and lipoprotein in blood.

CLASSIFICATION OF HYPOLIPEDEMIC DRUGS

CLASSES DRUGS
HMG-CoA reductase inhibitors Lovastatin, Simvastatin [GATE-04], Pravastatin,
(Statins) Atorvastatin, Rosuvastatin, Pitavastatin
Bile acid sequestrant Cholestyramine, Colestipol, Colesevalam
Lipoprotein lipase activator Clofibrate, Gemfibrozil, Bezafibrate, Fenofibrate
(PPARa agonist: Fibrate)
Lipolysis and triglyceride Nicotinic acid
synthesis inhibitors
Sterol absorption inhibitors Ezetimibe
Others Probucol, Gugul lipids, Omega-3-fatty acid
Site and mechanism of action of hypolipidaemic drugs
Gut Inhibited by Liver
HMG-CoA
reductase
HMG-CoA Blood
inhibitors
HMG-CoA reductase
(statin)
l

Mevalonate Protein and

Choles tero

Triglycerides Adipose
Inhibited by tissue
Cholesterol
ezetimibe VLDL
Bile
acids Bile acids Inhibited by VLDL
Niacin
Fatty acids
Bile IDL LL
acids LDL receptor Triglycerides

Inhibited by LDL Stimulated by

bile acid- gemfibrozil
binding resins

Fig : MECHANISM OF ACTION OF HYPOLIPIDAEMIC DRUGS

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

HMG-C O A REDUCTASE INHIBITORS

Drugs: Lovastatin, Simvastatin, Pravastatin, Atorvastatin, Rosuvastatin, Pitavastatin
 Statins are the most effective agents for treating hyperlipidaemias
 They competitively inhibits conversion of 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-
CoA) to mevalonate (rate limiting step in cholesterol biosynthesis) by the enzyme HMG-CoA
reductase, this results in a decrease in blood LDL and VLDL.
 HMG-CoA reductase activity is maximum activity in midnight so all statins are
administered at bed time to obtain maximum effectiveness.
 Atorvastatin has additional antioxidant property.
 Statins are metabolized by CYP3A4 except Rosuvastatin.
 HMG-CoA-reductase enzyme is a key enzyme in the pathway of reduction of the hydroxyl
group mevalonate to vitamin D [GATE-05]
 HMG CoA-reductase used in the treatment of familial hypercholesterolemia [GATE-05]
Mechanism of action
HMG-CoA
Statins HMG-CoA reductase
Mevalonic acid

Decrease cholesterol synthesis

Compensatory increase in LDL receptor expression in liver

(Catabolism of IDL and LDL)
LOVASTATIN
 This is the first clinically used statins which is lipophilic & given orally in the precursor
lactone form
 Absorbtion incompleted & first pass metabolism is extensive
 Lovastatin and simvastatin are prodrugs.
 Lovastatin is obtained from aspergillus terreus that can be very tightly bound to
HMG-CoA reductase [GPAT-10]
SIMVASTATIN
 More efficacious and twice potent than Lovastatin. It is also lipophilic and given in lactone
precursor form.
PRAVASTATIN
 It is hydrophilic and given in active form, It is causes decrease in plasma fibrinogen level
ATORVASTATIN - Newer statin, good LDL-cholesterol effect.
Adverse effect - (Trick: HMG)
H : Hepatotoxicity, Headache
M : Myopathy - muscular pain and weakness.
G : Gastrointestinal discomfort.
Uses: Statins are the frist DOC for primary hyperlipidaemia with raised LDL-cholesterol and total
cholesterol level.

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

BILE ACID SEQUESTRANTS

Drugs : Cholestyramine, Colestipol, Colesevalam

 They are neither digested nor absorbed in the GIT.
 Resins bind bile acids in the gut and interrupt their enterohepatic circulation, thus promote
conversion of cholesterol to bile acid in liver.
 Bile acids are synthesized in the liver from cholesterol.
 They also stimulate the formation of hepatic LDL receptors which take up more LDL
cholesterol from the circulation, net result is reduction of LDL level.
 These are basic in exchange resin supplied in the chloride form.
 Cholestyramine + Digoxin not administered in the case of congestive cardiac
failure (GATE-05)
Adverse effect - Constipation and Steatorrhea

LIPOPROTEIN LIPASE ACTIVATOR (PPAR AGONIST: FIBRATE)

Drugs : Clofibrate, Gemfibrozil, Bezafibrate, Fenofibrate, Ciprofibrate

 They are Fibric acid derivatives.
 They activate peroxisome proliferator-activated receptor  (PPAR-) present mainly in
the liver. [GATE-08]
 Fenofibrate is longest acting and is a prodrug.
 Tissue plasminogen activators that dispress blood clots, beneficial it is given within 3
days [GATE-05]
 The breakdown of fibrin is catalysed by plasmin (GATE-04)
 Fibrates are Contraindicated in pregnancy.
Mechanism of action -
 It results in increase in lipoprotein lipase activity and increase in hydrolysis of triglyceride
rich lipoprotein VLDL.
 They also increase in HDL, decrease in LDL level.
Fibrates

Activate PPAR-

se Lipoprotein lipase activity se Hepatic secretion of VLDL.

se HDL levels.

se Hydrolysis of triglyceride

rich lipoprotein VLDL.
Net effect - Increase Triglyceride levels in blood.

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

LIPOLYSIS AND TRIGLYCERIDE SYNTHESIS INHIBITORS

Drugs: Niacin
 Niacin is a B-Complex vitamin.
 It also increases lipoprotein lipase activity which is responsible for metabolism of lipoprotein.
 In larger dose it has hypolipidemic effect and reduces plasma TGs, LDl-cholesterol and raise
HDL level.
Mechanism of action:
 Niacin inhibits lipolysis in adipose tissue and thus reduces hepatic VLDL production.
 Niacin is most effective monotherapy for raising HDL Cholesterol [GPAT-11]

Triglycerides
se Lipoprotein lipase Naicin In adipose tissue
activity
Free fatty acids

se Hydrolysis of Triglycerides

triglycerides of VLDL In liver
VLDL
se VLDL levels
Adverse effect - Flushing and Dyspepsia.

STEROL ABSORPTION INHIBITORS

Drug - Ezetimibe
 It inhibits the absorption of dietary and biliary cholesterol in the intestine.
 It reduces LDL cholesterol.
 Hepatic dysfunction is main adverse effect.
 Inhibit cholesterol absorption by interfering with specific cholesterol transport protein in
intestinal mucosa.
 Compensatory increased in cholesterol synthesis take place.
OTHERS

OMEGA-3-FATTY ACIDS
 It is present in omega-3 fatty acids.
 Omega-3 fatty acids activate PPAR- and reduce triglyceride level.

PLASMA VOLUME EXPANDERS

 Plasma volume expanders are solutions used for temporary maintenance of blood volume in
emergency situation.
 Required in following condition- severe burn, shock, hemorrhage.
 These are high molecular weight substances which exerts colloidal osmotic pressure.

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TYPES OF VOLUME EXPANDERS

1. Crystalloids : Crystalloids are aqueous solution of mineral salt or other water soluble
molecules
2. Colloids : Colloids are larger insoluble molecule, such as dextran, Human albumin, Gelatin,
Blood.

IDEAL PROPERTIES OF PLASMA VOLUME EXPANDERS

 Iso-tonic with plasma
 Pharmacodynamic inert
 Non-pyrogenic, Non-allergenic and Non-antigenic
 Stable, easily sterilizable and cheap
The important colloidal solutions
 Human albumin
 Dextran 40 and Dextran 70
 Degraded gelatin polymer
 Hydroxyethyl starch
 Polyvinyl Pyrrolidine (PVP)

HUMAN ALBUMIN

 It is obtained from pooled human plasma.

 Albumin and plasma protein fraction, which are prepared from Blooded human plasma
are the commonly used plasma expanders.
 They do not carry the risk of hepatitis.
 It can be used without regard to patient’s blood group and doesn’t interfere with coagulation.
DEXTRAN
 Dextran is a water soluble glucose polymer produced by bacteria grown on sucrose media.
 Dextran 40 – It is given by i.v. infusion as a 10% solution.
 Dextran 70 – It is infused as a 6% solution and is prepared when small volumes are required.
 It is produced by using the bacterial enzyme dextran sucrase from the bacterium
leuconostoc mesenteriodes which grows in a sucrose medium.
HYDROXYMETHYL STARCH FOR HETASTARCH
 It is derived from starch. It acts by increasing oncotic effect similar to that of plasma albumin.
 The adverse effect flu-like syndrome.
DEGRADED GELATIN POLYMER
 Gelatin is a polypeptide obtained from ox collagen.
 Gelatin in degraded from is used commonly as a plasma expander.
POLYVINYL PYRROLIDINE
 This is a synthetic polymer. It interfere with blood grouping and cross matching of blood

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

6 DRUGS FOR PEPTIC ULCER

AND GASTROESOPHAGEAL
REFLUX DISEASE

INTRODUCTION
 Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, Peptic ulcer
results probably due to imbalance between
 Aggressive factors - Acid, Pepsin, NSAIDs and Helicobactor pyroli
 Defensive factors - Mucus, Bicarbonate, Prostaglandins
 Excessive use of Alcohol, Tea, Coffee and certain drugs like Corticosteroids, Reserpine,
indomethacine also cause ulcer.
 Most common form of ulcer is duodenal ulcer.

REGULATION OF GASTRIC SECRETION

 HCl is secreted by gastric parietal cells due to stimulation of H+K+ ATPase (Proton pump),
and it is activated by
 Histamine (H2 receptor)  Acetylcholine (M1 and M3 receptor)
 Gastrin (CCK receptor)

Canaliculus
H K
+ +

Active
pumps
PPI
Inhibitors
H
+
K+
Resting
Protein kinases
Gastrin pumps
(+)
P H2Receptor
CCK2-R cAM antagonists
Ca
Anticholinergics
M3-R H 2-R

Ach Histamine
Fig: MECHANISM OF ACITON OF DRUG DECREASE HCl SECRETION

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

 Histamine acting through H2 receptor, H2 receptor activates H+K+ATPase by generating cAMP

and increase acid secretion.
 PGE2 is produced by gastric mucosa, inhibits acid secretion by opposing cAMP generation.
 H.pyroli also plays a major role in the pathogenesis of ulcer by causing hypergastrinemia

MAIN STRATEGIES OF TREATMENT

Antacids Neutralize  PPIs

Decrease
ACID  H2-blockers
Secretion of
 Prostaglandins
r
lce Protect  Sucralfate
U
 CBS

A. Decrease acid secretion

MECHANISM OF ACTION DRUGS
Blocking histamine action H2 antihistaminics
Blocking acetylcholine action M1 selective anticholinergics
Inhibition of H+K+ ATPase Proton pump inhibitors, Prostaglandin
Decrease gastrin release Prostaglandin
Decrease gastrin level which Anti H.pyroli drugs
is increased by H.pylori
B. Neutralize the already secreted acid Antacids
C. Protect the ulcer from acid  Ulcer protective drugs

CLASSIFICATION OF DRUGS

CLASS SUBCLASS DRUGS

Gastric acid Proton pump inhibitors Omeprazole, Lansoprazole, Pantoprazole,
secretion Rabeprazole, Esomeprazole, Dexrabeprazole
inhibitors H2 Receptor antagonist Cimetidine, Ranitidine [GATE-90, 93],
Famotidine, Roxatidine, Loxatidine
Anticholinergic Pirenzepine, Telenzepine, Propantheline,
Oxyphenonium
Prostaglandin analogue Misoprostol, Enprostil, Rioprostil
Gastric acid Systemic Sodium bicarbonate, Sodium citrate
neutralizers Non-systemic Magnesium hydroxide, Aluminium
(Antacid) hydroxide, Calcium carbonate, Megaldrate
Ulcer protective Sucralfate [GPAT-2019], Colloidal bismuth subcitrate (CBS)
Anti H. pylori Amoxicillin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline CBS

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

1. DRUG DECREASING ACID SECRETION

PROTON PUMP INHIBITOR (PPIs)

 These drugs inhibit H+K+ATPase in parietal cells of stomach.
 PPIs are prodrugs, Omeprazole is the prototype drug of substituted benzimidazole.
 Lansoprazole is most potent than omeprazole and safest PPI in pregnancy and higher oral
bioavailability.
 Rabeprazole is most potent and longest acting PPI.
 These drugs have short half life (1.5 hours) but can inhibit acid secretion more than 24
hours (hit and run drugs)
 PPIs are given orally in early morning in empty stomach.
 Pantoprazole Esomeprazole and Lansoprazole are given by i.v. routs.
 Omeprazole also inhibit gastric mucosal carbonic anhydrase.
Mechanism of action
 These drugs inhibits H+K+ ATPase in parietal cell of stomach
Canaliculi
Blood Parietal cell (acidic pH)

PPIs PPIs PPIs

Proton Sulfenamide
Pump

Pharmacokinetics
 It is inactive at neutral PH but as <5 rearranges to two cationic form
 Sulphenic acid
 Sulfenamide That reacts covalently with -SH groups of H+K+ATPase (Proton pump)
inactivate it irreversibly.
 These drugs are weak bases and can be destroyed by gastric acid so given by enteric coated
forms.
 Bioavailability of all PPIs is reduced by food.
Side effect of Omeprazole
 Gynaecomastia, Erectile dysfunction and osteoporosis
Uses: (Peptic ulcer is the drug of choice)
 Peptic ulcer (duodenal or gastric ulcer)
 Zollinger - Ellison syndrome (ZES) (Drug of choice)
 Gastroesophageal refllux disease (GERD)
 Prophylaxis of aspiration pneumonia
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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

H2 ANTIHISTAMINICS
 Drugs are : Cimetidine, Ranitidine, Famotidine, Roxatidine, Loxatidine
Parietal cell
Histamine H2 receptor Cimetidine, Ranitidine, Famotidine, Nizatidine
(Agonist) (Antagonist)
 These drugs competitively inhibit H2 receptor in parietal cells, Thus inhibit the acid
secretion
 These drugs are less potent than PPIS.
 Cimetidine is the prototype drug and was the 1st H2 blocker developed.
 Cimetidine, Ranitidine and Famotidine are available both for oral and intravenous
administration.
 Uses- Peptic ulcer (Gastric and duodenal ulcer), Zollinger-Ellison Syndrome, Gastroesophageal
reflux disease(GERD)
RANITIDINE
 Furan ring, 5 times more potent then cimetidine.
FAMOTIDINE
 Thiazole ring, 8 time more potent that Ranitidine.
 Most potent H2 blocker.
Difference between Cimetidine and Ranitidine
S.NO CIMETIDINE RANITIDINE
1. Less Potent More Potent [5 times more]
2. Shorter duration [6-8 hour] Longer duration [24 hour]
3. Enzyme inhibitors Less affinity for enzymes
4. Has antiandrogenic action Has no antiandrogenic action
Gynecomastia and menstrual irregular
NOTE
 Antacids reduces absorption of all H2 blockers.
 Because of its higher potency and longer duration of action, Famotidine is more suitable
than other H2 blockers for Zollinger-Ellison syndrome and for prevention of aspiration
pneumonia.
ANTICHOLINERGICS
Drugs are: Pirenzepine, Telenzepine, Propantheline, Oxyphenonium
 Atropine drugs reduce the volume of gastric juice without raising its pH.
 Pirenzepine and Telenzepine are selective M1 blocker that is preferred antimuscarinic agent
for peptic ulcer.
 Anticholinergic drugs are not commonly used because of their low efficacy and anticholinergic
effect
PROSTAGLANDIN ANALOGUES
Drugs: Misoprostol (PGE1 analogue), Enprostil and Rioprostil (PGE2 analogue)
PGE1, PGE2 and PGI2 are produced in gastric mucosa and appear to serve a protective role by
 Inhibiting acid secretion
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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

 Promoting mucus and H2CO3 secretion.

 Misoprostol is used for prevention and treatment of NSAIDs induced ulcer
 Misoprostol enhance secretion of mucus bicarbonate ions and cytoprotective action
on GI mucus.

2. DRUGS THAT NEUTRALIZE GASTRIC ACID (ANTACIDS)

 They neutralizes gastric acid.
 They do not decreases acid production.
Types of Antacids
Antacids

Systemic Non Systemic

Absorb systematically Poorly absorbable

Reacts with gastric HCl and
Disturb acid base balance Basic compounds
form corresponding salt
Induces alkalosis (on large dose) Do not alter acid-base balance
 Systemic antacids
 Sodium bicarbonate, Sodium citrate
 Absorb systemically large dose will induce alkalosis.
 They are use to alkaline urine and to treat acidosis.
 Non systemic antacids
 Magnesium hydroxide [Mg (OH)2], Aluminum hydroxide [Al (OH)3],Magnesium
trisilicate, Calcium carbonate [CaCO3].
 Poorly absorb from GI tract.
 Al (OH)3 causes constipation and Mg (OH)2 can causes diarrhoea so given in
combination.
 Do not disturb systemic acid base balance.
 Na2CO3 and CaCO3 cause Milk alkali syndrome with calcium containing food like milk.
 Potency of antacid is generally expressed in terms of acid neutralizing capacity.
 Antacids decrease the absorption of Tetracycline, Ketoconazole, Fluoroquinolones ·
 Magnesium trisilicate is considered to be a better antacids than aluminium hydroxide
due to following reasons- [GPAT-11]
(1) It forms colloidal silicone dioxide.
(2) Magnesium ions overcome constipation.
Note :-
(1) Antacids reduces the absorption of many drugs like - Iron, Tetracyclines, Fluroquinolones
Ketoconazole etc.
(2) Methyl polysiloxanes (Simethicene & Dimethicene)
 They are antifoaning agents & reliver flatulence.
Oxethazine - Topical anaesthetics, used to anaesthetize gastric mucosa.

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3. ULCER PROTECTIVE AGENTS

 These drugs form a covering over the ulcer bed and prevent its exposure to gastric acid.
SUCRALFATE
 It is a complex of aluminum hydroxide and sulfated sucrose.
 Below PH 4 its molecule polymerises to form a sticky layer that covers the ulcer bed
 Side effect – Constipation
COLLOIDAL BISMUTH SUBCITRATE(CBS)
Probable mode of action
 CBS and mucus – forms a glycoprotein-Bi-Complex  Coat ulcer bed
 Stimulate secretion of PGE2, mucus and bicarbonate.
 Have antimicrobial effect against H. pylori
Adverse effects – Blackening of tongue and stool, Bismuth toxicity

4. ULCER HEALING DRUGS

CARBENOXOLONE SODIUM
 Obtained from root of liquorice.
 Steroidal drug having mineralocorticoid action i.e. Na+ and water retention.
 Increase mucus production especially thick viscid mucus that remains adherent to gastric
mucosa  so increase life span of gastric cells.
ANTI H. PYLORI DRUGS
Drugs: Amoxicillin,Metronidazole,Tinidazole, Clarithromycin, Tetracyclines, CBS
 H. pylori is a gram (-ve) bacilli cause ulcer.
 It attaches to the surface of epithelium beneath the mucus and produce ammonia which
maintain a neutral environment around the bacteria and promote back diffusion of H+ ion.

GASTRO ESOPHAGEAL REFLUX DISEASE (GERD)

 It is a condition in which acid in the stomach recheas into the esophagus and cause
mucosal inflammation.
 Inflammatory bowl disease is a chronic relapsing inflammatory disease of the ilium, Colon
or both that may be associated with systemic menisfestation.
Two strategies for management
a. Decrease acid production
LES
Alginate
b. Increase forward movement of GIT (So that the contents
do not reflux upward). Metoclopramide H2blocker PPI
 Drugs used for increasing the GI motility are - Prokinetic
drugs HCl
 Drugs used are
o PPIs o H2 blockers Antacid

o Antacids o Sodium alginate

Prokinetic drugs
Fig: SITE AND MECHANISM OF DRUG ACTING IN
o GASTROESOPHAGEAL REFLUX DISEASE

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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

7 EMETICS
ANTIEMETICS AND
OTHER GIT DRUGS

INTRODUCTION
 Vomiting (emesis) is the involuntary, forceful expulsion of the contents of one's
stomach through the mouth and sometimes from the nose.
 Nausea and vomiting are protective reflux that help to remove toxic subtance from GIT.
 Vomiting centre – Medulla oblongata
 The chemoreceptor trigger zone (CTZ) and Nucleus tractus solitarius (NTS) contains the
receptor like

REGULATION OF VOMITING

Histamine (H1)
Dopamine (D2)
Cholinergic (M) Through these emetic
signal relayed
Serotonin (5HT3)
Opioid ()

Smell, pain, sight, psychogenic stimuli

5-HT3
M, H1 CORTEX
receptors H1 Area Motion,
D2 postrema Ototoxic
(CTZ) drugs
NTS 5-HT3
Opioid

VC

M1, H1
Fauces Inner ear
ticking VOMITING Cerebellum
5-HT3R

5-HT
Gut Cytotoxic drugs
PGs.
Kinins
Levodopa,
G.l. irritation Apomorphine,
Inflammation
Chemotherapy Blood Digitalis,
Radiation
vessels Ergot,
Platelets
Infection Morphine,
Drugs Emetine,
Fig: CENTRAL AND VISCERAL STRUCTURE INVOLVED IN EMESIS

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

Drugs used for causing emesis - Mustard, Common Salt, Apomophine, Ipecac.

ANTIEMETICS DRUGS
 These are drugs used to prevent or suppress vomiting centre.
 These drugs have antimuscarinic, H 1 antihistaminic, D 2 antagonistic and 5-HT 3
antagonistic action.

CLASSIFICATION OF DRUGS

CLASS DRUGS
Anticholinergics Hyoscine, Dicyclomine
H1 antihistaminics Promethazine, Diphenhydramine,
Dimenhydrinate, Meclizine, Cyclizine
Neuroleptics[D2 blockers] Chlorpromazine, Prochlorperazine, Haloperidol
Prokinetics Domperidone, Metoclopramide,
Cisapride, Mosapride
5HT3 antagonist Ondansetron, Granisetron
Adjuvent antiemetics Dexamethosone, Benzodiazepenes

ANTICHOLINERGICS
Drugs are: Hyoscine, Dicyclomine
 Scopolamine (hyoscine) is the drug of choice to prevent motion Sickness.
 Acts by blocking conduction of nerve impulse across a cholinergic link in the pathway
leading from the vestibular apparatus to the vomiting centre.
 Other drugs used in motion sickness are- Dicyclomine, Promethazine, Cyclizine

H 1 ANTIHISTAMINICS
Drugs are: Promethazine, Diphenhydramine, Cinnarizine Dimenhydrinate, Meclizine,
Cyclizine
 They are mainly useful for the prevention of motion sickness.
 They are also effective in morning sickness.
 Cinnarizine - It is an antivertigo drug, acts by inhibiting influx of Ca+2 from
endolymph into the vestibular sensory cell which mediates labyrinthine reflexes.

NEUROLEPTICS
Drugs are: Chlorpromazine, Prochlorperazine, Haloperidol
 Have broad spectrum antiemetic action.
 Acts by blocking D2 receptor in the CTZ.

PROCHLORPERAZINE
 It is a labyrinthine suppressant has selected antivertigo and antiemetic action.
 Adverse effect- muscle dystonia

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PROKINETIC DRUGS
Drugs are : Domperidone, Metoclopramide, Cisapride, Mosapride
 These are drugs which promote gastrointestinal transit and speed gastric emptying
by enhancing coordinated propulsive motility.
 Acetylcholine is the major neurotransmitter in the GIT which is responsible for the
peristaltic movement
 5-HT4 receptors increases the release of Ach
 D2 and 5-HT3 receptors inhibits the release of Ach
So, prokinetic drug can act by-
 5HT4 agonistic activity and D2 and 5-HT3 antagonistic activity.
Mechanism of action

Blocks D2
Metoclopramide receptor in Extrapyramidal
basal ganglia symptoms

CTZ
5-HT3, D2 Blood-brain barrier

r
cke Poorly
lo
nc. B ks Blo crosses
o c ck
ighc Blo s
h
At
Metoclopramide Blocks Domperidone

Prokinetic
Increae tone of effect
lower oesophageal
sphincter
Relax the pyloric
sphincter and Increase the peristaltic
doudenal bulb movement of upper GIT

Fig: Mechanism of Action of prokinetic drugs

METOCLOPRAMIDE
Mechanism of Action
Metoclopramide

5-HT4 agonist D 2- antagonism 5-HT3 antagonism

 Ach secretion from the myenteric motor neurons

Domperidone - D2 antagonistic action.

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

Cisapride - 5HT4 agonistic and 5HT3 antagonistic action and have QT prolongation action.

NK1 RECEPTOR ANTAGONIST

 Realizing that activation of neurokinin (NK1) receptor in CTZ and NTS by substance
Preleased due to emetogenic chemotherapy and other stimuli plays a role in the causation
of vomiting.
APREPITANT
 Aprepitant is an oral formulation, highly selective and crosses the blood-brain barrier
Mechanism of action
 Emetogenic chemotherapy release substance by stimulating CTZ and NTS by acting on
NK1 receptor
 Blocking of NK1 receptor causes emesis blocking
 Little effect on 5-HT3 or D2 receptor

5HT 3 - RECEPTOR ANTAGONIST

Drugs are : Ondansetron, Granisetron

ONDANSETRON
 Developed to control cancer chemotherapy/radiotherapy induced vomiting.
 Side effect – Headache
GRANISETRON
 10-15 time more potent than ondensetron and transdermal patch available.
Mechanism of Action
Anticancer drug and radiotherapy

Tissue damage (in gut)

Release of serotonin (5-HT) from enterochromeffin cells of instestinal mucosa.

5HT3 Stimulation vagal afferent in the gut through 5HT3 Receptor

Antagonist
Impulse to and CTZ and NTS

Induce Vomiting

GALL STONE DISSOLVING DRUGS

 Chenodiol - Inhibits cholesterol synthesis in liver.

 Ursodiol - Inhibits cholesterol absorption in intestine.
Drugs used one - PPIs, H2 blockers, Antacids, sodium alginate, prokinetic drugs.

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8 DRUGS FOR
CONSTIPATION
AND DIARRHOEA
CONSTIPATION
 It is refers to bowel movements that are infrequent or hard to pass.
 The stool is often hard and dry.
Laxatives (Purgative, Cathartics)
 Laxatives are drugs that facilitate evacuation of formed stools from the bowel and milder in
action.
 Purgative are drugs that cause evacuation of watery stools and stronger in action.
 The term laxative, purgative and cathartics are often used interchangeably.

CLASSIFICATION OF LAXATIVES

CLASS OF LEXATIVE NAME OF DRUG

Bulk forming Bran, Psyllium Ispaghula, Methyl cellulose
Stool softener Docusates [Doss], Liquid Paraffin
Stimulant purgative
a. Diphenylmethanes Phenolphthalein, Bisacodyl
b. Anthraquinones Senna, Cascara
c. Fixed oils Castor oil
d. 5HT4 agonist Prucalopride
Osmotic purgative Magnesium salts, Sodium salts, Lactulose
BULK PURGATIVE
 Swell and increase water concentration of faces.
STOOL SOFTNER
 It is an anionic detergent, soften the stool by net water accumulation in lumen by an
action on the intestinal mucosa.
STIMULANT PURGATIVE
 Inhibits Na+K+ATPase so, transport of Na+ and water into interstitum is reduce.
 Stimulate PGE2 production.
 Irritate mucosa – Increase GI motility.
OSMOTIC PURGATIVE
 Retain water osmotically.
 Magnesium ion release cholecystokinin which may aid purgative action of magnesium salts.
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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

 Lactulose – Semisynthetic disaccharide of fructose and lactose neither digested nor absorb
in intestine.

DI ARRHOEA

 Diarrhoea denotes passage of unusually loose or watery stools at least three times or more in
a 24 hour period.
 Inhibition of Na+K+ATPase and structural damage to mucosal cell (by rota virus) cause
diarrohea by reducing absorption.

CLASIFICATION

CLASS SUBCLASS DRUGS

Absorbents - Isabgol , Psyllium
Adsorbents - Kaolin, Pectin, Chalk
Antisecretory drugs Opioids Codein, Loperamide, Diphenoxylate
a- adrenergic Clonidine,
receptor agonist
- Octreotide
Antimicrobial drugs - Ciprofoxacin, Cotrimoxazioe,
Erythromycin

NONSPECIFIC ANTIDIARRHOEAL DRUGS

 Absorbents – Absorb water, swells and modify consistency of stool.

 Adsorbents – Adsorb virus, bacteria etc. and prevent their contact with intestine.
CLASS DRUGS
Absorbents Isapaghula, Psyllium
Adsorbents Kaolin, Pectin, Chalk
Antisecretory drugs Racecadotril, Bismuth subsalicylate,
Anticholinergics, Octreotide, Opioids
Antimotility drugs Diphenoxylate, Loperamide
Other Drugs
(1) Antibiotics and Glucocorticoids.
(2) Immino modulatour drugs : Azathioprine, 6-mercaptopurine, Methotrexate.

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DRUGS FOR TREATMENT OF

INFLAMMATORY BOWEL DESEASE (IBD)

 Inflammatory bowel disease (IBD) is a term for two conditions (Crohn’s disease and
ulcerative colitis) that are characterized by chronic inflammation of the gastrointestinal
(GI) tract. Prolonged inflammation results in damage to the GI tract results in - diarrhoea,
abdominal discomfrot, anaemia.
Aminosalicylates

Sulphasalazine Olsalazine Balsalazide

(Product) (Product)

Sulphapyridine Mesalamine(5-ASA) (Active)

Therapeutic effect in RA.

Benificial effect in IBD.

SULFASALAZINE (SALICYLAZOSULFAPYRIDINE)
 Sulfasalazine is a parent compound of 5-aminosalicylates (5-ASA).
 5-ASA is the main active therapeutic moiety, but not used alone because when given alone
orally it is poorly absorbed and inactivated before reaching colon.
 Therefore it is given along with sulfapyridine as sulfasalazine which prevents its early
absorption and inactivation.
 In sulfasalazine, 5-ASA with sulfapyridine is linked through an azo bond and it is splited
by colonic bacteria after intake.
 They decrease prostaglandin synthesis – Decreases mucosal secretion.
 Sulfasalazine - 5-ASA + Sulfapyridine
 Olsalazine - 5-ASA + 5-ASA
 Balsalazide - 5-ASA + Amino benzyl alanine

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9 CHEMOTHERAPY
GENERAL
CONSIDERATION
GENERAL CONSIDERATION
 Chemotherapy -Process of uses of chemicals (synthetic or natural) to destroy harmful
microbes without disturbing the host cell body.
 Antibiotics - Produced by microbes and inhibits the growth of microbes at very low
concentration.
 Antimicrobial agent - Antimicrobial agent are the synthetic or natural substance that are
used to treatment of various infection e.g.- bacterial, fungi and viral .

ANTIBIOTICS ARE OBTAINED FROM

MICROORGANISM ANTIBIOTICS
Fungi Penicillin, Cephalosporins, Griseofulvin
Bacteria Polymyxin B, Colistin, Bacitracin, Tyrothricin, Aztreonam
Actinomycetes Aminoglycoside, Tetracycline, Chloramphenicol, Macrolides
[GPAT-20], Polyenes

ANTIBIOTICS AND THEIR MICROORGANISM

ANTIBIOTIC MICROORGANISM
Rifampicin [GATE-90] Streptomyces mediterranei
Nystatine [GATE-90] Streptomycec noursei
Candicidin [GATE-90] Bacillus polymyxa
AmphotericinB [GATE-90] Streptomycec nodosus
Bacitracin [GATE-92] Bacillus subtilis
Neomycin [GATE-92] Streptomyces fradiae
Tobramycin [GATE-92] Streptomycec tenebrsus
Gentamicin [GATE-92] Micromonospora purpura
Erythromycin [GATE-08] Streptomycec erythraeus
Mithromycin/Plicamycin [GPAT-15] Streptomycec argillaceus
Mitomycin C [GPAT-20] Streptomycec verticillus
Oxytetracycline Streptomycec rimosus
Tetracycline, Demeclocycline Streptomycec aureofaciens
Chlortetracycline
Polymyxin Bacillus polymyxa

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Chloramphenicol Streptomycec venezuelae

Streptomycin Streptomycec griseus
Sisomicin Micromonospora inyoensis
Colistin Bacillus calistinus
Bleomycin Streptomycec verticillus
Paromycin Streptomycec rimosus
Framycetin Streptomycec lavendulae
Streptozocin Streptomycec achoromogenes
Dactinomycin or Actinomycin D Streptomycec parvulus
Kanamycin Streptomycec panamyceticus
Mithromycin Streptomycec tanashiensis
Cephalothin Cephaloporium [fungi]
Griseofulvin Penicillium notatum [fungi]
Penicillin Penicillium notatum [fungi]

CLASSIFICATION OF ANTIMICROBIAL AGENTS

(A) ACCORDING TO THEIR TYPES OF ACTION

(1) BACTERICIDAL - Acts primarily by killing the bacteria.

Trick: I m Bactericidal Because A Very Quit Person is Rarely Protected
Drugs are  Isoniazid, Metronidazole, Beta-lactum antibiotics, Bacitracin, Aminoglycosides, Vancomycin,
Quinolones, Pyrazinamide Rifampicin and Polymyxin B.
(2) BACTERIOSTATIC - Acts primarily by arresting bacterial multiplication.
Trick: Static Causes Non Total Or Non Complete Through Massive Elimination.
Drugs are  Sulfonamide, Chloramphenicol, Nitrofurantoin, Tetracycline, Oxazolidinon, Novobiocin,
Clindamycin, Trimethoprim, Macrolides, Ethambutol.
BACTERICIDAL AND BACTERIOSTATIC DRUGS ACCORDING TO MOA

MECHANISM OF ACTION BACTERICIDAL BACTERIOSTATIC

Protein synthesis inhibitor Aminoglycoside Tetracycline, Chloramphenicol,
Streptogramins Macrolides, Lincosamide,
Linezolid, Tigecycline
Cell wall synthesis inhibitor Penicillin, Cephalosporins,
Vancomycin, Bacitracin,
Cycloserine, Fosfomycin -
Drug acting on cell Polymyxin B, Colistin, -
membrane Tyrothricin, Amphotericin B
Antitubercular Isoniazid, Rifampicin, Ethambutol
Pyrazinamide
Drug affecting intermediary Combination of two drug Sulfonamide, Trimethoprim,
metabolism may be bactericidal Ethambutol.
e.g. cotrimoxazole.
Drug affecting DNA Quinolones, Metronidazole. Nitrofurantoin, Novobiocin

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REMEMBER THE FACTS :- (GENERAL CONCEPT)

 All cell wall synthesis inhibitors are bacteriocidal.
 All antibacterial drugs that act on cell membrane are bacteriocidal.
 All 1 st line antitubercular drugs are bacteriocidal except ethambutol that is
bacteriostatic.
 All protein synthesis inhibitors are bacteriostatic except aminoglycoside and
streptogramins which are bacteriocidal.
 All drugs affect intermediary metabolism are bacteriostatic.

(B) ACCORDING TO THEIR SPECTRUM OF ACTIVITY

(1) Narrow-Spectrum antibiotics - Effective against specific type of bacteria either

gram positive or gram negative bacteria. eg : Penicillin G, Aminoglycoside.
(2) Broad-Spectrum antibiotics - Effective against a wide range of bacteria both gram
positive and gram negative bacteria. eg : Tetracyclines, Chloramphenicol.

(C) ACCORDING TO THEIR MECHANISM OF ACTION

MECHANISM OF ACTION ANTIBIOTICS

Drug that inhibits cell wall synthesis -lactam antibiotics (Peinicillin, Cephalosporin,
Monobactams, Carbapenems) Cycloserine,
Bacitracin, Vanconycin, Fosfomycin.
Drugs that affect cell membrane Polypeptides (Polymyxins, Colistin,Tyrothricin)
Polyenes (Amphotericin B, Nystatin, Hamycin),
Azoles (Ketoconazole, Fluconazole, Itraconazole).
Drugs that inhibit protein synthesis Tetracyclines, Chloramphenicol, Erythromycin,
Clindamycin, Linezolid
Drugs that alter protein synthesis by
Misreading of mRNA code
Drugs that inhibits DNA synthesis Acyclovir, Zidovudine
Drugs that affect DNA function Rifampin, Metronidazole
Drugs that inhibit DNA gyrase Nalidaxic acid and Fluoroquinolones.
Antimetabolites Sulfonamide, Sulfones, PAS, Dapsone,
Trimethoprim, Pyrimethamine, Ethambutol.

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Cell wall synthesis inhibitors

DNA replication (DNA gyrase)
Cycloserine
Vancomycin
Bacitracin Nalidixic acid DNA-dependent RNA polymerase
Fosfomycin Quinolones
Cephalosporins Rifampin
Monobactams DNA
Carbapenems Protein synthesis
PABA
mRNA (50S inhibitors)
Sulfonamides FA
DHFA Ribosomes Erythromycin
Folic acid
FR 50 50 50 Chloramphenicol
metabolism
THFA 30 30 30 Clindamycin
Trimethoprim Streptogramins
Protein Synthesis
Cell membrane (30S inhibitors)
Polymyxins Aminoglycoside
Tetracycline
Fig: MECHANISM OF ACTION OF ANTIBIOTICS

(D)ACCORDING TO THEIR CHEMICAL STRUCTURE

S.N. CHEMICAL CLASS DRUGS

1. Sulfonamides and related Sulfadiazine and others, Sulfones Dapsone
drugs (DDS), Para amino salicylic acid (PAS).
2. Diaminopyrimidines Trimethoprim, Pyrimethamine.
3. Quinolones Nalidixic acid, Norfloxacin, Ciprofloxacin,
Prulifloxacin.
4. -Lactam antibiotics Penicillins, Cephalosporins, Monobactams,
Carbapenems.
5. Tetracyclines Oxytetracycline, Doxycycline.
6. Nitrobenzene derivative Chloramphenicol.
7. Aminoglycosides Streptomycin, Gentamicin, Amikacin, Neomycin.
8. Macrolide antibiotics Erythromycin, Clarithromycin, Azithromycin,
Roxithromycin.
9. Lincosamide antibiotics Lincomycin, Clindamycin.
10. Glycopeptide antibiotics Vancomycin, Teicoplanin.
11. Oxazolidinone Linezolid.
12. Polypeptide antibiotics Polymyxin B, Colistin, Bacitracin, Tyrothricin.
13. Nitrofuran derivatives Nitrofurantoin, Furazolidone.
14. Nitroimidazoles Metronidazole, Tinidazole.
15. Nicotinic acid derivatives Isoniazid, Pyrazinamide, Ethionamide.
16. Polyene antibiotics Nystatin, Amphotericin B, Hamycin.
17. Azole derivatives Miconazole, Clotrimazole, Ketoconazole, Fluconazole.
18. Others Rifampin, Spectinomycin, Sod. fusidate, Cycloserine,
Vancomycin, Ethambutol, Clofazimine, Griseofulvin.

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Problems that arises with use of antibiotics -

(1) Toxicity - Local irritancy and systemic toxicity.
(2) Hypersensitivity reaction.
(3) Neutritional deficiency.
(4) Drug resistance.
(5) Masking the action.
(6) Super infection - This refers to the appearance of a new infection as a result of
antimicrobial therapy.
Test for antibiotic sensivity:
1. Disc susceptibility test (most commonly use)
2. Broth dilution susceptibility test
3. Kirby-Baur disc diffusion method [GPAT-17].
4. E-test (Epsilometer test)

DRUG RESISTANCE
 Drug resistance refers to unresponsiveness of a microorganism to on antimicrobial agents.
TYPES OF DRUG RESISTANCE DRUGS
Tolerance to drug Penicillin, Rifampin
(a) Loss of affinity of the target Molecule
(b) Acquisition of an alternate metabolic Sulfonamides
pathway
Destruction of drug by enzyme β-lactamase antibiotics, Chloramphenicol,
Aminoglycoside, Tetracycline
Impermeability to drug Aminoglycoside, Chloroquine,
(a) Decrease access into the bacterial cell Tetracycline
through porins
(b) Active efflux of the drug from cell Erythromycin, Fluoroquinolones

TOXICITY OF DRUGS

S. NO. DRUGS TOXICITY

1. Aminoglycoside Ototoxicity (Damage of 8th cranial nerve)
Nephrotoxicity
2. Tetracyclines Hepatotoxicity, Nephrotoxicity
3. Chloramphenicol Gray baby syndrome, Bone marrow depression,
Diarrhoea, Superinfection
4. Quinolones Phototoxicity
5. Bacitracin, Nephrotoxicity
Polyenes,
Polypeptide
6. Polymyxin B Neurotoxicity, Nephrotoxicity
7. Vancomycin Redman syndrome, Ototoxicity, Nephrotoxicity
8. Penicillin, Hypersensitivity reaction
Cephalosporin

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9. Sulfonamide Steven johnson syndrome, Kernicterus, Crystalluria,

Hypersensitivity reaction
10. Nitrofurantion Loffler’s syndrome
11. Streptomycin Ototoxicity
[GATE-90]
12. Rifampicin Jaundice
13. Cycloserine Neurotoxicity
14. Erythromycin Gut upset, Cholestatic hepatitis, HME inhibition

FACTORS AFFECTING THE CHOICE OF AN ANTIMICROBIAL AGENT

1. Age
 Chloramphenicol in new born baby may cause gray baby syndrome.
 Sulfonamide in new born baby may cause kernicterus.
 Tetracycline accumulates in the developing teeth and bone and cause discolouration it.
2. Pregnancy
 All antibiotics posses risk to the fetus when used in pregnancy. Penicillin, most cephalosporin
and macrolide (PCM) appear safe.
 Some drugs are contraindicated during pregnancy:
Trick: SAFE Moms Take Really Good Care
Drugs : Sulfonamides, Aminoglycosides, Fluoroquinolones, Erythromycin, Metronidazole,
Tetracyclines, Ribavirin, Griseofulvin, Chloramphenicol.
3. Renal functions
DRUGS CONTRAINDICATED IN DOSE REDUCTION REQUIRED IN
S.NO
RENAL DISEASE RENAL FAILURE
1. Cephalothin Aminoglycosides
2. Cephaloridine Amphotericin B
3. Nitrofurantoin Vancomycin
4. Nalidixic acid Ethambutol
5. Tetracyclines (expect doxycycline)
4. Liver functions
DRUGS CONTRAINDICATED IN DOSE REDUCTION REQUIRED
S.NO
LIVER DISEASE IN LIVER FAILURE
1. Erythromycin Chloramphenicol
2. Tetracyclines Isoniazid
3. Pyrazinamide Rifampicin
4. Pefloxacin Clindamycin
5. Genetic functions
Antimicrobials producing hemolysis in glucose-6-phosphate dehydrogenase (G-6PD) deficient
patients are Primaquine, Chloroquine, Quinine, Chloramphenicol, Nitrofurantoin,
Fluoroquinolones, Dapsone and Sulfonamide.
6. Secreted in bile:- Antimicrobial that are secreted in the bile, can be excrete in faces. Therefore,
does not require dose reduction in renal failure.

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Important drugs secretion bile are: Mnemonic:

Safe (Cef) in Cefriaxone, Cefoperazone
The Tigecycline
R Rifamycin
E Erythromycin
N Nafcillin
A Ampicillin
L Lincosamide (Clindamycin)
Disease Doxycycline

COMBINED USE OF ANTIMICROBIALS

1. TO ACHIEVE SYNERGISM : The activity of two drug in combination is greater to the sum of
their independence activity when studied separately.
e.g.:- Penicillin+ Sulfonamide for actinomycetes, Rifampicin + Isoniazid for tuberculosis
(a) Two bacteriostatic agent are often additive, rarely synergistic e.g.- combination of
Tetracyclines, Chloramphenicol, Erythromycin, etc.
(b) Two bactericidal drug are frequently additive and sometimes synergistic if the organism
is sensitive to both etc. e.g.- Penicillin/Ampicillin + Streptomycin/gentamicin for enterococcal,
Ticarcillin + Gentamicin for pseudomonas infection.
 Ceftazidime + Ciprofloxacin for pseudomonas orthopedic prosthesis.
(c) Combination of a bactericidal with a bacteriostatic drug may be synergistic or antagonistic
depending on the organism:-
1. If the organism is highly sensitive to cidal drug _ response to the combination is equal
to the static drug given along, because cidal drug act primarily on rapidaly multiplying
bacteria, while the static drug inhibit multiplication. e.g:- Penicillin + Tetracycline.
2. If the organism has low sensitivity to the drug cidal drug – synergistic drug
Streptomycin + Tetracycline for brucellosis.
3 To prevent emergence of resistance:- Mutation conferring resistance to one AMA is
dependent of that conffering resistance to another.
2. TO REDUCE ADVERSE EFFECT : Read the drug label carefully and only take the medication as
recommended by your doctor or as instructed on the label.
 Never take a medication with alcohol & Ask your doctor or pharmacist any questions.
 Never mix the medication with food or drink, unless your doctor says it’s ok.
3. TO PREVENT EMERGENCE OF RESISTANCE
(a) Treatment of mixed infection
 Bronchiectasis peritonitis, certain UTI infection.
(b) Initial treatment of severe infection
 For impirical therapy, since bacterial diagnosis is not known; drug covering gram positive
and gram negative e.g.:- Penicillin + Gentamicin.
(c) Topical
 Generally AMAs which are not used systemically, are poorly absorbed from the
local site and cover a broad range of gram positive and gram negative bacteria are
combined for topical application e.g:- Bacitracin, Neomycin, Polymyxin B.
4. TO BROADEN THE SPECTRUM OF ANTIMICROBIAL ACTION - Cotrimoxazole, Trimethoprim,
Ciprofoxacin.

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10 SULFONAMIDES,
COTRIMOXAZOLE AND
QUINOLONES
SULFONAMIDES
 Sulfonamide were the first antimicrobial agent (AMA) effective against pyogenic bacteria.
 Sulfonamide are Sulfanilamide derivative and have low aqueous solubility so administered
as Na+ salt to improve their aqueous solubility
 Sulfonamide are bacteriostatic agent and effective against gram +ve and gram -ve
microorganism.
 Act by inhibiting folic acid synthesis by inhibiting enzyme folate synthetase.
 Bacteria synthesize their own folic acid of which para aminobenzozoic acid (PABA) is
constituents-sulfonamide, being structural anlogues of PABA, inhibits bacterial folate
synthatase competitively.
 Human cells also required folic acid (FA) but they utilize preformed FA supplied in diet
so unaffected by sulfonamide
NH2 Solubility potency
HO Pharmacokinetics
C O O S O

Esstenial for
NH2 pharmacological NH2
action
PABA SULFANILAMIDE
 Sulfonamide are not effective in presence of pus and tissue extract because -
(a) Pus contains purines and thymidine which decrease bacterial requirement for folic acid
(b) Pus is rich in PABA.
 The solubility of sulfonamide decrease in the acidic urine, which may result in precipitation
of drug causing crystalluria, Minimum risk occurs with water soluble drug like Sulfisoxazole.

CLASSIFICATION

S.NO. CLASS DRUG

1 Short acting (4-8 hrs) Sulfadiazine
2 Intermediate acting (8-12 hrs) Sulfmethoxazole, Sulfamoxzole
3 Long acting (~ 7days) Sulfodoxine, Sulfamethopyrazine
4 Special purpose Sulfacetamide Sodium, Sulfasalazine,
Mafenide, Silver Sulfadiazine

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Mechanism of action
 Act by inhibiting folic acid synthesis by inhibiting enzyme folate synthatase

PABA + Glutamate + Pteridine

Sulfonamide Folate synthatase

Dihydrofolic acid
Cotrimoxazole Folate reductase

Tetrahydrofolic acid

DNA and RNA

Adverse Effect
Trick - SULFA
S - Steven Johanson Syndrome [GPAT-10]
U - Urine Precipitate/useful for UTI
L - Large spectrum
F - Folic acid synthesis blocker
A - Analogues of PABA

Bacterial resistance to sulfonamide

 Produce more amount of PABA.
 Folate synthatase has low affinity for sulfonamide.
 Efflux of the drug by bacteria.
 Adopt an alternative pathway in folate metabolism.
Pharmacokinetics
 Primary Pathway of metabolism of Sulfonamide is acetylation.
Metabolised by N-acetylation Their acetylated metabolite having low
at N1 by non-microsomal aqueous solubility especially at
enzyme acidic pH(in liver)

This can be minimized by taking Crystalluria occur

adequate amount of water
and use of alkylating agent Minimized by soluble
(NaHCO3) drug sulfisoxazole
Adverse effect -
 Allergic reaction [Skin reashes, Photosensitivity, etc]
 Phototoxicity
 Steven - johnson syndrome
 Crystalluria
 Kernicterus - In new born due to displacement of bilirubin from plasma protein binding
site.
 Acute haemolysis in G-6-PD deficiency patients
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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

DRUG INTERACTION
 Inhibits metabolism of Phenytoin, Methotrexate, oral anticoagulant, oral
hypoglycemic agents - so potentiate the effect
THERAPEUTIC USES
S.NO. DRUG USE
1 Sulfadiazine Preferred compound for meningitis
2 Sulfamoxazole For urinary tract infection
3 Sulfadoxine + Pyrimethamine Malaria treatment
4 Sulphadiazine + Pyrimethamine Toxoplasmosis
5 Sulfasalazine Treatment of ulcerative colitis
6 Sulfacetamide Treatment of ocular infection
7 Mafenide and Silver Sulfadiazine Used in burn patients
MAFENIDE
 Not a typical sulfonamide because a - CH2 bridge separate benzene and amino group
 In contrast sulfonamide, it is active against bacteria in presence of pus
SILVER SULFADIAZINE
 Silver Sulfadiazine is a topical Sulfonamide
 Used as 1% cream
 Slowly release silver ions, which is responsible for its antimicrobial action
 Effective against bacteria resistant to other Sulfonamide
Eg - Pseudomonas
 Sulfasalazine is a poorly g.i.t absorbed compound of sulfapyridine and 5-amino
salicylic acid.
 Sulfadoxine is longest acting wheras Sulfacystine is shortest acting

COTRIMOXAZOLE
 WHO approved fixed dose combination of
Cotrimoxazole = Salfamethoxazole + Trimethoprim
Dose ratio 5 : 1
[20 : 1 (This ratio obtained in plasma when two are given in a dose ratio 5 : 1)]
Advantage of Combination are
 Individually both are bacteriostatic but the combination has bacteriocidal effect.
 Chances of development of bacterial resistance are also greatly reduced .
 Have been selected because Both of them have similar t1/2 (10 hours)
 Cotrimoxazole is contraindicated during pregnancy. (GPAT-20)
 Trimethoprim adequately crosses blood brain barrier and placenta, while Sulfamethoxazole
have poor.
 Resistance to the combination has been slow to develop compared to the resistance to
either drug alone.
 Trimethoprim has 40% plasma protein bonding Sulfamethoxazole has 60% plasma
protein binding.
 Cotrimoxazole is ineffective in the treatment of respiratory tract infection.

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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

 Trimethoprim binds to bacterial DHFR about 50,000 times more strongly as compared to
the host DHFR. [GATE-04]
Mechanism of Action - Inhibits bacterial dihydrofotate reductase (DHFRase)
Adverse effect - Megaloblastic anaemia (Folate deficiency), Bone marrow depression.
Therapeutic use - Urinary tract infection, Respiratory tract infection Typhoid fever, Bacterial
diarrhoeas, Whooping cough.
POINTS TO REMEMBER
 Cotrimazine – Trimethoprim + Sulfadiazine
 Other DHFRase inhibitors are – Pyrimethamine, Methotrexate, Proguanil, Pentamidine
 All DHFRase inhibitors cause – Megaloblastic anaemia
 Cotrimoxazole is the DOC for – Toxoplasmosis, pneumocystis carinii pneumonia.

FLUOROQUINOLONES (FQ)
 Quinolones are potent synthetic antimicrobials having quinolone structure
e.g. : Nalidixic acid.
 Fluoroquinolones are quinolone antimicrobials having one or more fluorine substitutions,
e.g. : Ciprofloxacin.
 It is effective against gram negative bacteria.
 Fluoroquinolones are relatively more susceptible to development of resistance. [GPAT-12]
O
O
F COOH
COOH
5 4
6 3
7 1 2
HN N N
8

H3 C N N
C2H5
NALIDIXIC ACID CIPROFLOXACIN

CLASSIFICATION

CLASS DRUGS
1st generation Nalidixic acid, Oxalinic acid.
2 generation
nd Norfloxacin, Lomefloxacin, Ciprofloxacin, Ofloxacin
3rd generation Levofloxacin, Sparfloxacin, Gatifloxacin, Pefloxacin,
Temafloxacin, Moxifloxacin
4th generation Gemifloxacin, Prulifloxacin, Sitaloxacin, Clinafloxacin,
Trovafloxacin.

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MECHANIMS OF ACTION
Fluoroquinolone inhibits

DNA gyrase in Topoisomerase IV in

gram -ve bacteria gram +ve bacteria

Inhibition of nicking, formation Inhibition of separation of daughter

of negative supercoil and resealing DNA strand following DNA replication
of strand of DNA

Block bacterial DNA synthesis

USES
 UTI, Bacterial diarrhoea, Typoid fever, STD (Gonorrhoea, Chancroid) Respiratory
infection
Adverse effect:-
 They are contraindicated in pregnancy because of concern of teratogenicity.
 Cartilage damage in weight baering joints (Contraindicated in children).
 Sparfloxacin, Gatifloxacin, and Moxifloxacin can prolong Qt interval (Torsade de point).

IMPORTANT POINTS
 Ciprofloxacin is (Prototype) most potent second generation fluroquinolones.
 Ciprofloxacin rapidly absorbed orally, but in present of food its absorption is slow
 Ciprofloxacin and Levofloxacin are the only fluoroquinolones which are effective against
pseudomonas.
 Sparfloxacin has maximum plasma protein binding and longest acting
fluoroquinolones.
 Norfloxacin has least oral bioavailability.
 Pefloxacin is the methyl derivative of Norfloxacin which is more lipid soluble and completely
absorbed orally.
 Pefloxacin has highest first pass metabolism.

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11 -LACTAM
ANTIBIOTICS

INTRODUCTION
 β -lactam antibiotics are those drug that contain β -lactam
am in their ring structure.
 All β -lactam antibiotics are bactericidal in nature.
 All drugs in this class are acting by inhibiting the cell wall synthesis in bacteria.
 These drug bind to penicillin binding protein on cell membrane and inhibit
transpeptidation.
 These are active against multiplication of bacteria only.
Different class of drugs are
(1) Penicillin’s
(2) β -lactamase inhibitors
(3) Cephalosporins
(4) Monobactam
(5) Carbapenems

O
H S O
R C N CH3 H S
R1 C N
N CH3
O N
COOH O R2
Acyl
group Acyl COOH
group
lactam + Thiazolidine lactam + Dihydrothiazine

Penicillin Cephalosporin
NH
R2 O
-lactam ring O
R1 C CH2OH
R3 N
N H
O O COOH
COOH
lactam + Pyrolidine lactam + Oxazolidine

Carbapenam Clavulanic acid

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PENICILLINS
Chemistry and properties
 Natural Penicillins are dextrorotatory.
 Aqueous penicillin G is drug of choice for neurosyphilis.
 Valine is the biosynthetic precursor for natural penicillin. (GPAT-14)
First time - Penicillium notatum
 Obtained from
Commercially - Penicillium chrysogenum
O S CH3
H H Ring A - lactum ring
R C N C CH C
A B CH3 Ring B - Thiazolidine
broken O C N C COOH
by amidase H
Site of action of penicillinase
 Penicillinase is β -lactamase (enzyme) developed by most of staphylococci and many y
microorganism that is responsible for breakdown of β - lactam ring (thus resistance to
o
penicillin).
 Penicillin G is the original penicillin used clinically.
 Side chain can be split off by an amidase to produce 6-amino penicillanic acid
β-lactamase Penicillanic acid..
Beta lactam amide bond  
GM GM GM GM
PP PP PP PP
PP PP PP PP
Vancomycin GM GM GM GM
ng
Transpeptidase
nki
-lactams
-l i
o ss
cr
PP PP PP PP PP
chain elongation
G-M GM GM GM GM
Transglycosylase
Membrane
BP BP
Bacitracin
G-M M-PP
UDP-M L-Ala
PP
PP Alanine racemase
D-Ala
Alanine ligase
UDP-G UDP-M D-Ala-D-Ala
Enolpyruvate
transferase
Cycloserine
Fosfomycin
Fig. Biosynthesis of Bacterial Cell wall
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 GPAT DISCUSSION CENTER : MAKES STUDY EASY PHARMACOLOGY

 Cell wall synthesis starts by conversion of UDP-N-acetylglucosamine (UDP-G) to

UDP-N-acetylmuramic acid (UDP-M) in the presence of enzyme enolpyruvate
transferase.
 UDP-M then acquires the pentapeptide.
 Alanine racemase and alanine-alanine ligase helps in the formation of pentapeptide
unit.
 UDP is the then removed from UDP-M-pentapeptide by bactoprenol (membrane lipid
carrier)and N-acetylglucosamine is added to it (which is carried by UDP-G).
 The resulting molecule formed is transported across the plasma membrane by bactoprenol.
 Elongation of the peptidoglycan chain occurs with the help of enzyme transglycosylase.
 Strength to peptidoglycan chain is provided by cross linking of elongated chains with the
help of transpeptidase.
NOTE :
Gram +ve bacteria- The cell wall is almost entirely made of peptidoglycan (Higher Susceptible).
Gram -ve bacteria - The cell wall consists alternative layer of lipoprotein & mucopeptide
(Less susceptible).
MECHANISM OF ACTION

These drug binds to specific receptor of bacterial cell membrane

(Penicillin binding protein, PBP)

These enzyme responsible for

Inhibit the transpeptidase & carboxypeptidase
cross linking of peptidoglycan
chain
So cross linking of cell wall does not takes place

Bacteria formed in the presence of these drugs are without cell

wall and die due to imbalance of water

RESISTANCE TO PENICILLINS
 By producing β -lactamase which destroy β -lactum ring..
 Due to altered protein binding penicillin which have less affinity for β -lactums.
 Due to decrease ability of the drug to penetrate to its site of action .
 All MRSAs have multidrug resistance and MRSA is treated by vancomycin (DOC).
 Vancomycin resistance staph aureus (VRSA) is treated by Linezolid or Streptogramins.
Pharmacokinetics
 Plasma t1/2 of penicillin G in healthy adult is 30 minutes.
 Mainly given by i.v. route.
 If oral administration (destroyed by gastric acid).
 Excreted in urine mainly by tubular secretion.
 Probencid has also been shown to decrease the Vd of penicillin.
Tubular Secretion (90%) - Secretion inhibited by Probencid
Cleared by
Glomeular filtration (10%)
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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

PREPARATION OF PENICILLINS
 Penicillin G, Natural penicillin (Benzyl Penicillin).
 Sodium Penicillin G (Crystalline Penicillin) injection.
 Procaine Penicillin G - Procaine help to prolong action.
 Fortified Procaine Penicillin G.
 Benzathine Penicillin G
Disadvantage
 It is not effective orally.
• It has short duration of action due to its rapid excretion from kidney through tubular
secretion.
• It has narrow spectrum of activity, against gram positive bacteria only. .
• It can cause hypersensitivity reaction.
TEST OF ALLERGINICITY
 Allegic reaction can be diagnosed by (Scratch test)
Intradermal test (Benzyl Penicilloyl Polylysine)
Jarisch-Herxheimer reaction
 Penicillin injected into a syphilis patient may produce Shivering, Fever, Chills,
Myalgia, Hypotension and even Vascular Collapse.
 Treated with Aspirin and Corticosteroids.
Adverse effect
 Anaphylactic reaction is most common associated with these drugs.
 Aztreonam  No cause sensitivity.
 Ampicillin  Diarrhoea
 Oxacillin  Hepatitis
 Methicillin  Intestinal nephritis.
Clinical use
Mnemonics
BLAST My Penicillin G
B Bacillius (Anthrax)
L : Leptospira (Rat bite fever)
A : Actinomyces
S : Streptococcus
T : Treponema Pallidum (Syphilis), Teatanus
My : Meningococcus meningitis
Penicillin : Pertunae (Yaws), Pasturella mutocida
G : Gas gangrene

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Limitation / Drawbacks of Penicillin G

Mnemonics
SAPNA
S : Short duration of action.
S : Suscept ibility to -lactamase, Penicillinase.
A : Acid liability.
P : Poor GIT absorption, food also decrease absorption.
N : N arrow Spectrum.
A :
Allerginicity.

Penicillin G is drug of choice for:

Mnemonics
LASTMAn
L : Leptospira
A : Actinomyces
S : Streptococcus, Staphylococcus
T : Treponema, Tetanus
M : Meningococcus
A : Anthrax

SEMISYNTHETIC PENICILLINS
 Semisynthetic Penicillins are synthesized to over come draw back of Penicillin G.
 Penicillin is the antibiotic for drug in choice of meningococcal meningitis and anthrax.
 It is also used in Rat bite fever.

CLASSIFICATION

S.NO. CLASS DRUGS

1. Acid resistant Penicillin V (Phenoxymethyl Penicillin)
Penicillins
2. Penicillinase resistant Methicillin[GATE-88], Oxacillin,Cloxacillin,
Penicillin Dicloxacillin [GATE-90]
3. Extended Spectrum Penicillins
(a) Aminopenicillins : Ampicillin, Amoxicillin, Bacampicillins
(b) Carboxy Penicillins : Carbenicillin, Ticarcillin
(c) Ureidopenicillins : Piperacillin [GPAT -15], Mezlocillins
(d) Mecillinam : Amdinocillins
CLOXACILLIN : Isoxazolyl side chain and it is highly Penicillinase as well as acid resistant.
AMPICILLIN
 Acid resistant, oral absorption is incomplete but adequate.
 Food interferes with its absorption
 Diarrhoea - most common adverse effect.
AMOXICILLIN : It is a Congener of Ampicillin (but not prodrug).
BACAMPICILLIN : Ester prodrug of ampicillin.

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CARBENICILLIN
 Its activity against Pseudomonas aeruginosa and indole positive Proteus which
are not inhibited by Penicillin G or aminopenicillins
Carbenicillin in high dose can result in bleeding.
PIPERACILLIN : About 8 times more active than carbenicillin.
INTERACTION :
Ampicillin + Hydrocortisone  Inactivates Ampicillin if mixed in i.v. solution.
Ampicillin + oral contraceptive  Failure of oral contraception

-LACTAMASE INHIBITORS

CLAVULANIC ACID SULBACTUM TAZOBACTUM

 Obtained from Streoptomyces  Semisynthetic -lactamax Combined with
Clavuligenus piperacillin
 It is a progressive inhibitor  Related chemically as Tazobactum
because inhibition increase well as in activity to +
with time clavulanic acid. Piperacillin
 Also called as suicide inhibitor  Ampicillin + Sulbactum
because it gets inactivated
after binding to the enzyme. Sultamicin

Co-amoxyclar
More effective against
Drug of choice for -lactamase
gonorrhoea

CEPHALOSPORINS
 The 1st Cephalosporins was obtained from a fungus Cephalosporium acremonium
 Cephalosporins are β -lactam antibiotics with 7-aminocephalosporanic acid nucleuss.
 Cefoxitin and Cefotetan are cephamycins except these all other are cephalosporins.
O
7
H H S
R1 C N C CH CH2 Ring A - lactum ring
A B
3 Ring B - Dihydrothiazine ring
O C N C R2
Altering spectrum C
of activity Affect pharmacokinetics
COOH

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CLASSIFICATION

S.NO. CLASS DRUGS

1. First generation (a) Parenteral - CephaLothin, CefaZolin
(b) Oral - CefaDroxil, CephaLoridine, CephaleXin
2. Second generation (a) Parenterals - CefUroxime, CefoXitin
(b) Oral - CeFaclor, CefUroxime axetil, CefProzil
3. Third generation (a) Parenterals - CefoTaxime, CefTizoxime, CefTriaxone,
CefTazidime, CefoPerazone
(b) Oral - CefDinir, CefpoDoxime, CefiXime, CeftibuTen
4. Fourth generation Parenteral - Cefepime, Cefpirome
5. Fifth generation Parenteral - Ceftaroline fosamil, Ceftobiprole medocaril
Trick : with some additional drugs
MNEMONICS
First generation Second generation Third generation
Dr CefaDroxil Fa CeFaclor Delhi CefDinir, CefpoDoxime
Lo : CephaLoridine Lo : Loracarbef P : CefoPerazone
Lo’s : CephaLothin Ma : CefoMandole M : Moxalactam
X in : CephaleXin Ur : CefUroxime T : CefTriaxone, CefTizoxime,
Zoo : CefaZo lin Ta : CefoteTan CefoTaxime, CefTazidime
Xi : CefoXitin Exam : CefiXime
Pr : CefProzil
Note: FaLo (Fallow) Ma Ur
(mayur=peacock) Ta Xi (taxi)
Pr(per=on)

Pharmacokinetics
 Most cephalosporine are excreted by kidney mainly by tubular secretion.
 Ceftriaxone and cefoperazone are excreted mainly in bile.
Resistance
 Alteration in target proteins (PBPs) reducing affinity for the antibiotics.
 Impermeability to the antibiotic or its efflux so that it does not reach its site of action.
 Elaboration of -lactamases which destroy specific cephalosporins (Cephalosporinases);
the most common mechanism
Adverse effect
 Diarrhoea.
 Hypersensitivity reaction.
 Disulfiram like reaction.
 Nephrotoxicity - Highest with Cephaloridine [GATE-91].
 Superinfection- most common organism are candida and pseudomonas.
 Bleeding - Ceftriaxone and Cefoperazone can cause hypoprothrombinemia and bleeding.
 Ceftazidime cause neutropenia and thrombocytopaenia.
Clinical use
 Cefazolin is the drug of choice for surgical prophylaxis.
 Cefotetan, Cefmetazole and cefoxitin are active against anaerobes like bacteriodes fragilis.
 Ceftazidime + Aminoglycoside is the drug of choice for pseudomonas infection.
 Ceftriaxone is the first drug of choice drug for gonorrhea.
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MONOBACTAM
 It is active against gram negative organism including pseudomonas and H. influenza at very
low concentration, but has no activity against gram positive organism or anaerobs.
AZTREONAM
 It is an atypical β -lactam antibiotics with only one ring in its structure.
 Having single ring so called monobactam.
 Lack of cross sensitivity to other β -lactum antibiotics, so used in person allergic to
o
penicillin or cephalosporin.

CARBAPENEMS
 Drugs: Imipenem, Meropenem, Feropenem, Ertapenem.
 Effective against gram positive and gram negative organism.
 It is resistant to β -lactamase.
 Carbapenems have the widest spectrum of all currently available antimicrobials.
 Inactivated by enzyme dehydropeptidase-I in renal tubules so we use - dehydropeptidase
inhibitor -Cilastatin with carbapenem
IMIPENEM
 Imipenem - Cilastatin has proved effective in a wide range of serious hospital acquired
infection including those in neutropenic cancer and AIDS Patient.
ERTAPENEM
Ertapenem is long acting carbapenems and longer t ½ of 4 hours, and it is
inactive against Pseudomonas.
FEROPENEM
 Feropenem is only carbapenems effective orally.
 Feropenem is beta lactam antibiotics that is orally active against many gram positive
and gram negative bacteria.
Drug used for Extended Spectrum Beta Lactamase (ESBL) producing bacteria are:
A) - lactamase inhibitor combination
 Clavulanic acid +Amoxicillin  Clavulanic acid +Ticarcillin
 Sulbactam + Ampicillin  Tazobactam +Piperacillin
B) Cefamycins: Cefoxitin, Cefotetan
C) Carbapenems: Imipenem, Meropenem
OTHER CELL WALL SYNTHESIS INHIBITOR DRUGS

TRICK DRUGS STEPS IN CELL WALL SYNTHESIS INHIBITOR

Firmly Fosfomycin Enolpyruvate transferase
Bind to lactam antibiotics Transpeptidase
Bacterial Bacitricin Dephosphorylation of bactoprenol
Cell Cycloserine Alanine racemase and alalnine ligase
Vall Vancomycin Transglycolase

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12 TETRACYCLINES AND
CHLORAMPHENICOL

TETRACYCLINES

INTRODUCTION
 These are the class of antibiotics having a nucleus of four cyclic rings.
 Tetracyclines are primary bacteriostatic and broad spectrum antibiotics.
 Obtained from soil actinomycetes.
OH O OH O
OH
CONH2

OH
H3C OH H H N(CH3)2
Tetracyclines

CLASSIFICATION OF DRUGS

GROUPS DRUGS
Group I Tetracycline, Chlortetracycline, Oxytetracycline
Group II Demeclocycline, Methocycline, Lymecycline
Group III Doxycycline, Minocycline
A new synthetic subclass ‘glycylcyclines’ represented by Tigecycline
has been added recently

MECHANISM OF ACTION
 Tetracyclines binds to 30-S ribosomal subunit and inhibit the binding of aminoacyl-tRNA
to A site.

Tetracyclines Actively taken up by Bind reversibly to 30S

susceptible bacteria ribosomal subunit

Prevent the addition of Prevent binding of

Inhibit bacterial aminoacyl t-RNA to m-RNA
amino acid to the
protein synthesis Ribosomal complex
growing peptide chain

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CHAIN ELONGATION TRANSLOCATION

t-RNA(t) 3 4
a4 a5
2 a1 a1
a1 50 S a1 a2 a2
1
a2 a2 a3 a3
a3 a3 a4 a4 a4

mRNA P A P A P A P A
C3 C4 C3 C4 C3 C4 C3 C4 C5

30 S
Amino acid Peptide bond Ribosome moves to
transport formation next mRNA codon
Fig: BACTERIAL PROTEIN SYNTHESIS AND SITE OF ACTION OF ANTIBIOTIC
 The messenger RNA (mRNA) attaches to the 30S ribosomes.
 The initial complex of mRNA starts protein synthesis and polysome formation.
 The nascent peptide chain is attached to the peptidyl (P) site of the 50S ribosomes.
 The next amino acid (a) is transported to the acceptor (A) site of the ribosome by its specific
tRNA which is complementary to the base sequence of the next mRNA codon (C). The nascent
peptide chain is transferred to the newly attached amino acid by peptide bond formation.
 The elongation peptide chain is shifted back from the ‘A’ to the ‘P’ site and the ribosome
moves along the mRNA to expose the next codon for amino acid attachment.
 Finally, the process is terminated by the termination complex and the protein is released.
(a) Aminoglycoside binds to several sites at 30S and 50S subunit as well as to their interface –
Freeze initiation, interfere with polysome formation and cause misreading of mRNA code.
(b) Tetracycline binds to 30S ribosome and inhibit aminoacyl tRNA attachment to the ‘A’ site.
(c) Chloramphenicol bind to 50S subunit – Interfere with peptide bond formation and transfer of
peptide chain from ‘A’ site.
(d) Erythromycin and Clindamycin also bind to 50S ribosome and hinder translocation of the
elongation peptide chain back from ‘A’ site to ‘P’ site and the ribosomes does not move along
the mRNA to expose the next codon. Peptide synthesis may be prematurely terminated.
Freeze initiation Aminoglycoside
Inhibit elongation Tetracycline and Chloramphenicol
Inhibit translocation Erythromycin and Clindamycin
Tricks to remember
Buy AT 30 and SCELL to 50

Aminoglycoside, Binds to 30S Streptogramins, Binds to 50S

Tetracycline Chloramphenicol,
Erythromycin,
Lincosamide,
Linezolid

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Resistance
 Decreased influx or increased effect of tetracyclines.
 Inactivation of the drug by enzymes.
 Ribosomal protection.
 Enzymatic inactivation of drugs.
PHARMACOKINETICS
 Tetracyclines having the chelating properly so food, dairy products, antacid, Iron
preparation etc decrease their absorption [except doxycyclines & minocycline] So taken
in empty stomach.
 All tetracycline are nephrotoxic drugs with the exception of Tigecycline, Doxycycline, and
Minocycline which can be safely used in renal failure.
 Tetracyclines are extreme photosensitivity. [GPAT-17]
 Tetracycline cross the placenta and effects foetus [teratogenic]
 All tetracyclines are excreted in urine exept doxycycline and minocycline.
 Food decrease absorption of all tetracycline except doxycycline and minocycline.
 Doxycycline and Minocycline are primarily excreted through bile where as minocycline is
also excreted through saliva and tears.
 All tetracycline are secreted through breast milk.
DOXYCYCLINES
 Doxycyclines are excreted in faeces so can’t be used in presence of renal failure.
 Doxycycline can be used in renal failure.
 Treatment of choice for early stage lyme’s disease and prophylaxis of anthrax.
TIGECYCLINE
 It belong to a new group of antibiotics called glycylcyclines, which act by inhibiting protein
synthesis.
 It is a broad spectrum tetracycline including MRSA, VRSA, Streptococci.
 Tigecycline is administered intravenously.
 It is mainly excreted in bile, so does not require dose adjustment in case of renal failure.
 Active against most bacteria that are resistant to traditional Tetracycline.
 Binds with higher affinity to 30s ribosomal unit and is 20 time more potent.
Adverse effect
Mnemonics
KAPIL DEv to BaT
K : Kidney damage (Except Doxycycline)
A : Antianabolic effect
P : Phototoxicity (Demeclocycline and Doxycycline)
I : Increase intracranial pressure
L : Liver damage
D : Diabetes insipidus, Deposited on bone and teeth
Ev : Expired drug can cause fanconi syndrome
Ba : Bone deformation, Bone growth of foetus [GATE-97]
T : Teratogenic
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 Tetracycline may cause superinfection diarrhoea and pseudomembranous colitis.

 Gastrointestinal side effect are most common adverse effect. 
 Minocycline may lead to dose dependent vestibular toxicity (more in women).
 Tetracycline are avoided during pregnancy because it may effect the bone growth of
foetus (GATE-97)
TherapeUtic uses
Mnemonics
RBC IN PLASMA
R : Rickettsia,Relapsing fever
B : Brucellosis
C : Cholera, Chlamydia
IN : INguinale (Granuloma)
P : Plague, Peptic ulcer, Pleurodesmosis
L : LGV, Lyme, Leprosy
A : Atypical pneumonia
S : Siadh
M : Malaria
A : Ameobiasis

CHLORAMPHENICOL
 Isolated from - Streptomyces Venezualae in 1947
 Chloromphenicol is primary bacterostatic and broad spectrum antibiotics.

Responsible for antibacterial

activity
CH2OH O
O2 N CHCH NH C CHCl2
OH

MECHANISM OF ACTION
 Inhibit protein synthesis by binding to 50 s ribosomal subunit of the microbe.
 Bone marrow cells are most susceptible.
 Bacteriostatic to most organism but bactericidal to H. influenza and N. meningitidis.
Chloromphenicol

Binds reversibly to 50S ribosomal subunit

Interferes with peptide bond formation and transfer of peptidechain from “P” site

Inhibit protein synthesis
PHARMACOKINETICS
Detoxified by Conjugation Not fully developed Accumulation of Gray baby
with glucuronic acid in liver in new born chloramphenicol syndrome

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Adverse effect
Mnemonics
BIG Super Hypersensitivity
:
B Bone marrow depression
I : Irritative effect
G : Gray baby syndrome [GATE-90]
Super : Superinfection
Hypersensitivity
Therapeutic use
(1) Typhoid fever
(2) Bacterial meningitis
(3) Rickettsial infection
(4) Eye and ear infection
(5) Brucellosis

DRUGS AND THEIR MECHANISM OF ACTION

S.NO. DRUGS BINDS TO MECHANISM OF ACTION

1. Aminoglycosides Several sites at 30s and 50s  Freezing of initiation
subunits as well as to their  Interference with polysome
interface formation
 Misreading of mRNA code
2. Tetracyclines 30s ribosome  Inhibits aminoacyl-tRNA
and Glycylcyclines attachment to A site
3. Chloramphenicol 50s ribosome  Inhibits peptidyl transferase
that result in the inhibition
of peptide
4. Macrolides 50s ribosome  Inhibit translocation of
Lincosamides peptide chain from P to A site
Streptogramins
5. Linezolid 23s fraction  Inhibit translocation of
peptide chain from P to A site

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13
AMINOGLYCOSIDE

 These are a group of natural and semisynthetic antibiotics having polybasic amino groups
linked glycosidically to two or more aminosugar (streptidine, 2-deoxy streptamine,
garosamine)residues.
 All aminoglycosides are produced by soil actinomycetes.
 All are used as sulfate salts, which are highly water soluble.
 All are bacteriocidal and more active at alkaline pH.
 Aminoglycoside produce synergistic effect against gram positive bacteria when combined
with -lactamase inhibitor or Vancomycin.
 Aminoglycoside antibiotic cause tubular epithelial cell damage. (GPAT-17)

DRUGS AND THEIR SOURCES

DRUG SOURCE
Gentamicin Micromonospora purpurea
Streptomycin Streptomycec griseus
Kanamycin Streptomycec kanamyceticus
Tobramycin Strepatomycec tenebrarius
Sisomicin Micromonospora inyoensis
Neomycin Streptomycec fradiae
Framycetin Streptomycec lavendulae
Paromomycin Streptomycec rimosus var

CLASSIFICATION

SYSTEMIC AMINOGLYCOSIDE TOPICAL AMINOGLYCOSIDE

GST Ka SNAP kiye Top brand ke Naye F (phone) se
G : Gentamicin N : Neomycin
S : Sisomicin F : Framycetin
T :Tobramycim
K : Kanamycin
S : Streptomycin
N : Netilmicin
A : Amikacin
P : Paromomycin

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Imporatant point
MNEMONICS
AMINOG
A : Active against all aerobic gram negative bacilli
M : MOA - Misreading of m-RNA Codon
I : Ionize Completly in solution (hydrophillic) so not cross BBB, so not absorbed orally
N : N ephrotoxic, Neuromuscular blockage
O : Ototoxic [GATE-91], O2 dependent uptake
G : Gentamicin is the prototype drug
GNATS can NOT kills anaerobes
MECHANISM OF ACTION
 Initially they penetrate bacterial cell wall, to reach periplasmic space through porin channels

Aminoglycoside are bacteriocidal - Inhibits Protein synthesis

Entry of aminoglycoside in bacterial cell (O2 required)

Binds to 30 S ribosomal subunit

Block the initiation of Incorporation of incorrect Amino acid into

protein synthesis the growing peptide chain

Formation of defective or non functional protein

PHARMACOKINETICS
 Aminoglycoside are not absorbed orally and do not cross blood brain barrier.
 These are excreted primarily by glomerular filtration and the dose should be decreased in
renal insufficiently.
Resistance
 Resistance to aminoglycoside develops due to the formation of inactivating enzyme and
acetylate, posphorylate or adenylate the aminoglycoside.
 All aminoglycoside except Amikacin and Netilmicin are susceptible to these enzymes.
Thus amikacin and netilmicin may be effective against organism resistant to other
aminoglycosides.
 Mutation decreasing the affinity of ri bosomal protein that normally bind the
aminoglycoside.
 Decreased efficiency of the aminoglycoside transporting mechanism.
Side effect
 Nephrotoxicity : Neomycin is the most nephrotoxic whereas Streptomycin is the least
nephrotoxic aminoglycoside.
 Ototoxicity : Maximum with KAN(Kanamycin, Amikacin, Neomycin).
 Neuromuscular toxicity : Neomycin casuses maximum neuromuscular toxicity whereas it
is least with Tobaramycin.
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 Neuromuscular blockage:- streptomycin has maximum propensity, while Tobramycin is

least likely to produce this effect.
 Teratogenicity: should be avoided during pregnancy.
STREPTOMYCIN
 1st aminoglycoside discovered obtained from streptomyces griseus.
 Streptomycin is highly ionised, It is neither absorbed nor destroyed in the GIT.
 Aminoglycoside antibiotic, capable of binding to 30S ribosomal subunit. [GATE-96]
 Miscoding of bacterial protein synthesis. [GPAT-16]
 Ribosomal resistance develops fast
 Limited usefulness as single agent
 Plague, tularemia and brucellosis – In combination with tetracycline
 SABE : due to Streptococcus Viridans & faecalis – With penicillin but gentamicin preferred
 Reserve first line drug for tuberculosis used only in combination
Streptomycin = Streptidine + Streptose + N-methyl L-glucosamine
(Hexose ring) (Sugar) (Polybasic amino group)
Drug fo Choice for - Tuberculosis, Plague, Tularemia.
GENTAMICIN
 Cheapest and first line aminoglycoside antibiotics.
 Gentamicin is most commonly used of all the Aminoglycosides.
 Gentamicin, Tobramycin and Amikacin are effective against gram negative organism
including, Pseudomonas.
 Gentamicin is ineffective against mycobacterium tuberculosis and other mycobacteria
[GPAT-19].
 Gentamicin is primarily excreted through renal tubular secretion. [GATE-95]
NETILMICIN
 It is a semisynthetic derivative of Gentamicin.
NEOMYCIN
 Highly toxic to internal ear and kidney.

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14 MACROLIDE, LINCOSAMIDE,
GLYCOPEPTIDE AND OTHER
ANTIBACTERIAL ANTIBIOTICS,
URINARY ANTISEPTICS

Mr. Lallu GOPU

M - Macrolide antibiotics
L - Lincosamide
G - Glycopeptide
O - Oxazolidinones
P - Polypeptic antibiotics, Pristinamycin antibiotics
U - Urinary antiseptics

MACROLIDE ANTIBIOTICS
 Having a macrocyclic lactone ring (14 membered ring) attached with attached deoxy sugar.
 Erythromycin is the first member that was discovered in 1950.
 An Immunosuppresants drug - Tacrolimus is also a macrolide.
Drugs used are -
RACE
R : Roxithromycin A : Azithromycin C : Clarithromycin E : Erythromycin

MECHANISM OF ACTION
 These antibiotics inhibit translocation of peptide chain from A to P site by binding on
50S ribosomes, thereby inhibiting protein synthesis (translocation)
 Macrolide antibiotics exert action by post-translational modification. (GATE-02)
ERYTHROMYCIN
 It was isolated from streptomyces erythreus.
 Erythromycin is an enzyme inhibitor and hence can cause drug interactions.
 Erythromycin is bacteriostatic at low but cidal at high concentration.
 Erythromycin stimulates motilin receptors in the GIT-thereby, induces gastric
concentrations, hansentens gastric emptying and promotes intestinal motility.
 Erythromycin inhibit CYP3A4 can cause QT prolongation if concurrently Terfenadine
Ostemizole, Cisapride are used.
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PHARMACOLOGY GPAT DISCUSSION CENTER : MAKES STUDY EASY

 Methyl ester of Erythromycin is Clarithromycin (GPAT-16).

 Erythromycin is the drug of choice for treatment of diphtheria and pertussis.
E - Enteric coated tablets
E - Erythromycin estolate
E - Enternal toxicity mainly
E - Enzyme inhibitors
PHARMACOKINETICS
 Erythromycin destroyed by gastric acid (acid liable) hence must be enteric coated.
 Food delayed the absorption.
 Excreted by biliary route.
Drawback of erythromycin
 Narrow Spectrum, Hypersensivity
 Low oral bioavailibility, Short duration of action .

TO OVERCOME THE ABOVE PROBLEM, SEMISYNTHETIC MACROLIDE HAVE

BEEN DEVELOPED

Drugs: Roxithromycin, Chrithromycin and Azithromycin.

 Telithromycin is a ketolide congener of erythromicin.
 Azithromycin is Azalide congener of erythromycin has an expanded spectrum, having
longest half life.
 Azithromycin does not effect CYP3A4 enzyme – have no any QT prolongation and other
drug interaction.
 Azithromycin is now preferred over erythromycin because of higher efficacy, better
gastric tolerance and convenient one a day dosing.
 Spiramycin:- Spiramycin, another macrolide antibiotics, is used for toxoplasma infection
during pregnancy.
Uses of macrolides
 As an alternative to pencillin.
 1st Choice of drug for - Atypical pneumonia, Whooping cough, Chancroid (STD)
 Tetanus, Diphtheria.
Adverse effect of macrolides

Tricks to remember : MACRO

M : Motilin receptor agonists
A : Allergy
C : Cholestasis
RO : Reversible Ototoxicity

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LINCOSAMIDE ANTIBIOTICS
Drugs: Clindamycin, Lincomycin.
MECHANISM OF ACTION - Same as macrolides
CLINDAMYCIN
 Used against Propionbacterium (responsible for acne)
Clindamycin + Pyrimethamine - for toxoplasmosis.
Clindamycin + Primaquine - Pneumocystic Carinni pneumonia.
 Use of Clindamycin is restricted to anaerobes.
 Main use of clindamycin is against anaerobes
 Lincosamide is another lincosamide antibiotics, it is not used now because it produce a
higher incidence of diarrhoea and colitis.
Uses of clindamycin
(Mnemonics: CAP Me Tea)
C : Cocci (gram positive)
A : Anaerobes
P : Parasites
M : Malaria
T : T. gondi

GLYCOPEPTIDE ANTIBIOTICS
Drug : Vancomycin, Teicoplanin
VANCOMYCIN
 It is a bacterioidal glycopeptide antibiotics.
 Inhibits bacterial cell wall synthesis by inhibiting transglycolase enzyme (involved in
chain elongation)
 It is drug of choice for MRSA (Methicillin Resistant Staphylococcus aureus)
 Rapid i.v. injection of vancomycin can cause Red Man Syndrome or Red Neck Syndrome
(diffuse flushing due to histamine release)
 Other toxic effect - Chills, ototoxic, nephrotoxic.
Adverse effect : ototoxicity and nephrotoxicity.
Vancomycin is drug of choice for :
 Methicillin-Resistance Staphylococcus Aureus (MRSA).
 Corynebacterium jeikeium.
 Serious infection in penicillin is allergic patients.
TEICOPLANIN
 Does not causes Red Man Syndrome or nephrotoxicity
 Teicoplanin is another glycopeptide with similar characteristic but can be given once daily
due to long t1/2 (45-70 hours).

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Mechanism of Action
 Inhibiting to 23’S part of 50’S ribosomes subunit and inhibit the ignition of protein
synthesis.
OXAZOLIDINONES
Drug are : Linezolid, Tedizolid
 MOA - Inhibits protien synthesis
 Adverse effect - Thrombocytopenia, Neutropenia.
 Treatment of resistan gram +ve coccal (aerobic and anaerobic) and bacillary infection.
 Active against methicillin resistant and some Vancomycin Resistant Staphyllococcus
Aureus (VRSA)
 Because Linezolid is MAO inhibitor, interactions with adrenergic/serotogenic drugs
and excess dietary tyramine are expected.

PRISTINAMYCIN ANTIBIOTICS
Drug are : Quinupristin, Dalfopristin.
 MOA - Inhibits bacterial protein synthesis.
 Quinapristin-Dalfopristin combination is effective against gram positive bacteria
including penicillin resistance pneumococci, methicillin resistance faecium, MRSA as
well as VRSA.
 It is also effective against leginonella and mycoplasma.

LIPOPEPTIDE ANTIBIOTICS
Drug are : Daptomycin
MOA
 The lipoidal tail of daptomycin molecules gets inserted in the bacterial cell membrane
followedby aggregation of several molecules to form a pore through which K+ and other
ions leak out and the membrane gets depolarized.
 Synthesis of DNA, RNA and proteins is inhibited

POLYPEPTIDE ANTIBIOTICS
Drugs are - Polymyxin B, Colistin, Bacitricin, Tyrothricin.
POLYMYXIN B
 Obtained from Bacillus Polymyxa.
 It is used for serious Gram positive infection including penicillin resistant and
pneumococci, MRSA and VRSA.
 Polymyxin B : get accumulated at cell wall membrane and counteract with phospholipid.
[GATE-88]

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COLISTIN
 Obtained from Bacillus Colistinus.
 Have detergent like action on cell membrane.
 Bacterial cell membrane causing membrane distortion or pseudopore fomation.
THROTHRICIN
 Obtained from Bacillus bravis.
 It acts on cell membrane causing leakage and uncouples oxidative phosphorylation in
the bacteria.
BACITRICIN
 Obtained from Bacillus Subtilis.
 Act by inhibiting cell wall synthesis.
 Because of neurotoxicity and renal damage these antibiotics are used only topically.
 Bacitracin is isolated from several amino acid. [GATE-98]

OTHER ANTIBIOTICS
MUPIROCIN
 It inhibits bacterial protein synthesis by blocking the production of t-RNA for isoleucin.
 This topically used antibiotics obtained from a species of pseudomonas is active mainly against
gram positive bacteria.
FUSIDIC ACID
 It is topically used for staphylococcus infection.
 It is narrow spectrum steroidal antibiotics, blocks bacterial protein synthesis.

URINARY ANTISEPTICS
 Urinary anti-infectives are drugs that are used to prevent or treat urinary tract infections
 Organism involved in UTI are - E.coli, Proteus, Klebsiella and pseudomonas
 These are more effective in acidic urine because low pH is an independent inhibitory of
bacterial growth.
 High volume of distribution in body characteristic for an effective urinary tract antimi
crobial drugs. (GPAT-16)

Urinary Antiseptic

Methenamine
Phenazopytidine Nitrofurantoin
(Hexamine)

METHANAMINE

in acid pH
Methenamine Formaldehyde + Ammonia
(Prodrug) (pH<5.5) (Antiseptic)
Inhibits bacteria
Adverse effect: Gastritics due to release of HCHO in stomach.

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NITROFURANTION

In suseptible bacteria nitrofuratoin

Damage bacterial DNA.
converted into highly reactive metabolite.
 Dark brown urine - when exposue to air
PHENAZOPYRIDINE
 It is an orange dye
 Exerts analgesic action in urinary tract and affords relief of burning sensation.
 Not having antibacterial property.
Other drugs - Quinolones, Cotrimoxazole, Ampicillin, Cephalosporins etc
Others drugs used in the treatment of UTI
Cotrimoxazole
Quinolones
Ampicillin / Amoxicillin
Piperacillin / Ticarcillin
Cephalosporins
Gentamicin
Chloramphenicol
Chloramphenicol
Tetracycline
Drugs useful in Sexual transmitted disease:
CLASS DRUGS
Gonorrhoea Cetriaxone, Cefixime
Syphilis Benzathine Penicillin, Doxycycline
Granuloma Doxycycline, Azithroumycin
Chancroid Ceflriaxone, Azithromycin
Anipseudomonal Agents
CLASS DRUGS
Sulphonamide Silver sulfadiazine, Mafenide (Topical)
Aminoglycoside Gentamicin, Amikacin, Tobramycin
Fluoroquinolones Ciprofloxacin, Levofloxacin
-lactum antibiotics Antipseufomonal Penicillin - Carbonicillin, Ticarcillin,
Cephalosporin Cefoperazone, Ceflazidime, Cefepime, Carbapenems - Imipenum,
Meropenem, Monobactum - Aztreonam

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15 ANTITUBERCULAR
DRUGS

INTRODUCTION
 Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis
(MTB) bacteria. Tuberculosis generally affects the lungs.
• All first line drugs are tuberculocidal except ethambutol which is tuberculostatic.
 All first line drugs are hepatotoxicity except Streptomycin and Ethambutol.
• First line drug can be safely used in pregnancy except streptomycin which is
contraindicated because of its associated with foetal ototoxicity.
Respiratory tuberculosis effected organs: (GPAT-20)
 Pleural cavity
 Mediastinal lymph nodes
 Larynx

CLASSIFICATION

FIRST LINE DRUGS SECOND LINE DRUGS

High antitubercular efficacy Low antitubercular efficacy as well as high toxicity
as well as low toxicity
P - Pyrazinamide (Z) Fluoroquinolones Other oral drugs Injectable drugs
E - Ethambutol (E) Ofloxacin Ethionamide Kanamycin
R - Rifampicin (R) Levofloxacin Cycloserine Amikacin
I - Isoniazid (H) Moxifloxacin Para amino salicylic Capreomycin
S - Streptomycin (S) Ciprofloxacin acid
Rifabutin
Rifapentine
Prothionamide

FIRST LINE DRUGS

ISONIAZID (INH)
INH - Isonicotinic Acid Hydrazide

Insanity Neurotoxicity Hepatitis

(Psychosis)
 It is most widely and most effective drug against tuberculosis.

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 It is a prodrug activated by catlase peroxidase (coded by KatG), Active metabolite

inhibits the enzyme ketoenoylreductase (coded by inh A),required for mycolic acid
synthesis, an essential component of mycobacterial cell wall.
• It is the single dose important drug used in TB (Drug of choice for TB)
• It is the drug of choice for prophylaxis of tuberculosis.
 It cause peripheral neuritis that can be prevented and treated by Pyridoxine
(Vitamin B6) (GATE-03)
 Isoniazid is restricted due to occurance of neurotoxicity. (GATE-92)
 Isoniazid antitubercular drug that require pyridoxine supplement (GATE-03)
MECHANISM OF ACTION

Isoniazid Converted to active Inhibit the synthesis of

(Prodrug) Inside form mycolic acid (Component
mycobacteria of mycobacterium cell wall)

Death of bacteria (Tuberculocidal)

PHARMACOKINETICS
 It is widely distributed in the body including CSF.
 It is effective orally and metabolized by Acetylation.
 It is an essential component of multi-drug therapy.
 PAS inhibits isoniazid metabolism and prolongs its action.
 It caues peripheral neuritis that can be prevented and treated by pyridoxine.
 It is also hepatotoxic and can cause hemolysis in G-6-PD deficient patients.
 Essential component of MDT (Multi Drgu Therapy)
 PAS Inhibits INH metabolism and prolong its action.
 Pyridoxine (Vitamin B6) given prophylactically prevents neurotoxicity
DRUG INTERACTION
 Isoniazid inhibit metabolism of phenytoin are excreted in urine.

R IFAMPICIN (RIFAMPIN)
Red orange discoloration of urine .
 It is a derivative of Rifamycin (other derivatives are rifabutin and rifapentine).
 Acts by inhibiting DNA dependent RNA polymerase.
 It is the most effective and fastest acting drug in leprosy.
 Rifampicin + Doxycycline  Treatment of Brucellosis.
 Rifampicin is tuberculocidal for both dividing and nondividing mycobacteria.
 Rifampicin is the most potent sterilizing antitubercular drug, Fastest to kill all bacilli in the
lesion.
 Safest drugs used in pregnancy and renal failure.

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PHARMACOKINETICS
 It undergoes enterohepatic circulation and is partly metabolized in the liver.
 Metabolites are coloured and can cause orange discolouration of the urine and
secretions.
 It is eliminated mainly in the faces and can be used safely in renal dysfunction.
RIFABUTIN
 Rifabutin has longer half life than rifampicin.
 For the same reason rifabutin is used in treatment of tuberculosis in AIDS patient instead
of rifampicin.
 Rifabutin is an example of ansamycin. [GPAT-10]
 Rifabutin is very useful in treating mycobacterium avium complex. [GATE-06]
Adverse effect
Flu syndrome Cutanious syndrome
R i FA my C i n , H e p a t i t i s
Respiratory Abdominal
syndrome syndrome

P YRAZINAMIDE

Pain in joints, plus Hepatotoxicity & hyperuricemia

 It mechanism is similar to isoniazid.
 Pyrazinamide interferes with cellular metabolism, specially in synthesis of Mycolic acid.
[GATE-97]
 It is bacteriocidal in nature.
 Pyrazinamide is most hepatotoxic antitubercular drugs.
 It’s adverse effect is hepatotoxicity, hyperuricemia & pain in joints.

E THAMBUTOL
Eye toxicity
 Acts by inhibiting the synthesis of arabinogalactan (a component of cell wall) due to
inhibition of arabinosyl transferase.
 Ethambutol acts by inhibiting peptide synthesis in mycobacteria. [GATE-89]
 It causes visual disturbances like optic neuritis & Red-green blindness.
• Ethambutol doesn’t cause hepatotoxic.
• The main adverse effect is retrobulbar neurosis, hyperuricemia and peripheral
neuritis.
STREPTOMYCIN
 Mechanism of action is similar to aminoglycoside.
 It is Tuberculocidal aminoglycoside.
 Not effective orally, must be injected intramusculary.
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 It can cause nephrotoxicity, ototoxicity and NM receptor blockage.

 It is not hepatotoxic.

SECOND LINE ANTITUBERCULAR DRUG

AMIKACIN
 Amikacin is a antibiotics produces concentration dependent bactericidal action
and also possesses post-antibiotic effect. [GPAT-11]
THIACETAZONE
 Tuberculostatic, Low efficacy drug.
 Adverse Effect - Stevens - Johnson Syndrome (other drug-sulfonamide) Hepatitis,
Bone marrow suppression.
CYCLOSERINE
 Obtained from Streptomyces orchidaceus .
 Inhibits bacterial cell wall synthesis by inactivating the enzyme which racemize L-adanine.
D-Alanine + L-Analine
Enolopyruvate
UDP-4 Transferase
UDP-m Alanine ligase Cycloserine

Fosfomycin PP
G M
Vancomycin Transglycolase Chain elongation

PP PP PP PP
G M G M G M G M
-lactum Transpeptide Cross linking
antibiotics
PP PP PP PP
G M G M G M G M
PP PP PP PP
G M G M G M G M
 Cycloserine is exists in equilibrium with its tautomeric enolic form and stable inalkaline
solution, destroyed in alkaline pH. [GATE-04]
ETHIONAMIDE
 Ethionamide is only the antitubercular drug which develops cross resistance to INH.
 Ethionamide is a prevents and a synthesis of protein and DNA and reduces RNA
synthesis. [GATE-89]
PARA AMINO SALICYLIC ACID (PAS)

 Para amino salicylic acid (PAS) is related to sulfonamides, acts by similar mechanism and is
bacteriostatic.

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 Para amino salicylic acid is a competitive inhibitor of DHFR. [GATE-89]

IMPORTANT POINTS

 Hypothyroidism can be cause by Para amino salicylate and Ethionamide.

 Active against Extracellular mycobacteria Rifampicin, Isoniazid, Streptomycin.
 Dexamethasone is used in meningeal TB.
TREATMENT OF TUBERCULOSIS
WHO Recommends the use of multidrug therapy (MDT)
Objective
(a) To prevent the development of drug resistant bacilli.
(b) Decrease the time of whole course.
(c) To make patient non-infection as early as possible by rapidly killing the diving by using
3-4 drugs at a time.
(d) To prevent relapse.
(e) Always treat with more than one drugs
MULTIDRUG-RESISTANT TB
 The standard short course treatment for TB is isoniazid, Rifampicin, Pyrazinamide and
Ethambutol for 2 months, then isoniazid and rifampicin along for a further 4 months.

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16 ANTILEPROTIC
DRUGS

INTRODUCTION
 Leprae was discovered by G.A. Hansen, that why this is also called ias hensen disease
 Leprosy is caused by Mycobacterium leprae

CLASSIFICATION

CLASS DRUGS
Sulfone Dapsone
Phenazine derivatives Clofazimine
Antitubercular drugs Rifampin, Ethionamide
Other antibiotics Ofloxacin, Minocyline, Clarithromycin, Moxifloxacin
DAPSONE

O
H2N S NH2
O
 It is chemically diaminodiphenyl sulfone (DDS)
 It is the simplest, oldest, cheapest most active and most commonly used member of its class.
 It is a leprostatic drug related to sulfonamides with similar mechanism.
 Metabolised by acetylation and undergoes enterohepatic circulation.
 Haemolytic anaemia is common (G-6-PD deficient people are more susptible)
 Sulfone syndrome develops 4-6 weeks after starting dapsone treatment.
 Inhibition of PABA incorporation into folic acid by folate synthetase.
CLOFAZIMINE

 It is a phenazine dye with leprostatic and antiinflammatory activity.

 Because of antiinflammatory action it is valuable in lepra reaction.
 Clofazimine binds to mycobacterial DNA to inhibits its template function.
 Major disadvantage is reddish-black discolourtion of skin, especially on exposed parts.
 Clofazimine : Clofazimine causes raddish skin pigmentation within a week of the
initiation of the therapy. (GATE-03)

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RIFAMPICIN
 It is leprocidal and most effective in leprosy.
 It prevent development of resistance to dapsone.
TREATMENT OF LEPROSY - MDT (Multidrug Therapy)
 Multi drug therapy (MDT) is a key element for cure.
 For MB leprosy patients
 Rifampicin and Dapsone for PB leprosy patients.
 Treatment of leprosy with only one anti leprosy drug will always result in development of
drug resistance.
(1) Dapsone + Rifampin + Clofazamine
(2) Clofazamine + Ofloxacin + Clorithromycin.
(3) Rifampin + Ofloxacin + Minocyclines.
DRUGS MULTIBACILLARY PAUCIBACILLARY
Rifampin 600 mg once a month supervised 600 mg once a month supervised
Dapsone 100 mg daily self-administered 100 mg daily self-administered
Clofazimine 300 mg once a month supervised
+ 50 mg daily self-administered
Duration 12 months 6 months
Child dose
Rifampin 10 mg/kg once monthly
Clofazimine 1 mg/kg daily + 6 mg/kg once monthly
Dapsone 2 mg/kg daily

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17 ANTIFUNGAL
DRUGS

INTRODUCTION
 Most common fungal pathogens are - Dermatophytes, Candida, Aspergillus, Cryptococcus,
Rhizopue, Histoplasma, Pneumocystis, Stachybotrys, Coccidipidomycosis, Mucormycosis,
Albicans, Blastomycosis etc.
 These are the drugs used for superficial and deep (Systemic) fungal infection.

Antibiotics A 2 Polyenes, Hetrocyclic benzofuran

Antimetabolite A 1 Antimetabolite
Azoles A 2 Imidazole, Triazole
Allylamines A 1

CLASSIFICATION BASED ON STRUCTURE

CLASS SUB-CLASS DRUGS

Antifungal Polyenes Amphotericin B, Nystatin, Hamycin,
Antibiotics Natamycin.
Hetrocyclic benzofuran Griseofulvin.
Echinocandins Caspofungin, Micafungin, Anidulafungin
Antimetabolite - Flucytosine (5-FC)
Azoles Imidazoles Topical Econazole, Miconazole, Clotrimazole,
Oxiconazola
Systemic Ketoconazole.
Triazoles (Systemic) Fluconazole, Itraconazole, Voriconazole,
Posaconazole
Allylamines Terbinafine
Morpholine Amorolfine
Peptide nucleoside Nikkomycin
Other topical Whitfield’s Ointment, Tolnaftate, Sodium Thiosulphate, Selenium
agents Sulphate.
Trick to easy remember - KMC FIT
Available for systemic administration Ketoconazole
Miconazole
Griseofulvin K M C FIT Nystatin Clotrimazole
Fluconazole
Only for dermatophytes. Only for candida
Itraconazole
Available for Topical administration Terbinafile

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CLASSIFICATION BASED ON MECHANISM OF ACTION

S.NO. CLASS MECHANISM OF ACTION

1. Polyenes antibiotics Cell membrane inhibitors
2. Echinocandins Cell wall synthesis inhibitors
3. Heterocyclic Disruption of mitotic spindle and inhibition of
benzofuran fungal mitosis.
4. Azoles, Griseofulvin Ergosterol synthesis inhibitors by inhibiting the
14-demethylase
5. Allylamines Lanosterol synthesis inhibitors by inhibiting
squalene epoxide
6. Antimetabolites Nucleic acid synthesis inhibitors

MECHANISM OF ACTION

Acetate

Acetyl Co-A

HMG Co-A
Bifonazole
HMG CoA reductase
Mevalonic Acid

Squalene
Allylamines
Squalene 2, 3 epoxidase
Squalene 2,3 oxide

Lanosterol
Imidazoles and Triazoles
C14 alpha demethylase
C-14 methylated anosterol
Amorolfine
 reductase
14

Zymosterol

Fecosterol

Amphotericin B (Polyenes) Episterol

Ergosterol
(Fungal cell wall membrane synthesis)
Griseofulvin

Fungal cell wall replication

Fig. : MECHANISM OF ACTION ANTIFUNGAL DRUGS

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TARGET OF ANTIFUNGAL DRUGS

Fungal Cell Fungal cell membrane and cell wall

Proteins

-glucons

chitin

Cell
membrane
FLUCYTOSINE bilayer

-glucon
Squalene Ergosterol Amphotericin B
synthese
Nystatin
Terbinafine
Azoles Echinocandine
Squalene epoxide Lanosterol
Fig : MECHANISM OF ACTION OF ANTIFUNGAL DRUGS

ANTIFUNGAL ANTIBIOTICS

DRUG SOURCE
Amphotericin B (Streptomyces Nodosus)
Nystatin (Streptomyces Noursei)
Hamycin (Streptomyces Pimprine)
Natamycin (Streptomyces Natalonsis)
(A) POLYENES :
 It is a Fungicidal
OH
OH
O OH

HO O OH OH OH OH O OH
H
O

O H
O
HO

H2 N OH
One side has conjugated double bonds
 Have macrocyclic ring
Other side has many-OH group.

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Mechanism of action
Amphotericin B Binds tightly to Form
Nystatin ergosterol in fungal ‘Pores’ and ‘Channels’ in
Hamycin cell membrane the membrane

Death of the fungi Leakage of intracellular Permeability of the

(fungicidal) contents membrane increase
AMPHOTERICIN B
 Broad spectrum antifungal antibiotics and amphoteric in nature.
 Not absored from the gut, hence not suitable orally for systemic infection. So administered
by slow i.v. infusion .
 Slow i.v.  Administered as colloidal suspension with Doxycholate.
 It is fungicidal at higher concentration fungistatic, but is at lower concentration.
 It binds to ergosterol and increase permeability of cell membrane.
Adverse effect
 Nephrotoxicity - Manifested by renal tubular acidosis.
Amphotericin B formation
 For reduction of toxicity and achieve target therapy 3 lipid formation are prepered.
(1) Liposomal Amphotericin B.
(2) Colloidal dispersion Amphotericin B.
(3) Lipid Complex Amphotexicin B.
Drug interaction
(1) Amphotericin B - Increase 5-FC Penetration into the fungus - Synergistic effect.
(2) Co-administration of Amphotericin B with other nephrotoxic drug. (Aminoglycoside) -
Increase renal impairement.
(B) HETEROCYCLIC BENZOFURAN
GRISEOFULVIN
 It is extracted from Penicillium griseofulvum.
 Administered as microcrystalline form, absorption increase with fatty food.
 It is deposited in keratin forming cells of hair, nails and skin - Keratinophilic drugs.
 It can also cause Disulfiram like reaction with alcohol.
Mechanism of Action
 Interfere with mitosis by distortion of microtubule including abnormal metaphase
configuration. 6P’ of Griseofulvin
P - Peripheral neuropathy.
P - Porphyria
P - Pseudo inducer
P - Potentiation of ethanol (Disulfiram)
P - Photosensitivity.
Side effects
 Headache (most common), Photoallergy
Drug interaction
 Griseofulvin is a enzyme inducer – Increase activity of warfarin.
 Absorption is improved by taking it with fatty food.
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ANTIMETABOLITES

FLUCYTOSINE - (5-FC)
 Flucytosine is a Pyrimidine antimetabolite
 Flucytosine has supraadditive action with Amphotericin B.
 AMB makes holes in cell membrane of fungus and flucytosine enter and inhibits DNA
Synthesis.
 Flucytosine (5-FC) is given orally with amphotericin B for systemic infection.
 It is used for treatment of cryptococcal meningitis, in conjugation with Amphotericin-B.
Mechanism of action
Flucytosine
Amphotericin B
Cytosine deaminase
5-FU

5-Fd UMP

Decreases dTMP leads to

dUMP dTMP
Thymidylase inhibition of DNA synthesis
synthase DNA and cell division
Adverse effect -
 Bone marow toxicity (anaemia, thrombocytopemia)
DIFFERENCE BETWEEN AMPHOTERICIN & FLUCYTOSIN

AMPHOTERICIN B FLUCYTOSINE
Active drug Prodrug
Has broad spectrum of activity Has narrow spectrum of activity
Antifungal antibiotics Antimetabolites
Fungicidal Fungistatic
Not absorb through GI tract Well absorb through GI tract
Highly bound to plasma protein and Poorly bound to plasma protein
sterols in tissue
Does not cross BBB Freely crosses BBB and reaches high
concentration in CSF
Metabolized in liver and excreted Excreted in urine mainly in unchanged
slowly in urine and bile form
Highly efficacious and highly toxic Less effective and less toxic than
drugs Amphotericin B
Given intravenously, intrathecal and Given orally
Topically

AZOLES

 Azoles antifungals are broadly divided into imidazoles and triazoles.

 Broad spectrum antifungal activity.
 Azoles impairs ergosterol synthesis by inhibiting 14 α  demethylase enzyme..

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Mechanism of Action
Squalene 14 -
Squalene Lenosterol Ergosterol
2-3 epoxidase demethylase

Terbinafine Azoles
KETOCONAZOLE
 Ketoconazole decreases androgen production from testis and it displaces testosterone from
protein binding sites.
 Ketoconazole is extensively metabolized by liver.
 Useful both in dermatophytosis and deep mycosis.
 Decrease androgen production leads to gynaecomastia.
Drug Interaction
 Antacid and H2 blocker  Increase absorption of azoles.
 Ketoconazole inhibits human CYP-45O  Decrease metabolism of drug.
 Ketoconazole X Warfarin  Increase risk of bleeding.
 Ketoconazole X AMB  Inhibition.
 Ketoconazole X Sulfonylureas  Hypoglycaemia.
Fluconazole is the DOC for
C-Candiasis
C-Cryptococcus meningitis
C-Coccidiodomycosis
ITRACONAZOLE
 Itraconazole is the drug of choice for blastomycosis.
 Neuromuscular blocking causing spastic paralysis.
 Inhibit the Helminth specific enzyme fumarate reductase.
 Itraconazole Co-Administered with Terfenadine may lead to life threatening cardiac
dysrhythmia. [GATE-2001]
VORICONAZOLE
 Voriconazole is the widest spectrum among azoles and is DOC for invasive aspergillosis.
POSACONAZOLE
 Posaconazole is the only azole active against muromycosis.
 Caspofungin (Antifungal antibiotics): Inhibit needed for synthesis of (1-2) glycan
[GATE-09].
ALLYLAMINES

Terbinafine :- Fungicidal agent that act by inhibiting squalene epoxidase (early step enzyme
in ergosterol biosyntheis)
Other topical Agents -
(1) Whitfiels’s ointment - 6% benzole acid + 3% salicylic acid [GPAT-14]
(2) Undecylenic acid - Available as Soap, Cream, Powder
(3) Selenium Sulphide - Antidandruff
(4) Sodium thiosulphate (5) Potassium iodide (6) Ciclopirox

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18 ANTIVIRAL
DRUGS

INTRODUCTION
 Antiviral drugs can act at any step of viral replication.
 Virus are connective link between living & non-living systerm virus viruses replicate only
the inside the cell.
Virus have 3 parts only
(i) DNA or RNA carying genetics information.
(ii) Protein coat that protect the genes.
(iii) Envelop of lipids which surrounds the lipid coat when they outside the cell.
Maximum antiviral drugs target the viral DNA or RNA.
 Many antivirals drugs are purine or pyrimidine analogues.
Trick : Vir - At start, middle or end.
Antiviral drugs – Used to treat infection caused by viruses other than HIV.

CLASSIFICATION OF NON-RETROVIRAL DRUGS

CLASS DRUGS
Anti-herpes virus drugs Idoxuridine, Trifluridine, Acyclovir, Valacyclovir,
Famciclovir, Ganciclovir, Valganciclovir, Cidofovir,
Foscarnet
Anti-influenza virus drugs Amantadine, Rimantadine, Oseltamivir, Zanamivir,
Peramivir
Anti-hepatitis For hepatitis B Lamivudine, Etanercept, Adefovir dipivoxil,
virus drugs Tenofovir, Telbevudine
For hepatitis C Ribavirin, Interferon , Sofosbuvir, Simeprevir

STEPS INVOLVED IN MECHANISM OF ACTION OF ANTIVIRAL DRUGS

(a) FUSION OF THE VIRUS WITH HOST CELL MEMBRANE - inhibited by antiretroviral drug
enfluviritide
(b) UNCOATING OCCURS – inhibited by anti-influenza drug amantadine
(c) EARLY PROTEIN SYNTHESIS OCCURS – inhibited by antiherpes drug fomivirsen
(d) REPLICATION OF VIRAL NUCLEIC ACID OCCURS – this is the main step where most of
the antiviral drugs act
(e) Release of virion takes place, in case of influenza this release is mediated by neuraminidase
– Neuraminidase inhibitors drugs (oseltamivir, zanamavir) inhibits this step.

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Blocket by Blocked by
Amantadine
Enfuvirtide (HIV),
maraviroc

Virus fusion Penetration

with host Uncoating
Blocked by
cell & entry Fomivirsen (CMV)
Early protein
synthesis
HOST
CELL Blocked by
Blocked by Nucleic acid purine, pyrimidine
neuraminidase synthesis analogues, reverse
inhibitors transcriptase
Zanamivir, inhibitors
Oseltamivir Late protein
Packaging synthesis and
processing Blocked by
and
protease inhibitors
Release of virus assembly
‘Navir’

Fig : MECHANISM OF ACTION OF NON-RETROVIRAL DRUGS

Herpes infection due to

HSV-1 HSV - 2 VZV Epstein - Ban Cytomegalo Virus

Herpes Genital Chickenpox VMS (EOV) Pneumonia
encephalitis. Herpes Herpes Zoster Infectious Encephalitis.
mononucleasis. Retinitis
Gastroentenitis.
ANTIHERPES AGENTS

ACYCLOVIR
 It is synthetic, Purine nucleoside anlogeues that has antiherpes activity.
 It is more effective against HSV-1 and HSV-2 than varicella zoster virus (VZA) infection.
 Available for oral, topical and i.v. administration.
 It is a potent antihepes drugs.
 Acyclovir is a fastest acting drug.
 Acyclovir is antiviral agents exhibits the greatest selective toxicity for the invading virus.
(GATE-2000)
 Acyclovir has activity against Herpes simplex virus type I and is used topically. (GATE-01)

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Mechanism of Action
 Irreversible inactivation of DNA polymerase. (GATE-98)
Virus Kinase Host Kinase

Thymidine Acyclovir Cellular

Acyclovir Acyclovir triphosphate
Kinase monophosphate Kinase
Inhibits Viral DNA Synthesis
and Viral replication
Pharmacokinetics
 Only about 20% of an oral dose of acyclovir has absorbed, it is little plasma protein
binding capacity and is widely distributed info CSF concentration that is 50% of plasma
protein binding.
 Acyclovir is primarily excreted unchanged in urine, both by glomerular filtration and
tubular secretion.
Adverse effect
 Seizure, nephrotoxicity, Hepatic dysfunction [GATE-2001], hypotension, dehydration
increase the nephrotoxic potential.
Uses
(1) Genital Herpes (2) Herpetic encephalitis
(3) Herpes Simplex Keratitis (4) Chickenpox
(5) Herpes Zoster (6) Mycocytanious HSV

Acyclovir Valacyclovir Famciclovir Penciclovir

(Prodrug) (Prodrug)

Intracellular Inhibits DNA Synthesis Intracellular activation

activation to of HSV-1, HSV-2 to Peniciclovir
Acyclovir triphosphate Hepatitis-B Virus triphosphate.
IDOXURIDINE
Thymidine analogue
Idoxuridine Idoxuridine triphosphate
host cell kinase
Mechanism of Action
Compete with thymidine and get incorporated in DNA.

Faulty DNA is formed breaks easily

This DNA directs the Synthesis of wrong viral protein.

Uses
 Used topically because of higher systemic toxicity, Keratoconjuctivitis
FOSCARNET
 Inorganic Phosphonate Compound
 Does not require phosphorylation for activity.
 Directly Inhibit viral DNA polymerase activity and reverse transcriptase.
 It inhibit viral DNA polymerase and reverse transcriptase enzyme.
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 Foscarnet is used for all acyclovir and ganciclovir resistance herpes infection.
Antiretroviral drugs - Used to treat infection caused by HIV, the virus that caused AIDS.

CLASSIFICATION OF ANTIRETROVIRAL DRUGS

CLASS DRUGS
Nucleoside reverse Zidovudine, Didanosine, Stavudine, Lamivudine,
transcriptase Inhibitors Abacavir, Emtricitabine, Tenofovir
(NRTIs)
Non-nucleoside reverse Nevirapine, Efavirenz, Delavirdine, Etravirine,
transcriptase Rilpivirine
Inhibitors (NNRTIs)
Protease inhibitors (Pls) Ritonavir, Atazanavir, Indinavir, Nelfinavir, Saquinavir
Fosamprenavir, Lopinavir, Darunavir
Entry inhibitor Enfuvirtide (T-20)
CCR-5 Receptor Inhibitor Maraviroc
Integrase Inhibitors Raltegravir, Dolutegravir (DTG)

NRTI, NNRTI Raltegravir

Eltegravir

Enfuvirtide - -

RT Integrase
HIV Human
Viral RNA Viral DNA DNA

Maraviroc
RNA

Activated Protein
Protease

Proteins (Inactive)
Protease
Protease
inhibitor

Fig : MECHANISM OF ACTION OF ANTIRETROVIRAL DRUGS

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTI)

 These drugs after entering. HIV infected cells, are converted to active triphosphate formed
bycellular kinase and and competitively inhibits HIV reverse transcriptase.
 They get incorporated into the growing viral DNA and cause termination of chain
elongation of proviral DNA.
ZIDOVUDINE
 It can also be used for the prophylaxis of needle stick injury patients and for the prevention
of vertical transmission of HIV from mother to fetus.

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 Major adverse effect of zidovudine is bone marrow suppression leading to megaloblastic

anemia, neuropathy, thrombocytopenia.
Host Cell
Zidovudine   Zidovudine triphosphatee
Kinase
Viral reverse
Single Stranded viral DNA   Double Stranted viral DNA.

transcriptase
(RNA dependent DNA
Polymerase)
Uses
 Its efficacy as monotherapy in AIDs has been confirmed.
 Prevention of HIV transmission from mother to new born.
Didanosine
Stavudine Transported into cell and activated Inhibits HIV reverse
Zalcitabine to respective triphosphate forms. transcriptase
Lamivudine Orally effective DNA chain termination
NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTI)

 Block activity of the enzyme reverse transcriptase, preventing production of new viral DNA.
Nevirapine 
Bind directly to reverse transcriptase enzymeand inhibit their function.
Delavirdine 
(Do not require intracellular phosphorylation)
Efavirenz 

PROTEASE INHIBITOR
 Inhibit the protease retroviral enzyme, preventing viral replication.
 Protease act at a last step in HIV replication.
 Because they act at a late step of viral cycle, they are effective in both newly and chronically
infected cells.
 Inhibitors of this enzyme can be used in treatment of HIV infection.
 This group of drug inhibit the metabolism of several drug by inhibiting CYP3A4.
 All protease inhibitor are metabolized by liver and all caN cause metabolic abnormalities
including hypercholesterolemia.
 Marketed in India are - Ritonavir, Indinavir, Nelfinavin

FUSION INHIBITORS
 Inhibit viral fusion, preventing viral replication
 Newest classes of antiretroviral drugs.
 Enfuvirtide and Maraviroc prevents fusion of HIV membrane with that of host cell
membrane

INTEGRASE INHIBITORS

 Raltegravir inhibits integrase enzyme  Prevents integration of viral DNA with host..

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ANTIINFLUENZA DRUGS

AMANTADINE
 It is an antiviral drugs that has antiparkinsonian effect as well.
 It inhibits the uncoating and assembly of influenza A virus, thus prevents viral
replication. [GATE-98]
RIMANTADINE - More Potent, longer acting & better tolerable.
NEURAMINIDASE INHIBITOR
It selectivity inhibits influenza A and B virus neuraminidase thus interfecing with the release of
virus from infected cell.
Use - Bird flue (H5N1)
Swine flue (H1N1)
OTHER ANTIVIRAL DRUGS

INTERFERON
 Proteins produced by virus infected cells.
 andinterferons are produced by all the cells in response to viral infections.  interferons
are produced only by T lymphocyte and NK cells in response to cytokinin – Immune
regulating effects
 Interferon with Ribavirin drug combination is used for the treatment of patients suffering
from Hepatitis C (GPAT-10)
 Also prepared by recombinant DNA technology.
 Saccharomyces cerevisiae is used for the effective synthesis of interferon. (GPAT-20)
Use - Treatment of Veneral Warts, Chronic hepatits B and C.
RIBAVIRIN
 Purine nucleoside analogue.
 Effective against influenza A and B, measels in immunocompressed patients.
 It’s mono and triphosphate derivative inhibits GTP and viral RNA Synthesis

POINTS TO REMEMBER

 Oseltamivir is used in the treatment of bird and swine flu.

 Interferon  is used for the treatment of hepatitis B and C virus.
 All NRTIs requires triphosphate for activity, NNRTIs doesn’t require triphosphate for activity.
 Mefloquine, Proguanil, Primaquine effectively used against protozoa produced diseases.
(GATE-07)
 Trifluridine is used as ophthalmic slutin in Herpes keratitis. (GATE-05)
 Acute pancreatitis drug (Major): Stavudine, Didanosine, Jalcitavir.
 In pregnancy safest drug are Zidovudine(GPAT-10), Indinavir, Lamivudine.
 Transfusions of blood and blood products is HIV transmission carries highest relative

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19 ANTIMALARIAL
DRUGS

INTRODUCTION
 Malaria is a protozoal infection caused by genus Plasmodium parasite.
 Malaria caused by four species of protozoal parasite- Plasmodium vivax, Plasmodium
ovale, Plasmodium malariae, Plasmodium falciparum
 50% malaria cases arises due to Plasmodium falciparum.

CLASSIFICATION OF DRUGS

S.NO. CLASS DRUGS

1 4-Aminoquinolines Amodiaquine,Chloroquine, Piperaquine
2 8-Aminoquinolines Bulaquine, Primaquine
3 Acridine Mepacrine (Atabrine, Quinacrine)
4 Biguanides Proguanil (Chloroguanide)
5 Cinchona Alkaloids Quinine, Quinidine
6 Diamino Pyrimidines Pyrimethamine
7 Napthoquinone Atovaquone
8 Phenanthrene methanol Halofantrine
9 Quinoline methanol Mefloquine
10 Sulfonamide and Sulfone Sulfadoxine, Sulfamethopyrazine, Dapsone
11 Sesquiterpine lactones Artesunate, Artemether, Arteether
12 Tetracyclines Tetracycline, Doxycyclines
The aim of using drug in relation to malaria infection is
 To prevent and treat clinical attack of malaria.
 To completely eradicate the parasite from the patient’s body.
 To reduce the human reservoir of infection - Cut down transmission to mosquito.

LIFE CYCLE OF MALARIAL PARASITE

1. PRE-ERYTHROCYTIC CYCLE
 The pre-erythrocytic cycle, when the mosquito bites, sporozoites are injected with the
saliva into the blood stream. Within 30 minutes they invade the liver cells and multiply
there for 7-10 days forming thousands of merozoites.
2. ERYTHROCYTIC CYCLE
 The erythrocytic cycle inside human red blood cells (RBC).

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3. SPOROGONIC CYCLE
 The sporogonic cycle in the mosquito. The mosquito acquires gametocytes when it bites
an infected person. These fertilise in the gut and eventually migrate as sporozoites to the
saliva.
4. EXO-ERYTHROCYTIC CYCLE
 The exo-erythrocytic cycle outside RBC.
Human Liver Stage
Liver cell Infected
liver cell
Mosquito Stages
Ruptured
Oocyst Mosquito takes
a blood meal Exo-erythrocytic cycle
Release of (injects sporozoites)
Oocyat .
sporozoites ........
.... Ruptured schizont
...
.......
Schizont

Sporogonic cycle Human Blood Stages

Immature
trophozoite
Ookinete Mosquito takes (ring stage)
a blood meal
(Ingests gametocyte)
Macrogametocyte ..
.... . ....
... .. .. .
.. ....... ...
.... Erythrocytic Cycle Mature
. . . ............ trophozoites
Microgamete
entering
macrogamates P. Falciperum
Ruptured
Exflagellated schizont
microgamotocyte Schizont
Gametocytes
i : infective stage P. Vivax Gametocytes

d : diagnostic stage P. Ovale

P. Malariae

Fig: LIFE CYCLE OF MALARIA PARASITE

 Some schizonts remains dormant in liver and this dormant hepatic stage is
Exo-erythrolytic stage is Responsibe for relapse of malaria.
 Exo-erythrocytic stage is absent in P. falciparmrum So relapse donot occurs.
DRUGS USED FOR TREATMENT ON THE BASIS OF THE STAGE IN THE LIFE CYCLE OF
PARASITE
1. PRE-ERYTHROCYTIC CYCLE
 These are the drugs that kills schizonts in liver.
eg -Primaquine for all species, Proguanil for P.falciperum
2. ERYTHROCYTIC CYCLE
 These are the drugs that kills schizonts in blood.
Fastest acting - Chloroquine, Mepacrine, Quinine, Mefloquine.
Slower acting - Proguanil, Pyrimethamine, Sulfonamide
3. EXO-ERYTHROCYTIC CYCLE
 These drugs kills the exoerythrocytic form. eg - Primaquine.

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4. SPORONTICIDES OR GAMETOCYTES
 These drugs kills the gametes and thus prevent transmission of malaria.
 Chloroquine, Mepacrine, Quinine - Kill gametes of P.vivax proguanil, Pyrimethamine,
Primaquine and anrtemisinin - kill gametes of both P.vivax as well as p.falciperum.
CHLOROQUINE
 Drug possessing largest Vd (1300L)
 It is a rapidly acting erythrocytic schizonticide against all species of plasmodium.
 It has no effect on pre-erythrocytic and post-erythrocytic stage.
 Chloroquine- it is selectively accumulated in retina - Occular toxicity.
 Plasmodial resistance of chloroquine is due to decreased carrier-mediated drug transport.
[GATE-2001]
 Prolonged use of high dose can result in retinal damage and arrhythamia.
 Drug of choice for treatment of malaria in pregnancy.
Mechanism of Action
 It prevents polymerization of hence to hemozoin resulting in accumulation of hence
that is toxic for the parasite.
 Haemoglobin  Haeme (toxic)  Hemozin (Non-toxic)
 Chloroquine  Concentrated in acidic vacuole of parasitee

Binds to haeme

Drug - haeme complex (Prevent formation of hemozoin)

Damage Plasmodial membrane
Use of Chloroquine
MNEMONICS
RED LIP Mahatma Gandhi.
R: Rheumatoid arthritis.
E: Extraintestinal amoebiasis.
D: Discoid Lupus erythematosis.
L : Lepra reaction.
I : Infectious mononucleosis.
P: Pathogenic reaction.
M: Malaria.
G: Giardiasis.
QUININE
 It is a d-isomer of Quinidine (antiarrhythmic) & levorotatory alkaloids
 Quinine does not cause toxicity even at higher concentration in patients with malaria
because of binding to -1 acid glycoproteins.

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Mechanism of Action
 Similar to Chloroquine.
 Inhibition of hame polymerase.
Use

Antimalarial and depresses the skeletal muscle contraction.

It is referred drug of choice in treatment of P.falciparum resistant to chloroquine. [GPAT-10]
Quinine + Tetracycline  Standard treatment for complicated malaria.
 Antimalarial
 Depresses the skeletal muscle contraction
 Noctural leg cramps and spermicidal
Adverse effect - Hypoglycemia, Ringing in ear.
MEFLOQUINE
 Used for chloroquine resistant P.falciparum infection both for treatment as well as
prophylaxis.
 It has no effect on hepatic form.
Mechanism of Action
 Similar to chloroquine & quinine
 Mefloquine is contraindicated in epilepsy and Psychiatric disorders.
PRIMAQUINE
 Act by forming interfering mitochondrial function that act as cellular antioxidal
exo-erythrocytic stage.
 Primaquine is the only antimalarial which is active an exoerythrocytic stage.
 Should be avoided during pregnancy.
 It has no role in P.falciparum malaria because has no exo-erythrocytic stage.
ANTIFOLATE
Drugs - Pyrimethamine, Proguanil, Sulfadoxine and Dapsone.
 They are not used as single agents in malaria owing to rapid development of resistance.
Mechanism of Action
Para-aminobenzoic acid
Sulfadoxine, Dapsone Folate Synthatase
Dihydrofolic acid
Pyrimethamine, Proguanil Folate reductase
Tetrahydrofolic acid
 Proguanil (Prodrug) Cycloguanil Can be employed during pregnancy.
ARTEMISIN DERIVATIVES - (Fastest acting drug)
 Obtained from plant Artemisia annua. (Chinese tree) ‘Quinghoso’ Plant
 Artemisinin is used for management of complicated malaria [GPAT-17].
 It does not cure relapsing malaria. [GPAT-11,10]
 It is useful in treatment of cerebral falciparum malaria. [GPAT-11]

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20 ANTIAMOEBIC
DRUGS

INTRODUCTION
 Amoebiasis is a protozoal infection caused by Protoza Entamoeba histolytica .
 Infective Stage - Trophozoite.
Life cycle of Entamoeba histolytica
Entamoeba histolytica exists in two forms:
1. Cysts form (That can survive out side the body).
2. Trophozoites form (That are labile and don’t persist outside the body).

LIFE CYCLE CONSISTS OF FOLLOWING STEPS

1. INGESTION OF CYSTS
 Cysts are ingested through feces, contaminated food or water.
2. FORMATION OF TROPHOZOITES
 Cysts are passed into the lumen of intestine, where the trophozoites are liberated.
3. PENETRATION AND MULTIPLICATION OF TROPHOZOITES
 Trophozoites are penetrated in intestinal wall and multiply within colon wall. They
either invade and ulcerate the mucosa of large intestine or simply feed on intestinal
bacteria.
4. SYSTEMIC INVASION LARGE NUMBERS OF TROPHOZOITES
 Within the colon wall can also lead to systemic invasion and caused liver abscess.
5. CYSTS DISCARDED
 The trophozoites within the intestine are slowly carried toward the rectum, where they
return to cyst form and are excreted in feces.

CLASSIFICATION (According to Their Site of Action)

1. Tissue amoebicides - They attain high concentration in blood and tissues following oral or
parenteral administration.
2. Luminal amoebicides - They are poorly absorbed after oral administration, hence attain high
concentration in the bowel. They act on trophozoites in the gut lumen and kill them.

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CLASS SUB-CLASS DRUGS

Tissue For intestinal + Nitroimidazole Metronidazole, Tinidazole,
amoebicides extraintestinal Secnidazole, Ornidazole,
amoebiasis Satrinidazole
Alkaloids Emetin, Dehydroemetin
For extraintestinal 4-aminoquinoline Chloroquine
amoebiasis only
Luminal Amides Diloxanide furoate
amoebicides 8- hydroxyquinolines Quiniodochlor,
Diiodohydroxyquin
Antibiotics Tetracyclines,Paromomycin
Trick to Remember - “A G T ”

........
....
... A moeba
(by oral route)

G I. infection
(by hematogenous spread)

T issue infection
eg : Hepatitis

Antimoebic drugs are -

A - Amoebicides for both GI & tissue infection
eg. : Metronidazole, Tinidazole, Secnidarzole, Emetine, Dehydroemetine.
G- G.I. lumen amoebicide only.
eg. : Diiodo-hydroxyquin, Iodochloro hydroxyquin, Diloxanide furoate
T- Tissue amoebicide only.
eg : Chloroquine.

NITROIMIDAZOLES

METRONIDAZOLE
 Metronidazole is having broad spectrum activity.
 Effective against most anaerobic bacteria and several protozoa, such as E.histolytica,
Giardia lambia and Trichomonas Vaginalis.
 It helps in the extraction of gunea worm (Dranunculus medinensis)
 Metronidazole and diloxanide drugs useful in the treatment of both intestinal and
extraintestinal symptoms of amoebiasis in orally. (GATE-02)
Mechanism of Action
Metronidazole Nitrogroup is reduced
Microorganism
(Prodrug) by ferrodoxins

Death of the organism Damage Active

(cidal effect) microbial DNA metabolite
Note :- In presence of oxygen (aerobes) metronidazole can’t be reduced to its active metabolite,
hence it is ineffective against aerobes.

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Clinical use
A - Amoebiasis & Anaerobic infection.
G - Giardiasis & Guinea worm infection.
T - Trichomoniasis, Trench mouth, Ulcerative gingivitis.
Adverse effect
A - Anorexia, Abdominal crams, Alcohol intolerance (Disulfuram like reaction).
G - Glossitis & Giddiness.
T - Taste - metallic, Thrombophlebitis (on i.v. insection of conc. drug ) Teratogenic Potential..
SECNIDAZOLE - Longest t1/2 - 17 to 29 hours.
SATRANIDAZOLE
 Better tolaribility than others.
 Absence of neurological and disulfiram like reaction.
 Satranidazole is longest acting.
 Satranidazole does not cause nausea & vomiting, metallic taste.
EMETINE
 Emetine is alkaloids and dehydroemetine is semisynthetic derivative
Mechanism of Action
 Inhibits protein synthesis in amoeba by arresting intraribosomal translocation of t-RNA
amino acid complex.
 Used Parenterally in severe hepatic amoebiasis.
Adverse effect - EMETINE
Emesis, Muscle weakness, ECG changes, Tachycardia, Itching, Nausea, Eczematoid
CHLOROQUINE
 Used in hepatic amoebiasis.
 It kills trophozoite of E.histolytica and highly concentrated in liver.
 Therefore it is only used in hepatic amoebiasis.
DILOXANIDE FUROATE
Diloxanide furoate
Spilit into

Diloxanide Furoic acid

in gut
(Parthy absorbed) (Unabsorbed)

exerts antiamoebic activity

8 - HYDROXYAQUINOLINES
 Activity against Entamoeba, Giardia, Trichomonas.
 Prolong use can cause SMON (Subacute Myelo Optic Neuropathy),

DRUG FOR GIARDIASIS

 Giardiasis is caused by flagellate Protozoan Giardia Lambia.
 Invade mucosa and cause diarrhoea.
Preffered drugs - Metronidazole (Oral)
Alternative drugs - Tinidazole, Furazolidone, Mepacrine.
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DRUGS FOR TRICHOMONIASIS

 Trichomonas Vaginalis is another flagellate Protozoan which cause vulvo vaginitis.
Drugs used are - Metronidazole, Tinidazole, Nimorazole.

DRUGS FOR LEISHMANIASIS

 Visceral Leishmaniasis (kala azar) is cuased by Leishmania donovani
 1st Choice of drug - Sodium Stibogluconate.
 Allopurinol used because Leishmania also have drugs high % of ergosterol and is suspectible
to it.

CLASSIFICATION

CLASS DRUGS
Antimonials Sod. Stibogluconate, Meglumine antimonate
Diamidine Pentamidine
Others Amphotericin B, Ketoconazole, Allopurinol, Meltefosine
Paramomycin

K Ketoconazole
A Antimonials
L Liver Stored drugs eg : Pentamidine
A Amphotericin B
A Allopurinol Inhibits topoisonease II.

DRUGS FOR TOXOPLASMOSIS - (Congestial fever, Jaundice, Diarrhoea)

 Caused by Toxoplasma gondii Drug - Clindamycin, Pyrrimethamine, Spiramycin.

DRUGS FOR TRYPNOSOMIASIS (Sleeping Sickness)

 Caused by Trynosoma brucei
Drugs used - Suramicin, Pentamidine.

DISEASE CAUSING ORGANISM & THEIR DRUG OF CHOICE

ORGANISM DRUG OF CHOICE (DOC)

Leishmania donovani Liposomal amphotericin B
Chages disease Benznidazole
Giardia lamblia Metronidazole
Trichomonas vaginalis Metronidazole
Toxoplasma Pyrimethamine + Sulfadiazine
Pneumocystis Cotrimoxazole
Early African Trypanosomiasis Suramin

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21
ANTIHELMINTICS

INTRODUCTION

 Antihelmintics are drugs used in the treatment of infection with helmintics in the
intestinal tract or tissue of the body.
Vermicides (Kills worms)
They are two types
Vermifuge (Expel the worms)

VARIOUS HELMINTIS CAUSE INFECTIONS ARE

CLASS SUBCLASS MICROORGANISM

Nematodes - (Round Round worms Ascaris Lumbricoides
worms) Hook worm Ancyclostoma duedenale
Pin worm Enterobius Vermiculris
Whip worm Trichuris trichviura
Thread worm Strongyloides Stercoralis
Filaria worm Wuchereria bancrofti
Treamatodes - (Flukes) Blood fluke Schistosoma haematobium
Liver fluke Fasciola hepatica
Cestodes - (Tape worms) Beef tapeworm Taenia Saginata. [GATE-98]
Pork tapeworm Taenia Solium.
3 Drugs
Piperazine
Diethylcarbamazine
Pyrantal Pamoate
(DEC) Ivermectin
Praziquantal
MAT P e D og N ahi L eta ha I
Mebendazole Lavamisole
Albendazole Niclosamide
& Tetramisole
Thiabendazole

CLASSIFICATION BASED ON MECHANISM OF ACTION

MECHANISM OF ACTION DRUGS

Drugs inhibiting polymerization of Albendazole, Mebendazole,
-tubulin Thiabendazole
Drugs causing flaccid paralysis by Piperazine
GABAA agonistic action
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Drugs causing spastic paralysis by Pyrantel pamoate

stimulating N N receptor
Drugs causing influx of calcium Praziquantal
Drugs altering microfilarial membrane Diethylcarbamazine(DEC)
and increasing phagocytosis
Drugs causing uncoupling of oxidative Niclosamide, Bithional
phosphorylation
Drugs causing tonic paralysis by Levamisole, Tetramisole
stimulating ganglia
Drugs acting by special type of Ivermectin
glutamate gated Cl- channel
MEBENDAZOLE
 It is a prototype and broad spectrum of activity.
 It is a benzimidazole derivative, Contraindicated in pregnancy.
Mechanism of Action
 Mebendazole binds to -tubulin and inhibits microtubule polymerization. [GATE-00]
 It acts probably by blocking glucose uptake in the parasite and deplete glycogen stores.
PIPERAZINE
 Causes flaccid paralysis of worm.
 Hyperpolarization of ascaris muscles GABA agonistic action of Cl- channel opening.
Decreased responsiveness to Ach contractile response  So Paralysis occur  worm
expel out.
 Causes hyperpolarization of ascaris muscle by GABA opening Cl- channel that cause
relaxation and depress responsiveness to contractile action of acetylcholine
 Safe during pregnancy.
PYRANTAL PAMOATE
 Causes spastic paralysis
 Highly effective for treatment of Roundworm, Pinworm and Hookworm infections.
 Pyrantal Pamoate - Effective against ascaris, enterobious.
Mechanism of action
Pyrantal Pamoate Inhibits cholinesterase
in worms

Stimulate nicotinic cholinergic  Ach conc

receptor in warn

Persistant depolarization

Spastic paralysis

Worm expelled (Vermifuge)

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PRAZIQUANTAL
 Effective against schistosomes trematodes and cestode only.
 Praziquantal - Highly effective against Schistosomes.
Praziquantal  Increase influx of Ca +2 into the tegument  Increased Muscular
ar
Contraction and spastic paralysis of the worms.
DIETHYLCARBAMAZINE CITRATE (DEC)
 Available in citrate salt
 Most effective drug used in treatment of filariasis.
 Diethylcarbamazine (DEC) - DOC for filariasis
DEC damages the microfilarial membrane structure so that they are destroyed by host
defences.
NICLOSAMIDE

This drug inhibits oxidative phosphorylation (ATP formation stop) In the mitochondria
of the parasite and rapidly kill worms.
LEVAMISOLE
 It is a immunomodulator.
 It is also used as adjunct in rheumatoid arthritis & cancer therapy.
 In worms drug causing tonic paralysis by stimulating ganglia.
IVERMECTIN
 Activates glutamate gated chloride channels.
 Ivermectin should be avoided in children below 5year old.
 Increases GABA (  -aminobutyric acid) transmission in worms.

Hyperpolarization and Paralysis of worm.

Death / Phagocytosis of worms.

POINTS TO REMEMBER
 Albendazole is the drug of choice for the treatment of all nematode.
 Mebendazole, Albendazole - Broad Spectrum.
 Praziquantal - Highly effective against schistosomes.
 Pyrantal Pamoate - Effective against ascaris, enterobious.
 Albendazole - DOC for all Nematodes.
 Niclosamide - Highly effective against taenia.
 Ivermectin - Antinomatodal drugs.

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22 ANTICANCER
DRUGS

INTRODUCTION
 Cancer is a disease of cells characterized by progressive, persistant, pervected
(abnormal), purposeless and uncontrolled proliferation of tissue.
 Cancer cell produce oncoproteins in the absence of growth factor or external stimuli.
[GPAT-20]
 Clinically available anticancer drugs acts by cell growth inhibitor [GATE-97]
 Lungs cancer is the most common cancer in men.
 Breast cancer is most common cancer in women.

Genetic
change

Normal cell Cancer cell

Doubling Malignant cancer
Fig: PROCESS OF CANCER CELL DEVELOPMENT

TYPES OF CANCER
BASED ON ORIGIN
CARCINOMA
 Carcinoma is a type of cancer that starts in cells that make up the skin or the tissue
lining organs, such as the liver or kidneys.
 Carcinomas are abnormal cells that divide without control. They are able to spread
to other parts of the body.
SARCOMA
 Cancer that begins in bone, cartilage, fat, Muscle, Blood vessels, or other connective
or supportive tissue.
LEUKEMIA
 Cancer that start in blood-forming tissue such as the bone marrow and causes
large numbers of abnormal blood cells to be produced and enter the blood.
LYMPHOMA AND MYELOMA – Cancers that begin in the cells of the immune system.
CENTRAL NERVOUS SYSTEM CANCERS –Cancers that begin in the tissue of the brain and
spinal cord.
GERM CELL CANCER - Germ cell, Testicle, and ovarian cancers
BLASTOMS – Resemble embryonic tissue.
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BOTH NORMAL AS WELL AS CANCEROUS CELLS MUST PASS THROUGH

THE FOLLOWING PHASES OF CELL CYCLE

(1) G1 phase (Presynthetic phase) - Synthesis of enzymes and other cellular compounds
needed for DNA synthesis.
(2) S phase (Synthesis phase) - DNA synthesis takes place.
(3) G2 Phase (Premitotic phase) - Synthesis of cellular components for mitosis (Proteins
& RNA Synthesis)
(4) M Phase (Mitotic Phase) - Mitotic cell division take place.
(5) G0 Phase (Resting Phase) - Cell stop dividing temporarily or permanently.
G0- Resting phase
Vincristine, Vinblastine
Paclitaxel, Docetaxel G1- Pre-replicative phase
Cyclophosphamide G2- Post-replicative phase
Bleomycin S - DNA synthesis
Actinomycin D M - Mitosis of cell division
M G0
Resting

G2 G1

Actinomycin D
S 5-Fluorouracil
Purine antagonists Cytosine arabinoside
Methotrexate Methotrexate
Cyclophosphamide 6-Mercaptopurine
5-Fluorouracil 6-Thioguanine
Cytosine arabinoside

Fig: CELL CYCLE SPECIFICITY OF ANTI-NOEPLASTIC AGENTS

ANTICANCER DRUGS MAY BE DIVIDED INTO TWO GROUPS

1. Cell cycle specific (CCS)
 Act mainly in dividing cell
2. Cell cycle non-specific (CCNS)
 Act mainly in dividing cell as well as resting cell
PHASE CELL CYCLE SPECIFIC DRUGS C ELL CYCLE NON-SPECIFIC DRUGS
G1 Etoposide Platinum compound
S ANTIMETABOLITE ALKYLATING AGENT
 Methotrexate  Melphalan
 6- mercaptopurine  Cyclophosphamide
 5-flurouracil  Nitrosoureas
 Capecitabine
 Cytarabine
 Cytosine arabinoside [GATE-05]
 Paclitaxel [GPAT-14]

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G TOPOISOMERASE INHIBITOR ANTHRACYCLINS

 Irinotecan  Doxorubicin
 Topotecan  Daunorubicin
 Etoposide  Epirubicin
 Bloemycin  Mitoxantrone
M VINCA ALKALOIDS MITOMYCINS C
 Vincristine  Dactinomycin
 Vinblastine  Camptothecin
 Vinorelbine
TAXENES
 Paclitaxel
 Docetaxel

CLASSIFICATION

A . DRUGS ACTING DIRECTLY ON CELLS (CYTOTOXIC DRUGS)

S.NO CLASS SUB-CLASS DRUGS

1. Alkylating agents Nitrogen Mechlorethamine, Bendamustine
mustard Cyclophosphamide, Melphalan,
Chlorambucil, Ifosfamide
Ethylenimines Thiotepa, Altretamine
Alkyl sulfonates Busulfan
Nitrosoureas Carmustine, Lomustine
Triazine Dacarbazine
Methyl hydrazine Procarbazine, Temozolomide
2. Platinum co-ordination complex Cisplatin, Carboplatin, Oxaliplatin
3. Antimetabolites Folate antagonist Methotrexate, Pemetrexed
Purine 6-mercaptopurine (6-MP), 6-
antagonist Thioguanine (6-TG), Azathioprine
Pyrimidine 5-Fluorouracil (5-FU), Cytarabine,
Antagonist Gemcitabine, Cytarabine
4. Microtubule Vinca Alkaloids Vincristine, Vinblastine, Vinorelbine
Damaging Agents Taxenes Paclitaxel, Docetaxel
5. Epidophyllotoxin Etoposide, Teniposide
6. Camptothecin Topotecan, Irinotecan
Analogue
7. Antibiotics Actinomycin D, (Dactinomycin),
Doxorubicin, Daunorubicin, Mitoxantrone, Bleomycins,
Mitomycin C, Mithramycin (Plicamycin)
8. Miscellaneous Hydroxyurea, Procarbazine,
L-asparaginase, Cisplatin, Carboplatin

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B . TARGETED DRUGS

CLASS DRUGS
BCR-ABL tyrosine protein kinase inhibitor Imatinib, Nilotinib, Dasatinib
EGF receptor inhibitors Gefitinib, Cetuximab, Erlotinib
Angiogenesis inhibitors Sunitinib, Sorafenib
Proteasome inhibitors Bortezomib
Monoclonal antibody Rituximab, Trastuzumab

C . HORMONAL DRUGS

S.NO CLASS DRUGS

1. Glucocorticoids Prednisolone
2. Estrogens Fosfestrol, Ethnyl estradiol
3. SERMs Tamoxifen, Toremifene
4. Antiandrogens Flutamide,Bicalutamide
5. Aromatase inhibitor Letrozole, Anastrozole
6. 5-α reductase inhibitor Finasteride, Dutasteride
7. GnRH analogues Nafarelin, Goserelin
8. Progesting Hydroxyprogesterone acetate
9. SER. down regulator Fulvestrant

TOXICITY OF ANTICANCER DRUGS

S.NO. DRUGS TOXICITY

1. Anthracycline(Doxorubicin Cardiotoxicity
[GPAT-16], Daunorubicin)
2. Busulphan, Bleomycin[GPAT-16] Pulmonary fibrorsis
3. Vincristine, vinblastine, Peripheral neuropathy
Vinorelbine
4. Methotrexate [GPAT-17] Megaloblastic aneamia, Hepatotoxicity,
Obstructive nephropathy
5. Cyclophosphamide [GPAT-14], Haemorrhagic cystitis, Alopecia
Ifosfamide
6. Cisplatin [GPAT-16] Emesis, Nephrotoxicity, Neuropathy,
Ototoxicity
7. 5-Flourouracil, Capecitabine, Hand and foot syndrome, Neurotoxicity
Fludarabine, Cytarabine
8. 6- Mercaptopurine, 6- Hepatotoxicity
Thioguanine
9. Paclitaxel, vincristine Peripheral neuropathy,
Hypersensitivity
10. Docetaxel Peripheral neuropathy, Fluid retention
11. Irinotecan, Gemcitabine Diarrhoea
12. Doxyfluridine Bone marrow depression, Hearing loss,
Neuritis.
13. Cytarabine Cerebral ataxia (neurotoxicity]
14. Chlorambucil Lymphatic leukemia
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Note - Natural anticacer agents

 Vinca alkaloids.
 Epipodophyllotoxin.
 Toxenes.
 Antibiotics
 Camptothecins.
 Enzymes.

ALKYLATING AGENTS
 Having radiomimetic action (like ionizing radiation)
 They get converted to azindinum ions and bind to 7th position -N atom of guanine of DNA
base pairs.
Mechanism of action
Alkylating Agents

Form highly reactive carbonium ion

Transfer alkyl groups to nucleophilic sites of DNA bases

Results in

Cross linkage Abnormal base pairing DNA strand breakage

(Inhibiting DNA (Alkylated guanine base pairs with (Alkylating agents can also bind
replication) thymine rather than cytosine and results to protein and damage them)
in production of defective protein).

Cell proliferation
NITROGEN MUSTARD
CYCLOPHOSPHAMIDE
 Cyclophosphamide is prodrug and activated in liver.
Phospharamide Cytotoxoic effect
Meta
Cyclophosphamide Aldophoshamide mustard
Acrolein Toxic metabolite
(Damage kidney blood
vessels)
Mesna (2-mercaptoethane Sulphonate)
Mesna
Binds with cyplophosphamide and
Acrolein

(-SH compound) cause haemorrhagic

Ifosfamide
cystitc

se toxicity
Adverse effect
 Hemorrhagic cystitis, Bone marrow suppression
 Pancytopenia, Alopecia

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MELPHALAN
 It is a phenyl alanine derivative
 An alkylating agent add an alkyl group to DNA. It attaches the alkyl group to the guanine
base of DNA, at the number 7 nitrogen atom of the imidazole ring.
 Common toxicity Bone marrow depression.
BUSULFAN
It is a bifunctional methane sulfonic ester that forms transferred cross-linking with DNA.
Adverse effect
 Interstitial pulmonary fibrosis
 Thrombocytopenia and anemia, Gynecomastia.
CHLORAMBUCIL
 A very slow acting alkylating agent.
 A drug of choice for lymphatic leukemia.
Mechanism of Action
 Interfering with DNA replication and damage the DNA cell.
 Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, including
 DNA damage via three different methods of covalent adduct generation with double
helical DNA.
 Adverse effect - Pulmonary fibrosis
NITROSOUREAS
 Highly lipid soluble agents.
 Cross BBB - effective in meningeal leukemia and brain tumour.
 The nitrosoureas appear to function by cross-linking through alkylation of DNA.
DACARBAZINE
 It is triazine derivative.
 Primarily inhibit RNA and protein synthesis.
 After activation in liver, the active metabolite methylate the DNA and interfere with its
function
 Used for malignant melanoma and Hodgkin’s disease.

PLATINUM CO-ORDINATION
CISPLATIN
 Heavy metal complex with highly effective neoplastic activity.
Cisplatin Forms highly reactive Intrastrands and
enter cells platinum complexes interstrand cross linking

Inhibit cell proliferation DNA damage

Uses
 Very powerful against testicular cancer
 Also useful in the treatment of Bladder, Ovary, Head and Neck carcinoma.

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Adverse effect
 Renal tubular damage, ototoxicity, and Peripheral neuropathy.
CARBOPLATIN
It is a derivative of cisplatin with less neuro, Nephro and Ototoxicity.

ANTIMETABOLITES

 These drugs act in the S-phase of cell cycle - only dividing cells are responsible.

FOLATE ANTAGONIST
METHOTREXATE
 Methotrexate is most commonly used anticancer drugs.
 Have antineoplastic, immunosupprasants and antiinflammatory effects.
Mechanism of action
Methotrexate

Dihydrofolate Tetrahydrofolic Synthesis of Purines

Reductase (DHFRase) acid & Pyrimidines

DNA & RNA

Synthesis

PURINE ANTAGONIST
 6- Mercaptopurine, 6- Thioguanine are converted into corrosponding ribonucleotide which
inhibit the conversion of Inosine monophasphte to adenine & guanine nucleotide
(Inhibit protein synthesis)
 Pentostatins is a purine derivative antimetabolite drugs and its mechanism of action
inhibit adenosine deaminase. [GATE-05]
 6-mp also has immunosuppresant action.
 Allopurinol interface with the metabolism of 6-mp by inhibiting the enzyme xanthine
oxidase and increases the antineoplastic effect of 6-mp.
Mechanism of action
6-MP and 6-TG is converted intracellularly to
TGMP (6-thioguanylic acid) by the enzyme
Hypoxanthine guanine phosphoribosyl transferase (HGPRT)

TGMP is further converted to the di and triphosphate,
thioguanosine diphosphate and thioguanosine triphosphate

Which inhibit the biosynthesis of purines and
also the phosphorylation of GMP to guanosine diphosphate.

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FLUDARABINE
 It is a prodrug useful in the treatment of chronic lymphocytic leukemia.
 Fludarabine is also effective against hairy cell leukemia and non-hodgkin’s lymphoma.

PYRIMIDINE ANTAGONIST
FLUROURACIL (5-FU)
 5-FU is activated to fluorodeoxyuridine monophosphate (FdUMP) This interferes with
DNA Synthesis and function by inhibiting thymidylate synthetase enzyme.
 5-fluorouracil the anticancer effect in the S phase of the cell cycle.
Mechanism of action
5-fluorouracil is converted into 5-fluoro-2-deoxyuridine monophosphate (5-FdUMP)

Inhibit thymidylate synthetase

Block the conversion of deoxyuridilic acid to deoxythymidylic acid

Inhibit DNA synthesis
PLANT PRODUCTS
GEMCITABINE
 Incorporated into cytosine containing sites in the growing strands Inhibit DNA synthesis
Mechanism of Action
Inhibit Decrease generation
Decrease
ribonucleotide of deoxynucleoise
DNA synthesis
reductase triphosphate
VINCA ALKALOIDS
 Vincristine and vinblastine differ only in the substitution on the N-atom of the
dihydroindole nucleus.
Mechanism of Action

Binds to beta-tubulin Disruption of Chromosomes

(drug-tubulin complex) mitotic spindle fail to move apart
during mitosis

Cell division Metaphase

inhibited arrest
VINCRISTINE
 Vincristine used in the treatment of leukemia in children, Small cell lung cell and vaginal
cancer.
 Vincristine - (oncovin) - used for childhood acute leukemia.
VINBLASTINE
 Vinblastine - Hodgkin’s desease, Breast Carcinoma.
 Vinblastine (Leukoblastine) is produced by coupling of catharanthine and vindoline
 Used in the treatment of Hodgkin’s cancers

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TAXANES
 Taxanes are a class of diterpene
 Taxanes enhance stability of microtubule, preventing the separation of chromosomes
during anaphase.
 Paclitaxel is a taxane derived from the bark of the western yew tree.

Binds to Enhances Formation

Inhibits Death of
Paclitaxel of abnormal
-tubulin Polymerization mitosis the cell
microtubules
 Major toxicity is reversible myelosuppresion (decrease ability bone marrow to produce
blood cells) and stocking and globe neuropathy.

EPIPODOPHYLLOTOXINS
 Etoposide and Teniposide act by inhibiting topoisomerase II.
 Epipodophyllotoxin inhibit topoisomerase II by stabilizing topoisomerase II -DNA com
plex and prevent the unwinding of DNA.
 Etoposide is used in testicular and lung cancer in combination with other cytotoxic drugs.
Mechanism of action
Form complex with Prevent release of
Etoposide Cell
DNA and topoisomerase II broken DNA strand
and Teniposide death
(Drug DNA topoisomerase II)
Side effect are - Bone marrow suppression, GI side effect.

CAMPTOTHECIN ANALOGUS
 Obtained from plant Camptotheca acuminater.
 They act in S-G2 phase of cell cycle.
 Two semisynthetic derivatives are - Topotecan & Irinotecan
 Act by inhibiting topoisomerase I (this enzyme nicks, negative supercoils and reseal DNA
Strend)
 Common side effect are bone marrow suppresion and GI disturbance
TOPOTECAN
Use – In metastatic carcinoma of ovary and small cell lung cell
IRINOTECAN
 It produces the cholinergic effects because it inhibits the acetylcholinesterase.
ANTIBIOTICS
 Practically all intercalate between DNA strand and interfare with its template function.
ACTINOMYCIN (Dactinomycin )
 Obtained from streptomycer parvulus
 Doxorubicin is isolated from Streotourvces neucetius varcaesius.
 Doxorubicin act by inhibit topoisomerase II
 Highly effecacious in wilm’s tumour & rhabdomyosarcoma(Cancer of Skeletal muscle)

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Mechanism of action
Daunorubicin and Doxorubicin

They Activate topoisomerase I & generate quinone like free radical

Have mutagenic & carcinogenic potential
 Adverse effect:- A potentially irreversible cumulative dose related cardiac toxicity.
MITOXANTRONE
 Anlogue of doxorubicin.
 Donot Produce quinon etypr free raducals.
BLEOMYCIN
 A mixtur e of glycopeptide antibiotics.
 Bleomycin has been shown to cause cell cycle arrest in G2 phase and in mitosis.
 Bleomycin can also cross the blood brain barrier as it is used to treat cancers in the brain
 Used in the treatment of melanoma, Sarcoma, testicular cancer
MITOMYCIN C
 Mitomycin metabolic activation to produce a DNA alkylating agent

ENZYME
L- ASPANAGINASE
 It is an enzyme isolated from bacteria E.coli [GATE-08]
L-asparaginase Aspartic acid..
Asparagine  
 Asparagine is amino acid required for protein synthesis. (Essential for leukamia cell)
 L-asparaginase is obtained from E. coli and is administered parenterally. [GATE-08]
Toxicity - Hypersensitivity, Hyperglycaemia, Haemorrhage

MISCELLANIOUS AGENTS
HYDROXYUREA
 Acts in the S phase of cell cycle
Ribonucleotide
Hydroxyurea Ribonucleotide
Diphosphate reductase
Deoxyribonucleotide

DNA Synthesis
Major toxicity - Bone marrow suppression leukopenia, Anaemia.

TYROSINE KINASE INHIBITOR

IMATINIB
 Imatinib bined to a segment of BCR-ABL tyrosine kinase domain that fixes it in a closed or
non-functional state.
 Used for chronic myeloid leukaemia. [GPAT-10]
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 Imatinib is prescribed for the treatment of Philadelphia chromosome positive patient

with chronic myeloid leukemia. [GPAT-10]
HORMONES AND ITS LEVEL AFFECTING DRUGS
 They are not cytotoxic but modify the growth of hormones dependent tumours.
 All hormones are only palliative (relieving the symptoms of desease without affecting
cure).
GLUCOCORTICOIDS
 Have marked lympholytic action.
 Primarily used in acute childhood leukemia and lymphomas.
ESTROGEN
 Highly effective in Prostate Carcinoma.
TAMOXIFEN
 Highly effective in breast Carcinoma.
THALIDOMIDE
 Banned in 1960 for its teratogenic effect.
 Acts by suppressing TNF  as by modulating IL2.
FLUTAMIDE AND FINESTEROID
 Use full for pallitative treatement of advanced carcinoma of prostate -

DESEASE AND THEIR DRUG OF CHOICE

DISEASE DRUG OF CHOICE

Brain tumour Nitrosoureas
Lung cancer Cyclophosphamide
Ovarian and Testicular carcinoma, Melphalan
Multiple myeloma
Acute myeloid leukemia Cytarabine + Idarubicin/ Daunorubicin
Cancer testis Bleomycin + Cisplatin + Etoposide
Hodgkin’s disease stage I, II stage III
Doxorubicin + Bleomycin + Vinblastine+
and IV Dacarbazine
Myeloid leukemia Busulfan
Wilm’s tumour Surgery + radiotherapy followed by
Vincristine + Dactinomycin
Chronic myeloid leukemia Chlorambucil
Highly effective in breast carcinoma Tamoxifen
Highly effective in Prostate Estrogen
carcinoma
Colon cancer 5-Fluoro uracil + Leucovorin + Oxaliplatin
Pancreatic carcinoma Gemcitabine
Non-hodgkin’s lymphoma Cyclophosphamide + Hydroxydaunorubicin
+ Oncovin + Prednisolone + Rituximab
[GPAT-10]

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23 IMMUNOSUPPRESSANTS
AND
IMMUNOMODULATORS

IMMUNOSUPPRESSANTS

 They are drugs that suppress the immune response, they inhibit cell-mediated /humoral
immunity or both.
 Their main therapeutic application is in autoimmune disease and organ transplantation .

CLASSIFICATION

CLASS DRUGS
Calcineurin inhibitors (Specific T- Cyclosporine, Tacrolimus [GATE- 05, 07 GPAT-10]
cell inhibitors)
m-TOR inhibitors Sirolimus, Everolimus, Temsirolimus
Antiproliferative drugs Azathioprine, Methotrexate, Cyclophosphamide,
Chlorambucil, Mycophenolate mofetil
Glucocorticoids Prednisolone
TNF  inhibitors Etanercept, Infliximab, Adalimumab
IL-1 receptor antagonist Anakinra
Biological
IL-2 receptor antagonist Basiliximab, Daclizumab
agents
Anti-CD3 antibody Muromonab CD3
Polyclonal antibiotics Antithymocyte antibody, Rho(D) immune globulin

CALCINEURINE INHIBITORS
CYCLOSPORINE
 It is a polypeptide obtained from fungus Beauveria nivea.
 Inhibits T-lympholyte Proliferation,IL-2 and other cytokine production leads to a reduced
function of effector T-cells. It does not affect cytostatic activity.
Mechanism of action
NFAT-Poy (Inactive) - Nuclear factor of activated T-cell.
 Calcineurine Tacrolimus, Cyclospoorine
NFAT (Active)

Increase IL-2 transcription.

Immunity
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 Cyclosporine is the most effective drug for prevention`and treatment of graft rejection
reaction and it can be given i.v.
Drug interaction
 All nephrotoxic drugs like Aminoglycoside, Vancomycin, Amphotericin B and NSAIDs
increase its toxicity.
 Enzyme inducers decrease their levels of transplant rejection
Adverse effect - Nephrotoxicity, Hepatotoxicity.
TACROLIMUS
 Obtained from Streptomyces tsukuliansis.
 Tacrolimus is a macrolide antibiotics binds with cytoplasmic peptidyl-propyl-isomerase and
can be used in liver and kidney transplant. [GATE-05, 07]
 Chemically different from cyclosporine but same machanism of action
 Matabolized by CYP3A4 and excreted in bile and plasma t1/2 is 12 hours
 Tacrolimus inhibit the activated T-lymphocytes (inhibit the cytoplasmic phosphate
calcineurin]. [GATE-03, GPAT-10]
 Available for oral, parenteral and topical use.
 Used topically in psoriasis and atopic dermatitis.

CYTOTOXIC IMMUNOSUPPRESENTS

ANTIPROLIFERATIVE DRUGS
 Exhibits prominent immunosuppresants action mainly by preventing clonal expansion of
T and B lympholytes.
AZATHIOPRINE (Prodrug)
 It selectively affects differentiation and function of T-cells and inhibit cytolytic lymphocyte.
 The most important application is prevention of renal and other graft rejection.
 Azathioprine is the only antimetabolite drug that is used as immunosuppressant.
 Azathioprine inhibit the synthesis of both DNA and RNA.
 Used as ‘add on’ therapy to cyclosporine + Glucocorticoids in renal transplantation.
Mechanism of action
It is taken up into immune cell

Activated to 6-mp

Suppresses cell mediated and humoral immune response.
METHOTREXATE
 Has marked immunosuppresants and antiinflammatory activities.
 It decreases cytokine production and cell mediated immunity.
 Used in autoimmune disease like rheumatoid anthritis.
 Markedly depresses cytokine production and cellular immunity and has anti-inflammatory
property.
 Used in first line drug in many autoimmune diseases like rapidly progressive rheumatoid
arthritis, Pemphigus, Myasthenia gravis, Uveitis, Chronic active hepatitis.
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CYCLOPHOSPHAMIDE
 Used in bore marrow transplantation in which short course with high dose is given.
 Cyclophosphamide suppress B-lymphocyte proliferation but can enhance T-cell responses.
MYCOPHENOLATE MOFETIL
 It is a prodrug which is converted to mycophenolic acid.
 Lymphocyte proliferation and functions are inhibited.
 Selective inhibit inosine monophosphate dehydrogenase an enzyme essential for denove
synthesis of guanosine nucleotide in the T and B cells.
GLUCOCORTICOIDS
 Act by inhibiting the production of Prostaglandin, Leukotriens, Histamine, Bradykinin, &
PAF.
 Most immunosuppressant and anti-inflammatory drugs.
 Glucocorticoids inhibiting IL-1 production, these drug cause a decrease in IL-2 and INF
production.
 Continuous administration of Glucocorticoids can increase the catabolism of IgG.
 Autoimmune thrombocytopenia is treated by intravenous immunoglobulin. [GATE-05]
Uses of Glucocorticoids
 Transplant rejection, Psoriasis
 Inflammatory bowel disease, Eye condition
 Autoimmune disease- Rheumatoid arthritis, Hematological conditions.
Toxicity
Cataract, Hyperglycemia and Hypertension.

IMMUNOSUPPRESANTS ANTIBODIES

MUROMONAB CD3
 It is a monoclonal antibody against CD3 molecule on T-lymphocyte.
 It blocks the function of T cells.
Mechanism of action
Binding of Obstruction of binding
muromonab CD3 of MHC2 antigen complex Antigen recognition
antigen to the cell T-cell receptor is interfered

T-cell rapidly Precipitation of

Immune
disappear from T-cell in immune
block stage
circulation response is prevented
Uses
Treatment of acute organ transplant rejection.
Toxicity
Cytokine release syndrome

 Myalgia, Tremor, Arthralgia, Chills
ANTITHYMOCYTE GLOBULIN (ATG)
 Polyclonal antibodies
 It destroys T-cells .
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 Used in acute renal transplant rejection reaction.

 Polyclonal antibody purified from horse or rabbit immunized with human thymic lym
phocytes which binds to T-lymphocyte and depletes them.

IMMUNOSTIMULANTS
 An immostimulant is defines as a chemical, drug that ennhnces the innate or non-specific imuune
response by interacting directly with cells of the system activating them.
 Specific immunostimulant are those which improve specific immune response.
Eg. : vaccines or any antigen.
 Non-specific immunostimulant are those which help general immune response.
Eg. : immunoglobulins.
LEVAMISOLE
 Levamisole is an antihelmintics chemical compound used to treat the nematodes
infection.
 Levamisole enhanced the phagocytic activity, the NBT reaction and increase antibody
producing cells.
 Oral administration of levamisole increased the number of leucocyte, lysozyme
activity in serum and the stimulate NBT reduction and the phagocytic cells.
THALIDOMIDE
 Rheumatoid arthritis, Lepra reaction and multiple myeloma.
 Suppress TNF  production
 Inhibit leukocyte chemotaxis into site of administration.
 Reduces phagocytosis and polymorphonuclear leukocyte
 Enhances mononuclear cell production of cytokines like IL-2, IL-10 and inhibit IL-6
and IL-12 production.
BCG VACCINES
 Carcinoma in situ of the urinany bladder.
 Live, attenuated culture of BCG strain of Mycobacterium Bovis.
 It causes activation of macrophages to make them more effective killer cells.
Therapeutic uses
 Treatment and prophylaxis of carcinoma of the urinary bladder, Prophylaxis of primary and
recurrent stage of papillary tumors after transurethral resection.
Adverse effect
 Hypersensitivity, Shock and Immune complex disease.
INTERFERONS
 Hairy cell leukemia, Malignant melanoma, AIDS - related Kaposis sar coma.
 Interferon  - Used in antivirus drugs (HBV, HCV, HHV-8, HTLV-2)
 Interferon  - Used in multiple sclerosis.
 Interferon  - Used in chronic granulomatous D.

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24 DRUGS ACTING ON
SKIN AND MUCOUS
MEMBRANE
DEMULCENTS - Inert substance which sooth skin by preventing contact with air.
Eg : Gum acacia, Tragacanth, Methyl celluluse, Glycene etc.
EMOLIENTS - Bland oily substance, restres elasticity of cracked and dry skin.
Eg : Vegetable oil, Animal product, Petroleum product.
ADSORBENT - Finely powdered, inert and insoluble solid capable of binding to their adsorbing
noxious and imitant substance.
PROTECTIVES - Affort physical protection to skin or mucosa.
CLASS CHEMICAL NAME & USE
Talc Magnesium Silicate
Bentonite Aluminium Silicate
Zinc oxide Ingredient of calamine lotion
Starch Used in dusting powder and for surgical gloves
Boric acid Antiprunitic, Deodrant action
Collodian (Pyroxylon) Nitrated cellulose ,used as dressing on cut
Dimethicone Silicon polymer, Coat ulcer
Sucralfate Aluminium salt of sulfated sucrose
ASTRINGANT -
 These are the substance which precipitate protein.
 Drugs are - Tannins Alcohol
IRRITANT : Stimulate sensory nerve ending .
VESICANTS : Increase capillary permeability & collect fluid under epidemis.
RUBIFACIENTS : Cause local hypermia.
Eg :Terpentine oil, Clove oil, Capsicum,
 Mustard oil.
 Contain glycoside - Sirigrin.
 Enzyme - Myrosin
 Cantherids - Obtained from spanish fly
 Methylsalicylate - Oil of wintergreen.
Caustics (Corrosive) and Eschanotics (Cauterizer)
 These chemicals cause local tissue destruction and sloughing.
 Use to remove mole, papilloma.
Eg :Podophyllum resin silver nitrate, phenol etc.

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Anti-Seborrheics
 Drugs effective in seborrheic darmatitis which affects area rich in sebaceous glands.
 Dandruff is caused by yeast Pityrrosporum ovale
 Antidandruff agent - Selenium, Zinc Pyrithime, Ketoconazole.
MELANIZING AGENTS
 Increases sensitivity to solar radiation and promote repigmentation.
Eg : Psoralin, Methoxsalen, Trioxsalen etc.
DEMELANIZING AGENT
 Lighten hyperpigmented patch on skin.
Eg : Hydroquinone, Azelic acid etc.
SUNSCREENS
 Protect the skin from harmful effect of exposure to sunlight.
Eg : Tio2, Zno, Calamine etc.
CHEMICAL SUNSCREEN
  They absorb and scatter UV rays that are responsible for sunburn and phototoxicity, but
allow longer wavelength to penetrate, so that tannin occurs.
Eg : Para-aminobenzoic acid and its esters, Benzophenones, Cinnamates
PHYSICAL SUNSCREEN
  Heavy petroleum jelly, Titanium dioxide, zinc oxide and Calamine that stop and scatter not
only UV but also visible light.
  They are also called “sun shades”

DRUGS FOR ACNE

  Acne vulgaris is a skin condition that occurs when hair follicles are blocked with dead
skin cells, bacteria, and oil (sebum).
  The blocked follicles cause blemishes on the skin, including pimples, blackheads,
whiteheads, and cysts.
CLASS SUBCLASS DRUGS
Topical Antimicrobial Benzoyl peroxide, Erythromycin, Clindamycin,
Nadifloxacin
Retinoids Tretinoin, Adapalene, Tazarotene
Systemic Antibiotics Doxycycline, Minocycline, Erythromycin
Retinoids Isotretinoin

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25 ANTISEPTICS AND
DISINFECTANTS

STERILIZATION - It is the destruction of all micro-organism including spores.

GERMICIDES
 It is an agent used to kill micro-organism but not spores. It includes disinfectant and
antiseptics.
Germicides

Antiseptics Disinfectant
ANTISEPTIC
 It is an agent used to eliminate micro oraganisum or living tissues.
 These are chemical substance which inhibit the growth or kill of micro-organism on
living surface such as skin and mucous membrane.
DISINFECTANT
 It is an agent used to eliminate micro organisum or inanimate ojects.
 Destruction or inhibition of growth of all pathogenic organism (Bacteria, Viruses, Fungi)
on non-living surface.

CLASSIFICATION
Mnemonics “PHARMA GOD”
CHEMICAL CLASS DRUGS
Phenols and related agents Phenol, Cresol, Chlorhexidine, Resorcinol, Chloroxylenol
Halogens Chlorine, Iodine, Iodophores
Alcohols Ethyl alcohol, Isopropyl alcohol
Aldehydes Formaldehyde Glutaraldehyde
Surface active agents Common soap, Cetrimide, Benzal Konium Chloride
(Detergents)
Metallic Salts Silver nitrate, Zinc oxide
Miscellaneous Nitrofurazone
Acids Benzoic acid, Boric acids
Gases Ethylene oxide & P-Propionlactone
Oxidizing agents Hydrogen Peroxide & Potassium Permanganate
Dyes Gentian violet, Brilliant green & Methylene blue
CRESOL
 Methyl derivative of phenol, less damaging to tissue than phenol
 3-10 times more active
 Used to disinfectant of utensils, excreta and for washing hands.
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PHENOL (CARBOLIC ACID)

 One of the earliest used antiseptics and still the standard for comparing other germicides.
 Weak agent’s static at -0.2% bactericidal at >1%
 It is act by denatured protein (irritant/toxic to tissue)
 The antibacterial activity of phenols is increased by increasing the temperature. [GPAT-13]
Uses
Disinfectant of urine, Pus, Faces.
CHLOROXYLENOL (DETTOL)
 It is a phenol derivative, Chloroxylenol - Active ingredient of dettol
 Does not coagulate proteins, Non corrosive, Non irritating to skin
 Commercially 4.8% solution used for surgical antiseptic
 Skin cream and soap 0.8% used.
CETRIMIDE
 It is a quaternary ammonium antiseptics
 Widely used as antiseptic and disinfectant for surgical instrument gloves etc.
SOAP
 Weak antiseptic with cleansing action
 Effect only in gram positive bacteria.
ALCOHOLS
ETHANOL
 Antiseptic, Cleansing agent at 40-90% concentration.
 Act by precipitating bacterial proteins
ALDEHYDES
FORMALDEHYDE
 Used for fumigation, 40% aqueous solution called as formalin.
 Use as antiseptic restricted due to bad odour and irritation
IODINE
 Rapidly acting broad spectrum (Bacteria, Fungi and Viruses)
 Iodine tincutre - 2% iodine in alcohol
 Lugol iodine - Contain 5% iodine in 10% solution of pottassium iodine.
 Act by iodinating and oxidizing microbial protoplasm.
ECTOPARASITICIDES
 These are drugs used to kill parasite that live on body surfaces.
 Lice - Cause pediculosis (hair infection)
 Mites – Cause scabies (skin infection)
POINT TO REMEMBERS
 Mandal paints - Contain 125% iodine and 25% of potassium iodide in peppermint oil and
90% alcohol in glycerin.
 Red blood vessels is used to identify the strength of antiseptic and disinfectant (Phenol]
[GATE-90]

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26 CHELATING
AGENTS
 These are the drugs used to prevent heavy metal poisoning
Examples
 Dimercaprol (BAL)
 Disodium edetate
 Calcium disodium edetate
 Calcium disodium DTPA
 Penicillamine
 Desferrioxamine
 Deferiprone
DIMERCAPROL (BRITISH ANTILEWISITE, BAL)
 Developed during World War II by Britishers as an antidote to the arsenical war gas lewisite.
 Used for As, Hg, Au, Bi, Ni, Sb poisoning.
DISODIUM EDETATE
 It is a disodium salt of EDTA.
 Potent chelator of calcium.
CALCIUM DISODIUM EDETATE
 Higher affinity for metals like Pb, Zn, Cd, Mn, Cu and some radioactive metals.
 Used for lead poisoning and also used in Fe, Zn, Cu,Mn and radioactive metal.
 Not used in Hg poisoning because Hg is more firmly bound to body constituents.
PENICILLAMINE
 Used for Wilson’s disease.
 It is used in cystinuria, scleroderma and as an adjuvant to CaNa2 EDTA in lead poisoning
and to BAL in mercury poisoning.
 Penicillamine is the drug of choice for copper poisoning.
DESFERRIOXAMINE
 Chemical removal of iron from ferrioxamine yields desferrioxamine and it has very high
affinity for iron.
 It causes histamine release, fall in BP, flushing, itching, urticaria, rashes.
 Desferrioxamine is given only by parenteral route and it is the drug of choice for acute
iron poisoning.
 Ferrioxamine obtained from actinomycete, long chain iron poisoning containing complexes.
 Hypovolemic shock due to histamine release.

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DEFERIPRONE
 It is an orally active iron chelator.
 Used for the treatment of transfusion siderosis in thalassemia patients.
 Defepirone and deferasirox are given by oral route only and defepiron is used drug of
choice for chronic iron overload
 In arsenic poisoning, dimercaprol is injected intramusculary, to act as antidote by forming
metal complex. (GPAT-12)
 EDTA acts as an antidote in lead poisoning, by solubilizing the toxic metal ions from the
tissues. (GPAT-12)

DRUG USED IN POISONING

DRUGS USES IN POISONING

Dimercaprol (BAL) Pb, Hg, As, Au (contraindicated in Fe and Cd
poisoning)
Diethylenetriamine penta Urenium, Plutonium
acetic acid (DPTA)
Calcium disodium, EDTA Pb, Hg, Zn, Cd, Fe, Mn
D-penicillamine Pb, Hg, Cu (GPAT-13), Wilson disease, cystinuria,
scleroderma
Unithiol Pb, Hg, As,
Deferoxamine Fe
Defepirone, Deferasirox Fe
(oral)
Succimer Pb, Hg, As, Cd,
Dicobalt EDTA Cyanide
Trientine Cu

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27 VACCINES AND
SERA

INTRODUCTION
 Vaccines, sera and immunoglobulins are biological products which act by reinforcing the
immunological defense of the body against foreign agencies.
 Immunization is the process where by a person is made immune or resistance to an
infectious disease, typically by the administration of a vaccines
VACCINES
 Impact active immunity - Act as atigen.
 Antisera and immunological impart immunity - Readymade antibody.
 Vaccines are only prophylactic (Prevention of disease) Antisera (Curative)
 Vaccines are antigenic material consisting of the whole micro organism as one of its
products.

VACCINES ARE OF THREE TYPES

CLASS SUB CLASS DRUGS

Bacterial Typhoid-paratyphoid, Cholera, Wooping cough,
Killed
Haemophilus influenzae type B, Plague
(Inactivated)
Viral Poliomyelitis inactiavated, Rabies, Influenza,
vaccines
Hepatitis A, Hepatitis B
Bacterial BCG, Typhoid Ty 21a
Live attenuated
Viral Poliomyelitis oral vaccine (Sabin), Mumps, Measles,
vaccines
Rubella, Varicella
Toxoids Tetanus, Diphtheria.

DIFFERENCE BETWEEN LIVE ATTENUATED & KILLED VACCINES

LIVE ATTENUATED KILLED VACCINES

Usually single dose is sufficient Repeated dose is required
Produces long lasting immunity Produce short lasting immunity
More efficacious Less efficacious
Less Stable at room temp. More stable at room temp.

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BACTERIAL VACCINES
Live attenuated Vaccines : Bacillus-calmette geurin (BCG) Typhoid - Ty 21a (oral)
Killed Vaccines : Typhoid-paratyphoid (TAB Vaccine) Cholera, whoopingcough, Plagne
Haemophilus influenza typed.
CHOLERA VACCINES
 It is a suspension of phenol / formalation killed Inaba and ogawa strans of v-cholera.
BACILLUS CALMETTE GUERIN (BCG) VACCINES
 It is a live vaccine beaning an attenuate brovine serum of m.tuberculosis.
 BCG vaccines has also been used to enhance Immunity run specifically by stimulating the
reticuloend thelid system.
VIRAL VACCINES
 Live attenuated : Poliomyelitis oral live (sabin), Mumps,Measles,Rubella, and vericella.
 Killed vaccines : Poliomyelitis inactivated (Salk),Rabies,Influenza, Hepatitis A&B.
POLIOMYELITIS
The Virus grown or monkey kidney cell culture.
(a) Oral Polio vaccine (Sabine vaccine)
(b) Killed Polio vaccine (Salk vaccines)
RABIES
(a) Antirabatic vaccine combolized -
 It is 5% suspension of sheep brown can containing carbolic acid.
(b) Purified chick embryo cell vaccine (PCEV).
(c) Human diploid cell vaccines (HDCV).
 It is hyphilised inactivated rabies virus grown in human diploid cell culture .
HEPATITIS B VACCINES
 New hepatitis B vaccine is prepared in yeast cell by recombinend DNA technique and contants
 Al(OH)3 adsurb hepatitis B virus surface antigen 20mg in 1ml.
HEPATITIS A VACCINES
 Prepaned by inactivating with formaldehyde hepatitis A virus grown in human diploid cell
culture .
MUMPS
 Prepared from mumps virus grown in cell culture of chick embryo.
MEASLES
 Vaccines grown or chick embryo.
TOXOIDS VACCINES
 Tetanus and Diphtheria .
COMBINED VACCINES
 Double antiger (DT-DA)
 Triple antiger (DPT)
 Typhoid Paratyphoid cholera (TABC)
 Measles, Mumps, Rubella (MMR).

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GENE THERAPY

INTRODUCTION
 Gene therapy is the introduction of genes into existing cells to prevent or cure a wide range
of disease.
 It is technique for correcting defective genes responsible for disease development.
 The first approved gene therapy experiment occurred on 14-september, 1990 in US, When
Ashanti Desliva was treated for ADA-SCID.
 Gene therapy refuse to introduction of functional genetic material in to target cell to replace or
supplement defective genes or to modify target cell so as to achive the therapentic goal.
[GATE-07]

TYPES OF GENE THERAPY

SOMATIC CELL GENE THERAPY GERM CELL GENE THERAPY

Therapeutic genes transferred into Therapeutic genes transferred into germ
somatic cells cells
Will not be inherited later generation It is heritable and passed on to later
generation
At present all researchers directed to For safety, Ethical and technical reasons,
correct genetic defect in somatic cells It is not being attempted at present

APPROACHES IN GENE THERAPY

IN-VIVO GENE THERAPY
 Direct delivery of genes into the cells of a particular tissue in the body.
 Carried out by viral and non viral vector system.
 It can be the only possible option in patient’s where individuals cells cannot be cultured in
vitro in sufficient numbers (Brain cells)
Example of in vivo gene therapy (Cystic fibrosis)
 In pateint with cystic fibrosis, a protein called cystic fibrosis transmembrane regulator
(CFTR) is absent due to a gene defect
 Treated by in vitro replacement of defective gene by adenovirus vector.
EX VIVO GENE THERAPY
 Transfer of genes to cultured cells and reinsertion.
Isolate cells with genetic defects from a patient

Grow the cells in culture

Introduce the therapeutic genes

Select genetically corrected cells and grow

Transplant the modified cells to the patient.

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Example of ex vivo gene therapy (Cystic fibrosis)

 First gene therapy to correct deficiency of enzyme, Adenosine deaminase (ADA) Performed
in Ashanti Desliva was suffering from severe combined immunodeficiency (SCID)
Causes due to defect in gene coding for ADA

VECTOR IN GENE THERAPY

 To transfer the desired gene into a target cell, a carrier is required. Such vehicle of gene
delivery are known as vectors
VECTORS ARE TWO TYPES
Viral vector
 Retrovirus vectors system
 Target diving cell
 Adenosine virus vectors system
 Target Non-diving cells
 Adenosine associated vectors system
 Herpex simplex vectors system
Non-viral vectors
 Pure DNA obstructs
 Lipoplexes
 DNA molecular chromosomes

METHODS OF GENE THERAPY

PHYSICAL METHOD
Gene Gun
 Employs a high-pressure delivery system to shoot tissue with gold or tungsten particles
that are coated with DNA.
Microinjection
 Process of using a glass micropipette to insert microscopic substance into a single living
cell.
CHEMICAL METHODS
Using detergent mixtures
 Certain charged chemical compounds like calcium phosphate are mixed with functional
cDNA of desired function.
Lipofection
 Liposomes are artificial phospholipid vesicles used to deliver a variety of molecules
including DNA into the cells
APPLICATION
 Cystic fibrosis, Growth harmone deficiency
 Diabetes mellitus, Treatment of cancer and AIDS
 Gene discovery, Gene therapy and vaccines development

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