BASIC CONCEPTS IN PHARMACOLOGY

PHARMACOLOGY
Pharmacology is the study of drugs and its origin, 2. Brand name or trade name:
chemical structure, preparation, name given by the manufacturer of the drug
administration, action, metabolism and excretion. e.g. Adol or Panadol or Biogesic
The study of drugs that alter functions of living 3. Chemical name
organisms. name that describes the atomic or chemical structure.

PHARMACY – art of preparing, compounding, and

SOURCES OF DRUGS:
dispensing drugs. It also refers to the place
where drugs are prepared and dispensed 1. Natural sources -
PHARMACIST – a person licensed to prepare and a. Plants
dispense drugs to make up prescriptions. → One of the oldest forms of health care, herbal
medicine has been practiced in virtually every culture
dating to antiquity.
HISTORY OF PHARMACOLOGY
→ The Babylonians recorded the earliest surviving
Babylonians “prescriptions” on day tablets in
→ Earliest surviving “prescriptions” on clay tablets in 3000 B.C.
3000 B.C. → The Chinese recorded the Pen Tsao (Great
Chinese Herbal), a 40-volume compendium of plant remedies
dating to 2700 B.C.
→ Recorded the Pen Tsao (Great Herbal) – a 40-
→ The Egyptians followed in 1500 B.C. by archiving
volume compendium of plant remedies dating to
their remedies on a document known as Eber’s
2700 B.C. Papyrus.
Egyptians e.g morphine, colchicine, cocaine - At that time, chemists
→ Archives of remedies on a document known as were making remarkable progress, isolating specific
Erb’s Papyrus in 1500 B.C. substances from complex mixtures, this enabled scientists
Pharmacologia sen Manuductio and Materia to isolate the active agents from scarce natural sources,
Medicum ex. morphine.
→ First recorded reference to the word Cocaine from - cocoa leaves
pharmacology
Early 1800s b. Animals - Biologic - are agents naturally produced
→ Chemists isolates specific substances from in animal cell, by microorganisms, or by the body
itself.
complex mixtures
e.g. hormones, monoclonal antibodies, natural blood
→ Pharmacologists then study their effects in animals
products,
→ Fredrich Serturner (first isolated morphine from Interferons and vaccines.
opium, injected himself and three other friends others.
with huge doses (100mg))
DRUGS DRUG USES SPECIES
→ are chemicals that alter physiochemical processes Crestor High Rats, Rabbits,
in body cells. cholesterol Dogs
→ They can stimulate or inhibit normal cellular Diovan High blood Rats, Rabbits
functions. pressure
→ Used interchangeably with medicines. Lantus Type 1 & 2 Dogs, guinea
Diabetes pigs
DRUG NAMES
1. Generic or Nonproprietary Name: 2. Inorganic compounds
e.g. Lithium carbonate
name approved by the Medical or Pharmaceutical Cisplatin
Associations in the original country of manufacture
and is adopted by all countries. 3. Synthetic
e.g Ecstasy or Molly - stimulants that mimic the effect of
e.g. Paracetamol cocaine
 DRUG EVALUATION
→ a series of scientific tests to evaluate the actual
therapeutic and toxic effects of chemicals

STEPS:
PRECLINICAL TRIAL
→ testing done on laboratory performed in animals
→ tests efficacy and toxicity, at different doses, it
predicts whether the drug will cause harm to
humans. 2. CAPSULE
→ do not always reflect the way a human respond, a. soft gel
testing may overestimate or underestimate
the actual risk to humans.

ORPHAN DRUGS
→ are chemicals that are discarded Phase I
→ will not participate in the next phase
Criteria:
→ lack therapeutic activity in humans
→ too toxic
→ produce unacceptable side effects
→ teratogenic
PHASE II b. hard gel
→ chemicals cleared for limited clinical studies
→ some may not further proceed with the evaluation
due to the following criteria
→ less effective than expected
→ are too toxic
→ produce unacceptable side effects
→ have a low benefit-to-risk ratio
→ are not as effective as available drugs
PHASE III
→ chemicals cleared for large-scale clinical studies
→ some chemicals may not advance further in the
next phase due to the following criteria:
3. LOZENGES
→ produce unacceptable side effects
→ produce unexpected responses
PHASE IV
→ drugs approved for marketing by FDA
→ continues evaluation

DOSAGE FORMS OF DRUGS

A. SOLID FORMS
1. TABLET :
a. scored.
b. layered.
4. SUPPOSITORY
c. enteric-coated.
d. chewable.
e. sustained release
B. LIQUID
FORMS:
1. SYRUP

C. TOPICAL FORMS
2. SUSPENSION 1. CREAM

2. OINTMENT

3. ELIXIR

3. LOTION

4. EMULSION
4. PATCH

5. GEL

5. INHALANTS
 PRINCIPLES OF DRUG ADMINISTRATION to administration
Medication orders may be prescribed by:
MEDICATIONS ➢ Physician
✓ Are substances administered for the diagnosis, ➢ Dentist
cure, treatment, or relief of symptom or ➢ Podiatrist
prevention of disease ➢ License health care provider such as advance
practice
PRACTICE GUIDELINES ➢ registered nurse
✓ RNs are responsible for own actions, illegible order ➢ With authority from the state to order medication
should be questioned or clarified ➢ Prescriptions:
✓ RNs should be knowledgeable about the  Component of drug order
medication  Date and time the order is written
✓ If the RN is uncertain about the calculation, ask  Drug name
another nurse to double check  Drug dosage
✓ What you prepare, you administer  Route of administration
 Frequency and duration of administration
✓ Do not leave medications at bedside
 Any special instructions for withholding or
✓ If the client vomits, report to charge nurse, MD, or
adjusting dosage based on
both.
nursing assessment, drug effectiveness, or
✓ When error is made, assess the patient first and laboratory result
report to MD immediately
 Physician or other health care provider
Correct identification of the patient:
signature or name if TO or VO
✓ ID band or ID bracelet (BEST: Kozier)  Signature of license practitioner taking TO or
✓ Ask the patient’s name VO
✓ Avoid: calling the client in NAME ➢ Categories of drug orders:
✓ May answer “YES” to the wrong name  Standing
 One-time
OBSERVE TEN RIGHTS  PRN
✓ Right Client  STAT
Right time – is the time at which the prescribed dose
✓ Right Medication
should be administered
✓ Right Dose
 Daily drug dosages are given at specified time
✓ Right Time during a day such as
✓ Right Route  Twice a day b.i.d
✓ Right Client Education  Three time a day t.i.d
✓ Right Documentation  Four times a day q.i.d.
✓ Right to Refuse  Every 6hrs q6h
✓ Right Assessment Right route – is necessary for adequate or
✓ Right Evaluation appropriate absorption
 Oral
Right client – can be measured by checking the  Sublingual
client identification bracelet by having and by  Buccal
having the client state her or his name  Inhalation
➢ Some client answer to any name or unable to  Topical
respond, soclient identification should verified  Inhalation
each time of medication  Instillation
administered  Suppository, etc.
➢ In the event of missing identification bracelet, Right assessment – requires the appropriate data be
the nurse collected before administration of drugs
must verify the client identity before any drug Right documentation – requires that the nurses
administration immediately record the appropriate information
Right drug – means that the client receives the drug about drug administered
that was prescribed, check at least three times prior
 Name of the drug ✓ Gauge: #25, #26, #27
 Dose ✓ Length: ⅜”, ⅝”, ½”
 Route ✓ Max cc: 0.1 to 0.2 ml
 Time and date Subcutaneous
 Nurse initial or signature ✓ SITE
Right to educate – requires that the client received ✓ Outer aspect of the upper arms
accurate and thorough information about
✓ Anterior thighs
the medication and how it relates to his or her
✓ Abdomen
situation
• Client teaching also includes therapeutic purpose, ✓ Upper back
possible side effect of the drugs, any dietary ✓ Ventrogluteal
restriction or requirements skills administration, and ✓ Dorsogluteal
laboratory monitoring ✓ Angle: 45-degrees (1 inch of tissue can be grasped)
Right evaluation – requires that the effectiveness of 90-degrees (2 inches of tissue can be grasped)
the medication be determined by the client ✓ Gauge: #25, #26, #27
response to medication ✓ Length: ⅜”, ⅝”, ½”
Right to refuse – client can and do refuse to take ✓ Max cc: 1-3 ml
medication
• It is the nurses responsibilities to determine when Intramuscular
possible the reason for refusal and to take
✓ SITE
reasonable measure to facilitate the client taking the
✓ Ventrogluteal
medication
✓ > 1 y/o and adult
ORAL MEDICATION ✓ No large nerve or blood vessels
Most common route ✓ Sealed off by bone
Most common route ✓ Contains less fat than buttocks
✓ CONTRAINDICATIONS: ✓ Vastus Lateralis
Client is vomiting ✓ Site of choice for 1 y/o and younger
Client with intestinal or gastric suction ✓ Infants with fully developed gluteal muscles
Unconscious Client ✓ SITE
Inability to Swallow ✓ Dorsogluteal
✓ Tablet or Capsules
✓ For adults and children with well developed gluteal
✓ (+) difficulty in swallowing muscles
✓ Crush and mix with small amount of water ✓ CONTRAINDICATED:
✓ Avoid Crushing children under 3 y/o
✓ Enteric Coated ✓ Increased risk of striking the SCIATIC NERVE
✓ Buccal and Sublingual tablets ✓ DELTOID
✓ Liquid Medication ✓ Small muscle, very close to the radial nerve and
✓ Mix before pouring artery
✓ Place medication cup on flat surface at eye level ✓ Rapid absorption for adults
✓ Fill the cup with the desired level using the ✓ Cannot administer more than 1 ml.
BOTTOM of the meniscus ✓ Recommended site for Hepa B vaccine
administration
PARENTERAL MEDICATIONS ✓ RECTUS FEMORIS
✓ Can be used for self administration
Intradermal
✓ SITE
✓ Disadvantage: causes discomfort
✓ Inner lower arm
✓ Gauge: #24, 23, 22, 21, 20
✓ Upper chest
✓ Length: 1”, 1 1/2”, 2”
✓ Anterior chest
✓ Max. cc: 2-5 ml
✓ Upper back beneath the scapula
✓ Angle: 90 degrees
✓ Angle : almost parallel to the skin 10 - 15 degrees
✓ INTRAVENOUS/INTRAVASCULAR ✓ Instruction After:
✓ Gauge: #24, 23, 22, 21, 20 Remain in side-lying for 5 minutes
✓ Length: 1”, 1 ½”, 2”
✓ Max. cc: Push 10 ml
BRANCHES OF PHARMACOLOGY
Infusion: 4L in 24 hrs.
→ Pharmacodynamics - pharmaco means
“medicine” dynamic means “change”.
TOPICAL MEDICATIONS
Refers to how a medicine changes the body the
branch of pharmacology concerned with mechanisms
✓ Transdermal Patch
of drug action and the relationships between drug
✓ SITE
concentration and responses in the body.
✓ Trunk or lower abdomen → Pharmacokinetics - pharmaco means
Areas that are: hairless “medicine”, kinetic means “movement or
(+) hair (clip, do not shave) motion”. The study of drug movement throughout the
Avoid: cuts, burns, abrasions, distal extremity body. How the body deals with medications. Actions
and side effects of medications in patients.
OPTHALMIC MEDICATIONS → Pharmacognosy - the branch of knowledge
concerned with medicinal drugs obtained from plants
✓ Preparation: or other natural resources
✓ Clean the eyelid and lashes from inner to outer → Pharmacotherapeutics - the study of the
canthus therapeutic uses and effects of drugs.
✓ Instruction before administration Beneficial and adverse effects of drugs.
Look up → Pharmacovigilance - the practice of monitoring
the effects of medical drugs after they have been
✓ Where and How to Apply: licensed for use especially in order to identify and
LIQUID: evaluate previously unreported adverse reactions.
Instill correct number of drops → Toxicology - the branch of science concerned
Outer third of the lower conjunctival sac with the nature, effects, and
✓ Instruction after Instillation detection of poisons. The measurement and analysis
Do PUNCTAL OCCLUSION for 30 seconds of potential toxins, intoxicating or banned substances,
OINTMENT: and prescription medications present in a person’s
Discard the first bead body.
Squeeze 2 cm on the lower conjunctival sac
✓ Instruction after Instillation DRUG ACTION
CLOSE but not SQUEEZE the eyelid Therapeutic effect
→ also referred as the DESIRED EFFECT (primary
OTIC MEDICATIONS effect intended)
✓ Preparation: Side effect
→ also referred as the SECONDARY EFFECT
✓ Clean the pinna and the meatus of the ear canal
(unintended effect)
✓ Warm the medication:
In between hands → ADVERSE EFFECT (severe side effects)
Place in warm water Drug Toxicity
✓ Straighten The Auditory Canal: → Deleterious effects of a drug resulting from over
Adult: (>3 y/o): Pull the Pinna UPWARD and
dosage, ingestion of external use drug, and
BACKWARD
accumulation on the blood stream
Child: (<3 y/o): Pull the Pinna DOWNWARD
and BACKWARD Drug Allergy
✓ INSTILL THE MEDICATION: → immunologic reaction to drug
Along the side of the canal Drug Tolerance
✓ ACTIONS AFTER: → exists in person with unusually low physiologic
Gently press the TRAGUS response to a drug
Insert small piece of cotton fluff loosely
 PHARMA INTRO KINETIC
Chemical name
PHARMACOLOGY
 (+/-)-2-(p-isobutylphenyl) propionic acid
→ Greek “pharmakon” drug and “ Logo”
Generic name
science
 ibuprofen
→ deals with study of drugs and their actions
Trade name
on living organism
 Motrin
→ Is the science which is concerned with the
history, sources, physical and chemical DRUG DEFINITION AS TO NOMENCLATURE
properties of the drugs as well as the ways
(CANADA)
in which drugs affect living system.

THERAPEUTIC METHODS Official Name

 Approaches to therapy  Any drug for which a standard is described
either specifically in the Food and Drug
 Drug therapy
Regulations or in any publications named in
 Diet therapy
the Food and Drug Act as satisfactory.
 Physiotherapy
Proper Name
 Psychological therapy
 Non proprietary (generic name) used to
Drug describe an official drug in Canada.
 Are chemical substances that have an effect on
living organism SOURCES OF DRUG STANDARDS
Therapeutic Drugs or Medicines United State Pharmacopeia (USP)
 Drugs used for the prevention or treatment of National Formulary(NF)
disease  Standardization – to ensure drug products
Prescription produce by different manufacturer, will be
 Written direction for the preparation and uniformly pure and potent
administration of drug. United state Adopted Name (USAN)
 USP Dictionary of USAN and International
PHARMACOLOGY Drug
Official Name
POSOLOGY
 The name after which the drug is listed in one
of the official publications (US Food and Drugs The study of dosage or amount of drugs given
Administration). in the treatment of diseases.
Chemical Name
 The name which describes the constituents of PHARMACIST
drugs precisely. A person licensed to prepare and dispensed
drugs.
Generic Name
 Common or non proprietary name DRUGS DEFINITION AS TO CLASSIFICATION
 The name given to a drug before it becomes
official.  As to the Body System they Affect
 Given by USAN  As to Therapeutic Use or Clinical Indication
Brand Name  As to Physiologic or Chemical Action
 trademark or proprietary name  As to Prescription or Non prescription drugs
 The name given to a drug by the manufacturer  Prescription Drugs
 Non Prescription Drugs or Over The
PHARMACOLOGIC PRINCIPLES: DRUG  Counter Drugs OTC
NAMES  Illegal or Recreational Drugs
 REGULATED DRUGS
Drugs with potential abuse decrease temp.
Definition of Terms:  Ex. Alcohol, sleeping pills
 Drug abuse  Stimulants
 excessive self administration of a drug that could  Increase alertness
result in  Flushing, dry mouth, inc HR, inc BP
addiction and that could be detrimental to the  Hallucinogens
individual’s  Hear, see , feel something that is not there
health  Lysergic acid diethylamide,MESCALINE
 Addiction
 drug seeking behavior in which the abuser is unable  Opiates
to  Relieves pain
control the desire for the drug  ex. Morphine, heroine,codeine
 Withdrawal  Consrict pupil
 physical effects resulting when drug is discontinued  Volatile solvents
in an  Ex. Rugby
individual who is addicted to a drug
PHARMACOLOGIC PRINCIPLES
 Physical dependence
 withdrawal of the drug produces physical effects  Pharmaceutics
on the individual.  Pharmacokinetics
 Psychological dependence(habituation)  Pharmacodynamics
 Intense desire or craving for the drug when it is  Pharmacotherapeutics
not available(no physical or withdrawal effects)  Pharmacognosy

CONTROLLED SUBSTANCE SCHEDULE

PHARMACEUTICS
 Schedule 1
 drugs with high abuse potential,no accepted medical  The study of how various drug forms influence
use. pharmacokinetic and pharmacodynamic activities
•mj,h
 Schedule II
 high potential for drug abuse,can lead to strong
physical and psychological dependency
• meperidine,Morphine,Amphetamine
 Schedule III
 medically-accepted drugs, potential abuse is less
than 1 & II.
•may cause dependence ex.codeine
 Schedule IV:
 medically-accepted drugs,may cause dependence
• diazepam,phenobarbital
 Schedule V:
 medically- accepted drugs
• Very limited potential for dependence
• Ex. Opioid-controlled substance for diarrhea or
cough,lomotil,robitussin

CLASSES OF DRUG ABUSE

 CNS Depressant
 Relieves anxiety and induce sleep,dilatepupils,
 Drug effect:
 The physiologic reaction of the body to the drug

Onset
 The time it takes for the drug to elicit a
therapeutic response
Peak
 The time it takes for a drug to reach its maximum
therapeutic response
Duration
 The time a drug concentration is sufficient to elicit
a therapeutic response

PHARMACOTHERAPEUTIC
 The use of drugs and the clinical indications for
PHARMACOKINETICS drugs to prevent and treat diseases
 The study of what the body does to the drug:  Is the study of how drugs may best be used in
 Absorption the treatment of disease, i.e. which drug would
 Distribution be most or at least appropriate to use for a
 Metabolism specific disorder, what dose of the drug would
 Excretion required

 Deals with the absorption, distribution, PHARMACOTHERAPEUTICS: MONITORING

biotransformation and excretion of drugs. Each  Therapeutic index
of these factors is related to the concentration  Drug concentration
of drug and/or its chemical byproducts in  Patient’s condition
various body sites as well as the time required  Tolerance and dependence
for these drug concentrations to develop and/or  Interactions
change.
 Side effects/adverse drug effects

Therapeutic Index
 The ratio between a drug’s therapeutic benefits
and its toxic effects
Therapeutic Index =

Interactions may occur with other drugs or food

 Drug interactions: the alteration of action of
a drug by:
 Other prescribed drugs
 Over-the-counter medications
PHARMACODYNAMICS  Herbal therapies
 The study of what the drug does to the body: PHARMACOGNOSY
 The mechanism of drug actions in living tissues
 Is the study of biochemical and physiological The study of natural (plant and animal) drug sources
effects of drugs as their mechanisms of action
SUBDIVISION OF PHARMACOLOGY
Drug actions:
 The cellular processes involved in the drug and Toxicology
cell interaction  Is the study of poisons and poisonings. Since
almost all drugs are capable of being toxic DRUG ABSORPTION OF VARIOUS
under some circumstances, toxicology is an
essential part of the study of all drugs.

PHARMACOKINETICS: ABSORPTION

 The rate at which a drug

leaves its site of
administration, and the
extent to which absorption
occurs.
 Bioavailability
 Bioequivalent
 The process by which a drug is transferred
from its site of entry into the body to the
circulating body fluid for distribution
 Rate depend on several factors
 Route of administration
 Blood flow through the tissue site of administration
 Solubility of the drug
 Note
 Administer oral drug with an adequate amount of
fluid
 Give parenteral form properly
 Reconstitute and dilute drug with recommended
diluent
 The rate at which adrug leaves its site of
administration, and the extent to which CATEGORIES OF DRUG ADMINISTRATION
absorption occurs. Bioavailability-fraction of  Enteral
administered drug that gains access to the  Oral, rectal, nasogastric
systemic circulation in a chemically unchanged form.  Must be dissolve in body fluids
 Conversion process involved if administrating drug
BIOAVAILABILITY with or
without meal
 Parenteral
 Subcutaneous (subQ), intramuscular (IM),
intravenous (IV)
 Rate of blood flow to the tissue
 Cooling the site of injection is afactor
 Percutaneous
 Inhalation, sublingual, topical
 Factors (topical)
 Drug concentration
 Length of drug contact time
Factors That Affect Absorption
 Hydration of tissue
 Administration route of the drug
 Degree of skin disruption
 Food or fluids administered with the drug
 Factors (inhalation)
 Dosage formulation
 Depth of inhalation
 Status of the absorptive surface
 Fineness of droplet particles
 Rate of blood flow to the small intestine
 Available surface area of mucous membrane
 Acidity of the stomach
 Contact time
 Status of GI motility
 Hydration
 Blood supply  Rectal* Intramuscular
 Concentration of drug  Intravenous Subcutaneous
 Intranasal Inhalation
*Rectal route undergoes a higher degree of first-
pass effects than the other routes listed.

The metabolism of a drug and its passage

from the liver into the circulation.
 A drug given via the oral route may be extensively
metabolized by the liver before reaching the
systemic circulation (high first-pass effect).
 The same drug—given IV—bypasses the liver,
preventing the first-pass effect from taking place, and
more drug reaches the circulation.

Parenteral Route
 Intravenous*
 Intramuscular
 Subcutaneous
 Intradermal
 Intrathecal
 Intraarticular
*Fastest delivery into the blood circulation
FIRST PASS EFFECT

Routes that bypass the liver:

 Sublingual Transdermal
 Buccal Vaginal
Topical Route  Barbiturates
 Skin (including transdermal patches)  Rifampin therapy
 Eyes
 Ears Delayed drug metabolism results in:
 Nose  Accumulation of drugs
 Lungs (inhalation)  Prolonged action of the effects of the drugs
 Vagina
Stimulating drug metabolism causes:
PHARMACOKINETICS DISTRIBUTION  Diminished pharmacologic effects
Refers to the way in which the drug are
transported by the circulating body fluids to the PHARMACOKINETICS EXCRETION
site of action (receptor), metabolism and
excretion  Elimination of drug metabolite and active drug
 Factors  Kidney and Bowel –major sites
 Chemical property of drug  Secretions from skin, lungs, mouth and breast
 Fat
 Protein PHARMACOKINETICS HALF-LIFE
 Affected by blood and tissue in contact
 The amount of time required for 50 % the drug
Chemical property of drug to be eliminated from the body
 Lipid soluble drugs  The measure of time required for elimination
 Protein binding drugs  Determined by an individual patient to
 GENERAL metabolized and excrete a particular drug
 SELECTIVE  Example:
 Digoxin 36 hrs
The transport of a drug in the body by the  Aspirin 5 hrs
bloodstream to its site of action.
 Protein-binding
 Water soluble vs. fat soluble
 Blood-brain barrier
 Areas of rapid distribution: heart, liver,
kidneys, brain
 Areas of slow distribution: muscle, skin, fat

PHARMACOKINETICS METABOLISM A.K.A

BIOTRANSFORMATION

 BIOTRANSFORMATION
 Is a process by which the body inactivates the
drug
 Primary site of metabolism= LIVER
 Other site WBC, GIT tract, Lungs

Factors that decrease metabolism:

 Cardiovascular dysfunction
 Renal insufficiency
 Starvation
 Obstructive jaundice
 Slow acetylator
 Erythromycin or ketoconazole drug therapy

Factors that increase metabolism:

 Fast acetylator
The biologic transformation of a drug into  A measure of the rate at which drugs are
an inactive metabolite, a more soluble compound, or removed from the body.
a more potent metabolite.
 Liver (main organ)
 Kidneys
 Lungs
 Plasma
Intestinal mucosa

The elimination of drugs from the body

 Kidneys (main organ)
 Liver
 Bowel
 Biliary excretion
 Enterohepatic circulation
Half-Life
 The time it takes for one half of the original
amount
of a drug in the body to be removed.

PHARMACODYNAMICS
Pharmacodynamics is the study of the effect of drugs If the ED50 and TD50 are close- drugs have a narrow
on the body. therapeutic index. require close monitoring to ensure
Drugs act within the body to mimic the actions of the patient safety.
body’s own chemical messengers. Dose-Response Onset – is the time it takes for a drug to reach the
Relationship is the body’s physiological response to minimum effective concentration (MEC) after
changes in drug concentration at the site of action. administration. Time from drug administration to first
Potency – refers to the amount of drug needed to observable effect (T0-T1)
elicit a specific physiologic response to a drug. Peak – occurs when it reaches its highest
Efficacy – magnitude of effect a drug can cause when concentration in the blood/plasma concentration. T0-
exerting its maximal effect. Maximal efficacy – the T2
point at which increasing a drug dosage no longer Duration of action – is the length of time the drug
increases the desired therapeutic response exerts a therapeutic effect. period from onset until the
drug effect is no longer seen. T1-T3
PARAMETERS OF DRUG ACTION
Therapeutic Index – (TI) describes the relationship Therapeutic Drug Monitoring
between the therapeutic dose of a drug (ED50) and Drug concentration can be determined by measuring
the toxic dose of a drug (TD50) peak and trough drug levels.
Therapeutic dose of a drug – is the dose of a drug peak – highest plasma concentration. 30 minutes
that produces a therapeutic response in 50% of the after infusion.
population. trough – lowest plasma concentration. 30 minutes
Toxic dose of a drug – is the dose that produces a prior to the next infusion. Theories of Drug Action
toxic response in 50% of the population
 Act by biophysical means that do not affect
cellular/enzymatic reactions. drugs do not bind to
receptors but instead saturate the water or lipid part
of a cell- drug actions occur based on the degree of
saturation. Neutralization of stomach acid by
antacids.

D. Selective Toxicity Specific

action on cellular structures that are unique to the
microbe. All chemotherapeutic agents would act only
in one enzyme system needed for life of a pathogen
or neoplastic cell. It is essential to the pathogen but
not to the host.

DRUG RESPONSE

Drug Response may be:

1.Primary- always desirable/physiologic effects
2.Secondary- desirable or undesirable Example:
THEORIES OF DRUG ACTION
Diphenhydramine (Benadryl)
A.Drug-Receptor Interaction Primary effect: antihistamine; treat symptoms of
Certain portion of drug molecule (active site) allergy
selectively combines with some molecular structure Secondary: Drowsiness
(reactive site) on the cell to produce a biologic effect
CLASSIFICATION OF DRUG ACTION
Receptor site- drugs act at specific areas on cell
membranes; react with certain chemicals to cause an 1.Rapid- few seconds to minutes
effect within the cell - IV, SL, Inhalations
2. Intermediate- 1-2 hours after administration
“Lock and Key Theory”- specific chemical (key) - IM, SC
approaches a cell membrane and finds fit (the lock) at 3. Delayed/Slow- several hours after administration
receptor site- affects enzyme system within cell- - Oral, rectal
produce certain effects. Drug+Receptor=Effect

B. Drug-Enzyme Interaction
Interferes with enzyme systems that act as catalyst
from various chemical reactions
If single step in one of enzyme system is blocked-
normal function is disrupted

C. Nonspecific Drug Interaction

 CATEGORIES OF DRUG ACTION
1.Stimulation/Depression has been previously exposed to the agent/ chemical
Stimulation- increased rate of cell activity/ secretion related compound
from the gland T3/T4 for hypothyroidism 3. Idiosyncratic Reaction
Depression- decreased cell activity and function of a Occurs when the patient is first exposed to the drug
specific organ. Iodine, propylthiouracil Abnormal reactivity to the drug caused by a genetic
2. Replacement- replaces essential body compounds difference between the patient and normal individual.
Example: Insulin a patient with G6PD deficiency will have anemia by
3. Inhibition/Killing of Organism ¡Interfere with using antioxidants.
bacterial cell growth ¡Example: Antibiotics 4. Toxicity
4. Irritation The degree to which a drug can be poisonous and
Example: Laxative- irritate the inner wall of colon--- thus harmful to the human body.
increased peristalsis--- increased defecation Drug- 5. Iatrogenic responses
Unintentional responses as a result of medical
Drug Interaction treatment Nephrotoxicity; ototoxicity
1.Additive Effect-2 drugs with similar actions are
taken for a doubled effect 1+1=2 Ibuprofen +
paracetamol= added analgesic effect Codeine with
acetaminophen = better pain control
2. Synergistic- combined effect of 2 drugs is greater
than the sum of the effect of each drug given alone;
1+1=3 Aspirin = 30% analgesic effect codeine – 30%
analgesic effect combination = 90% analgesic effect
3. Potentiation- a drug that has no effect enhances
the effects of the second drug 0+1=2 Alcohol
enhances the analgesic activity of aspirin. Prozac +
Zestril
4. Antagonistic- one drug inhibits the effect of
another drug 1+1=0 Tetracycline + antacid=
ADVERSE DRUG EFFECTS
decreased absorption of tetracycline
Charcoal in alkaloidal poisoning • is the body’s physiologic response to changes in
drug concentration at the site of action.
ADVERSE DRUG EFFECTS • Potency – refers to the amount of drug needed to
1.Side Effects elicit a specific physiologic response to a drug.
Results from the pharmacologic effects of the drug • Efficacy – magnitude of effect a drug can cause
Most common as a result of lack of specificity of when exerting its maximal effect.
action within the therapeutic range. • Maximal efficacy – the point at which increasing a
2. Allergic Reactions drugs dosage no longer increases the desired
Unpredictable adverse drug effects; more serious therapeutic response.
Response to patient’s immunological system to the
presence of the drug Do not occur unless the patient

PHARMADYNAMICS THERAPEUTIC
PHARMACODYNAMICS: MECHANISMS OF  Enzyme interaction
 Nonspecific interactions
ACTION
The ways by which drugs can produce therapeutic
effects:
 Once the drug is at the site of action, it can
modify the rate (increase or decrease) at which
the cells or tissues function.
 A drug cannot make a cell or tissue perform a
function it was not designed to perform.
 Receptor interaction
 DRUGS
 Drugs interact with biological systems in ways
that mimic, resemble or otherwise affect the
natural chemicals of the body.
 Drugs can produce effects by virtue of their acidic
or basic properties (e.g. antacids, protamine),
surfactant properties (amphotericin), ability to
denature proteins (astringents), osmotic
properties (laxatives, diuretics), or
physicochemical interactions with membrane
lipids (general and local anesthetics).

RECEPTORS
Most drugs combine (bind) with specific receptors
to produce a particular response. This association or
binding takes place by precise physicochemical and
steric interactions between specific groups of the
drug and the receptor.
I. Proteins
I. Carriers
II. Receptors
◼ G protein-linked
◼ Ligand gated channels
◼ Intracellular
III. Enzymes
II. DNA
 ENDOGENOUS COMPOUNDS ACT ON THEIR
RECEPTORS

TYPES OF RECEPTORS
MEMBRANE BOUND RECEPTORS
 G-Protein-linked receptors
Serotonin, Muscarinic, Dopaminergic, Noradrenergic
 Enzyme receptors
Tyrosine kinase
 Ligand-gated ion channel receptors
Nicotinic, GABA, glutamate
CLASSIFICATION OF RECEPTORS INTRACELLULAR AND NUCLEAR RECEPTORS
1) Pharmacological  Hormone receptors
Mediator (i.e. Insulin, Norepinephrine, estrogen)  Autocoid receptors
2) Biophysical and Biochemical  Growth factors receptors
Second messenger system (i,.e. cAMP, PLC, PLA)  Insulin receptors
3) Molecular or Structural
G PROTEIN-LINKED RECEPTORS
Subunit composition (i.e. 5-hydroxytryptamine
5HT1A )
4) Anatomical
Tissue (i.e muscle vsganglionicnAChRs)
Cellular (i.e. Membrane bound vs Intracellular)
 ENZYME-LIKE RECEPTORS

LIGAND-GATED ION-CHANNEL RECEPTORSC

NUCLEAR RECEPTORS

DRUG-RECEPTOR INTERACTION

Physicochemical and steric interactions

1) Lipophilic 1. Ions (Ca2+, Na+, K+, Cl-)
2) Hydrophilic 2. cAMP, cGMP, IP3, Diacylglycerol
3) Ionic 3. DNA binding – Transcriptional regulation.
4) Hydrogen bonds 4. Phosphorylated proteins and enzymes via
5) Steric (stereospecificity) effects tyrosine kinase receptors.
6) Electronic effect Third Messengers:
7) pK effects 1. Enzymes (Protein Kinase PKC, PKA)
2. Ions (Ca2+, K+)

RECEPTOR SIGNALING PATHWAYS

 Drug-receptor interactions serve as signals to

trigger a cascade of events. This cascade or
signaling pathway, is a collection of many cellular
responses which serve to amplify the signal and
produce a final effect.
 Effectors are thus the molecules that translate the
drug-receptor interaction into changes in cellular
activity.

DRUG-RECEPTOR INTERACTIONS
Theory and assumptions of drug-receptor
interactions.
 Drug Receptor interaction follows simple mass-
action relationships, i.e. only one drug molecule
RECEPTOR SIGNALING PATHWAYS occupies each receptor and binding is reversible
(We know now there are some exceptions).
Second Messengers:
  For a given drug the magnitude of the response is 
proportional to the fraction of total receptor sites Overresponse
occupied by drug molecules.  happens in patients inability to metabolized
 Combination or binding to receptor causes some the drug (genetic defect)
event which leads to a response. Allergic Reaction
 Response to a drug is graded or dose-dependent.  occurs to patient who has been previously
exposed to a drug and have developed
antibodies to it from the immune system
LAW OF MASS ACTION
Anaphylactic Reaction
When a drug (D) combines with a receptor (R), it  severe life threatening reaction that causes
does so at a rate which is dependent on the respiratory distress and cardiovascular
concentration of the drug and the concentration of collapse
the receptor. Carcinogenecity
 the ability of a drug to induced living cells to
D = drug mutate and became cancerous
R = receptor Teratogen
DR = drug-receptor complex  a drug that induced birth defect
k1 = rate forassociation
k2 = rate for dissociation Variable factors influencing drug action
KD = Dissociation Constant  Age
KA = Affinity Constant  Body Weight
 Metabolic Rate
 Illness
 Psychological Aspect
 Tolerance
 Dependence
 Cummulative Effect

Psychological Aspect
 Placebo effect
 patient’s positive expectation about
treatment and care received can
PHARMACODYNAMICS DRUG ACTION
positively affect the outcome
DESIRED ACTION  Placebo
 expected response  A drug dosage form with no
ADVERSE EFFECT OR SIDE EFFECT pharmacologic activity
 drugs have potential to affect more than one body  Nocebo Effect
system simultaneously producing a response  patient’s negative expectation about
ADVERSE DRUG REACTION (ADR) treatment and care received
 any noxious, unintended and undesired effect of a TOLERANCE
drug, which occurs at doses used in human  occurs when person begins to require a
prophylaxis, diagnosis and therapy (WHO) higher dosage to produce the same effects
 Predictable – had to be measured that a lower dosage once provided
 Parameter (therapeutic action, side effect, DEPENDENCE
adverse effect, drug interaction)  Addiction/ habituation, occurs when a person
 Most common reaction is unable to control the ingestion of drugs
 rash, nausea, itching, thrombocytopenia,  Physical and Psychological Dependence
vomiting, hyperglycemia and diarrhea
 Class of medicine with large account Cumulative Effect
 Antibiotics, cardiovascular drug, chemotherapy  A drug may accumulate in the body if the next
drugs, analgesics and anti-inflammatory dose is administered before the previously
Idiosyncratic Reaction administered dose has been metabolized or
 occurs when something unusual or abnormal excreted.
happens when drug is first administered  Excessive Drug Accumulation may result to Toxicity
 PHARMACODYNAMICS DRUG INTERACTION  Absence of enzyme needed for HYDROLYSIS
 Intestinal Transit
Categories of Drug Interaction altering:
 Absorption Gender consideration
 Distribution  Slower Gastric emtying
 Metabolism  Greater gastric acidity
 Excretion  Lower gastric enzyme (alcohol
dehydrogenase)
Additive Effect  Body weight
 Two drug with similar action are taken for a
doubled effect DRUG ACTION ACROSS THE LIFE SPAN
Synergistic Effect
DISTRIBUTION
 Combined effect of two drugs are greater than the
sum of the effect of each drug given alone Factors
Antagonistic Effect  ph
 One drug interfere with the action of another  body water concentration,
Displacement  quantity fat tissues,
 Displacement of the first drug by a second drug  protein binding
increases the activity of the first drug  cardiac output
Interference  regional blood flow
 First drug inhibits the metabolism or excretion of
the second drug, causing increase activity of the DRUG ACTION ACROSS THE LIFE SPAN
second drug. METABOLISM
Incompatibility
 The first drug is chemically incompatible with the Factors
second drug, causing deterioration when both  Genes
drug are mixed in the same syringe or solution  Diet
 Age
DRUG ACTION ACROSS THE LIFE SPAN  Maturity of enzyme system
Gender
Gender- specific  CYP3A4 component of of cytochrome p450
 Study of the difference in the normal function (erythro, predn, verapamil and diazepam)
of men and women and how each sex
perceive and experience disease
Pharmacogenetics
 Study how drug response may vary according
to inherited differences in drug metabolism
Polymorphism
 Naturally occuring variation in the structure
of gene and product
DRUG ACTION ACROSS THE LIFE SPAN
ABSORPTION
Age consideration
 Medications
◼ Topical
◼ Transdermal
◼ Enteric tablet/ capsule/ chewable tablets
 GI absorption
 Passive diffusion
◼ Drug destroyed by gastric (ampicillin and
penicillin)
◼ Acidic environment(phenobarbital and
acetaminophen)
 DRUG ACTION ACROSS THE LIFE SPAN
EXCRETION  Maintenance therapy
 Supplemental therapy
Factors  Palliative therapy
 Genes  Supportive therapy
 Diet  Prophylactic therapy
 Age
 Maturity of enzyme system
Gender PHARMACOTHERAPEUTICS: MONITORING
 CYP3A4 component of of cytochrome p450
(erythro, predn, verapamil and diazepam)  The effectiveness of the drug therapy must be
evaluated.
 One must be familiar with the drug’s
 intended therapeutic action (beneficial)
 and the drug’s unintended but potential side
effects (predictable, adverse drug reactions).
 Therapeutic index
 Drug concentration
 Patient’s condition
 Tolerance and dependence
 Interactions
 Side effects/adverse drug effects

Therapeutic Index
 The ratio between a drug’s therapeutic
benefits
and its toxic effects

Therapeutic Index = TxD50

AGE ED50
 15% premature Interactions may occur with other drugs or food
 35% term  Drug interactions: the alteration of action of
 50% 4wks a drug by:
 100% 9-12 months  Other prescribed drugs
 Over-the-counter medications
DRUG ACTION ACROSS THE LIFE SPAN  Herbal therapies
THERAPEUTIC DRUG MONITORING
Interactions
 Blood , saliva, urine  Additive effect
 Epilepsy, arrythmia, heart failure and  Synergistic effect
antimibrobial  Antagonistic effect
 Timing  Incompatibility

PHARMACOTHERAPEUTIC Medication Misadventures

Adverse drug events
Pharmacotherapeutics  ALL are preventable
 The use of drugs and the clinical indications for  Medication errors that result in patient harm
drugs to prevent and treat diseases
 Is the study of how drugs may best be used in Adverse drug reactions
the treatment of disease, i.e. which drug would  Inherent, not preventable event occurring in
be most or at least appropriate to use for a the normal therapeutic use of a drug
specific disorder, what dose of the drug would  Any reaction that is unexpected, undesirable,
required and occurs at doses normally used
TYPES OF THERAPIES
 Acute therapy
Some adverse drug reactions are classified as side  Pathology
effects.  Drug may aggravate underlying pathology
 Expected, well-known reactions that result in  Hepatic disease may slow drug metabolism
little  Renal disease may slow drug elimination
or no change in patient management  Acid/base abnormalities may change drug
 Predictable frequency absorption or elimination
 The effect’s intensity and occurrence is
related to INFLUENCING FACTORS
the size of the dose
 Genetic effects
Adverse Drug Reaction  Lack of specific enzymes
An undesirable response to drug therapy  Lower metabolic rate
 Idiosyncratic  Psychological factors
 Hypersensitivity reactions  Placebo effect
 Drug interactions
PEDIATRIC PATIENTS

FACTORS ALTERING DRUG RESPONSES  Higher proportion of water

 Lower plasma protein levels
 Age  More available drug
 Pediatric or geriatric  Immature liver/kidneys
 Immature or decreased hepatic, renal  Liver often metabolizes more slowly
function  Kidneys may excrete more slowly
 Weight
 Big patients “spread” drug over larger
GERIATRIC PATIENTS
volume
 Gender  Chronic disease states
 Difference in sizes  Decreased plasma protein binding
 Difference in fat/water distribution  Slower metabolism
 Environment  Slower excretion
 Heat or cold  Dietary deficiencies
 Presence or real or perceived threats  Use of multiple medications
 Fever  Lack of compliance
 Shock

PHARMACOKINETICS

PHARMACOKINETICS is the process of drug disintegration, disaggregation and dissolution. A

movement throughout the body that is necessary to limiting factor in the adsorption of pharmaceutical
achieve drug action. drugs is the degree to which they are ionized, as cell
Processes: membranes are relatively impermeable to ionized
1. Liberation molecules. The characteristics of a medication's
2. Absorption excipient play a fundamental role in creating a
3. Distribution suitable environment for the correct absorption of a
4. Metabolism – biotransformation drug. This can mean that the same dose of a drug in
5. Excretion - elimination different forms can have different bioequivalence, as
they yield different plasma concentrations and
1. LIBERATION therefore have different therapeutic effects. Dosage
is the first step in the process by which medication forms with modified release (such as delayed or
enters the body and liberates the active ingredient extended release) allow this difference to be usefully
that has been administered. The pharmaceutical drug applied.
must separate from the vehicle or the excipient that it
was mixed with during manufacture. Some authors
split the process of liberation into three steps:
2. ABSORPTION
is the movement of the drug into the bloodstream
after administration. 80% of drugs are taken by
mouth – enteral. Movement of drug molecules from
site of administration to circulatory system

FACTORS AFFECTING DISTRIBUTION

1. Size of the organ
2. Blood flow
3. Solubility- lipid soluble drugs can also cross the
blood-brain barrier and enter the brain.

4. METABOLISM
or biotransformation is the process by which the body
chemically changes drugs into a form that can be
excreted. First-pass effect or first-pass metabolism GI
tract --- intestinal lumen -- liver---some drugs are
metabolized to an inactive form and excreted---
reduced amount of active drug liver enzymes –
cytochrome P450 system – convert drugs to
metabolites. decreased drug metabolism rate will
Movement of drug particles from GIT to body fluids result in excess drug accumulation that can lead to
involve 3 processes: toxicity. Drug half-life is the time it takes for the
1. Passive transport amount of drug in the body to be reduced by half.
Diffusion – drugs move across the cell membrane
from an area of higher concentration to one of lower Example:
concentration. Ibuprofen has a half life of about 2 hours.
2. Facilitated diffusion –Active transport – requires a if the patient takes 200 mg, in 2 hours, 50% of the
carrier such as enzyme or protein to move the drug drug will be gone, leaving 100 mg.
against a concentration gradient. Energy is required. after 2 hours - 50 mg.
3. Pinocytosis – is the process by which cells carry a after 2 hours – 25 mg
drug across their membrane by engulfing the drug after 2 hours – 12.5 mg
particles in a vesicle. after 2 hours – 6.25 mg

FACTORS AFFECTING DRUG ABSORPTION By knowing the half-life, the time it takes for a drug to
reach a steady state (plateau drug level) can be
Drug solubility – lipid soluble drugs pass readily determined. it can be achieved when the amount of
through GI membrane, water- soluble drugs need an drug being administered is the same as the amount of
enzyme or protein drug being eliminated. a steady state of drug
Local condition at site of absorption- weak acids less concentration is necessary to achieve optimal
ionized in stomach --Readily pass through the small therapeutic benefit.
intestine.
Pain/stress/solid foods/fatty or hot foods- slows Half-life/ Elimination half-life (t ½)- time it takes for
down gastric emptying time one half of drug concentration to be eliminated Short
t1/2= 4-8hrs: given several times a day (ex. Penicillin
3. DISTRIBUTION G)
process by which drug becomes available to body Long t ½ = >12 hours: given 2x or 1x/day (Ex.
fluids and tissues. is the movement of the drug from Digoxin)
the circulation to body tissues.
Other Sites of Metabolism Routes:
1. Plasma Kidney- main organ for drug elimination: leave the
2. Kidneys body through urine Free or/unbound/water soluble
3. Membranes of intestines drugs- filtered in the kidney (+) kidney disease- dose
must be decreased. kidneys – main route of drug
excretion bile, lungs, saliva, sweat and breast milk.
FACTORS AFFECTING BIOTRANSFORMATION
urine pH influences drug excretion. normal urine pH
1. Genetic- some people metabolize drugs rapidly, 4.6-8 acidic urine promotes elimination of weak base
others more slowly drugs. alkaline urine promotes elimination of weak
2. Physiologic acid drugs. prerenal, intrarenal and postrenal
3. Liver disease conditions
4. Infants- decreased rate of metabolism
5. Elderlies- decreased liver size, blood flow, enzyme ● L = Liberation, the release of the drug from it's
production- slows metabolism dosage form.
6. Environment- cigarettes may affect the rate of ● A = Absorption, the movement of drugs from the
some drugs. site of administration to the blood circulation.
7. Stressful environment- prolonged illness, surgery, ● D = Distribution, the process by which drug
illness. diffuses or is transferred from intravascular space
to extravascular space (body tissues).
5. EXCRETION - ELIMINATION ● M = Metabolism, the chemical conversion or
- removal of the drug from the body. Drug is changed transformation of drugs into compounds which are
into inactive form and excreted by the body. easier to eliminate.
● E = Excretion, the elimination of unchanged drug
or metabolite from the body via renal, biliary,
or pulmonary processes.

PHARMACOKINETICS PHASE

WHEN DRUG IS TAKEN BY MOUTH, IT EXCIPIENTS

UNDERGOES 3 PHASES:  Tablets are not 100% drug.
1.Pharmaceutic/dissolution  Fillers and inert substances – excipients.
2. Pharmacokinetics  Allow drug to take on particular size and
3. Pharmacodynamics shape and to enhance drug dissolution.
 Rate of dissolution is the time it takes the
PHARMACEUTIC PHASE (DISSOLUTION) drug to disintegrate and dissolve to become
available for the body to absorb it.
 the 1st phase of drug action.
 In the GI tract, drugs need to be in solution so
they can be absorbed.
 disintegrate into small particles to dissolve into a
liquid.

2 PHASES OF DISSOLUTION
 Disintegration – breakdown into smaller parts
 Dissolution – further breakdown into smaller
parts in GIT – absorption; dissolve into liquid
 FACTORS AFFECTING RATE OF DISSOLUTION
Factors affecting dissolution
 Form of drug ( LIQUID VS. SOLID) – liquids
more absorbed than solid, already in solution,
rapidly available for GI absorption
 Gastric ph ( acidic vs. alkaline) – acidic media
faster disintegration & absorption
 normal gastric pH – 1.5-3.5
 Age – young & elderly – increase pH decrease
absorption
 Enteric coated drugs – resist disintegration in
gastric acid
 Disintegration occurs only in alkaline
environment ( intestine)
 Should not be crushed
 Presence of food – interfere with dissolution &
absorption, enhance absorption of other drugs,
may be protectants of gastric mucosa.

PHARMACOKINETICS ABSORPTION
 is the process of drug movement throughout the - is the movement of the drug into the bloodstream
body that is necessary to achieve drug action. after administration.
- 80% of drugs are taken by mouth – enteral.
- Movement of drug molecules from site of
administration to circulatory system

- MOVEMENT OF DRUG PARTICLES FROM GIT

TO BODY FLUIDS INVOLVE 3 PROCESSES
FOUR PROCESSES: 1. Passive transport
1. Absorption 1. Diffusion – drugs move across the cell
2. Distribution membrane from an area of higher
3. Metabolism – biotransformation concentration to one of lower
4. Excretion – elimination concentration.
2. Facilitated diffusion –Active transport –
requires a carrier such as enzyme or protein
to move the drug against a concentration
gradient. Energy is required.
2. Pinocytosis – is the process by which cells
carry a drug across their membrane by
engulfing the drug particles in a vesicle.
 FACTORS AFFECTING DRUG ABSORPTION

 Drug solubility – lipid soluble drugs pass readily

through GI membrane, water- soluble drugs need
an enzyme or protein
 Local condition at site of absorption- weak acids
less ionized in stomach --Readily pass through the
small intestine.
 Pain/stress/solid foods/fatty or hot foods- slows
down gastric emptying time FACTORS AFFECTING DISTRIBUTION:
Factors affecting distribution:
DRUG DISTRIBUTION  Size of the organ
 Blood flow
 process by which drug becomes available to body
 Solubility- lipid soluble drugs can also cross the
fluids and tissues.
blood-brain barrier and enter the brain.
 is the movement of the drug from the circulation
to body tissues.
DRUG METABOLISM
 or biotransformation is the process by which the
body chemically changes drugs into a form that
can be excreted.

FIRST-PASS EFFECT OR FIRST-PASS

METABOLISM
PROTEIN BINDING  GI tract --- intestinal lumen -- liver---some drugs
are metabolized to an inactive form and excreted-
• as drugs are distributed in the plasma --- bind with -- reduced amount of active drug
plasma protein.
• albumin, lipoproteins, alpha-1-acid glycoprotein
 DRUG EXCRETION
 liver enzymes – cytochrome P450 system – - removal of the drug from the body. Drug is changed
convert drugs to metabolites. into inactive form and excreted by the body.
 decreased drug metabolism rate will result to
excess drug accumulation that can lead to
toxicity.
 Drug half-life is the time it takes for the amount of
drug in the body to be reduced by half.

 Example:
 Ibuprofen has a half life of about 2 hours.
 if the patient takes 200 mg, in 2 hours, 50% of the
drug will be gone, leaving 100 mg.
 after 2 hours - 50 mg.
 after 2 hours – 25 mg
 after 2 hours – 12.5 mg
 after 2 hours – 6.25 mg

 Routes:
 Kidney- main organ for drug elimination: leave
the body through urine
 Free or/unbound/water soluble drugs- filtered in
the kidney
 (+) kidney disease- dose must be decreased.
 kidneys – main route of drug excretion
 bile, lungs, saliva, sweat and breast milk.
 urine pH influences drug excretion.
 normal urine pH 4.6-8
 acidic urine promotes elimination of weak base
drugs.
 alkaline urine promotes elimination of weak acid
drugs.
 prerenal, intrarenal and postrenal conditions.

PHARMA CONTROLLED DRUGS

CONTROLLED SUBSTANCE ACT

 Comprehensive Drug Abuse Prevention and
Control Act
 Controlled Substance Act 1970
 Drug Enforcement Administration DEA
 ENFORCE
 GATHER INFORMATION
 TRAIN
 AND CONDUCT RESEARCHES
MARIJUANA (CANNABIS)
 CONTROLLED SUBSTANCE ACT  Ordered in special hospital forms to maintain
inventory and dispersion control record
 Register biannually with the DEA  Nurse must enter in controlled substance
 Manufacturer record
 Physician  Name of patient
 Nurse practitioner  Date of administration
 physician assistant  Drug administered
 Dentist  Drug dose
 Pharmacy  Possession of these drug is a crime
 Prescription  Conditions that allow nurses to have possession
 Health providers name of these drugs
 address  Under the direction of the physician or dentist
 DEA registration number licensed to prescribed these meds/giving them to
 Signature patient under doctors order
 Patient’s name and address  The nurse is the patient him/herself
 Date of issue  The nurse is the custodian of the limited supply of
 Pharmacist cannot refill w/o approval of health these substances in the ward or hospital
care provider  Controlled substances ordered but not used
 Ward stock should be returned to the source

DRUG ABUSE
 I. DRUG ABUSE IV. DRUG TOLERANCE

Inappropriate and usually excessive, self-  After chronic use, the same amount of drug is
administration of a drug for non-medical purposes. insufficient to cause the desired effect and thus,
• Abused drugs exert their effects in the CNS. more drug is used.
• Compulsive drug-seeking behavior.  A compensatory response.
• Preoccupation with the procurement and use of
the drug may be so demanding as to decrease the A) Innate Tolerance
users productivity. 1. Sensitivity
• Prolonged abuse may cause chronic toxicity. 2. Insensitivity

II. DRUG DEPENDENCE B) Acquired Tolerance

1. Pharmacokinetic or metabolic
Repetitive use of substances that produce an optimal 2. Pharmacodynamic or functional
state of well being because of their positive 3. Learned or behavioral
reinforcing effects in the CNS.
A) Psychological dependence. C) Tachyphylaxis
B) Physical dependence. Rapid development of tolerance to the drug after a
C) Psychological Dependence few doses or a single administration.
◼ Motivational component: great subjective
need, compulsion, drive to get the drug.
◼ Will take drug periodically.
◼ Although physical dependence for a drug may
not occur, “drug-seeking behavior” is present.
◼ Habituation; Just "like" the drug; Drug effects
serve as “positive reinforcers”.
◼ No tolerance increase.

Physiological Dependence
• The body needs the drug for normal V. CROSS DEPENDENCE
physiological function.  When a drug is administered to achieve the same
• Tend to increase dose because of tolerance. outcome as that of another drug.
• Withdrawal Symptoms/Absence Syndrome ◼ i.e. heroin Û methadone.
(negative reinforcement). In a heroin user, methadone can be substituted for
◼ Predictable group of signs and symptoms heroin in preventing the withdrawal syndrome.
resulting from abrupt removal of a drug.
• Psychological dependence is also present.
VI. CROSS-TOLERANCE
III. DRUG ADDICTION  When an individual has become tolerant to a
drug and requires higher than normal doses
 The drug-use and drug-seeking behavior of of a second drug to have its effects.
dependent individuals is maintained by the • i.e. Barbiturates Û BDZ.
reinforcing central activity of the drug Amphetamine Û cocaine.
despite its negative social, psychological and BARBs or BDZs Û Anesthetics.
physical consequences.  In general there is cross-dependence and
 Physiological and psychological dependence cross-tolerance between drugs of the same
is present. class, but not between drugs in different
Physiological changes classes.
have occurred. Exceptions:
Symptoms of  Sedative-hypnotics and volatile intoxicants.
withdrawal, will be  LSD and phenylethylamines, but not with
involved. other hallucinogens.
 High tendency to
relapse. VII. Co-administration/Co-abuse
 Many of these drugs are used in combination Acute use
with other drugs from one or more categories. ▪ Lack of motivation.
▪ Alcohol and Heroin ▪ Lack of judgment.
▪ Nicotine and Alcohol ▪ Loss of concentration.
▪ Speed balls ➔ cocaine + heroin ▪ Violence ➔ death.
▪ Cocaine + BDZs Alcohol, narcotics, stimulants, PCP,
▪ Heroin and BARBs marihuana,hallucinogens, CNS depressants.
 Be aware of the possibility of combination of
drugs when treating withdrawal or overdose, Chronic use
each drug will require a specific treatment. ▪ Amotivational syndrome
▪ Loss of productivity.
Because of the diverse character of these drugs, ▪ Decrease hygiene.
there is no “single reason” for their use, ▪ Decrease health.
nor is there an “addictive personality". Alcohol, narcotics, stimulants, PCP, marihuana,
hallucinogens, CNS depressants.
IT IS NOT NECESSARY TO HAVE A
D) Associated Diseases
PREEXISTING EMOTIONAL OR PSYCHIATRIC
Infections
PROBLEM TO BECOME DRUG DEPENDENT!!!
AIDS
Venereal diseases
VIII. TOXICOLOGY E) Others:
Tobacco-related fires.
A) Tissue and organ toxicity
Toxicity due to bad batches of drug can produce
Acute use
permanent damage such as Parkinson-like disorders -
▪ Respiratory depression --- narcotics, inhalants,
-- heroin (MPTP).
barbiturates.
▪ Cardiovascular effects and seizures --- cocaine,
Amphetamines
amphetamines.
▪ Arrhythmias --- volatile intoxicants. d, l-Amphetamine,
▪ Lack of motor coordination ➔Accidents (car
accidents, big machinery accidents)➔ death --- Methylphenidate (Ritalin®, use to treat attention
alcohol, narcotics, stimulants, PCP, marihuana, deficit and hyperactivity disorders in children),
hallucinogens, CNS depressants.
Phenmetrazine (used to treat obesity),
Chronic use Methamphetamine (“crystal”, “speed”, “ICE”).
▪ Abnormal neuronal activity --- ALL methylendioxyamphetamine, (MDA).
▪ Liver damage --- alcohol. methylenedioxymetamphetamine, (MDMA, ecstasy,
▪ Increase incidence of lung, breast, gastrointestinal XTC).
and rectal cancer, and cardiovascular diseases ---
tobacco. A. Pharmacology:
▪ Pregnancy complications and babies born ◼ Used as nasal decongestants (benzedrine,
dependent --- narcotics. replaced by propylhexedrine).
◼ Used as antidepressants and to treat obesity
B) Psychic toxicity (anorectic) => can cause dependence.
Acute use ◼ Used to stay awake.
▪ Bad trips, flashbacks --- hallucinogens, CNS ◼ Present clinical therapeutic use, only in
stimulants.
narcolepsy.
▪ Mood liability --- marihuana, hallucinogens, PCP.
▪ Panic attacks --- cocaine, amphetamines, ◼ Amphetamine and methamphetamine -HCl
marihuana, hallucinogens, PCP. (speed),
Chronic use
▪ Reality distortion --- alcohol, hallucinogens, ◼ Amphetamine or methamphetamine => I.V.
stimulants .

C) Behavioral toxicity
 ◼ D-methamphetamine (“ice”) => smoked like CNS STIMULANTS
cocaine but has a much longer duration of
action. I. Cocaine, Crack (free base or hydrochloride).
II. Amphetamines.
Psychological Dependence
III. Khat: Cathinone, methcathinone.
- Similar to Cocaine IV. Methylxanthines: caffeine, theophyline,
- May cause hallucinations ➔ MDA, DOM, MDMA theobromide.
V. Nicotine

OPIOIDS or NARCOTICS
COCAINE
I. Morphine
II. Codeine A. Pharmacology
III. Meperidine  Cocaine and the amphetamines have very similar
IV. Methadone effects on mood, patterns of abuse, the type of
dependence produced, and their toxic effects.
Acute effects  Differences are mainly in the pharmacokinetics
1. Positive Effects (t½ of cocaine is shorter (50-90min) vs longer (5-
Desirable 10hrs) t½ for amphetamines).
Subjective  Cocaine-HCl is injected I.V. => “rush” or “flash
2. Negative Effects => euphoria.
Undesirable  Rate of absorption is limited by local
vasoconstriction. Cocaine free base (“crack”,
“rock”) is smoked => delivered directly to
pulmonary circulation, left heart and brain.

a. Acute effects
Causes an initial but temporary euphoria, “rush”.
Causes craving within 30 minutes of taking the drug.
Increase alertness, feeling of elation and well being,
increased energy, feelings of competence, increased
sexuality.
The user becomes more talkative, restless and often
more irritable. Consciousness is clear, but delusions
may occur as well as visual, tactile (formication) and
auditory hallucinations.
B. Acute Toxicity/Overdose These drugs are sympathomimetic, thus, they cause
1.Disruption of central control of peripheral HR, BP, skeletal muscle tension, but musculature of
sympathetic activity. the bronchi and intestines relax.
Brainstem ➔ Respiratory depression ➔ DEATH
➔ Circulatory depression ➔ ¯BP  Given unlimited access to the drugs, animals
Pupils constricted (miosis), (may be dilated with will self-administer these drug until they die.
meperidine or severe hypoxia) B. Acute toxicity/Overdose
Nausea and Vomiting  “Runs” – Uninterrupted sequences of
Pulmonary edema stimulant abuse to maintain a continuous
2. CNS depression state of intoxication, to extend the pleasurable
Drowsiness ➔ Sedation ➔ Coma feeling, and to postpone the postintoxication
3. CNS abnormal neuronal activity “crash” than ensues as the drug effects
Convulsions -- with propoxyphene or meperidine subside.
Reflexes ¯
 - Ice baths ➔ for high fever.
- Acidify urine ➔ to hasten excretion.

After the acute toxic effects are handled:

 Antidepressants ➔ for depression
 Haloperidol ➔ for psychosis.
 Alprazolam ➔ for panic attacks.

SEDATIVE HYPNOTICS
I). Barbiturates:
Used clinically as anticonvulsant, anti-anxiety drugs
or preanesthetics.
Street Names
◼ Phenobarbital purple hearts
◼ Pentobarbital yellow jackets
 Acute tolerance may occur in such people,
◼ Secobarbital red devils
particularly in those taking the drug I.V.,
◼ Amobarbital blue angels
resulting in the need of increasingly larger
II.) Benzodiazepines:
doses.
Used as anxiolytics and hypnotics.
 This spiral of tolerance and dose increases
✓ Flurazepam => sleeping pills.
continues until the drug is depleted or the
✓ Flunitrazepam => “date rape drug”.
person collapses from exhaustion.
✓ Diazepam (Valium) => tranquilizer.
 Drug taking and drug seeking take a compulsive
✓ Chlordiazepoxide (Librium) =>
character.
tranquilizer.
 Stimulant overdose results in excessive
✓ Clonazepam => anticonvulsant.
activation of the sympathetic nervous system
❖ They all cause sedation and muscle
and cardiac toxicity.
relaxation.
 tachycardia and hypertension
❖ Induce sleep (hypnosis).
 myocardial infarction
❖ Abuse may cause "BDZ-induced aggression".
 cerebrovascular hemorrhage
 Cocaine can cause coronary vasospasms
and cardiac dysrhythmias.
 CNS symptoms include anxiety feelings of
paranoia and impending doom, and
restlessness.
 Users exhibit unpredictable behavior and may
become violent.

Treatment of overdose

- Beta blockers => for autonomic hyperactivity.

1 blockade (Atenolol, metoprolol,
esmolol and non-selective : labetolol).
◼ This treatment is controversial:
Problems with using non-selective b III.) Methaqualone (Quaalude) => "Downer",
blockers may lead to unopposed a works as Valium, seriously abused, very addictive.
effects => BP - Synthesized as part of an Indian program looking
- Nitroglycerine or other nitrites/nitrates ➔ for for antimalarial drugs.
angina. - In 1965 it was approved for prescription use and
- Calcium channel blockers (verapamil, diltiazem) ➔ placed in Schedule V.
for hypertension.
- In 1984 methaqualone was transferred to VI. Anticholinergics. Mandrake root, jimson
Schedule I of the CSA. weed, atropine, scopolamine.

B. Acute toxicity/Overdose HALLUCINOGENS

Acute Intoxication
Pupils are normal; BP and respiration are depressed; A. Pharmacology
nystagmus on lateral gaze; tendon reflexes depressed;
These four classes of drugs are usually
ataxia; slurred speech; confusion; coma; shock =>
considered together because of their prominent
Risk of Death, particularly with BARBs.
feature of intoxication (hallucinations, delusions,
illusions), but they differ in almost every aspect:
Treatment of overdose
chemical structure, mechanism of action, CNS
Treatment of overdose w/BDZs: flumazenil (BDZ
receptor involved, picture of intoxication, type and
receptor blocker).
seriousness of their toxic effects.
No treatment for Barbiturates.
They occur naturally in plants, mushrooms and in
C. Withdrawal: some frogs
 Minor: tremors; insomnia (REM rebound); high
fever; clonic blink. Anxiety and dysphoria. Sleep a. Acute Effects
disturbances. At low doses:
 Euphoria; Changes in affect (mood): anxiety,
 12-16hrs: minor symptoms plus abdominal
tension, labile mood; Thought and feeling
cramps; nausea and vomiting, o. hypotension; Ý
disorders: perceptual changes (distortion),
deep tendon reflexes, hyperreflexia.
depersonalization, illusions visual hallucinations,
 24hrs: pronounced weakness, course tremors
time and visual distortions, synesthesias;
(“the shakes”), hyperactive reflexes, early illusions
nausea, pupils are dilated, HR, BP,
and hallucinations. Hyperpyrexia.
temperature, reflexes, tremors.
 48-72hrs: convulsive seizures (“rum fits”); vivid
auditory and visual hallucinations (“the horrors”),  Panic, paranoia.
formication, agitation, disorientation, delirium,
paranoid delusions. At high doses:
 Dangerous behavior may cause accidents.
For the amphetamines:
DRUGS CAUSING HALLUCINATIONS, OR
 Visual hallucinations => convulsions,
DELUSIONS coma.
I. Psychedelics and hallucinogens Subjective reason for taking these drugs:
II. Marihuana (Cannabis) Allows insight into oneself and new ways of looking
III. Dissociative anesthetics (PCP) at the world.
IV. Anticholinergics  Cross-tolerance between LSD and mescaline.
 Usually polydrug users.
I. Psychedelics and hallucinogens.
II. Indolamines: B. Acute toxicity/Overdose
Lysergic acid diethylamide (LSD), morning glory seed Depends on the individual drug .
(LSM), psilocybin, psilocin, ibogaine, 1. Tissue toxicity. Some are neurotoxic.
dimethyltryptamine (DMT). 2. Psychic toxicity. Acute transient
III. Phenyethylamines: psychosis. Flash backs.
mescaline, bufotenin, dimethoxymethyl-amphetamine 3. Behavioral toxicity. Distorted behavior,
(DOM). aggressive, violent.
IV. Cannabis. Marihuana, delta-9-THC. C. Withdrawal
V. Dissociative anesthetics. Ketamine, These drugs do not cause physical dependence, but
Phencyclidine (PCP). they have tremendous abuse potential (psychological
dependence).
- Use is occasional. in spleen, lymph nodes and leukocytes. Thus, they
appear confined to the immune system.
MARIHUANA (CANNABIS) - Cannabinol, a compound also found in marihuana
but with less psychotropic effects seems to have
A. Pharmacology preference for this receptor.
 From the Indian hemp plant, or Cannabis sativa. - Dronabinol. Medicinal grade cannabinol. Approved
 Medicinal powers => Egyptians. Probably as an antiemetic.
originated in Central Asia.
 Delta-9-tetrahydrocannabinol (THC) is the active
ingredient.
 Marihuana, marijuana, bhang, ganja, hashish or
charas, sinsemilla, red oil.
 High lipid solubility but does not dissolve well in
water so if taken orally they are absorbed through
the digestive system rather slowly.
 Smoking causes 50% of cannabinoids to enter the
lungs. Holding the smoke in the lungs maximizes
absorption.

CANNABIS

B. Mechanism of Action
 In 1990 the THC receptor was cloned and in 1992
the endogenous cannabimimetic was discovered.
They named it anandamide (ànanda, in PCP (PHENCYCLIDINE, ANGEL DUST, HOG)
Sanskrit = bliss). A. Pharmacology
 Anandamide is the ethanolamine of arachidonic  It is a synthetic phenylcyclohexylamine
acid. derivative.
 Cannabinoids as well as anandamide inhibit  Initially introduced in 1957 as a “dissociative
Adenylate Cyclase (which produces cAMP) both anesthetic”, which caused no loss of
in brain and periphery, via G protein-coupled consciousness. It was removed from the market
cannabinoid receptors. for use in humans, but it was used in veterinary
 They also inhibit the N-type calcium channel practice.
current, which may affect regulation of  It is the most commonly used hallucinogenic
neurotransmitter release. agent.
- Cannabinoids have effects not related to receptor  It may be snorted, taken orally, smoked with
function, including activation of PLA2 and tobacco, or injected IV.
intracellular calcium mobilization.  Usually gives bad trips.
- THC causes the release of serotonin, causes an  Behavior under the influence of the drug may be
elevation of ACh and inhibits the synthesis of unpredictable, bizarre and violent.
prostaglandins.
- They have also been known to influence levels of
NE, DA and GABA.
- THC concentrates in the limbic system, particularly
in hippocampus and amygdala and sensory centers
for hearing.

- A new peripheral cannabinoid receptor, with only

44% homology to the brain receptor, has been found
 Displacement
 Displacement of the first drug by a second
drug increases the activity of the first drug
Interference
 First drug inhibits the metabolism or
excretion of the second drug, causing
increase activity of the second drug.
Incompatibility
 The first drug is chemically incompatible with
the second drug, causing deterioration when
both drug are mixed in the same syringe or
C. Acute toxicity /Overdose solution
 Intoxication may last 4 to 6 hrs.
 Usually not lethal.
Treatment of Intoxication/Overdose
 No treatment
 Physical dependence is not clear.

PHARMACODYNAMICS DRUG ACTION

TOLERANCE
 occurs when person begins to require a
higher dosage to produce the same effects
that a lower dosage once provided
DEPENDENCE
 Addiction/ habituation, occurs when a person
is unable to control the ingestion of drugs
 Physical and Psychological Dependence
Cumulative Effect
 A drug may accumulate in the body if the next
dose is administered before the previously
administered dose has been metabolized or
excreted.
 Excessive Drug Accumulation may result to Toxicity
 Occurs when the action of one drug is altered by
the action of another drug
 2 ways
 Increase the action of one or both drugs
 Decrease the effectiveness of one or both
drugs
Additive Effect
 Two drug with similar action are taken for a
doubled effect
Synergistic Effect
 Combined effect of two drugs are greater
than the sum of the effect of each drug given
alone
Antagonistic Effect
 One drug interfere with the action of another