Clinical pharmacology

Instructor: -Tamiru N. (BSC Pharmarmy & In Nursing and MPH)

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 PHARMACOLOGY FOR NURSES

• Course Code: Phrm: 211

• Credit hr 4
• Pre-requisite - (Anatomy, physiology, biochemistry,
microbiology, Parasitology & Microbiology)
• Instructional hr 64

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 Course objective

• After the completion of this course student will be able to:

– Understand classification, mechanism of action clinical uses
and contraindications of commonly used drugs
– Understand drugs adverse effect/toxicity; particularly their
Recognition. Prevention and treatment
– Master the principles and practice of rational drug therapy
– Share the responsibilities to solve the emerging social,
economic and medical problems of drugs misuse and abuse
in Ethiopia
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 Course Content

• Unit one: Introduction to general pharmacology

• Unit two: Autonomic Nervous System Pharmacology
• Unit three: Cardiovascular Pharmacology
• Unit Four: Blood pharmacology
• Unit Five: GIT Pharmacology
• Unit Six: Pharmacology of Broncho–pulmonary systems
• Unit Seven: Central Nervous system Pharmacology
• Unit Eight : Therapy of Endocrine Disorders
• Unit Nine : Chemotherapy 4
 1.1. Introduction to pharmacology

1.1.1. What is pharmacology

Def: study of drugs and their interaction with living system

Definitions:
Pharmacology: is the study of interaction of drugs with
living organisms.
- The properties, uses and effects of drugs on the function of
living system
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 Introduction…
Clinical pharmacology: evaluate the pharmacological
action of drug, preferred route of administration and safe
dosage range in human by clinical trails.
Clinical pharmacology evaluate the:
• pharmacological action of drug,

• preferred route of administration and

• safe dosage range in human by clinical trails.

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 Reading Assignment

• History of pharmacology

• Subdivision of pharmacology

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 Introduction…

Drug?
• Is a chemical substance that alter the function
of living cells at small concentration
• It may have therapeutic or illegal use

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 Introduction…
• When clinically used it has different definition

– A chemical substance that are used for diagnosis,

treatment, prevention or control disease

Medication: Drug that can be given for prevention,

therapeutic and/or diagnostic purpose
– All medications are drugs but all drugs are not
medications
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 Properties of Ideal Drug

1. Reversible action
– Effects can be reversible(E.g: General Anesthetic;
Contraceptives)

2. Predictability
– Know how patient will respond

3. Ease of Administration
– Number of doses should be low and easy to administer
(increase compliance, Decrease errors)
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 Additional Properties of Ideal Drug…

4. Free from drug interactions

– Should not augment/decrease action of other drugs
or have adverse combined effects
• Diazepam vs alcohol (Respiratory depression)
• Aspirin vs warfarin

5. Low Cost
– Easy to afford (especially with chronic illness)
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Additional Properties of Ideal Drug …

6. Chemical Stability
– No lose of effectiveness with storage

7. Possession of a simple generic name

– Easy to remember and pronounce

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 Because No Drug is Ideal……..

• Because no drug is ideal…….

– No drug is safe (all drugs produce side effects)

– Drug responses may be difficult to predict
– Drugs may be expensive
– Drugs may be hard to administer

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 Cont…

All members of health care team must exercise

care to:
• Promote therapeutic effects and
• Minimize drug induced harm (Minimizing
adverse interaction, Management of toxicity)

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 Purpose of Drug Therapy
• “… to diagnose, prevent, control or cure various
disease states”
• To achieve this, every nurse must know…
– Speed of onset of drug action
– Intensity of drug effect
– Duration of drug action

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 1.1.2. Sources of drugs
1. Minerals: E.g. Magnesium sulfate
2. Animals: E.G. Insulin
3. Plants: E.G. morphine, digoxin, atropine
4. Synthetic source: E.G. Aspirin, chloroquine, PCM
5. Microorganism: E.G. penicilline
6. Genetic engineering: E.g. human growth hormone

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 1.1.3. Drug Nomenclature
• Can a given drug have more than one name?

1) Chemical/molecular/scientific name
- Name given to the drug based on its
chemical/molecular structure
- Long & complex
- Mostly used in manufacturing laboratory
Eg. N-acetyl-para-aminophenol
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 Drug Nomenclature …
2) Generic/ non proprietary/approved name
- Official medical name of the drug
- Avoids confusion of giving several names to the drug
regardless of whom manufactures them
- Each drug has usually one generic name
- Less complex than the chemical name
- best to write on prescription

E.g. Acetaminophen 18
 Drug Nomenclature …

3) Trade name (proprietary/brand name)

- Name given by manufacturing and trading Companies
- Drug can have several trade name
- Less complex than the Generic name
E.g. Tylenol, paramol, panadol

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Drug components
• Active – which is responsible for both desired
and undesired effect.
• Inactive/additive/ - which increase the
appearance of drugs

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 1.2 Branches of pharmacology
1.2.1. pharmacokinetics
• Two Greek words

Pharmaco-drug
Kinesis – motion –
• Pharmacokinetics -motion of the drug

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• “What the body does to the drug”
• When a drug enters the body, the body begins
immediately to work on the drug: absorption,
distribution, metabolism (biotransformation), and
excretion; pharmacokinetic process

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 What Happens after Drug
Administration?
Drug at site
of administration
1. Absorption
Drug in plasma 2. Distribution
Drug/metabolites
3. Metabolism
in tissues

4. Excretion
Drug/metabolites
in urine, feces, bile
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1. Drug absorption
• Movement of drug from site of administration into the
central compartment (systemic circulation) except
intravenous or intra-arterial administration.

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Drug absorption rate of various oral preparations
Fastest
Suspension
Powder
Capsules
Tablet
Coated tablet slowest
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Bioavailability
 is the rate and amount of drug that is absorbed from a
given dosage form and reaches the systemic circulation
following non-vascular administration.
 The fraction of the administered dose reaching into
systemic circulation
 IV route- 100% bioavailability
 non IV range 0-100%
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 II. Distribution
Introduction
• Unless a drug acts topically (i.e., at its site of
application),it first must enter the bloodstream and
then be distributed to its site of action.
• The rate at which a drug reaches its site of action
depends on two rates: absorption and distribution

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 Distribution…

Def: is Penetration of a drug to the sites of action

through the walls of blood vessels or
• the movement of drug throughout the body
from the administered site after absorption to
plasma,

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 Factors affecting drug concentration at its site of action

• Once a drug has been absorbed into the blood, it

may be subjected to:
– varying degrees of metabolism,
– storage in non target tissues, and excretion.

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 Cont…
Factors determining the rate of distribution of drugs:
1. Protein binding of drug and specific organ binding,
2. Physico chemical properties of the drug like Lipid solubility ,
ionization , molecular weight
3. Blood flow/perfusion rate
E.g. heart ,liver, kidney, brain – high Blood flow
Adipose tissue, muscle, skin – low BF
4. physiological barriers to distribution
- blood brain barrier (BBB)
- placental barrier
5. Affinity of drugs to certain organs 31
 Protein binding of drug

• Drugs can form reversible bonds with various protein

in the body
– only the unbound drug can diffuse through the
capillary wall, produce its systemic effects, be
metabolized, and be excreted
– Protein binding is restriction of drug distribution
– Extensive plasma protein binding may prolong drug
availability and duration of action
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 III. Metabolism of drugs /biotransformation:

• is process by which the body brings about change

in drug molecule

• Involve enzymatic conversion of one chemical

entity to another

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 Metabolism…
• Drug metabolism changes the chemical structure of a
drug
– to produce a drug metabolite, which is frequently but
not universally less pharmacologically active
– Renders the drug compound more water soluble and
therefore more easily excreted
• liver, kidney, lung, plasma, intestinal mucosa are
organs of biotransformation
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 Metabolism…
Enzymes responsible for metabolism of drugs:
a. Microsomal enzymes: located in smooth
endoplasmic reticulum of kidney, liver, GIT e.g.
P450
b. Non-microsomal enzymes: located in
cytoplasm, mitochondria of different cells e.g.
esterases
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 Metabolism…
Types of biotransformation: are phase-I and phase-II
reaction.

Phase-I reactions
a. Oxidation e.g. barbiturates, ibuprofen
b. Reduction e.g. cholarmphenicol, halothane
c. Hydrolysis (to esters and amine by esterases and amidases
in plasma and liver) e.g. lidocaine, pethidine
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 Metabolism…
 Classified as the functionalization phase

Usually leads to
 Inactivation of active drug e.g. ibuprofen
 Bioactivation of prodrug e.g. levodopa
Drug is converted in to more polar form (will
be excreted in urine)
Production of toxic and reactive produces
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 Phase – II reaction

• Conjugation or synthetic reaction

• Responsible for
– Detoxification process i.e. producing inert and non
toxic products (Generally in phase I drug
metabolism the product formed may be toxic but can
be converted to non toxic form by phase II reaction)

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 Phase – II reaction…
– Drug inactivation
– Facilitate renal excretion of drugs
• By converting drug to more polar form.

Phase II reaction includes:

• Sulfate conjugation
• Glycine conjugation (e.g. salicylic acid)
• Acetylation

• Methylation (e.g. adrenaline)

• Glucouronidation (e.g. phenobarbitone) 39
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 Variation in metabolism
• Variation factors

1. Genetic factor with in the population

2. Drug interaction enzyme induction (faster
elimination of substrate drugs

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Eg: Phenobarbitone, Phenytoin Carbamazepine,
Rifampin) and enzyme inhibition : inhibit the
activity of CYP enzymes & reduce elimination of
substrate drugs Eg : Ciprofloxacin, Cimetidine,
Ketoconazole, Omeprazole

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 IV. Excretion of drugs

• is means the transportation of unaltered or altered

form of drug out of the body.
 major process are: renal excretion, hepatobiliary
excretion and pulmonary excretion.
 minor routes are: saliva, sweat, tears, breast milk,
vaginal fluid, nails and hair.

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 Excretion…

 rate of excretion influences duration of action

Different routes of drug excretion

a. Renal excretion
b. Hepatobiliary excretion: (chloramphenicol)

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 Excretion …
C. Gastrointestinal excretion: Aluminium
hydroxide
D. Pulmonary excretion: inhalation anaesthetics,
alcohols.
E. Sweat excretion : rifampicin
F. Mammary excretion: coffee, morphine
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 Plasma Site of
Dosage Effects
Concen. Action

Pharmacokinetics Pharmacodynamics

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 2. Pharmacodynamics
Deals with
• How the drug act on target cells to alter cellular function,
– what action the drug produce in the body.

– What the drug does to the body.

A. Mechanisms of action:
The ways by which drugs can produce therapeutic effects,
• mode of action & response produced by the drug
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Mechanism can be receptor or non receptor:

• Most of the drugs act by interacting with a

cellular component called receptor.
• Some drugs act through simple physical or
chemical reactions.

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 Receptors are protein molecules present either on
the surface or within the cell where the drug
binds and produce measurable response.
e.g. Adrenergic receptor, cholinergic receptors,
insulin receptors, histamine receptors.
 Non- receptor mechanisms

e.g. Aluminium Hydroxide, Magnesium trisilicate

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 Pharmacodynamics…
 Many drugs are similar to or have similar chemical
group to the naturally occurring chemical and have
the ability to bind on to a receptor.
 A drug which is able to fit onto a receptor is said
to have affinity
 efficacy is the ability of a drug to produce an
effect at a receptor.
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 Pharmacodynamics…
 Agonist drug has both the affinity, efficacy and stimulate
receptor so as to mimics endogenous transmitter
Eg : morphine, epinephrine
Antagonist drugs has affinity but not efficacy or intrinsic
activity, so blocks the action of endogenous transmitter.
Eg : atenolol, metoprolol, prazosin
 most drug binding is reversible, there will be competition
between the drug and the natural stimulus to the receptor.
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 Pharmacodynamics…
 Chemical bonds that attract the drug to its receptor are:

- Ionic bond - Covalent bond (strongest bond)

- Vander waals force

• Most macromolecular receptors have a number of ionizable

groups at physiological pH (e.g., carboxyl, hydroxyl)that are

available for interaction with an ionizable drug.

K1

D+R DR K3 Biological effect

K2 52
 Pharmacodynamics…

where D = Drug, R = Receptor DR = Drug receptor

complex

K1 = Association constant K2 = Dissociation constant

K3 = Intrinsic activity
•First messengers like neurotransmitters (ach, dopamine,
nor-epinephrine), hormones, autacoids (Angiotensin,
Serotonin, Bradykinin…) and drugs bind to form complex.

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 B. Site of drug action

A drug could act:

• Extracellularly e.g. osmotic diuretics
• On the cell surface e.g. digitalis, penicillin
• Inside the cell e.g. anticancer, steroid hormones

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 C. Dose response relationship

• For a drug to act should reach a critical conc. at its site

of action.
• Above critical concentration drug exhibits response
related to dose up to certain range till its maximum
therapeutic response is reached.
• Once maximum drug response is reached rise in dose has
no enhancement in response but leads to increase in toxic
effects.
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 Measuring drug responses

1. Graded dose effect :

• As the dose administered to a single subject or tissue
increases, the pharmacological response also increases in
graded fashion up to ceiling effect (maximal responding
capacity of the given responding system)
– Further increases in dose do not produce greater
responses.

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• When a graded dose–response relationship exists, the
response to the drug is directly related to the number of
receptors with which the drug effectively interacts.
• The concentration that is required to produce 50 % of
the maximum effect is termed as EC50 or ED50.
– ED50 (effective dose, 50%)

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 2. Quantal dose effect:
• It is all or none response characterized by stating the
median effective dose and the median lethal dose.
• Median lethal dose or LD50: is the dose (mg/kg),
which would be expected to kill one half of a population
of the same species and strain.
• Median effective dose or ED50: is the dose (mg/kg),
which produces a desired response in 50 percent of test
population.
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 Cont…
Therapeutic index: is approximate assessment of the safety
of the drug. It is also known as therapeutic window or
safety.
TI= LD50
ED50
 The larger the therapeutic index, the safer is the drug.

e.g. penicillin (higher therapeutic index)

digitalis (smaller therapeutic index) 59
 Cont…
Onset: is 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.
Half-life: the time it takes for one half of the original amount
of a drug in the body to be removed.
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 Cont…
• Potency: the measure of how much drug is required to
elicit a given response. The lower dose required for a
given response, the more potent the drug.
• Effectiveness : the greatest ability of a drug to produce
a response, regardless of dosage.

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Cont…
 Drug B is most potent
 Drug A, C and D are
equally effective
 Drug A is more potent
than drug C and D
 Drug C is least potent

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 Exercise
1) What are different routes of drug administration
and write about advantages and disadvantages of
parenteral route of administration.
2) Define bio-availability and describe the factors
affecting drug absorption.
3) Define the following: a) Half-life of a drug
b) Steady state plasma concentration
c) Adverse drug reactions
4) Write about the factors modifying drug action.
5) Write about different types of drug interactions.
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