PROF.

CHARLES EZEAMUZIE

.PhD (London), MIBiol., C.Biol

Professor of
Immunopharmacology
 DEFINITIONS
Pharmacology:
A study of the interaction of drugs with living
tissues/organisms
Toxicology:
Aspect of Pharmacology dealing with undesirable
effects of drugs
Drug:
Any chemical substance that alters the body’s function
Pharmacodynamics:
What the drug does to the body (drug actions)
Pharmacokinetics:
What the body does to the drug (absorption,
metabolism, excretion)
 NATURE OF DRUGS

Drugs vary widely with respect to:

a. Molecular size
b. Structure and configuration (including isomers)
c. Chemical nature (reactive/inert; weak acid/base)
d. Sources (synthetic, natural products)
CLASSIFICATION OF DRUG EFFECTS

Therapeutic Effect: Desired Effect

Side Effect: Any effect other than desired one
Adverse Effect: Side effect that is harmful
Toxic Effect: Adverse effect resulting from high
(toxic) dose
Idiosyncrasy: Abnormal response to a drug
occurring only in a minority
of individuals
 DRUG RECEPTORS
Definition:
A receptor is a specific binding site for a drug
on or within the cell, which when activated leads
to a biological response.
Why do receptors exist?
To serve endogenous chemical mediators
( neurotransmitters, hormones etc).
(Note: Exogenous drugs merely fit receptors by chance or are custom-designed to fit)
 CHARACTERISTICS OF CLASSICAL
RECEPTORS
Structural specificity:
Drug interacts with receptor in lock and key manner
(Basis for structure-activity relationship)
Optical specificity:
Optical isomers of active drug may be inactive
Saturability:
High concentrations of a drug saturates the receptors.
Receptor number finite.
Dynamic expression:
Receptors can be up - or down - regulated
Response:
Activation of a receptor result in biological response
 Drug-Receptor Interaction
))Lock and key

Agonist Antagonist

Receptor

Response No Response

Drug X

Receptor No fit,
no response
TYPES OF RECEPTOR COUPLING
 As part of ion channel
(eg nicotinic Rec.)

 Connected via G-proteins

(e.g. adrenoceptors)

 Have direct enzyme activity

(e.g. insulin receptor)

 Directly activates enzymes (kinases)

(e.g. cytokines)

 Directly controls DNA transcription

RECEPTOR COUPLING MECHANISMS
Do all drugs have to act through
?receptors
 DRUGS THAT DEPEND ON NON-SPECIFIC
PHYSICOCHEMICAL MECHANISMS

PROPERTY DRUG EXAMPLES

Possession of osmotic properties Osmotic laxatives
Neutralization of acid Antacids
Precipitation of proteins Silver compounds
Formation of protective barriers Glycerol
Adsorptive Properties Natural fibers, Kaolin
Radioactivity Radioactive iodine
 MEASUREMENT OF DRUG
EFFECT
Graded Response
Small increment in dose causing corresponding
increase in effect.
Quantal Response (Yes or No Response)
Drug effect measured on all or none basis
(eg sleep, death, convulsion) in a population.
 Information Obtainable From A
Dose-Response Curve
ED50:
The dose of a drug that produces 50% of the desired
effect.
LD50:
The dose that results in the death of 50% of the
test organism.
Therapeutic index (TI):
Ratio of LD50 to ED50. It is a measure of safety
margin of a drug (compare penicillin with digoxin).
Emax:
Maximum effect produced by the drug on a given
tissue - a measure of efficacy of a drug.
Quantal Dose-Response Curves
 SPECIFIC LEARNING OBJECTIVES
1. Appreciate the molecular nature of drugs and
receptors.
2. Define and differentiate therapeutic effect,
side effect, adverse effect, toxic effect and
idiosyncrasy.
3. Classify the different binding sites for drugs.
4. Describe the different types of receptor coupling,
with examples.
5. Understand the meaning and significance of
ED50, LD50 and therapeutic index.
 THE DOSE-RESPONSE CURVE

Hyperbolic curve Sigmoid curve

125 125
Emax Emax
100 100
% Response

% Response
75 75

50 50

25 25
ED50 ED50
0 0
0 25 50 75 100 125 -9 -8 -7 -6 -5 -4 -3
Concentration Log Concentration
 TARGETS OF DRUG ACTION
Typical Receptors
Acetylcholine receptor Bethanechol
Insulin receptor Insulin
Ion Channels
Voltage-gated sodium channel Local anaesthetics
Calcium channels Nifedipine
Enzymes
Acetylcholinesterase Neostigmine
Xanthine oxidase Allopurinol
Carriers (Transport systems)
Noradrenaline uptake 1 Cocaine
Weak acid carrier Probenecid