pharmacology

Leture # 6
DOSE–RESPONSE RELATIONSHIPS
A. Graded dose–response relations
As the concentration of a drug increases, its pharmacologic effect also
gradually increases until all the receptors are occupied (the maximum
effect).
1. Potency: Potency is a measure of the amount of drug necessary
to produce an effect of a given magnitude. The concentration
of drug producing 50% of the maximum effect (EC50) is
usually used to determine potency.
2. Efficacy: Efficacy is the magnitude of response a drug causes when
it interacts with a receptor. Efficacy is dependent on the number of
drug–receptor complexes formed and the intrinsic activity of the drug
(its ability to activate the receptor and cause a cellular response).
B. Effect of drug concentration on receptor binding
The quantitative relationship between drug concentration and receptor
occupancy applies the law of mass action to the kinetics of the
binding of drug and receptor molecules:

Drug ?Receptor _Drug?receptor complex ?Biologic effect
C. Relationship of drug binding to pharmacologic effect
INTRINSIC ACTIVITY
A. Full agonists
B. Partial agonists
C. Inverse agonists
Antagonists
Competitive antagonists
Irreversible antagonists

Allosteric antagonists
Functional antagonism
QUANTAL DOSE–RESPONSE RELATIONSHIPS
The therapeutic index (TI) of a drug is the ratio of the dose that produces
toxicity in half the population (TD50) to the dose that produces
a clinically desired or effective response (ED50) in half the population:
Clinical usefulness of the therapeutic index
1. Warfarin (example of a drug with a small therapeutic index)
2. Penicillin (example of a drug with a large therapeutic index)