Factors Modifying Drug Action Antagonism

1. Factors Modifying
Drug Action
Antagonism Raj Mendpara
Pharmacology & Toxicology of Ayurvedic Drugs
ITRA – Pharmacy, Jamnagar

2. Antagonism : (1+1=0)
When one drug decreases or abolishes the action
of another, they are said to be antagonistic:
effect of drugs A + B < effect of drug A + effect of drug B
Usually in an antagonistic pair one drug is inactive as
such but decreases the effect of the other.

3. Depending on the mechanism involved,
antagonism may be:
Antagonism
Chemical
antagonism
Physiological
antagonism
Receptor
antagonism
Noncompetitive
antagonism
Competitive
antagonism

4. 01. Chemical antagonism.
The two drugs react chemically and form an inactive product.
or
The biological activity of a drug can be reduced or abolished by
a chemical reaction with another agent.
e.g. heparin and protamine, BAL and arsenic.
KMnO4 oxidizes alkaloids—used for gastric lavage in
poisoning.

5. 02. Physiological/functional antagonism
 The two drugs act on different receptors or
by different mechanisms, but have opposite
overt effects on the same physiological
function, i.e. have pharmacological effects
in opposite direction,
 e.g.Histamine and adrenaline on bronchial
muscles and BP.
 Glucagon and insulin on blood sugar level.

7. 03. Receptor antagonism
 One drug (antagonist) blocks the receptor action of the other
(agonist).
 Receptor antagonism can be competitive or noncompetitive.

8. Competitive or reversible antagonism:
 When the agonist and the antagonist compete for the primary
binding site on the same receptors, it is designated as competitive
antagonism.
 The extent to which the antagonist opposes the pharmacological
action of the agonist will be decided by the relative numbers of
receptors occupied by the two compounds.
 Competitive antagonism can be overcome by increasing the
concentration of the agonist at the receptor site
 e.g. acetylcholine and atropine antagonism at muscarinic receptors.
If the concentration of acetylcholine at the receptor level is
increased by the administration of an anticholinesterase, the
blockade produced by atropine can be reversed (reversible
antagonism). Similar is the case between noradrenaline and
prazosin, an alpha-adrenergic blocking agent.

9. Non-competitive or irreversible antagonism:
• In this type of antagonism an antagonist inactivates the receptor (R)
so that an effective complex with the agonist cannot be formed,
irrespective of the concentration of the agonist. This may happen in
various ways
• (a) The antagonist might combine with R at the same site, but the
combination is so firm that even higher agonist concentration
cannot displace it (irreversible).
• (b) The antagonist binds to an alloasteric site so as to prevent the
expected characteristic biologic response to the agonist; or
• (c) The antagonist might itself induce a certain change in R so that
the reactivity of the binding site where agonist should interact is
reduced or abolished.
• e.g. noradrenaline and phenoxybenzamine on vascular smooth
muscle; acetylcholine and decamethonium at the neuro-muscular
junction.

10. Different between Competitive & Non-competitive
Competitive Non-competitve
Antagonist bind with the same
receptor as the agonist
Binds to another site of receptor
Antagonist resemble chemically with
the agonist
Dose not resemble
Intensity of response depends on the
concentration of both agonist
molecules
Maximal response depends only on the
concentration of antagonist

11. Importance of drug antagonism:
◍ Correcting adverse effects of drug: e.g., chlorpromazine induced
extrapyramidal reactions which are due to cholinergic activation
can be countered by benzhexol
◍ Treating drug poisoning; e.g., morphine with naloxone,
organophosphorus compounds with atropine; and
◍ Predicting drug combinations which would reduce drug efficacy,
e.g., the penicillin and tetracycline combination is inferior to
penicillin alone in pneumococcal meningitis.
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