Drug Antagonism The effect of one drug blocked (or inhibited) due to another drug is said to be antagonism. In other word, an interaction between two or more drugs that have opposite effects on the body. Drug antagonism may block or reduce effectiveness of one or more of the drugs. e.g., atropine blocks the action of acetylcholine Types of antagonism 1. Pharmacological antagonism: Competitive and Non-Competitive 2. Physiological antagonism 3. Chemical antagonism Competitive Antagonism If both the agonist and the antagonist compete for the same receptor in a reversible manner, they are said to be “competitive.” The antagonist drug interacts with the receptor and blocks it. Therefore it does not produce pharmacological action. The extent of antagonism depends on number of receptors occupied by the both drugs (agonist and antagonist), their affinity for receptors and their concentration. The increase in concentration of either one of these drugs can displace the other from receptor binding sites. Drugs interact with their receptors by weak bonds i.e. ionic bond or Hydrogen bond or Vander wal force. Hence duration of action of drug is short. Both agonist and antagonist have chemical resemblance (structural similarity).

1. DRUG
ANTAGONISM
Prof. Amol B. Deore
Department of Pharmacology
MVP’s Institute of Pharmaceutical
Sciences, Nashik

2. The effect of one drug blocked (or inhibited) due to another drug
is said to be antagonism.
In other word, an interaction between two or more drugs that
have opposite effects on the body.
Drug antagonism may block or reduce effectiveness of one or
more of the drugs.
Drug Antagonism

3. Types of antagonism
Pharmacological
antagonism:
Competitive and
Non-Competitive
Physiological
antagonism
Chemical antagonism

5. Competitive Antagonism
If both the agonist and the antagonist compete for the same
receptor in a reversible manner, they are said to be
“competitive.”
The antagonist drug interacts with the receptor, and blocks it.
Therefore it does not produce pharmacological action.
The extent of antagonism depends on number of receptors
occupied by the both drugs (agonist and antagonist), their
affinity for receptors and their concentration.

6. Competitive Antagonism
Drug A: An agonist
Drug C: An antagonist
of Drug A that binds
to the same receptor
sites as Drug A and
prevents Drug A
from binding
Molecule of Drug C
bound to receptor site

7. Competitive Antagonism
The increase in concentration of either one of these drugs can
displace the other from receptor binding sites.
Drugs interact with their receptors by weak bonds
i.e. ionic bond or Hydrogen bond or Vander wal force.
Hence duration of action of drug is short. Both agonist and
antagonist have chemical resemblance (structural similarity).

8. Ex. Competitive antagonist and their receptors
Agonist
Competitive
Antagonist
Receptors
Acetylcholine
Adrenaline
Histamine
Morphine
Atropine
Phentolamine
Cetrizine
Naloxone
Cholinergic receptors
Adrenergic receptors
Histamine receptors
Opioid receptors

9. Non-Competitive Antagonism
In this situation, the
antagonist forms a
more stable bond
(covalent bond)
with its receptors.
This drug-receptor
interaction is
irreversible and
long lasting.
One drug bind to the
receptor in a manner which
makes it is impossible to
reverse the binding (e.g., a
strong covalent bond).

10. Non-competitive Antagonism
Drug A: An agonist
Drug D: A non-competitive
antagonist of Drug A
that binds to different
receptor sites from
Drug A but still prevents
Drug A from binding
Molecule of Drug D
bound to receptor site
different from receptor
site for Drug A

11. The antagonist may bind with different receptor in such a
way that agonist cannot able to produce its action.
The antagonist has no chemical resemblance with agonist.
A fundamental difference between competitive and non-
competitive antagonists is that competitive agonists reduce
agonist potency and non-competitive antagonists reduce
agonist efficacy.

12. Ex. Non-competitive antagonist and their receptors
Agonist
Non-competitive
Antagonist
Receptors
Nor-Adrenaline
Acetylcholine
Diazepam
Organophosphorous
compounds
Phenoxybenzamine
Bungarotoxin
Bicuculine
Atropine sulphate
alpha receptors
Cholinergic receptors
GABA receptors
Cholinergic receptors

13. Physiological Antagonism
In this situation, both an agonist and antagonist
interact with different receptors and have different site
of action, but still their actions are opposite to each
other.
Ex. glucocorticoids increase blood sugar level, and
insulin lowers it, but the two drugs act by completely
different pathways.

14. Chemical Antagonism
In this situation, a chemical
reaction take place between
two or more drugs within
the body and hence
biological activity become
blocked or diminished.
Ex. protamine acts as
antidote of heparin
molecules
• Antacids neutralize the gastric acid
• Dimercaprol forms chelate with
mercury.

15. Prof. Amol B. Deore
Department of Pharmacology
MVP’s Institute of Pharmaceutical Sciences, Nashik