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Drug synergism and antagonism
 When two or more drugs are given simultaneously or in quick
succession, they may be either indifferent to each other or exhibit
synergism or antagonism.
 SYNERGISM (Greek: Syn-together; ergon-work)- When the action of
one drug is facilitated or increased by the other, they are said to be
synergistic.
3/23/2022 2
Synergism can be:
(a) Additive - The effect of the two drugs simply adds up:
effect of drugs A + B = effect of drug A + effect of drug B
 Aspirin + Paracetamol Analgesic
 Nitrous oxide+ Halothane General anaesthetic
 Amlodipine+ Atenolol Antihypertensive
 Ephedrine + Theophylline Bronchodilator
3/23/2022 3
(b) Supraadditive (potentiation)- The effect of combination is greater
than the individual effects or the components:
effect or drug A + B > effect of drug A - effect of drug B
 Acetylcholine+ Physostigmine
 Levodopa + Carbidopa
3/23/2022 4
ANTAGONISM
 -When one drug decreases or abolishes the action of another, they
are said to be antagonistic:
effect or drugs A + B < effect of drug A + effect of drug B
3/23/2022 5
TYPE OF ANTAGONISM
a) Physical antagonism –
Based on the physical property of the drugs
e.g. charcoal adsorbs alkaloids and can prevent their absorption- used
in alkaloidal poisoning
3/23/2022 6
(b) Chemical antagonism –
The two drugs react chemically and form an inactive product
e.g. Chelating agents (BAL) complex toxic metals (As, Pb) to form inactive
complexes
(c} Physiological antagonism –
The two drugs act on different receptors but have opposite effects.
e.g. Histamine- H1 receptors- bronchoconstriction, hypotension
Adrenaline – adrenergic receptors –bronchodilation,
hypertension
Glucagon and insulin on blood sugar level.
3/23/2022 8
(d} Receptor antagonism-
 Antagonist blocks the receptor action of the agonist
 Receptor antagonists are selective i.e. an anticholinergic will oppose
contraction of intestinal smooth muscle induced by cholinergic
agonists
3/23/2022 9
.
3/23/2022 10
.
Competitive antagonism
 Reversible
1. Surmountable
2. Agonist & antagonist bind to
the same receptor
3. Antagonist resembles the
agonist chemically
4. Parallel rightward shift of
agonist DRC
E.g. Ach- Atropine
Non competitive
1. Unsurmountable
2. Antagonist binds to a
different site
3. Antagonist does not resemble
the agonist
4. Flattening of agonist DRC
E.g. Diazepam- Bicuculline
3/23/2022 11
3/23/2022 12
Irreversible antagonism
Certain antagonists bind to the receptor with strong (covalent) bonds
or dissociate from it slowly (due to very high affinity) so that agonist
molecules are unable to reduce receptor occupancy of the antagonists-
an irreversible antagonism is produced.
The agonist DRC is shifted to the right and the maximal response is
lowered.
3/23/2022 13
Pharmacogenomics
 It is the use of genetic information to guide the choice of drug and dose on
an individual basis.
 The purpose is to identify individuals who are either more likely or less
likely to respond to a drug, as well as those who require altered dose of
certain drugs.
 Here , the genetic basis of an individual's profile of drug response is
studied and the best treatment option for him is predicted.
3/23/2022 14
.
There are some specific genetic defects which lead to discontinuous
variation in drug response . e.g.-
1. Atypical pseudocholinesterase results in prolonged succinylcholine
apnoea.
2. G-6PD deficiency is responsible for haemolysis with primaquine
3. lsoniazid neuropathy, procainamide and hydralazine induced lupus
occurs mainly in slow acetylators.
3/23/2022 15
.
4. Acute intermittent porphyria- precipitated by barbiturates is due to
genetic defect in repression of porphyrin synthesis.
5. Malignant hyperthermia after halothane is due to abnormal Ca
release channel (ryanodine receptor) in the sarcoplasmic reticulum
of skeletal muscles.
3/23/2022 16
Pharmacoeconomics
 Science that compares the cost of various treatment modalities to the
outcome.
 Value for money approach
3/23/2022 17

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Pharmacodynamics 2. AGONIST AND ANTIDONIST

  • 1.
  • 2. Drug synergism and antagonism  When two or more drugs are given simultaneously or in quick succession, they may be either indifferent to each other or exhibit synergism or antagonism.  SYNERGISM (Greek: Syn-together; ergon-work)- When the action of one drug is facilitated or increased by the other, they are said to be synergistic. 3/23/2022 2
  • 3. Synergism can be: (a) Additive - The effect of the two drugs simply adds up: effect of drugs A + B = effect of drug A + effect of drug B  Aspirin + Paracetamol Analgesic  Nitrous oxide+ Halothane General anaesthetic  Amlodipine+ Atenolol Antihypertensive  Ephedrine + Theophylline Bronchodilator 3/23/2022 3
  • 4. (b) Supraadditive (potentiation)- The effect of combination is greater than the individual effects or the components: effect or drug A + B > effect of drug A - effect of drug B  Acetylcholine+ Physostigmine  Levodopa + Carbidopa 3/23/2022 4
  • 5. ANTAGONISM  -When one drug decreases or abolishes the action of another, they are said to be antagonistic: effect or drugs A + B < effect of drug A + effect of drug B 3/23/2022 5
  • 6. TYPE OF ANTAGONISM a) Physical antagonism – Based on the physical property of the drugs e.g. charcoal adsorbs alkaloids and can prevent their absorption- used in alkaloidal poisoning 3/23/2022 6
  • 7. (b) Chemical antagonism – The two drugs react chemically and form an inactive product e.g. Chelating agents (BAL) complex toxic metals (As, Pb) to form inactive complexes
  • 8. (c} Physiological antagonism – The two drugs act on different receptors but have opposite effects. e.g. Histamine- H1 receptors- bronchoconstriction, hypotension Adrenaline – adrenergic receptors –bronchodilation, hypertension Glucagon and insulin on blood sugar level. 3/23/2022 8
  • 9. (d} Receptor antagonism-  Antagonist blocks the receptor action of the agonist  Receptor antagonists are selective i.e. an anticholinergic will oppose contraction of intestinal smooth muscle induced by cholinergic agonists 3/23/2022 9
  • 11. . Competitive antagonism  Reversible 1. Surmountable 2. Agonist & antagonist bind to the same receptor 3. Antagonist resembles the agonist chemically 4. Parallel rightward shift of agonist DRC E.g. Ach- Atropine Non competitive 1. Unsurmountable 2. Antagonist binds to a different site 3. Antagonist does not resemble the agonist 4. Flattening of agonist DRC E.g. Diazepam- Bicuculline 3/23/2022 11
  • 13. Irreversible antagonism Certain antagonists bind to the receptor with strong (covalent) bonds or dissociate from it slowly (due to very high affinity) so that agonist molecules are unable to reduce receptor occupancy of the antagonists- an irreversible antagonism is produced. The agonist DRC is shifted to the right and the maximal response is lowered. 3/23/2022 13
  • 14. Pharmacogenomics  It is the use of genetic information to guide the choice of drug and dose on an individual basis.  The purpose is to identify individuals who are either more likely or less likely to respond to a drug, as well as those who require altered dose of certain drugs.  Here , the genetic basis of an individual's profile of drug response is studied and the best treatment option for him is predicted. 3/23/2022 14
  • 15. . There are some specific genetic defects which lead to discontinuous variation in drug response . e.g.- 1. Atypical pseudocholinesterase results in prolonged succinylcholine apnoea. 2. G-6PD deficiency is responsible for haemolysis with primaquine 3. lsoniazid neuropathy, procainamide and hydralazine induced lupus occurs mainly in slow acetylators. 3/23/2022 15
  • 16. . 4. Acute intermittent porphyria- precipitated by barbiturates is due to genetic defect in repression of porphyrin synthesis. 5. Malignant hyperthermia after halothane is due to abnormal Ca release channel (ryanodine receptor) in the sarcoplasmic reticulum of skeletal muscles. 3/23/2022 16
  • 17. Pharmacoeconomics  Science that compares the cost of various treatment modalities to the outcome.  Value for money approach 3/23/2022 17