Pharmacodynamics - 2

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.
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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
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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
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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
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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
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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.
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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
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10. .
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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
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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.
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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.
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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.
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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.
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17. Pharmacoeconomics
 Science that compares the cost of various treatment modalities to the
outcome.
 Value for money approach
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