SN4 SHORT NOTE 5M ★ High-yield

Classify drug antagonism with examples. Add a note on synergism.

Pharmacology · 2nd Professional — Para-Clinical

Definition and Classification

Antagonism is the phenomenon in which one drug decreases or abolishes the effect of another.

Type	Mechanism	Examples
Chemical antagonism	The two drugs react chemically, so the antagonist inactivates the agonist directly; no receptor is involved	Protamine neutralises heparin; chelating agents — desferrioxamine for iron, dimercaprol for arsenic and mercury, penicillamine for copper, calcium disodium edetate for lead; antacids neutralise gastric acid
Physiological (functional) antagonism	The two drugs act on different receptors and produce opposite effects on the same physiological function	Adrenaline against histamine in anaphylaxis (bronchodilatation against bronchoconstriction, by entirely different receptors); insulin against glucagon; glucocorticoids against vitamin D on plasma calcium
Pharmacokinetic antagonism	One drug reduces the concentration of another at its site of action	Enzyme induction by phenobarbitone reducing warfarin levels; cholestyramine preventing digoxin absorption
Receptor (pharmacological) antagonism	Both act on the same receptor	See below

Receptor Antagonism

Feature	Competitive (reversible, surmountable)	Non-competitive (irreversible or allosteric)
Site of binding	The same site as the agonist	A different (allosteric) site, or the same site irreversibly
Bond	Weak and reversible	Covalent or very tight
Dose–response curve	Shifted to the right, remaining parallel	Flattened, with the maximum reduced
Emax	Preserved	Reduced
Overcome by more agonist?	Yes — surmountable	NO — insurmountable
Duration	Determined by the antagonist’s own half-life	Prolonged — requires synthesis OF new receptors or new enzyme
Examples	Atropine against acetylcholine; naloxone against morphine; propranolol against adrenaline; flumazenil against benzodiazepines; vitamin K against warfarin	Phenoxybenzamine against noradrenaline; aspirin on cyclo-oxygenase; omeprazole on the proton pump; organophosphates on cholinesterase

CLINICAL PEARL

Whether an antagonist can be overcome determines how you treat poisoning. A competitive antagonist is surmountable, so in organophosphorus poisoning enormous doses of atropine are given and titrated against secretions. An irreversible blocker cannot be outcompeted — which is why aspirin’s antiplatelet effect persists for the platelet’s whole lifespan, and why phenoxybenzamine gives such durable alpha blockade before phaeochromocytoma surgery.

Synergism — the Converse

Type	Meaning	Examples
Additive (summation)	The combined effect equals the sum of the individual effects (1 + 1 = 2)	Aspirin with paracetamol; two diuretics of the same class
Supra-additive (potentiation, true synergism)	The combined effect exceeds the sum (1 + 1 > 2)	Trimethoprim with sulphamethoxazole (sequential blockade of folate synthesis); penicillin with an aminoglycoside; levodopa with carbidopa; alcohol with benzodiazepines (an unwanted example)

Therapeutic Uses of Antagonism

Antidotes in poisoning — naloxone for opioids, flumazenil for benzodiazepines, atropine and pralidoxime for organophosphates, N-acetylcysteine for paracetamol, vitamin K for warfarin, protamine for heparin, desferrioxamine for iron
Reversal of drug effect — neostigmine to reverse non-depolarising neuromuscular blockade
Treatment of disease — beta-blockers, H2 blockers, angiotensin receptor blockers and antihistamines are all antagonists used therapeutically
Reducing adverse effects — carbidopa blocks the peripheral decarboxylation of levodopa; mesna inactivates acrolein

Applied Aspects

Naloxone is shorter-acting than most opioids, so a patient may relapse into respiratory depression after an initial response; repeated doses or an infusion, and prolonged observation, are required
Flumazenil may precipitate seizures in a patient dependent on benzodiazepines or who has co-ingested a tricyclic antidepressant, so it is used with caution
Physiological antagonism is what saves life in anaphylaxis — adrenaline does not block histamine receptors at all, but opposes every one of histamine’s effects through its own
Vitamin K takes hours to reverse warfarin, because new clotting factors must be synthesised; for immediate reversal, prothrombin complex concentrate or fresh frozen plasma is needed
Antagonism can be harmful as well as useful — a beta-blocker antagonises the effect of salbutamol in asthma and blunts the warning symptoms of hypoglycaemia in a diabetic

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