NSAIDs
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Direct answer
Non-steroidal anti-inflammatory drugs inhibit cyclo-oxygenase (COX) enzymes, reducing prostaglandin and thromboxane synthesis and thereby producing analgesic, antipyretic and anti-inflammatory effects. The exam core is the COX-1 versus COX-2 distinction: COX-1 is constitutive and protective in the gastric mucosa, platelets and kidney, while COX-2 is inducible at sites of inflammation — which explains why non-selective NSAIDs cause gastric ulceration and bleeding, and why selective COX-2 inhibitors spare the stomach but carry thrombotic risk.
What you must remember
- Mechanism: inhibition of COX-1 and COX-2 reduces prostaglandins (inflammation, fever, pain sensitisation) and thromboxane A2; all NSAIDs except aspirin do this reversibly.
- Aspirin is unique: it irreversibly acetylates COX, so a single dose suppresses platelet thromboxane for the platelet's lifetime — the basis of low-dose aspirin in secondary cardiovascular prevention.
- Gastrointestinal toxicity: prostaglandin depletion removes mucosal protection, causing dyspepsia, ulceration and bleeding — the commonest serious adverse effect; co-prescription of a proton pump inhibitor reduces risk.
- Renal effects: prostaglandins maintain afferent arteriolar dilation in volume-depleted states, so NSAIDs can precipitate acute kidney injury, sodium retention, worsening hypertension and hyperkalaemia, and cause chronic interstitial nephritis.
- Aspirin-specific syndromes: the triad of asthma, nasal polyposis and aspirin sensitivity causing bronchospasm is a classic stem; and Reye syndrome — aspirin avoided in children with influenza or varicella because of the hepatic encephalopathy association, paracetamol being safer.
- Selective COX-2 inhibitors (celecoxib, etoricoxib): less gastric toxicity and no platelet effect, but increased risk of myocardial infarction and stroke; contraindicated in established ischaemic heart disease.
- Salicylate toxicity: tinnitus, hyperventilation, respiratory alkalosis then high anion gap metabolic acidosis; treated with charcoal, urinary alkalinisation and dialysis in severe cases.
Common confusion
Aspirin versus other NSAIDs on platelets is the perennial confusion: only aspirin inhibits COX irreversibly, so only aspirin qualifies as an antiplatelet drug — ibuprofen and diclofenac reversibly inhibit platelet function and are not used for cardiovascular protection. The second recurring pair is NSAIDs versus paracetamol: paracetamol is analgesic and antipyretic through central mechanisms with negligible anti-inflammatory and antiplatelet activity, making it preferred in pregnancy, children and peptic ulcer disease; hepatotoxicity in overdose is its hallmark risk. Finally, remember the trade-off of COX-2 selectivity — stomach spared, thrombosis risk raised.
Exam-focused takeaway
NEET-PG questions on NSAIDs test mechanism-based inference: why ulcers occur (loss of cytoprotective prostaglandins), why renal function deteriorates in a dehydrated patient on ibuprofen, why aspirin is lifelong antiplatelet therapy, and why celecoxib differs from naproxen in cardiac risk. Vignettes feature the asthmatic with nasal polyps deteriorating after aspirin, the child with chickenpox given aspirin, and the overdose with tinnitus and mixed acid-base disturbance. Knowing each effect as a direct consequence of which COX isoform is blocked turns the whole topic into one logical chain.
Frequently asked questions
How do NSAIDs produce their three main effects?
By inhibiting COX-1 and COX-2 they reduce prostaglandins that mediate inflammation, fever and peripheral pain sensitisation, producing anti-inflammatory, antipyretic and analgesic actions.
Why is aspirin used as an antiplatelet drug but not other NSAIDs?
Aspirin irreversibly acetylates COX-1 in anucleate platelets, suppressing thromboxane A2 for their seven-to-ten-day lifespan; all other NSAIDs inhibit reversibly.
What is Reye syndrome and its link to aspirin?
Hepatic failure with encephalopathy in children given aspirin during influenza or varicella; paracetamol is therefore preferred for paediatric fever.
Why can NSAIDs precipitate acute kidney injury?
They block vasodilator prostaglandins that sustain renal perfusion when the patient is hypovolaemic or has heart failure or chronic kidney disease, constricting the afferent arteriole.
How do selective COX-2 inhibitors differ from traditional NSAIDs?
They spare gastric and platelet COX-1, causing fewer ulcers and no bleeding tendency, but reduce prostacyclin relative to thromboxane, raising thrombotic risk.
What is the antidote for paracetamol overdose?
N-acetylcysteine, which replenishes glutathione and detoxifies the accumulating NAPQI metabolite that causes centrilobular hepatic necrosis.