# Analgesics and NSAIDs > Analgesics and NSAIDs for FMGE Pharmacology: aspirin pharmacology, paracetamol ceiling, COX-2 selectivity, renal and cardiac risks and WHO ladder in notes. - Canonical URL: https://prepelephant.com/topics/fmge/pharmacology/analgesics-and-nsaids-fmge - Exam / course: FMGE · Subject: Pharmacology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Analgesics and NSAIDs", PrepElephant, https://prepelephant.com/topics/fmge/pharmacology/analgesics-and-nsaids-fmge ## Direct answer Aspirin acetylates cyclo-oxygenase-1 irreversibly, and because the anucleate platelet cannot rebuild the enzyme, a single 75–150 mg dose disables thromboxane production for the platelet's entire seven-to-ten-day lifespan — the fact underlying both its antiplatelet use and the rule of stopping it a week before surgery. Paracetamol, centrally acting with weak peripheral anti-inflammatory action, is the default analgesic of pregnancy, asthma and chronic kidney disease, capped at 4 g per day in adults because glutathione depletion beyond that converts it into a hepatotoxin. The non-selective NSAIDs share gastrointestinal, renal and blood-pressure toxicity in proportion to cyclo-oxygenase-2 inhibition, which is why diclofenac carries the highest cardiac risk and naproxen the lowest, while the COX-2 selective group spares the stomach at the price of the same cardiac risk that withdrew rofecoxib. ## What you must remember - Aspirin antiplatelet dosing is 75–150 mg daily; effects persist 7–10 days (platelet lifespan); stop 7 days before elective surgery. - Reye syndrome: no aspirin under 16 years with viral illness — replaced by paracetamol or ibuprofen. - Aspirin-exacerbated respiratory disease: asthma with nasal polyps and urticaria reacts to all COX-1 inhibitors; paracetamol is the safe analgesic. - Paracetamol: maximum 4 g/day (reduce in low body weight, liver disease, chronic alcohol); N-acetylcysteine replenishes glutathione and works best within 8 hours of overdose. - NSAID renal risk: prostaglandin-dependent afferent dilation means AKI in the dehydrated, elderly, cirrhotic or chronic kidney disease patient — and the "triple whammy" with an ACE inhibitor and diuretic. - Cardiovascular ranking within the class: diclofenac highest risk, naproxen lowest; ibuprofen can blunt aspirin's antiplatelet effect — separate doses by at least 2 hours, giving aspirin first. - COX-2 selective inhibitors (etoricoxib, celecoxib in India): gastrointestinal sparing but similar cardiovascular risk; rofecoxib was withdrawn for myocardial infarctions. - Interactions: NSAIDs raise lithium and methotrexate levels, potentiate warfarin, and blunt antihypertensives; ketorolac is restricted to about 5 days. - Aspirin overdose signature: tinnitus, hyperpnoea, then a mixed picture of respiratory alkalosis with high anion-gap metabolic acidosis, hyperthermia and dehydration — treated with alkalinised urine and dialysis in severe cases. - The WHO analgesic ladder still frames chronic cancer pain: non-opioid (± adjuvants), then weak opioid, then strong opioid, dosed by the clock and by the mouth. ## A worked case: analgesia in a cardiac patient A 65-year-old on aspirin after a stent wants pain relief for knee osteoarthritis. Walk the reasoning: his diclofenac habit — the commonest Indian over-the-counter default — is the worst choice, stacking myocardial risk on his stent and gastric risk on his aspirin. Step one is scheduled paracetamol 1 g three times daily; regular dosing outperforms as-needed dosing because it prevents pain cycling. Step two adds topical diclofenac or ketoprofen gel, which delivers drug to the joint with a fraction of the systemic exposure. Step three, if oral NSAID becomes unavoidable, chooses the lowest-risk agent (naproxen) at the lowest dose for the shortest period, with a proton pump inhibitor for gastroprotection and a review of renal function and blood pressure after two weeks. Physiotherapy and weight management are prescribed, not mentioned. The contrast stem writes itself: the same man's wife, with chronic kidney disease stage 4 and on ramipril, presents with doubled creatinine after a week of over-the-counter ibuprofen for back pain. Her ladder is paracetamol, topical agents, and non-drug measures — the oral NSAID was never on her ladder at all. ## Where students slip Diclofenac is prescribed by reflex in India and tested against the evidence: among NSAIDs it carries the highest cardiovascular risk, and post-stent patients are exactly the wrong recipients. Second, the aspirin–ibuprofen interaction is missed: ibuprofen competing at the COX-1 channel prevents aspirin's irreversible acetylation, so aspirin must go first by two hours. Third, paracetamol's "safety" collapses above 4 g daily or in the malnourished alcoholic whose glutathione is already low — the overdose question will use a staggered ingestion to hide the timing. Fourth, the triple whammy stem (NSAID + ACE inhibitor + diuretic in a vomiting elderly patient) is read as "contrast nephropathy" or missed entirely. Finally, aspirin overdose acid–base reasoning: the early respiratory alkalosis is a real finding, not a laboratory error, and its persistence into a mixed acidosis marks severity. ## Frequently asked questions ### Why does a single aspirin dose disable platelets for over a week? Irreversible acetylation of COX-1 in anucleate platelets, which cannot resynthesise the enzyme; new platelets restore function only as the population turns over in 7–10 days. ### What is the maximum daily paracetamol dose and its overdose antidote? 4 grams per day in healthy adults; N-acetylcysteine, ideally within 8 hours, replenishes glutathione and detoxifies the NAPQI metabolite. ### Which NSAID carries the lowest cardiovascular risk? Naproxen; diclofenac carries the highest among common agents — a ranking now printed into prescribing guidance. ### Why is aspirin avoided in children with fever? The association with Reye syndrome — acute encephalopathy and hepatic failure after aspirin use in viral illness, principally influenza and varicella. ### What is the "triple whammy" in kidney injury? Concurrent NSAID, ACE inhibitor or ARB, and diuretic — afferent vasoconstriction plus efferent dilation plus volume depletion, a classic cause of acute kidney injury in the elderly. ### How do COX-2 selective inhibitors trade risks? They spare gastric mucosa (fewer ulcers) but carry cardiovascular risk comparable to or exceeding non-selective agents — the mechanism behind rofecoxib's withdrawal and the caution around etoricoxib in coronary disease.