PH2.6-8 | Autacoids and Pain Pharmacology — Graded Quiz

Correct. H2 receptors on gastric parietal cells stimulate HCl secretion via cAMP. H2 blockers (ranitidine, famotidine) are used for peptic ulcer disease.

H1 receptors: smooth muscle (bronchospasm, vasodilation), endothelium, CNS (wakefulness). H2 receptors: gastric parietal cells (acid secretion), cardiac muscle. H3/H4: presynaptic auto-receptors and immune cells respectively.

Incorrect. H2 receptors are on gastric parietal cells. H1 receptors mediate bronchospasm, urticaria, and rhinorrhoea.

Correct. First-generation antihistamines are pharmacologically 'dirty' — they block not only H1 receptors but also muscarinic (M1/M3) receptors, causing dry mouth (parotid gland), urinary retention (bladder detrusor), and accommodation problems (ciliary muscle).

First-generation antihistamines are non-selective and block: H1 (desired allergy relief) + muscarinic receptors (dry mouth, urinary retention, constipation, tachycardia, blurred vision) + alpha-1 adrenoceptors (postural hypotension) + CNS H1 (sedation). Second-generation antihistamines are selective H1 blockers with minimal muscarinic activity.

Incorrect. Anticholinergic side effects are caused by muscarinic receptor blockade, not alpha-adrenergic, serotonergic, or GABAergic blockade.

Correct. Chlorpheniramine (first-generation) has been used in pregnancy for decades and has the most clinical safety data, classifying it as the preferred antihistamine in the first trimester despite sedation. Second-generation agents have less long-term safety data in pregnancy.

Pregnancy and antihistamines: Chlorpheniramine is the preferred antihistamine in pregnancy due to its long track record. Second-generation agents (loratadine, cetirizine, fexofenadine) are generally considered low-risk based on animal data and limited human studies, but the longest human safety data is with chlorpheniramine. All antihistamines should be used only when clearly needed in pregnancy.

Incorrect. While second-generation antihistamines are preferred in non-pregnant patients, chlorpheniramine has the most established safety record for use during pregnancy.

Correct. COX-1 is constitutively expressed in most tissues including the gastric mucosa (produces PGE2 and PGI2 that maintain the mucosal barrier), platelets (TXA2 for aggregation), and kidneys. COX-2 is inducible at sites of inflammation.

COX-1 (constitutive): gastric mucosa (cytoprotection), platelets (TXA2), kidneys (renal blood flow). COX-2 (inducible): inflammation, pain, fever — also constitutively expressed in kidneys and brain. Selective COX-2 inhibitors (coxibs) spare COX-1 gastrointestinal effects but retain renal toxicity. Non-selective NSAIDs inhibit both isoforms.

Incorrect. COX-2 is the inducible, pro-inflammatory isoform. COX-3 is a splice variant with uncertain clinical significance. Lipoxygenase is a separate enzyme.

Correct. Aspirin transfers its acetyl group to serine-530 in COX-1 (and serine-516 in COX-2), forming a covalent bond that permanently blocks the channel through which arachidonic acid accesses the active site. Because platelets lack nuclei, they cannot synthesise new COX, so platelet COX is inhibited for the platelet's lifetime (8–10 days).

Aspirin's irreversible COX acetylation explains: (1) antiplatelet effect lasts 8–10 days (platelet lifespan) — hence 75 mg/day is sufficient for antiplatelet prophylaxis; (2) bleeding risk after aspirin requires 7–10 days to recover; (3) other NSAIDs are reversible competitive inhibitors and their effects last only as long as the drug is present.

Incorrect. Aspirin's inhibition is irreversible covalent acetylation — not competitive, allosteric, or haem-based.

Correct. Paracetamol overdose produces a toxic metabolite (NAPQI) via CYP2E1 that depletes hepatic glutathione and causes centrilobular hepatic necrosis. N-acetylcysteine replenishes glutathione stores and is most effective when given within 8–10 hours. Even if asymptomatic at 4 hours, immediate NAC is indicated for doses >150 mg/kg.

Paracetamol toxicity: Normal doses — 90% glucuronidation/sulfation (non-toxic); 10% via CYP2E1 → NAPQI (toxic) → conjugated by glutathione. Overdose → glutathione depleted → NAPQI accumulates → centrilobular necrosis. Treatment: N-acetylcysteine (glutathione precursor) — oral or IV, within 8–10 hours. Presentation: 4-stage clinical course — initial nausea (0–24h), apparent improvement (24–72h), peak hepatotoxicity (72–96h), recovery or death.

Incorrect. The priority is hepatoprotection with NAC. Flumazenil is the benzodiazepine antidote; forced diuresis alone is ineffective.

Correct. Allopurinol is metabolised to oxypurinol, which irreversibly inhibits xanthine oxidase. This blocks the final steps of purine catabolism — hypoxanthine → xanthine → uric acid — reducing uric acid production.

Gout pharmacology: Allopurinol (xanthine oxidase inhibitor) → reduces uric acid synthesis → drug of choice for overproducers and first-line for most patients; febuxostat (also XO inhibitor, non-purine). Probenecid (uricosuric) → blocks URAT1 tubular urate reabsorption → increases excretion → for underexcretors. Rasburicase → IV for tumour lysis syndrome. Colchicine → anti-inflammatory (anti-neutrophil) — not urate-lowering.

Incorrect. Allopurinol inhibits uric acid synthesis, not secretion. Uricosuric agents (probenecid, sulfinpyrazone) increase tubular secretion. Rasburicase (recombinant uricase) converts uric acid to allantoin.

Correct. When NSAIDs and full-dose colchicine are both contraindicated (as in severe CKD), systemic corticosteroids (oral prednisolone 30–35 mg/day for 5 days or IM methylprednisolone) are the treatment of choice for acute gout.

Acute gout treatment hierarchy: (1) NSAID (e.g., indomethacin 50 mg TDS or naproxen 500 mg BD) — if no contraindications; (2) Low-dose colchicine (1 mg then 0.5 mg at 1 hour) — if NSAIDs contraindicated; use with caution in CKD (dose reduce); (3) Oral corticosteroids (prednisolone 30 mg/day for 5 days) — if both NSAID and colchicine are contraindicated. NSAIDs are contraindicated in eGFR <30 mL/min.

Incorrect. Allopurinol and probenecid are urate-lowering agents — not acute anti-inflammatory therapy. Indomethacin at any dose is harmful in severe CKD (eGFR <30 mL/min).

Correct. Rheumatoid arthritis requires early initiation of DMARDs to prevent joint erosion and disease progression. Methotrexate is the anchor DMARD — it is started early (within weeks of diagnosis), given weekly, and supplemented with folic acid to reduce toxicity.

RA management: NSAIDs (symptomatic relief only) + DMARDs (disease-modifying). Conventional DMARDs: methotrexate (first-line anchor), hydroxychloroquine, sulfasalazine, leflunomide. Biologic DMARDs: TNF-α inhibitors (adalimumab, etanercept), IL-6 inhibitors (tocilizumab) — for moderate-to-severe disease not responding to conventional DMARDs. Do not confuse RA management with gout management.

Incorrect. Allopurinol is for gout; colchicine is for gout/pericarditis, not RA; sumatriptan is an anti-migraine drug with no role in RA.

Correct. Triptans (e.g., sumatriptan) are serotonin 5-HT1B/1D agonists. 5-HT1B receptors are present in coronary and cerebral arteries — activation causes vasoconstriction. Triptans are absolutely contraindicated in ischaemic heart disease, uncontrolled hypertension, and cerebrovascular disease.

Triptan contraindications: ischaemic heart disease, Prinzmetal's angina, uncontrolled hypertension, prior stroke/TIA, peripheral arterial disease. Mechanism: 5-HT1B activation in coronary arteries → vasoconstriction → risk of coronary vasospasm in patients with existing coronary disease. In patients with cardiac comorbidities, NSAIDs + antiemetics can be used for acute attacks. Topiramate prophylaxis is safe with appropriate BP monitoring.

Incorrect. While ibuprofen should be used cautiously in hypertension, the absolute contraindication in this patient with IHD is the triptan. Paracetamol and topiramate have no cardiac contraindication.