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PH2.6-8 | Autacoids and Pain Pharmacology — Practice Quiz
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Which property of first-generation H1-antihistamines is primarily responsible for their sedative side effect?
Correct. First-generation antihistamines are lipophilic and cross the BBB readily, where they block central H1 receptors involved in wakefulness, causing sedation.
First-generation agents (e.g., chlorpheniramine, promethazine) are lipophilic and CNS-penetrant. Second-generation agents (cetirizine, fexofenadine, loratadine) have much lower CNS penetration and are non-sedating or minimally sedating.
Incorrect. The sedation is due to CNS penetration from lipophilicity, not protein binding, peripheral receptor subtype, or half-life.
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A patient prescribed fexofenadine 180 mg daily for allergic rhinitis asks whether she can take it with orange juice. What is the most appropriate advice?
Correct. Grapefruit, orange, and apple juices inhibit intestinal OATP1A2 and OATP2B1 uptake transporters. Fexofenadine depends on these transporters for absorption; juice co-ingestion reduces its bioavailability by up to 36%.
Fexofenadine is not metabolised by CYP enzymes; its absorption depends on OATP transporters. Fruit juices (grapefruit, orange, apple) inhibit these transporters, reducing fexofenadine bioavailability. Counsel patients explicitly to take fexofenadine with water only.
Incorrect. The interaction is via OATP transporter inhibition, not CYP enzymes, and fruit juices reduce — not increase — fexofenadine levels.
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A 34-year-old lorry driver presents to a rural PHC with watery rhinorrhoea, repeated sneezing, and nasal congestion for 3 days, consistent with allergic rhinitis. Which antihistamine is most appropriate?
Correct. Cetirizine is a second-generation antihistamine with minimal CNS penetration. It is once-daily (enhancing compliance) and does not cause sedation that would impair driving.
Occupation is a critical factor in antihistamine selection. First-generation agents (chlorpheniramine, promethazine, diphenhydramine) cause sedation and psychomotor impairment and are contraindicated in drivers. Second-generation agents (cetirizine, loratadine, fexofenadine) are the safe choice. Among these, fexofenadine is the most purely non-sedating; cetirizine is mildly sedating at high doses.
Incorrect. Chlorpheniramine, promethazine, and diphenhydramine are all first-generation sedating antihistamines — contraindicated in drivers or anyone operating heavy machinery.
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The analgesic and antipyretic effects of NSAIDs are primarily due to inhibition of which enzyme?
Correct. NSAIDs inhibit both COX-1 and COX-2 (or selectively COX-2 for coxibs). COX converts arachidonic acid to prostaglandins. Inhibiting prostaglandin synthesis reduces peripheral sensitisation of nociceptors (analgesia) and reduces PGE2-mediated hypothalamic fever-signalling (antipyresis).
NSAIDs inhibit COX-1 and/or COX-2, blocking prostaglandin synthesis. PGE2 and PGI2 sensitise peripheral nociceptors (peripheral analgesia) and signal the hypothalamus to raise body temperature (fever). Aspirin acetylates COX irreversibly; all other NSAIDs inhibit reversibly.
Incorrect. Phospholipase A2 is upstream (releases arachidonic acid) and is not directly inhibited by NSAIDs. Lipoxygenase is the leukotriene pathway. Thromboxane synthase is downstream and not the primary NSAID target.
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A 52-year-old man who received a renal transplant 2 years ago presents with pain in his right knee. He has CKD stage 3 (eGFR 32 mL/min). Which analgesic is MOST appropriate for short-term pain relief?
Correct. Paracetamol (acetaminophen) inhibits COX centrally but has minimal peripheral anti-inflammatory and renal effects. It does not reduce prostaglandin-mediated renal afferent arteriolar dilation and is therefore safe in CKD patients at standard doses.
In CKD or post-renal transplant patients, all NSAIDs (including selective COX-2 inhibitors like celecoxib) are nephrotoxic because they reduce prostaglandin-dependent maintenance of GFR. Paracetamol is the analgesic of choice in renal impairment at standard doses (dose-reduce in severe CKD). Opioids may be used for severe pain with appropriate dose adjustment.
Incorrect. NSAIDs (ibuprofen, diclofenac, celecoxib) reduce renal prostaglandin synthesis, causing vasoconstriction of afferent arterioles and reducing GFR — dangerous in CKD and post-transplant. They can also cause AKI and interact with calcineurin inhibitors.
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A 65-year-old hypertensive patient on enalapril 10 mg OD and furosemide 40 mg OD is prescribed ibuprofen 400 mg TDS for knee pain. Which complication is MOST likely?
Correct. The 'triple whammy' combination of ACE inhibitor + diuretic + NSAID causes AKI: (1) ACE inhibitor dilates the efferent arteriole; (2) diuretic reduces circulating volume, making GFR prostaglandin-dependent; (3) NSAID blocks the prostaglandin-mediated afferent dilation — together these three reduce GFR dramatically.
The triple whammy: ACE inhibitor (or ARB) + loop/thiazide diuretic + NSAID simultaneously impairs all compensatory mechanisms that maintain GFR under volume depletion. This combination should be avoided; if necessary, monitor creatinine within 1 week. Prescribers should check for this interaction routinely.
Incorrect. The dominant acute risk is AKI, not hypokalaemia, hepatotoxicity, or hypertension alone.
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A 48-year-old man presents to the district hospital with sudden severe pain, redness, and swelling of the right first metatarsophalangeal joint. He has no peptic ulcer disease, no renal impairment, and no cardiac disease. What is the MOST appropriate immediate treatment?
Correct. Indomethacin (or naproxen) is the first-line NSAID for acute gout attack in a patient with no contraindications. NSAIDs work by reducing prostaglandin-driven inflammation; they are given for 5–7 days during the acute attack.
Acute gout management: (1) First-line — NSAID (indomethacin 50 mg TDS or naproxen 500 mg BD) if no contraindications. (2) If NSAIDs contraindicated — low-dose colchicine (1 mg then 0.5 mg after 1 hour). (3) If both contraindicated (e.g., severe CKD) — oral prednisolone. NEVER start allopurinol during an acute attack. Begin allopurinol only after the attack has fully resolved (≥2–4 weeks).
Incorrect. Allopurinol is a urate-lowering therapy for chronic gout prophylaxis — never start it during an acute attack (can prolong inflammation). Methotrexate and hydroxychloroquine are for rheumatoid arthritis.
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A 58-year-old man with gout and coronary artery disease is on allopurinol 300 mg OD and aspirin 75 mg OD. His cardiologist asks whether low-dose aspirin affects his gout. What is the most accurate statement?
Correct. Aspirin has a dose-dependent, paradoxical effect on uric acid excretion: at high doses (>3 g/day), it is uricosuric; at low doses (<2 g/day), it blocks URAT1-mediated tubular secretion of urate, reducing uric acid excretion and raising serum uric acid. This can worsen or precipitate gout.
Dose-dependent aspirin effect on uric acid: Low-dose (≤1 g/day): blocks urate secretion by renal tubules → retains uric acid (raises serum UA). High-dose (>3 g/day): blocks urate reabsorption → uricosuric effect. Intermediate doses are unpredictable. In patients with gout on low-dose aspirin for cardiovascular prophylaxis, ensure adequate urate-lowering therapy with allopurinol. Do NOT stop the aspirin.
Incorrect. Low-dose aspirin retains uric acid by blocking tubular secretion — it does worsen hyperuricaemia.
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CLINICAL SCENARIO
A 26-year-old medical student presents with recurrent severe unilateral throbbing headache, preceded by visual zigzag lines, accompanied by nausea and photophobia. Attacks last 6–8 hours and occur 3–4 times per month. She has tried paracetamol without adequate relief.
Answer the following questions based on the scenario above.
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For acute treatment of an ongoing attack in this patient, which drug is MOST appropriate?
Correct. Sumatriptan (5-HT1B/1D agonist) is the first-line specific abortive treatment for acute migraine. It causes cerebral vasoconstriction and blocks trigeminal nociceptive transmission.
Incorrect. Amitriptyline, propranolol, and topiramate are all prophylactic (preventive) agents — taken daily to reduce attack frequency — not abortive (acute) therapy.
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Given her attack frequency of 3–4 per month with inadequate response to simple analgesics, which additional treatment strategy is indicated?
Correct. Migraine prophylaxis is indicated when attacks occur ≥3–4 times per month, are disabling, or do not respond adequately to acute therapy. Propranolol (40–160 mg/day) is a first-line prophylactic agent.
Incorrect. Increasing paracetamol dose is inadequate; opioids carry risk of medication-overuse headache; aspirin 75 mg is anti-platelet, not a proven migraine prophylactic.
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Statement 1 (Assertion):
Colchicine is effective in acute gout because it reduces uric acid synthesis.
BECAUSE
Statement 2 (Reason):
Colchicine binds to tubulin and disrupts neutrophil microtubule polymerisation, thereby impairing neutrophil migration to urate crystals.
Select the correct relationship:
Correct. The assertion is false — colchicine does NOT reduce uric acid synthesis (that is allopurinol's mechanism). The reason is true — colchicine binds tubulin and impairs neutrophil chemotaxis and degranulation, which is its actual mechanism in acute gout.
Colchicine mechanism in gout: binds to tubulin, disrupts neutrophil microtubule polymerisation → inhibits neutrophil migration, phagocytosis, and cytokine release (especially IL-1β) → reduces inflammation around urate crystals. It does NOT lower serum uric acid. Compare: allopurinol = xanthine oxidase inhibitor → reduces uric acid synthesis; febuxostat = also xanthine oxidase inhibitor; probenecid = uricosuric agent.
Incorrect. Colchicine's mechanism is anti-inflammatory via microtubule disruption in neutrophils, not reduction of uric acid synthesis.
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