A 38-year-old woman with acute gout takes colchicine. She develops profuse diarrhoea. This GI toxicity of colchicine is a dose-related effect. Colchicine's mechanism of action in acute gout involves:
- A Inhibition of xanthine oxidase, reducing uric acid synthesis in the acute phase
- B Blocking URAT1 in renal tubules, promoting rapid urinary urate excretion during acute attack
- C Competitive antagonism at IL-1 beta receptors on synoviocytes, blocking inflammatory signalling
- D Binding to tubulin and inhibiting microtubule polymerisation, impairing neutrophil chemotaxis, degranulation and NLRP3 inflammasome assembly ✓
Explanation
Colchicine binds tubulin dimers and prevents their polymerisation into microtubules. This disrupts multiple neutrophil functions essential for acute gout: chemotaxis towards urate crystals is impaired, crystal phagocytosis and degranulation are reduced, and assembly of the NLRP3 inflammasome (which generates IL-1β) is disrupted. GI toxicity occurs because rapidly dividing intestinal epithelial cells are also dependent on microtubule function for mitosis and cell trafficking. Colchicine does not affect uric acid production or excretion, distinguishing it from allopurinol and probenecid.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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