Pharmacology · NSAIDs and Autocoids (Histamine, Serotonin, Eicosanoids, Gout Drugs)

A patient with acute gouty arthritis who is intolerant to NSAIDs is started on colchicine. The anti-inflammatory mechanism of colchicine in gout is:

  • A Binds tubulin and prevents microtubule polymerization, impairing neutrophil migration, phagocytosis, and NLRP3 inflammasome activation
  • B Inhibits xanthine oxidase, reducing uric acid synthesis and crystal formation
  • C Blocks IL-1 receptor on synovial cells, preventing inflammatory cytokine signaling
  • D Inhibits phospholipase A2, reducing prostaglandin and leukotriene synthesis in the joint
Correct answer: A. Binds tubulin and prevents microtubule polymerization, impairing neutrophil migration, phagocytosis, and NLRP3 inflammasome activation

Explanation

Colchicine binds free tubulin dimers and prevents their polymerization into microtubules. This disrupts the cytoskeletal machinery required for neutrophil chemotaxis toward urate crystals, for pseudopod formation during phagocytosis, and for assembly of the NLRP3 inflammasome (which requires mitochondrial trafficking along microtubules). The NLRP3 inflammasome is the key molecular platform activated by MSU crystals, and its inhibition prevents IL-1beta and IL-18 processing and release. Colchicine does not lower uric acid levels and is not a uricosuric agent. Its toxicity at higher doses (nausea, vomiting, diarrhea) reflects disruption of rapidly dividing intestinal epithelial cells.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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