Colchicine is used in acute gout and familial Mediterranean fever. Its mechanism of action involves:
- A Competitive inhibition of xanthine oxidase, reducing uric acid synthesis
- B Direct blockade of IL-1beta receptor on synovial cells
- C Inhibition of NLRP3 inflammasome assembly by preventing tubulin polymerization, thereby blocking neutrophil migration and IL-1beta processing ✓
- D Uricosuric action by blocking URAT1 transporter in the proximal tubule
Correct answer: C. Inhibition of NLRP3 inflammasome assembly by preventing tubulin polymerization, thereby blocking neutrophil migration and IL-1beta processing
Explanation
Colchicine binds to free tubulin dimers and prevents microtubule polymerization. This arrests neutrophil motility, migration into joints, and phagocytosis of urate crystals, interrupting the inflammatory cascade. Additionally, by disrupting cytoskeletal function, colchicine prevents NLRP3 inflammasome assembly and subsequent caspase-1 activation and IL-1beta release. Xanthine oxidase inhibition is the mechanism of allopurinol/febuxostat; URAT1 blockade is the mechanism of probenecid/lesinurad.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.