Allopurinol treats gout by inhibiting xanthine oxidase. A patient on allopurinol who also takes 6-mercaptopurine (6-MP) for leukaemia will have:
- A Decreased 6-MP efficacy due to enhanced thiopurine methyltransferase activity
- B No interaction; 6-MP is metabolised exclusively by glucuronidation
- C Increased 6-MP toxicity because allopurinol inhibits its catabolism by xanthine oxidase ✓
- D Decreased uric acid production independent of 6-MP dose
Correct answer: C. Increased 6-MP toxicity because allopurinol inhibits its catabolism by xanthine oxidase
Explanation
6-Mercaptopurine is normally inactivated by xanthine oxidase to 6-thiouric acid; allopurinol inhibits this pathway, causing 6-MP to accumulate to toxic levels with severe myelosuppression. The dose of 6-MP must be reduced to 25% of normal when combined with allopurinol. TPMT is an alternate catabolic pathway but does not compensate fully. Glucuronidation is not the primary pathway for 6-MP.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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