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Pharmacology Miscellaneous (Pharmacology) 9849e7e1

Allopurinol acts by inhibiting:

A
Uric acid carboxylase
B
Hypoxanthine oxidase
C
Uric acid synthase
D
Xanthine oxidase
High-Yield Explanation
Ans. d (Xanthine oxidase). (Ref. Harriosn, Internal medicine 16th ed., 1704, 2047, 2311)Drugs used in Rx of GoutALLOPURINOL- Short acting.- Competitive inhibitor of xanthine oxidase (| conversion of xanthine to uric acid).- 80% absorbed orally.- Not bound to plasma proteins.- Inhibits 6-mercaptopurine and azathioprine degradation.- Potentiates warfarin and theophylline.- Uses: Chronic gout, secondary hyperuricemia,in lymphoma and leukemia to prevent tumor lysis-associated urate nephropathy.- It is known to cause liver granulomaProbenecidChronic gout. Inhibits reabsorption of uric acid in PCT (also inhibits secretion of penicillin).ColchicineAcute gout. Depolymerizes microtubules, impairing leukocyte chemotaxis and dcgranulation. Gl side effects, especially if given orally. (Note: indomethacin is less toxic, more commonly used in acute gout.) Educational Points:# Specific treatment of uric acid calculi requires reducing the urine uric acid concentration with a xanthine oxidase inhibitor, such as allopurinol or febuxostat.# FEBUXOSTAT (80-240 mg/d) is also taken once daily, and doses do not need to be adjusted in the presence of mild to moderate renal dysfunction.# A xanthine oxidase inhibitor is also indicated for the treatment of 2,8-dihydroxyadenine kidney stones.# Urate oxidase (RASBURICASE) can also be administered IV to prevent or to treat tumor lysis syndrome.

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