Which of the following drugs is useful in treatment of gout with recurrent renal urate stones because it decreases the excretion of uric acid?
(A) allopurinol
(B) aspirin
© colchicine
(D) indomethacin
(E) sulfinpyrazone
Explanation:
(A) Allopurinol and its metabolite alloxanthine inhibit xanthine oxidase, thus preventing conversion of xanthine and hypoxanthine to uric acid. Although xanthine and hypoxanthine then accumulate, these compounds are more soluble than uric acid and less likely to deposit in joints or precipitate in the urine. Most doses of aspirin (choice B) increase retention of uric acid, especially low doses. Colchicine (choice C) is an inhibitor of microtubule function that brings relief in an acute gout attack by inhibiting the motility of granulocytes and preventing the formation of mediators of inflammation by leukocytes. Because of its toxicity at higher doses, it is now used chiefly at low doses to prevent acute attacks. Indomethacin (choice D) is an NSAID that inhibits COX and reduces formation of prostaglandins and eicosanoids involved in gouty arthritis. It has no effect on the formation of uric acid and very little on its excretion. Sulfinpyrazone (choice E) and probenecid are uricosuric agents—they increase the excretion of uric acid by the kidney. Renal uric acid excretion is determined by the balance between the amount filtered plus that
actively secreted and the amount undergoing passive and active reabsorption. At very low doses, these agents inhibit active secretion and thus promote retention of uric acid. At higher (clinical) doses, both active secretion and active reabsorption are inhibited, with the result that excretion is enhanced.