Uricosuric

Oxyphenbutazone (712), y-hydroxyphenylbutazone and kebuzone (715) are metabolites of phenylbutazone in liver. The first cited is an equally potent antiinflammatory agent but slightly less toxic. Compounds (711) and (712) are rarely used as analgesics and antipyretics because of their toxicities. The first one is used in therapy of rheumatoid disorders characterized by a lack of detectable antiglobulin and antinuclear antibodies in the serum. The y-hydroxyphenylbutazone has marked uricosuric activity but little antirheumatic effect. Kebuzone (715) is an antiinflammatory agent still widely used in Europe. 

Replacement of the methyl ketone moiety in 78 by a phenyl sulfoxide, interestingly, leads to a relatively potent uricosuric agent with diminished antiinflammatory action. This effect in lowering serum levels or uric acid leads to the use of this drug in the treatment of gout. Alkylation of diethyl malonate with the chlorosulfide, 79, gives the intermediate, 80. The pyrazolodione (81) is prepared in the usual way by condensation with hydrazobenzene. Careful oxidation of the sulfide with one equiv-... 

Uricosuric. An agent that enhances the excretion of uric acid. 

Therapeutic Function Skeletal muscle relaxant uricosuric Chemical Name 5-Chloro-2-benzoxazolamine Common Name —... 

Uricosuric dtugs increase the renal excretion of uric acid by inhibiting its renal reabsorption. Therapeutically used uricosuric dtugs are benzbromarone, probenecid and sulfinpyrazone. 

Urea Transporter Uric Acid Uricostatic Drug Uricosuric Drug Urodilatin... 

Salicylates antagonize probenecid s uricosuric action. Concurrent administration of probenecid increases die effects of acyclovir, barbiturates, benzodiazepines, dap-sone, mediotrexate, NSAIDs, rifampin, and the sulfonamides. 

Probenecid is a uricosuric agent that blocks the tubular reabsorption of uric acid, increasing its excretion. Because of its mechanism of action, probenecid is contraindicated in patients with a history of uric acid stones or nephropathy. Probenecid loses its effectiveness as renal function declines and should be avoided when the creatinine clearance is 50 mL/minute or less. Its uricosuric effect is counteracted by low aspirin doses, which many patients receive for prophylaxis of coronary heart disease. 

Uricosuric Pertaining to, characterized by, or promoting renal secretion of uric acid. 

The major side effects associated with uricosuric therapy are GI irritation, rash and hypersensitivity, precipitation of acute gouty arthritis, and stone formation. These drugs are contraindicated in patients who are allergic to them and in patients with impaired renal function (CLcr <50 mL/min) or a history of renal calculi, and in patients who are overproducers of uric acid. 

Chronic hyperuricemia, because of under-excretion, is treated with a uricosuric drug (probenecid). 

Management of an acute attack of gout involves the use of high doses of nonsteroidal anti-inflammatory agents (NSAIDs). Colchicine is useful in patients with heart failure where the use of NSAIDs is contraindicated because of water retention. Allopurinol and other uricosuric agents are not indicated for acute attacks as they may aggravate the condition. The use of an intra-articular corticosteroid injection in gout is unlicensed. 

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