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Uricosuric medications (drugs) are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. Generally, this effect is achieved by action on the proximal tubule. Drugs that reduce blood uric acid are not all uricosurics; blood uric acid can be reduced by other mechanisms (see Template:Antigout preparations). Uricosurics often are used in the treatment of gout, a disease in which uric acid crystals deposit in joints. By decreasing plasma uric acid levels, uricosurics help dissolve these crystals and limit the formation of new crystals. However, by increasing urinary uric acid levels these drugs may contribute to uric acid nephrolithiasis (stones or calculi of uric acid in the kidneys and urinary system). Thus, use of these drugs is contraindicated in persons who already have a high urine concentration of uric acid (hyperuricosuria). In borderline cases, hydration sufficient to produce 2 liters of urine per day may be sufficient to permit use of an uricosuric drug. By their mechanism of action some uricosurics (eg Probenecid) increase the blood plasma concentration of certain other drugs and their metabolic products. Assessment of likely drug interactions is important, when using uricosuric drugs in the presence of other medications.
[edit] Primary uricosuricsPrimarily uricosuric drugs include probenecid, benzbromarone and sulfinpyrazone. [edit] Secondary uricosuricsDrugs with other primary uses, that have known uricosuric properties, include guaifenesin,[1] losartan,[2] atorvastatin, and fenofibrate. Although these drugs may have significant uricosuric action, because they have other significant pharmacological actions their off-label use as a uricosuric requires careful assessment of the patient to achieve the most benefit and least risk.[3][4]
Abdominal surgery also has a uricosuric effect, as well as the potential to precipitate an acute attack of gout.[5] [edit] PharmacologyGenerally, uricosuric drugs act in the kidneys, specifically in the proximal tubules, where they interfere with the absorption of uric acid from the kidney back into the blood. Several uricosurics are known to act in vitro by blocking the function of a protein encoded by the gene SLC22A12 also known as urate transporter 1 or URAT1. URAT1 is the central mediator in the transport of uric acid from the kidney into the blood. In some persons with loss-of-function mutations of URAT1, the uricosurics benzbromarone and losartan had no effect, suggesting that these drugs act on URAT1 in vivo.[2] Thus, uricosuric drugs may be candidates for management in a personalized medicine model. [edit] AntiuricosuricsAntiuricosuric drugs raise serum uric acid levels and lower urine uric acid levels. These drugs include all diuretics,[citation needed] pyrazinoate, pyrazinamide, ethambutol, and aspirin. The NSAID diclofenac has an antiuricosuric action, which may be partly responsible for the extraordinary toxicity of this drug in vultures.[6] Pyrazinamide, a drug indicated only for treatment of tuberculosis, is a potent antiuricosuric[7] and consequently has an off-label use in the diagnosis of causes of abnormal uric acid clearance.[8] It acts on URAT1.[8] Antiuricosuric drugs are useful for treatment of hypouricemia and perhaps also hyperuricosuria, but are contraindicated in persons with conditions including hyperuricemia and gout. [edit] See also
[edit] External links[edit] References
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