Uricosuricmedications (drugs) are substances that increase the excretion ofuric acid in theurine, thus reducing the concentration of uric acid inblood plasma. In general, this effect is achieved by action on theproximal tubule of thekidney. Drugs that reduce blood uric acid are not all uricosurics; blood uric acid can be reduced by other mechanisms (see otherAntigout Medications).
Uricosurics are often used in the treatment of gout, a disease in which uric acid crystals form deposits in the joints. By decreasing plasma uric acid levels, help dissolve these crystals, while limiting the formation of new ones. However, the increased uric acid levels in urine can contribute tokidney stones. Thus, use of these drugs iscontraindicated in persons already with a high urine concentration of uric acid (hyperuricosuria). In borderline cases, enough water 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 (such asprobenecid) increase the blood plasma concentration of certain other drugs and their metabolic products. While this is occasionally exploitable to good effect (seeoseltamivir), assessment of drug interactions is very important when using uricosuric drugs in the presence of other medications.
The primary uricosuric drugs includeprobenecid,benzbromarone andsulfinpyrazone.[citation needed]
Drugs with other primary uses, that have known uricosuric properties, includelosartan,[1]atorvastatin, andfenofibrate. Although these drugs may have significant uricosuric action, their other significant pharmacological actions inoff-label use as a uricosuric requires careful assessment of the patient to achieve the most benefit and least risk.[2][3]
Abdominalsurgery also has a uricosuric effect, as well as the potential to precipitate an acute attack of gout.[4]
In general, uricosuric drugs act on theproximal tubules in thekidneys, where they interfere with the absorption of uric acid from the kidney back into the blood. Several uricosurics are known to actin vitro by blocking the function of a protein encoded by the geneSLC22A12, 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 these drugs act on URAT1in vivo.[1] Thus, uricosuric drugs may be candidates for management in apersonalized medicine model.[citation needed]
Antiuricosuric drugs raise serum uric acid levels and lower urine uric acid levels. These drugs include alldiuretics,pyrazinoate,pyrazinamide,ethambutol,niacin, andaspirin.[5] TheNSAIDdiclofenac has an antiuricosuric action, which may be partly responsible for the extraordinarytoxicity of this drug invultures.[6]
Pyrazinamide, a drugindicated only for treatment oftuberculosis, is a potent antiuricosuric[7] and, as a consequence, has anoff-label use in the diagnosis of causes of abnormal uric acid clearance.[8] It acts onURAT1.[8]
Antiuricosuric drugs are useful for treatment ofhypouricemia and perhaps alsohyperuricosuria, but are contraindicated in persons with conditions includinghyperuricemia andgout.[citation needed]