Uricosuric Agents

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The uricosuric drugs (or urate diuretics) are anions that are somewhat similar to urate in structure; therefore, they can compete with uric acid for transport sites. Small doses of uricosuric agents will actually decrease the total excretion of urate by inhibiting its tubular secretion. The quantitative importance of the secretory mechanism is relatively minor, however, and at high dosages these same drugs increase uric acid elimination by inhibiting its proximal tubular reabsorption. Thus, uricosuric drugs have a seemingly paradoxical effect on both serum and urinary uric acid levels: at low doses, they increase serum levels while decreasing the urinary levels; they have the opposite effect on these two levels at high dosages.

The two most clinically important uricosuric drugs, probenecid and sulfinpyrazone, are organic acids. The initial phase of therapy with uricosuric drugs is the most dangerous period. Until uricosuric drug levels build up sufficiently to fully inhibit uric acid reabsorption as well as secretion, there may be a temporary increase in uric acid blood levels that significantly increases the risk of an acute gouty attack. Therefore, it is wise to begin therapy with the administration of small amounts of colchicine before adding a uricosuric drug to the therapeutic regimen. In addition, the initial rise in urinary uric acid concentrations during uricosuric drug therapy may result in renal stone formation.

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