Uricosuric Agents

Probenecid and sulfinpyrazone are uricosuric drugs employed to decrease the body pool of urate in patients with tophaceous gout or in those with increasingly frequent gouty attacks. In a patient who excretes large amounts of uric acid, the uricosuric agents should be avoided so as not to precipitate the formation of uric acid calculi. Uricosuric drugs are organic acids and act at the anionic transport sites of the renal tubule.

Pharmacokinetics: Probenecid is completely reabsorbed by the renal tubules and is metabolized very slowly. Sulfinpyrazone or its active hydroxylated derivative is rapidly excreted by the kidneys. Its effect after oral administration is almost that of probenecid.

Pharmacodynamics: Uric acid is freely filtered at the glomerulus. Like many other weak acids, it is also both reabsorbed and secreted in the middle segment of the proximal tubule. Uricosuric drugs probenecid, sulfinpyrazone, and large doses of aspirin affect these active transport sites so that net reabsorption of uric acid in the proximal tubule is decreased. Because aspirin in small doses causes net retention of uric acid by inhibiting the secretory transporter, it should not be used for analgesia in patients with gout.

Indications: Uricosuric therapy should be initiated if several acute attacks of gouty arthritis have occurred, when evidence of tophi appears, or when plasma levels of uric acid in patients with gout are so high that tissue damage is almost inevitable.

Adverse Effects: Both drugs cause gastrointestinal irritation, but sulfinpyrazone is more active in this regard. Probenecid is more likely to cause allergic dermatitis, but a rash may appear after the use of either compound. Nephrotic syndrome has resulted from the use of probenecid. Both sulfinpyrazone and probenecid may cause aplastic anemia.