Uricosurics and other antigout drugs

Uricosurics and other antigout drugs

Uricosurics, along with other antigout drugs, exert their effects through their anti-inflammatory actions.

Uricosurics

The two major uricosurics are:

• probenecid
• sulfinpyrazone.

Getting the gout out

Uricosurics act by increasing uric acid excretion in urine. The primary goal in using uricosurics is to prevent or control the frequency of gouty arthritis attacks.

Pharmacokinetics

Uricosurics are absorbed from the GI tract.

Distribution

Distribution of the two drugs is similar, with 75% to 95% of probenecid and 98% of sulfinpyrazone being protein-bound.

Metabolism and excretion

Metabolism of the drugs occurs in the liver, and excretion is primarily by the kidneys. Only small amounts of these drugs are excreted in stool.

Pharmacodynamics

Probenecid and sulfinpyrazone reduce the reabsorption of uric acid at the proximal convoluted tubules of the kidneys. This results in excretion of uric acid in urine, reducing serum urate levels.

Pharmacotherapeutics

Probenecid and sulfinpyrazone are indicated for the treatment of:

• chronic gouty arthritis
• tophaceous gout (the deposition of tophi or urate crystals under the skin and into joints).

A part-time promoter

Probenecid is also used to promote uric acid excretion in patients experiencing hyperuricemia.

Substitute when acute

Probenecid and sulfinpyrazone shouldn’t be given during an acute gouty attack. If taken at that time, these drugs prolong inflammation. Because these drugs may increase the chance of an acute gouty attack when therapy begins and whenever the serum urate level changes rapidly, colchicine is administered during the first 3 to 6 months of probenecid or sulfinpyrazone therapy.

Drug interactions

Many drug interactions, some potentially serious, can occur with uricosuric drugs:

• Probenecid significantly increases or prolongs the effects of cephalosporins, penicillins, and sulfonamides.
• Serum urate levels may increase when probenecid is taken with antineoplastic drugs.
• Probenecid increases the serum concentration of dapsone, aminosalicylic acid, and methotrexate, causing toxic reactions.
• Sulfinpyrazone increases the effectiveness of warfarin, increasing the risk of bleeding.
• Salicylates reduce the effects of sulfinpyrazone.
• Sulfinpyrazone may potentiate the effects of oral antidiabetic drugs, increasing the risk of hypoglycemia.

Warning!

Adverse reactions to uricosurics

Adverse reactions to uricosurics include uric acid stone formation and blood abnormalities.

Probenecid

• Headache
• Anorexia
• Nausea and vomiting
• Hypersensitivity reactions

Sulfinpyrazone

• Nausea
• Indigestion
• GI pain
• GI blood loss