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Uricosurics and other antigout drugs
Saturday, January 21, 2012 Posted by Piscean

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.

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