Allopurinol

An alternative to increasing uric acid excretion in the treatment of gout is to reduce its synthesis by inhibiting xanthine oxidase with allopurinol.

Allopurinol is absorbed after oral administration. Like uric acid, allopurinol is itself metabolized by xanthine oxidase. The resulting compound, alloxanthine, retains the capacity to inhibit xanthine oxidase and has a long duration of action.

Pharmacodynamics: Dietary purines are not an important source of uric acid. The quantitatively important amounts of purine are formed from amino acids, formate, and carbon dioxide in the body. Those purine ribonucleotides not incorporated into nucleic acids and those derived from the degradation of nucleic acids are converted to xanthine or hypoxanthine and oxidized to uric acid. When this last step is inhibited by allopurinol, there is a fall in the plasma urate level and a decrease in the size of the urate pool with a concurrent rise in the more soluble xanthine and hypoxanthine.

Indications

• in chronic tophaceous gout
• for recurrent renal stones
• in patients with renal functional impairment;
• When serum urate levels are grossly elevated.

Adverse Effects: Gastrointestinal intolerance, including nausea, vomiting, and diarrhea, may occur. Peripheral neuritis and necrotizing vasculitis, depression of bone marrow elements may occur. Hepatic toxicity and interstitial nephritis have been reported.