315-30-0

Chemical Properties

White to Off-White Solid

Odorless tasteless white microcrystalline powder.

Uses

Xanthine oxidase inhibitor; decreases uric acid production. Used in treatment of hyperuricemia and chronic gout. Antiurolithic

Allopurinol is utilized to prevent or reduce high uric acid levels in the blood, which can lead to conditions like gout or gouty arthritis. It is also employed to manage excess uric acid levels caused by cancer medications or in patients with kidney stones. Allopurinol functions by replacing purine in the body's purine metabolism pathway, thereby reducing the synthesis and accumulation of uric acid. Allopurinol is especially indicated in the treatment of chronic tophaceous gout, since patients receiving it show a pronounced decrease in their serum and urinary uric acid levels. Because it does not depend on renal mechanisms for its efficacy, allopurinol is particularly beneficial for patients who already have developed renal uric acid stones, patients with excessively high urate excretion (e.g., above 1,200 mg in 24 hours), patients with a variety of blood disorders (e.g., leukemia, polycythemia vera), patients with excessive tophus deposition, and patients who fail to respond well to the uricosuric drugs. Allopurinol also inhibits reperfusion injury. This injury occurs when organs that either have been transplanted or have had their usual blood perfusion blocked are reperfused with blood or an appropriate buffer solution. The cause of this injury is local formation of free radicals, such as the superoxide anion, the hydroxyl free radical, or peroxynitrite. These substances are strong oxidants and are quite damaging to tissues.

Indications

Allopurinol (Zyloprim) is the drug of choice in the treatment of chronic tophaceous gout and is especially useful in patients whose treatment is complicated by renal insufficiency.

Brand name

Lopurin (Abbott); Lopurin (BASF); Zyloprim (Promethus).

Therapeutic Function

Xanthine oxidase inhibitor, Gout therapy

Air & Water Reactions

Insoluble in water.

Fire Hazard

Flash point data for Allopurinol are not available; however, Allopurinol is probably combustible.

Biochem/physiol Actions

Inhibitor of xanthine oxidase and de novo pyrimidine biosynthesis. A classical agent in treatment of hyperuricemia and gout.

Pharmacokinetics

Allopurinol was synthesized in 1956 as part of a study of purine antagonists. It is well absorbed on oral administration, with peak plasma concentrations appearing within 1 hour. Decreases of uric acid can be observed within 24 to 48 hours. Excretion of allopurinol and its metabolite occurs primarily in the urine, with approximately 20% of a dose being excreted in the feces.

Side effects

Common toxicities associated with allopurinol administration include a variety of skin rashes, gastrointestinal upset, hepatotoxicity, and fever. These reactions are often sufficiently severe to dictate termination of drug therapy. It is advised that therapy not be initiated during an acute attack of gouty arthritis. As with the uricosuric drugs, therapy with allopurinol should be accompanied both by a sufficient increase in fluid intake to ensure water diuresis and by alkalinization of the urine. Prophylactic use of colchicine also helps to prevent acute attacks of gout that may be brought on during the initial period of allopurinol ingestion.

Safety Profile

Human poison by ingestion. Poison experimentally by intraperitoneal and subcutaneous routes. An experimental teratogen. Human systemic effects by ingestion: blood leukopenia, dermatitis, jaundice, muscle weakness, thrombocytopenia. When heated to decomposition it emits toxic fumes of NOx. An FDA proprietary drug used as a xanthine oxidase inhibitor.