Other antigout drugs

Other antigout drugs

Allopurinol is used to reduce production of uric acid, preventinggouty attacks, and colchicine is used to treat acute gouty attacks.

Pharmacokinetics

Allopurinol and colchicine take somewhat different paths through the body.

All aboard allopurinol

When given orally, allopurinol is absorbed from the GI tract. Allo-purinol and its metabolite oxypurinol are distributed throughout the body except in the brain, where drug concentrations are 50% of those found in the rest of the body. It’s metabolized by the liver and excreted in urine.

Following colchicine’s course

Colchicine is absorbed from the GI tract and is partially metabo-lized in the liver. The drug and its metabolites then reenter the in-testinal tract through biliary secretions. After reabsorption from the intestines, colchicine is distributed to various tissues. It’s ex-creted primarily in stool and to a lesser degree in urine.

Pharmacodynamics

Allopurinol and its metabolite oxypurinol inhibit xanthine oxi-dase, the enzyme responsible for the production of uric acid. By reducing uric acid formation, allopurinol eliminates the hazards of hyperuricuria.

Migration control

Colchicine appears to reduce the inflammatory response to mono-sodium urate crystals deposited in joint tissues. Colchicine may produce its effects by inhibiting migration of white blood cells (WBCs) to the inflamed joint. This reduces phagocytosis and lac-tic acid production by WBCs, decreasing urate crystal deposits and reducing inflammation.

Pharmacotherapeutics

Allopurinol treats primary gout, hopefully preventing acute gouty attacks. It can be prescribed with uricosurics when smaller dosages of each drug are directed. It’s used to treat:

§    gout or hyperuricemia that may occur with blood abnormalities and during treatment of tumors or leukemia

§    primary or secondary uric acid nephropathy (with or without the accompanying symptoms of gout)

§    patients who respond poorly to maximum dosages of urico-surics or who have allergic reactions or intolerance to uricosuric drugs (it’s also used to prevent recurrent uric acid stone forma-tion).

Acute alert

Colchicine is used to relieve the inflammation of acute gouty arthritis attacks. If given promptly, it’s especially effective in re-lieving pain. In addition, giving colchicine during the first several months of allopurinol, probenecid, or sulfinpyrazone therapy may prevent the acute gouty attacks that sometimes accompany the use of these drugs.

Drug interactions

Colchicine doesn’t interact significantly with other drugs. When allopurinol is used with other drugs, the resulting interactions can be serious:

·                 Allopurinol potentiates the effect of oral anticoagulants.

·                 Allopurinol increases the serum concentrations of mercapto-purine and azathioprine, increasing the risk of toxicity.

·                 Angiotensin-converting enzyme inhibitors increase the risk of hypersensitivity reactions to allopurinol.

·                 Allopurinol increases serum theophylline levels.

·                 The risk of bone marrow depression increases when cyclophos-phamide is taken with allopurinol. (See Adverse reactions to otherantigout drugs.)