Allopurinol

 
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More about Allopurinol

What is/are Allopurinol?

Generic Zyloprim (ALLOPURINOL) is a hyperuricemic agent used to treat gout and to prevent certain kidney stones from reforming. It may also be used to treat other conditions as determined by your doctor.

Mechanism of Action

Allopurinol is a purine analog; it is a structural isomer of hypoxanthine (a naturally occurring purine in the body) and is an inhibitor of the enzyme xanthine oxidase. Xanthine oxidase is responsible for the successive oxidation of hypoxanthine and xanthine, resulting in the production of uric acid, the product of human purine metabolism. In addition to blocking uric acid production, inhibition of xanthine oxidase causes an increase in hypoxanthine and xanthine. While xanthine cannot be converted to purine ribotides, hypoxanthine can be salvaged to the purine ribotides adenosine and guanosine monophosphates. Increased levels of these ribotides may cause feedback inhibition of amidophosphoribosyl transferase, the first and rate-limiting enzyme of purine biosynthesis. Allopurinol, therefore, decreases uric acid formation and may also inhibit purine synthesis.

Metabolism

A common misconception is that allopurinol is metabolized by its target, xanthine oxidase, but this action is principally carried out by Aldehyde oxidase. The active metabolite of allopurinol is oxypurinol, which is also an inhibitor of xanthine oxidase. Allopurinol is almost completely metabolized to oxypurinol within two hours of oral administration, whereas oxypurinol is slowly excreted by the kidneys over 18–30 hours. For this reason, oxypurinol is believed responsible for the majority of allopurinol's effect.

Side-effects

Because allopurinol is not a uricosuric, it can be used in patients with poor kidney function. However, allopurinol has two important disadvantages.

First, its dosing is complex. Second, some patients are hypersensitive to the drug, therefore its use requires careful monitoring. Allopurinol has rare but potentially fatal adverse effects involving the skin. The most serious adverse effect is a hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, worsened renal function, and, in some cases, allopurinol hypersensitivity syndrome. Allopurinol is one of the drugs commonly known to cause Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TENS), two life-threatening dermatological conditions. More common is a less-serious rash that leads to discontinuing this drug. Studies have found HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions that include Steven Johnson Syndrome and toxic epidermal necrosis caused by allopurinol.

More rarely, allopurinol can also result in the depression of bone marrow elements, leading to cytopenias, as well as aplastic anemia. Moreover, allopurinol can also cause peripheral neuritis in some patients, although this is a rare side effect. Another side effect of allopurinol is interstitial nephritis.

It is suspected to cause congenital malformations when used during pregnancy, and should be avoided whenever possible by women trying to conceive.

Brand names

Allopurinol has been marketed in the United States since August 19, 1966, when it was first approved by FDA under the trade name of Zyloprim. Allopurinol was marketed at the time by Burroughs-Wellcome. Allopurinol is now a generic drug sold under a variety of brand names including Allohexal, Allosig, Milurit, Alloril, Progout, Zyloprim, Zyloric, Zyrik and Aluron.

This article uses material from the Wikipedia article Allopurinol, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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