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Allopurinol
Allopurinol is a drug used primarily to treat conditions arising from excess uric acid, most notably chronic gout. Allopurinol does not alleviate acute attacks of gout, but is useful in preventing recurrence. Allopurinol has been used in the United States since 1964. Additional recommended knowledge
Mechanism of actionAllopurinol is a structural isomer of hypoxanthine (a naturally occurring purine in the body) and acts to inhibit xanthine oxidase. This enzyme is responsible for the successive oxidation of hypoxanthine and xanthine resulting in the production of uric acid, the product of human purine metabolism.[1] In addition to blocking uric acid production, inhibition of xanthine oxidase causes an increase in hypoxanthine and xanthine, which are converted to closely related purine ribotides adenosine and guanosine monophosphates. Increased levels of these ribotides causes feedback inhibition of amidophosphoribosyl transferase, the first and rate-limiting enzyme of purine biosynthesis. Allopurinol therefore decreases both uric acid formation and purine synthesis. Uses (other than in treatment of gout)In addition to its use in gout, allopurinol is also commonly used as prophylaxis with chemotherapeutic treatments, which can rapidly result in very high uric acid concentrations due to widespread cell death (tumour lysis syndrome). Other established indications for allopurinol therapy include ischaemic reperfusion injury, kidney stones (urolithiasis) and protozoal infections (Leishmaniasis). MetabolismAllopurinol is rapidly metabolized by its target, xanthine oxidase, to its active metabolite 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 to be responsible for the majority of allopurinol's effect. Side effectsSide effects of allopurinol are rare, though significant when they occur. A small percentage of people develop a rash and must discontinue this drug. The most serious adverse effect is a hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, worsening 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 Syndrome (TENS) which is an adverse drug reaction. Brand namesAllopurinol is marketed by GlaxoSmithKline in the United States as Zyloprim. Other brand names are Allohexal, Allosig, Progout, and Zyloric. References
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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Allopurinol". A list of authors is available in Wikipedia. |