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Allopurinol Review Article

 

Allopurinol (Zyloprim, and generics) is a drug used primarily to treat hyperuricemia (excess uric acid in blood plasma) and its complications, including chronic gout.

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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, 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.

The primary use of allopurinol is to treat hyperuricemia (excess uric acid in blood plasma) and its complications. Allopurinol does not alleviate acute attacks of gout, but is useful in chronic gout to prevent future attacks. Likewise, allopurinol commonly is used as prophylaxis with chemotherapeutic treatments (Ex: mercaptopurine and thioguanine), which can rapidly produce severe hyperuricemia. Other established indications for allopurinol therapy include ischemic reperfusion injury, kidney stones with a uric acid component (uric acid nephrolithiasis), and protozoal infections (Leishmaniasis).

Because allopurinol is not a uricosuric, it can be used in patients with poor kidney function. However, allopurinol has two important disadvantages: Its dosing is complex, and some patients will be hypersensitive to it. Therefore, use of this drug requires careful monitoring.

Allopurinol can be used in patients with poor kidney function, but it may also help them. A study of allopurinol use in patients with chronic kidney disease suggested that "Allopurinol decreases C-reactive protein and slows down the progression of renal disease in patients with chronic kidney disease. In addition, allopurinol reduces cardiovascular and hospitalization risk in these subjects."

A recent study has suggested that allopurinol can help reduce the effects of angina in ischaemic heart disease by reducing the workload on the heart.

Allopurinol is used as an add-on drug for refractory epilepsy, because it is an adenosine agonist, which inhibits glutamine release from excitatory neurons, but doesn't change the plasma concentration of other epilepsy drugs.

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-effects: 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.[citation needed] Allopurinol is one of the drugs commonly known to cause Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TENS), two life-threatening dermatological conditions.[citation needed] More common is a less-serious rash that leads to discontinuing this drug.

Study finds HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions which includes Steven Johnson Syndrome and toxic epidermal necrosis caused by allopurinol.

Allopurinol can cause severe pancytopenia if given with azathioprine or mercaptopurine, due to inhibition of xanthine oxidase, which metabolizes these drugs.

Allopurinol can lower blood pressure in mild hypertension.

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.


 

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