Allopurinol
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| Systematic (IUPAC) name | |
|---|---|
| 3,5,7,8-tetrazabicyclo[4.3.0] nona-3,5,9-trien-2-one | |
| Identifiers | |
| CAS number | 315-30-0 |
| ATC code | M04AA01 |
| PubChem | 2094 |
| DrugBank | APRD00435 |
| ChemSpider | 2010 |
| Chemical data | |
| Formula | C5H4N4O |
| Mol. mass | 136.112 g/mol |
| SMILES | eMolecules & PubChem |
| Pharmacokinetic data | |
| Bioavailability | 78±20% |
| Protein binding | Negligible |
| Metabolism | hepatic (80% oxypurinol, 10% allopurinol ribosides) |
| Half life | 2 hours (oxypurinol 18-30 hours) |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
C(USA) |
| Legal status | |
| Routes | tablet (100, 300 mg) |
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Allopurinol is a drug used primarily to treat hyperuricemia (excess uric acid in blood plasma) and its complications, including chronic gout.[1]
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[edit] Mechanism of action
Allopurinol is a structural isomer of hypoxanthine (a naturally occurring purine in the body) and is an enzyme inhibitor, inhibiting xanthine oxidase.[1] 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.[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.
[edit] Uses
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. Similarly, allopurinol commonly is used as prophylaxis with chemotherapeutic treatments, which can rapidly produce severe hyperuricemia. Other established indications for allopurinol therapy include ischaemic reperfusion injury, kidney stones with a uric acid component (uric acid nephrolithiasis) and protozoal infections (Leishmaniasis). Also used to prevent tumor lysis with certain types of cancer.
Because allopurinol is not a uricosuric, it can be used in patients who have poor kidney function. However, allopurinol has two important disadvantages: its dosing is complex,[2] and some patients will be hypersensitive to it. Therefore, use of this drug requires careful monitoring.
[edit] Metabolism
Allopurinol 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.
[edit] Side effects
Side 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, 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.
Allopurinol can cause severe pancytopenia if given with azathioprine or mercaptopurine, due to inhibition of xanthine oxidase which metabolizes these drugs. It can also cause breast enlargement in both males and females.
[edit] Brand names
Allopurinol has been marketed in the United States since 1964. Allopurinol is marketed by Prometheus in the United States as Zyloprim, while in other countries it continues to be marketed by GlaxoSmithKline. Other brand names are Allohexal, Allosig, Milurit, Progout, and Zyloric. In South Africa, Allopurinol is marketed under the brand name Puricos. It also known as Zyrik 300 in India.
[edit] References
- ^ a b c Pacher P, Nivorozhkin A, Szabó C (March 2006). "Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol". Pharmacol. Rev. 58 (1): 87–114. doi:. PMID 16507884.
- ^ Dalbeth N, Stamp L (2007). "Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events". Semin Dial 20The 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. Similarly, allopurinol commonly is used as prophylaxis with chemotherapeutic treatments, which can rapidly produce severe hyperuricemia. Other established indications for allopurinol therapy include ischaemic reperfusion injury, kidney stones with a uric acid component (uric acid nephrolithiasis) and protozoal infections (Leishmaniasis). Also used to prevent tumor lysis with certain types of cancer. Because allopurinol is not a uricosuric, it can be used in patients who have poor kidney function. However, allopurinol has two important disadvantages: its dosing is complex,[2] and some patients will be hypersensitive to it. Therefore, use of this drug requires careful monitoring. (5): 391–5. doi:. PMID 17897242.
[edit] External links
- Zyloprim (patient information)
[edit] Further reading
- Zahran AM, Azab KS, Abbady MI (2006). "Modulatory role of allopurinol on xanthine oxidoreductase system and antioxidant status in irradiated rats". Egypt. J. Rad. Sci. Applic. 19 (2): 373-388.
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