Allopurinol
254790
206928012
2008-04-20T18:21:55Z
Thijs!bot
1392310
robot Adding: [[it:Allopurinolo]]
{{drugbox
| IUPAC_name = 3,5,7,8-tetrazabicyclo[4.3.0] nona-3,5,9-trien-2-one
| image =allopurinol structure.png
| width = 200
| CAS_number = 315-30-0
| ATC_prefix = M04
| ATC_suffix = AA01
| ATC_supplemental =
| PubChem = 2094
| DrugBank = APRD00435
| C=5 | H=4 | N=4 | O=1
| molecular_weight = 136.112 g/mol
| bioavailability = 78±20%
| protein_bound = Negligible
| metabolism = hepatic (80% oxypurinol, 10% allopurinol ribosides)
| elimination_half-life = 2 hours (oxypurinol 18-30 hours)
| pregnancy_category = C(USA)
| legal_status = Schedule 6 (USA)
| routes_of_administration = tablet (100, 300 mg)
}}
'''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.
== Mechanism of action ==
Allopurinol is a structural [[isomer]] of [[hypoxanthine]] (a naturally occurring [[purine]] in the body) and acts to [[enzyme inhibitor|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.<ref>Pacher P, Nivorozhkin A, Szabo."Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol". Pharmacological 2006 Mar;58(1):87-114. PMID 16507884 </ref> 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 [[ribotide]]s 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 stone]]s (urolithiasis) and protozoal infections ([[Leishmaniasis]]).
== 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.
== 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]], 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 names ==
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''', '''Progout''', and '''Zyloric'''.
== References ==
<references/>
* Ahmed M. Zahran , Kh. Sh. Azab and M. I. Abbady. Modulatory Role Of Allopurinol On Xanthine Oxidoreductase System And Antioxidant Status In Irradiated Rats. ''Egypt. J. Rad. Sci. Applic.'', 19(2): 373-388 (2006).
{{Antigout preparations}}
[[Category:Antigout agents]]
[[ar:الوبيورينول]]
[[de:Allopurinol]]
[[fr:Allopurinol]]
[[it:Allopurinolo]]
[[nl:Allopurinol]]
[[ja:アロプリノール]]
[[pl:Allopurinol]]
[[pt:Alopurinol]]