Xanthine oxidase inhibitor

Therapeutic Function Xanthine oxidase inhibitor gout therapy Chemical Name 1 H-pyra2olo[3,4-d] pyrimidin4-ol Common Name —... 

Anti-gout Drugs. Figure 1 Xanthine oxidase-catalyzed reactions. Xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid, respectively. Hypoxanthine and xanthine are more soluble than uric acid. Xanthine oxidase also converts the uricostatic drug allopurinol to alloxanthine. Allopurinol and hypoxanthine are isomers that differ from each other in the substitution of positions 7 and 8 of the purine ring system. Although allopurinol is converted to alloxanthine by xanthine oxidase, allopurinol is also a xanthine oxidase inhibitor. Specifically, at low concentrations, allopurinol acts as a competitive inhibitor, and at high concentrations it acts as a noncompetitive inhibitor. Alloxanthine is a noncompetitive xanthine oxidase inhibitor. XOD xanthine oxidase. 

Allopurinol 1 mM Xanthine oxidase inhibitor, suppresses oxygen free radical production... 

Granger, D.N., McCord, J.M., Parks, D.A. and FloUwarth, M.E. (1986). Xanthine oxidase inhibitors attenuate ischaemia-induced vascular permeability changes in the cat intestine. Gastroenterology 90, 80-84. 

Administration of synthetic antioxidants and/or chelating agents that suppress iron ion-dependent free-radical reactions. Some enzyme inhibitors may be appropriate here, for example, xanthine oxidase inhibitors. 

Pharmacologic prevention strategies for tumor lysis syndrome are aimed at low- and high-risk patients (Fig. 96-7). Allopurinol is a xanthine oxidase inhibitor that is used for prevention only because it has no effect on preexisting elevated uric acid. Rasburicase is a recombinant form of urate oxidase that is useful for both prevention and treatment but is extremely expensive (Table 96-12). Although the approved dose is 0.2 mg/kg per day... 

The 4-hydrazino-pyrazolo[3,4-rf]pyrimidine derivative 80 yields pyrazolo[4,3-e]-[l,2,4]triazolo[4,3-c]pyrimidinones 82 through hydrazone derivatives 81 <00JCS(P1)33>, these compounds being a new class of potential xanthine oxidase inhibitors. 

Allopurinol and its major metabolite, oxypurinol, are xanthine oxidase inhibitors and impair the conversion of hypoxanthine to xanthine and xanthine to uric acid. Allopurinol also lowers the intracellular concentration of PRPP. Because of the long half-life of its metabolite, allopurinol can be given once daily orally. It is typically initiated at a dose of 100 mg/day and increased by 100 mg/day at 1-week intervals to achieve a serum uric acid level of 6 mg/dL or less. Serum levels can be checked about 1 week after starting therapy or modifying the dose. Although typical doses are 100 to 300 mg daily, occasionally doses of 600 to 800 mg/day are necessary. The dose should be reduced in patients with renal insufficiency (200 mg/day for CLcr 60 mL/min or less, and 100 mg/day for CLcr 30 mL/min or less). 

Allopurinol is the antihyperuricemic drug of choice in patients with a history of urinary stones or impaired renal function, in patients who have lymphoproliferative or myeloproliferative disorders and need pretreatment with a xanthine oxidase inhibitor before initiation of cytotoxic therapy to protect against acute uric acid nephropathy, and in patients with gout who are overproducers of uric acid. 

Westerfield, W. W., Richert, D. A., Higgins, E. S., Further studies with xanthine oxidase inhibitors. J. Biol. Chem. 234 (1959), p. 1897-1900... 

Dashti HM, Al-Sayer H, Behbehani A, et al. 1992. Liver cirrhosis induced by carbon tetrachloride and the effects of superoxide dismutase and xanthine oxidase inhibitor treatment. J R Coll Surg Edinb 37 23-28. 

Allopurinol, a xanthine-oxidase inhibitor, may decrease tissue urate deposits in patients who are overproducers of uric acid, i.e. patients with primary hypemricaemia, in myeloproliferative neoplastic diseases and in hyperuricaemia resulting from tissue breakdown after cancer chemotherapy or radiation therapy. Allopurinol may also be recommended, in certain circumstances, in undersecre-tors of uric acid. 

Pacher P, Nivorozhkin A, Szabo C. Therapeutic effects of xanthine oxidase inhibitors renaissance half a century after the discovery of allopurinol. Pharmacol Rev 2006 58(1) 87-114. 

Azathioprine can be administered both orally and intravenously. It is well absorbed orally and after its rapid conversion to 6-mercaptopurine it is inactivated by xanthine oxidase which converts 6-mercaptopurine to 6-thiouric acid. This final metabolite is then excreted in the urine. In combination with the xanthine oxidase inhibitor allopurinol dose adjustments of azathioprine are needed. Renal disease also raises 6-mercaptopurine concentrations and can make dose adjustments necessary. Azathioprine is still used in organ transplantation programs and for the management of several autoimmune diseases. Its adverse effects include nausea, vomiting, diarrhea and, more seriously, bone marrow suppression and hepatotoxicity. Azathioprine is not thought to cause fetal malformation. 

Allopurinol is an xanthine oxidase inhibitor. It reduces urate production and is used in primary and secondary urate overproduction. Therapy of hyperuricemia prevents recurring attacks of acute gouty arthritis. Allopurinol dosages are 300 mg/day for serum creatinine < 1.5 mg/dl and 100 mg/day for serum creatinine between 1.6-2.0 mg/dl. Reduction of tophi is slow with allopurinol, particularly in patients with giant tophi and renal insufficiency where drug dosage is limited. 

Isovitexin derivative from plant leaves as a xanthine oxidase inhibitor. Patent-Japan Kokai Tokkyo Koho- HV069 05,238,943 1993 10 pp. 

Chemical Class Hypoxanthine isomer, xanthine oxidase inhibitor... 

Mechanism of Action A xanthine oxidase inhibitor that decreases uric acid production by inhibiting xanthine oxidase, an enzyme. Therapeutic Effect Reduces uric acid concentrations in both serum and urine. 

Nagamatsu and co-workers also reported the reaction of 30 with hydrazine to produce 31, a key intermediate in the synthesis of potential xanthine oxidase inhibitors 32 <99CC1461>. The regioselectivity of this hydrazine displacement thus paralleled that observed with carbanionic nucleophiles. 

The best known xanthine oxidase inhibitor is allopurinol (248), first synthesized by Robins (56JA784) and still the drug of choice for treatment of gouty arthritis. The metabolism of this drug as well as its other effects have been extensively studied. 

MP is converted to an inactive metabolite (6-thiouric acid) by an oxidation reaction catalyzed by xanthine oxidase, whereas 6-TG undergoes deamination. This is an important issue because the purine analog allopurinol, a potent xanthine oxidase inhibitor, is frequently used as a supportive care measure in the treatment of acute leukemias to prevent the development of hyperuricemia that often occurs with tumor cell lysis. Because allopurinol inhibits xanthine oxidase, simultaneous therapy with allopurinol and 6-MP would result in increased levels of 6-MP, thereby leading to excessive toxicity. In this setting, the dose of mercaptopurine must be reduced by 50-75%. In contrast, such an interaction does not occur with 6-TG, which can be used in full doses with allopurinol. 

If the inherited defect involves certain enzymes then an enzyme inhibitor could also be effective. Allopurinol is a xanthine oxidase inhibitor, or purine antagonist, which can reduce the level of uric acid in organs and tissues. Its primary metabolite, alloxanthine, is also active which extends its half-life in the body (half-life of allopurinol is 2-3 hours, for alloxanthine is 18-30 hours). The drug is well-tolerated with few side... 

Astrup, H. N. 1963. Oxidized flavor in milk and the xanthine oxidase inhibitor. J. Dairy Sci. 46, 1425. 

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