Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allopurinol has been used for the treatment of gout and conditions associated with hyperuricemia for several decades. We explored the potential of allopurinol on cancer treatment. Allopurinol did not expose cytotoxicity as a single treatment in human hormone refractory prostate cancer cell lines, PC-3 and DU145. However, allopurinol drastically induced apoptosis of PC-3 and DU145 in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is a promising candidate for anticancer agent but its efficacy is limited by the existence of resistant cancer cells. We examined the underlying mechanism by which allopurinol overcomes the resistance of prostate cancer cells to TRAIL. Allopurinol up-regulated the expression of a proapoptotic TRAIL receptor, death receptor 5 (DR5). Allopurinol increased DR5 protein, mRNA, and promoter activity. Using DR5 small interfering RNA (siRNA), we showed that allopurinol-mediated DR5 up-regulation contributed to the enhancement of TRAIL effect by allopurinol. Furthermore, we examined the mechanism of allopurinol-mediated DR5 up-regulation. DR5 promoter activity induced by allopurinol was diminished by a mutation of a CAAT/enhancer binding protein homologous protein (CHOP)-binding site. In addition, allopurinol also increased CHOP expression, suggesting that allopurinol induced DR5 expression via CHOP. Allopurinol possesses the activity of a xanthine oxidase (XO) inhibitor. We used XO siRNA instead of allopurinol. XO siRNA also up-regulated DR5 and CHOP expression and sensitized the prostate cancer cells to TRAIL-induced apoptosis. Here, we show the novel potential of allopurinol in cancer treatment and indicate that the combination of allopurinol with TRAIL is effective strategy to expand the TRAIL-mediated cancer therapy.
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PMID:Anti-gout agent allopurinol exerts cytotoxicity to human hormone-refractory prostate cancer cells in combination with tumor necrosis factor-related apoptosis-inducing ligand. 1907 30

Treatment of gout and hyperuricemia can be difficult in patients with chronic renal failure. At present, there is no study available comparing the efficacy of the most widely used agent, allopurinol, and the uricosuric benzbromarone for the control of hyperuricemia in patients with renal insufficiency. We describe an open, randomized, actively controlled, comparative trial in patients with clearance of creatinine from 20 to 80 mL/ min/1.73 m(2). Patients were randomized to take benzbromarone (100-200 mg/day) or allopurinol (100-300 mg/day). Outcome variables were the following: reduction of serum urate (Sur), Sur & tl; 6 mg/dL (357 micromol/L), reduction of gouty bouts and reduction of tophi. During 9-24 months of follow-up 36 patients were studied.The reduction of Sur was higher with benzbromarone, and only 1 of 17 patients taking benzbromarone did not achieve Sur < 6 mg/dL versus 7 of 19 taking allopurinol. Patients who did not reach optimal Sur levels with allopurinol were more frequently taking diuretics and showed lower fractional excretion of urate and higher initial Sur levels than patients with proper control of Sur. Seven patients with suboptimal control of serum urate were changed to benzbromarone 100 mg/day, which showed efficacy similar in those who were initially randomized to benzbromarone. A reduction of gouty bouts and size of tophi was observed after proper control of Sur. Allopurinol is effective in controlling hyperuricemia, but patients with higher initial Sur levels or taking concomitant diuretic therapy are less prone to reach therapeutic goals.Benzbromarone is useful for the control of hyperuricemia in patients with renal insufficiency even with concomitant diuretic administration; patients benefited include those who previously had no improvement by taking allopurinol.
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PMID:Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study. 1907 56

This is a case report of a 36-year-old male with tophaceous gout for 16 years. He started therapy with 300 mg/day of allopurinol. He had received variable dexamethasone doses by self-prescription for 16 years. When allopurinol was initiated, he had hyperuricemia and normal renal function. Twenty days after starting allopurinol, he presented diffuse maculopapular rash, conjunctivitis, increase in serum creatinine values, leukocytosis and eosinophilia and the diagnosis of allopurinol hypersensitivity (AH) syndrome was made. He completely recovered from the AH and renal function normalized. However, the gout worsened over the following years in spite of treatment with benzobromarone, low doses of prednisone, and colchicine. Allopurinol desensitization was successful beginning with an oral low dose scheme (6.5 mug/day) until we reached 300mg/day. Today the patient receives allopurinol with no side effects. We believe that this is the first reported example of successful desensitization in full-blown AH with renal involvement. Our cautious regimen might be tried in other such patients.
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PMID:Desensitization to allopurinol after allopurinol hypersensitivity syndrome with renal involvement in gout. 1907 83

Gout and pain are synonymous, and a study in this issue of the BJP reports a novel anti-nociceptive effect of allopurinol, the drug most commonly used to treat gout. Allopurinol works by inhibiting xanthine oxidase (XO), the enzyme responsible for converting hypoxanthine to uric acid which is deposited as crystals in the joints of gout sufferers. Hypoxanthine is a metabolite of, and a possible precursor to, adenosine. Schmidt et al., find that acute inhibition of XO with allopurinol produces a modest adenosine A(1) receptor-mediated anti-nociceptive effect in common tests of chemical and thermal nociception in mice. A concomitant increase in cerebrospinal fluid levels of adenosine supports their hypothesis that inhibiting XO increases adenosine levels via salvage from hypoxanthine. Elevating endogenous adenosine levels by inhibiting metabolism is a well-established strategy for producing anti-nociception in many preclinical models, but inhibiting XO is likely to be particularly beneficial in some chronic pain states because of the pro-nociceptive reactive oxygen species that are produced by XO activity. Thus, allopurinol may have unexpected benefits in pain associated with chronic inflammation, diabetes and vascular dysfunction.
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PMID:Allopurinol for pain relief: more than just crystal clearance? 1913 97

Allopurinol, the first-line drug for serum urate-lowering therapy in gout, is approved by the US Food and Drug Administration for a dose up to 800 mg/d and is available as a low-cost generic drug. However, the vast majority of allopurinol prescriptions are for doses < or = 300 mg/d, which often fails to adequately treat hyperuricemia in gout. This situation has been promoted by longstanding, non-evidence-based guidelines for allopurinol use calibrated to renal function (and oxypurinol levels) and designed, without proof of efficacy, to avoid allopurinol hypersensitivity syndrome. Severe allopurinol hypersensitivity reactions are not necessarily dose-dependent and do not always correlate with serum oxypurinol levels. Limiting allopurinol dosing to < or = 300 mg/d suboptimally controls hyperuricemia and fails to adequately prevent hypersensitivity reactions. However, the long-term safety of elevating allopurinol dosages in chronic kidney disease requires further study. The emergence of novel urate-lowering therapeutic options, such as febuxostat and uricase, makes timely this review of current allopurinol dosing guidelines, safety, and efficacy in gout hyperuricemia therapy, including patients with chronic kidney disease.
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PMID:A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout. 1929 86

Oxidative stress plays an important role in the progression of vascular endothelial dysfunction. The two major systems generating vascular oxidative stress are the NADPH oxidase and the xanthine oxidase pathways. Allopurinol, a xanthine oxidase inhibitor, has been in clinical use for over 40 years in the treatment of chronic gout. Allopurinol has also been shown to improve endothelial dysfunction, reduce oxidative stress burden and improve myocardial efficiency by reducing oxygen consumption in smaller mechanistic studies involving various cohorts at risk of cardiovascular events. This article aims to explain the role of xanthine oxidase in vascular oxidative stress and to explore the mechanisms by which allopurinol is thought to improve vascular and myocardial indices.
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PMID:Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. 1943 71

There has been an increase in the incidence and prevalence of gout in the past several decades. A distinction needs to be made between the treatment of gout as an acute inflammatory disease and the lowering of the serum urate (SU) levels into a normal range. Treating acute gout attacks alone is not sufficient to prevent the disease from progressing. When treating gout one needs to treat acute attacks, and lower excess stores of uric acid to achieve dissolution of monosodium urate crystals through a long-term reduction of SU concentrations far beyond the threshold for saturation of urate and provide prophylaxis to prevent acute flares. The options available for the treatment of acute gout are NSAIDs, colchicine, corticosteroids, adrenocorticotropic hormone (ACTH) and intra-articular corticosteroids. The most important determinant of therapeutic success is not which anti-inflammatory agent is chosen, but rather how soon therapy is initiated and that the dose be appropriate. Prophylaxis should be considered an adjunct, rather than an alternative, to long-term urate-lowering therapy. For purposes of maintaining patient adherence to urate-lowering therapy, there is interest in improving prophylaxis of such treatment-induced attacks. The optimal agent, dose and duration for gout prophylaxis are unknown and require further investigation. The importance of long-term management of gout is the reduction and maintenance of SU in a goal range, usually defined as less than 6.0 mg/dL. Allopurinol and benzbromarone remain the cornerstone drugs for reducing SU levels lower than the saturation threshold to dissolve urate deposits effectively. Febuxostat and pegloticase help to optimize control of SU levels, especially in those patients with the most severe gout. Other agents, such as fenofibrate and losartan may be helpful as adjuvant drugs. Treatment for gout has advanced little in the last 40 years, until recently. The recent development of new therapeutic options promises to provide much needed alternatives for the many patients with gout who are intolerant of or refractory to available therapies. It is important to note that inappropriate use of medications as opposed to an apparent refractoriness to available therapies is not uncommon.
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PMID:Gout--what are the treatment options? 1946 70

Allopurinol is an inhibitor of xanthine oxidoreductase (XOR) and inhibits the generation of uric acid (UA) as the final product of purine catabolism, as well as the resulting generation of superoxide (O2(-)), in humans. Elevation of the serum UA (SUA) level, referred to as hyperuricemia (HU), eventually leads to gout and allopurinol has been used for the treatment of HU and gout. Studies have revealed the role of elevated SUA levels and the associated oxidative stress (OS) in a broad spectrum of pathological conditions and it is anticipated that these findings would also expand the use of allopurinol as a therapeutic drug. This article presents a review of reports, mainly of recent studies, on the efficacy of allopurinol in various diseases and explores novel potential uses of the drug. Important novel and potential uses of great interest include metabolic syndrome (MetS) and related disorders, chronic kidney disease (CKD), nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Ischemia-reperfusion injury and mucositis, encountered as adverse effects of cancer treatment, have also been under investigation as potential targets for allopurinol.
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PMID:Allopurinol, an inhibitor of uric acid synthesis--can it be used for the treatment of metabolic syndrome and related disorders? 1958 65

Allopurinol as an effective inhibitor of the enzyme xanthine oxidase (XO) has been used for several decades for the treatment of patients with gout and hyperuricemia. Because the inhibition of XO limits the formation of radical oxygen species as well as uric acid (UA) production, allopurinol has been used experimentally for the treatment of conditions associated with ischemia and reperfusion (I/R) injury.Although there have been many ischemic organs treated in the laboratory with allopurinol, the heart has been of particular interest. Therefore, we emphasize our attention to the administration of XO inhibitors such as allopurinol on cardiac I/R as well as cardiac failure. Experimental data also support allopurinol as a possible consideration for biochemical support after acute myocardial infarction. Anker and associates (Circulation. 2003;107:1991-1997) have observed a direct correlation between uric acid levels and mortality in treated heart failure patients. Anker and associates showed a 100% mortality rate in patients with UA levels 800 micromol/L or less over a period of 3 years. Comparing this to a 27% mortality rate in patients with UA levels 400 micromol/L or less over a period of 10 years, it seems that the suppression of XO activity ameliorates myocardial inefficiency, and poor vascular flow may present innovative contributions to the future treatment of I/R heart failure patients. Our review focuses on the role of allopurinol on ischemic hearts as well as those with added chronic heart failure.
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PMID:Allopurinol, xanthine oxidase, and cardiac ischemia. 1979 15

There have been recent advances in the understanding of underlying mechanisms and treatment of gout and chronic hyperuricemia, making this an important time to review the current state of the disease. The goal of this article is to provide a practical review of the current standard of care as well as discuss some new developments in the management. There is an increasing prevalence of gout and hyperuricemia worldwide. Gout confers a significant individual and societal burden and is often under-treated. Appropriate diagnosis and treatment of acute gout should be followed by aggressive and goal-oriented treatment of hyperuricemia and other risk factors. Allopurinol remains as a first-line treatment for chronic hyperuricemia, but uricosuric agents may also be considered in some patients. Febuxostat, a non-purine xanthine-oxidase inhibitor, is a new agent approved for the treatment of hyperuricemia in patients with gout, which may be used when allopurinol is contraindicated. Gout and hyperuricemia appear to be independent risk factors for incident hypertension, renal disease and cardiovascular disease. Physicians should consider cardiovascular risk factors in patients with gout and treat them appropriately and aggressively.
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PMID:Update on gout and hyperuricemia. 1990 78


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