Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telescoped digits of the hands and feet developed in a 69-year-old male with severe chronic tophaceous gout during allopurinol treatment. Extensive osseous tophi, resorbed rapidly during therapy with this xanthine oxidase inhibitor and not replaced by new bone matrix, were responsible for the deformity. Several hypotheses are advanced to explain the failure of bone erosions to heal.
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PMID:Allopurinol-associated hand and foot deformities in chronic tophaceous gout. 57 55

Gout may be a primary or a secondary disorder. In both types of gout, overproduction or underexcretion of uric acid, or a combination of these abnormalities, may be the underlying mechanism. Controversy exists over the need for treatment of asymptomatic hyperuricemia. Treatment of tophi requires use of both uricosurics and allopurinol. A xanthine oxidase inhibitor is the drug of choice for patients with uric acid stones and for those with renal insufficiency.
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PMID:Hyperuricemia and gout: an update. 689 39

Gout is a common disease with a worldwide distribution. The major risk factor for the development of gout is sustained asymptomatic hyperuricaemia. Although pharmacological therapy of asymptomatic hyperuricaemia is not recommended, primary prevention of gout can be achieved through lifestyle changes including weight loss, restricting protein and calorie intake, limiting alcohol consumption, avoiding the use of diuretics in the treatment of hypertension, and avoiding occupational exposure to lead. The arthritis of gout can be readily managed with the use of nonsteroidal anti-inflammatory drugs (NSAIDs); systemic steroids or corticotrophin (adrenocorticotrophic hormone; ACTH) should be used in patients with contraindications to NSAIDs, or who are intolerant of them. Because of potential toxicity, colchicine should not be used to treat acute gout, but should be used in low dosage (0.6 to 1.2 mg/day) for prophylaxis of recurrent attacks of gout. The other cornerstone of prevention of recurrent gouty attacks is control of hyperuricaemia, which can be effectively accomplished with antihyperuricaemic therapy. The choice of agents, either uricosuric drugs or xanthine oxidase inhibitors, is based on the level of urinary uric acid excretion, renal function, age of patient, history of renal calculi and presence of tophi. Treatment and prevention of gout are exceedingly effective and patients can usually be managed by their primary care physician.
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PMID:Prevention and management of gout. 768 72

Gout is a disease of antiquity but is increasing once again in prevalence despite availability of reasonably effective treatments. This may be related to a combination of factors, including diet, obesity, and diuretic use. Allergic reactions, noncompliance, drug interactions, and sometimes inefficacy all limit the effective use of current hypouricemic agents. There are new treatments for gout on the horizon, including febuxostat, a nonpurine inhibitor of xanthine oxidase with a potentially better combination of efficacy and side effects than allopurinol. Diagnostic progress is being made in that ultrasound may offer a noninvasive means of diagnosing tophaceous deposits in and around joints. The increasing prevalence of gout means that dermatologists will see more cutaneous manifestations of gout, including tophi, draining sinus tracts, panniculitis, and dystrophic calcifications.
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PMID:Metabolic diseases: gout. 1711 68

Gout is a common chronic arthritis that can lead to significant disability. Gout is one of the few rheumatological conditions that can be diagnosed with certainty, has a known cause and can be cured with appropriate therapy. Hypouricaemic agents reduce uric acid concentrations through inhibiting uric acid production (allopurinol) or enhancing uric acid excretion (probenecid, benzbromarone). Allopurinol is the most commonly used hypouricaemic agent but at recommended doses often fails to reduce adequately uric acid concentrations and prevent acute attacks of gout. The use of probenecid is limited by lack of efficacy in renal impairment. In the last few years, new agents in the management of hyperuricaemia and gout have become available. Febuxostat, a new xanthine oxidase inhibitor, is an effective hypouricaemic agent although further data are required for patients with renal impairment and other significant medical conditions. Rasburicase, a recombinant uricase (which catalyses the conversion of uric acid to the more readily excreted allantoin) is available for prevention of tumour lysis syndrome. However, its repeated use, as would be required in chronic gout, is limited by antigenicity. A less antigenic PEGylated uricase can rapidly reduce serum uric acid concentrations and promote resorption of tophi. However, further information with regard to the long-term risks and benefits of these agents is required. These agents may ultimately be used in the short term to rapidly deplete urate stores (induction therapy) followed by long-term therapy with an alternative hypouricaemic agent to prevent subsequent accumulation of uric acid (maintenance therapy).
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PMID:Emerging therapies in the long-term management of hyperuricaemia and gout. 1738 67

Urate lowering treatment is indicated in patients with recurrent acute attacks, tophi, gouty arthropathy, radiographic changes of gout, multiple joint involvement, or associated uric acid nephrolithiasis. Uricosuric agents like benzbromarone and probenecid are very useful to treat hyperuricemia as well as allopurinol (xanthine oxidase inhibitor). Uricosuric agents act the urate lowering effect through blocking the URAT1, an urate transporter, in brush border of renal proximal tubular cells. In order to avoid the nephrotoxicity and urolithiasis due to increasing of urinary urate excretion by using uricosuric agents, the proper urinary tract management (enough urine volume and correction of aciduria) should be performed.
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PMID:[Uricosuric agent]. 1840 25

Febuxostat is a new non-purine xanthine oxidase inhibitor that is more potent than allopurinol 300 mg daily. In two Phase III trials, significantly more febuxostat-treated gout patients met the primary endpoint [serum urate (sUA) <6 mg/dl (<360 mumol/l) at the last three visits] (48 and 53% with 80 mg; 65 and 62% with 120 mg), compared with those receiving allopurinol 300 mg (22 and 21%; P < 0.001 in both studies). Febuxostat was more effective than allopurinol in the subset with impaired renal function; no dose adjustment is required in mild-to-moderate renal impairment. Long-term extension studies confirmed the efficacy and tolerability of febuxostat. In patients who achieved the sUA target of 6 mg/dl (360 mumol/l), the incidence of gout flares fell steadily and tophi resolved in many patients. The incidence of adverse events such as dizziness, diarrhoea, headache and nausea with febuxostat was similar to allopurinol. The incidence of cardiovascular side-effects (Antiplatelet Trialists Collaboration events) was numerically higher with febuxostat than with allopurinol, but this was not statistically significant. Co-administration of febuxostat with AZA or 6-mercaptopurine is not recommended. Prophylaxis (colchicine and/or NSAIDs) against acute attacks should be used for at least the first 6 months, since early mobilization flares were observed in the clinical trials. In conclusion, febuxostat is more effective than allopurinol 300 mg daily in reducing sUA levels <6 mg/dl (360 mumol/l), the target recommended by EULAR, and offers a new option for the long-term treatment of gout.
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PMID:Febuxostat: a new treatment for hyperuricaemia in gout. 1944 78

Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than "standard dosage" allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol.
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PMID:Management of hyperuricemia in gout: focus on febuxostat. 2016 38

Around 1.4% of the UK population have gout, the prevalence of which increases with age to around 3% in women and 7% in men aged over 75 years. Acute gout is intensely painful and can reduce patients' quality of life. It occurs when the serum uric acid concentration (SUA) rises (hyperuricaemia) and persists above the solubility threshold of monosodium urate (400 micromol/L [6.8 mg/dL]), leading to urate crystal formation that causes arthritis, gouty tophi (nodules) in subcutaneous tissues and renal calculi. The mainstay of treatment for chronic gout is allopurinol, which inhibits xanthine oxidase (an enzyme involved in the production of uric acid in the body). However, this drug has to be stopped in a minority of patients due to rashes or hypersensitivity. Febuxostat (Adenuric - Menarini/Ipsen), another xanthine oxidase inhibitor, is a newly licensed treatment for chronic hyperuricaemia in conditions where urate deposition has occurred. Here we consider its place for patients with gout.
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PMID:Febuxostat for gout. 2063 Nov 96

The Western world appears to be in the midst of the third great gout epidemic of all time. In this century, gout is increasing in prevalence despite an increased understanding of its risk factors and pathophysiology, and the availability of reasonably effective treatment. The main cultural factors responsible for this appear to be diet, obesity, ethanol use and medications. Excess fructose consumption is a newly recognized modifiable risk factor. The debate has been renewed concerning hyperuricemia as an independent risk factor for renal insufficiency and cardiovascular disease. Prevention is still rooted in lifestyle choices. Existing treatments have proven to be unsatisfactory in many patients with comorbidities. New treatments are available today and on the horizon for tomorrow, which offer a better quality of life for gout sufferers. These include febuxostat, a nonpurine inhibitor of xanthine oxidase with a potentially better combination of efficacy and safety than allopurinol, and investigational inhibitors of URAT-1, an anion exchanger in the proximal tubule that is critical for uric acid homeostasis. New abortive treatments include interleukin-1 antagonists that can cut short the acute attack in 1 to 2 days in persons who cannot take nonsteroidal anti-inflammatory drugs, colchicine or corticosteroids. Lastly, newer formulations of uricase have the ability to dissolve destructive tophi over weeks or months in patients who cannot use currently available hypouricemic agents. Diagnostically, ultrasound and magnetic resonance imaging offer advanced ways to diagnose gout noninvasively, and just as importantly, a way to follow the progress of tophus dissolution. The close association of hyperuricemia with metabolic syndrome, hypertension and renal insufficiency ensures that nephrologists will see increasing numbers of gout-afflicted patients.
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PMID:New and improved strategies for the treatment of gout. 2169 41


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