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)

Two of our patients experienced myotoxicity associated with colchicine administration. The first was a 54-year-old woman who was receiving dialysis and came to the emergency department with progressive generalized weakness and vomiting. She recently had taken colchicine for the treatment of gout. Physical examination revealed proximal muscle weakness and tenderness on palpation. Her creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were elevated at 7185, 563, and 541 U/L, respectively. Drug-induced myopathy was suspected and colchicine was discontinued. The patient was discharged after symptom resolution 1 week later. The second patient was an 83-year-old woman with chronic renal insufficiency who came to the hospital with anorexia, diarrhea, and inability to get out of bed due to progressive weakness. Her colchicine dosage recently had been increased for gout management. Physical examination revealed generalized muscle weakness and tenderness on palpation. Her CK, ALT, and AST levels were elevated at 1797, 147, and 172 U/L, respectively. Electromyographic results were consistent with colchicine myopathy. The patient was discharged with minimal residual muscle weakness 1 week after discontinuation of colchicine. A literature search identified 82 documented cases of colchicine-induced myotoxicity. Most patients had a history of proximal weakness and pain with elevated CK, ALT, and AST levels. Onset of symptoms generally occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in underlying disease state in those receiving long-term therapy. Muscle toxicity was not necessarily accompanied by gastrointestinal symptoms. Concomitantly administered drugs often were cyclosporine or corticosteroids. Diagnosis may be confirmed by electromyography or muscle biopsy. Colchicine-induced myotoxicity is a rare adverse effect but is well described in the literature. Clinicians should recognize that renal impairment is the primary risk factor for development of colchicine-induced myotoxicity, and that dosage adjustment or alternative therapy may be required.
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PMID:Colchicine myotoxicity: case reports and literature review. 1558 44

Hypoxanthine phosphoribosyltransferase (HPRT) deficiency is an inherited disorder. Complete deficiency of HPRT activity is phenotypically expressed as the devastating Lesch-Nyhan syndrome. Partial HPRT deficiency usually causes hyperuricemia, precocious gout, and uric acid nephrolithiasis. We describe an 18-year follow-up of a 5-year old boy with partial HPRT deficiency and report a novel mutation in his HPRT gene. He presented with overproduction of uric acid and passage of uric acid renal stones, and without gout or neurological and behavioral abnormalities. Treatment with allopurinol, adequate hydration, urinary alkalization, and a low-purine diet was started. No subsequent nephrolithiasis has occurred. After 18-year of this therapy his physical and neuropsychological status were normal, merely his glomerular filtration rate (GFR, normal 97-137 mL min(-1)/1.73 m(2)) fell from normal to 65.1 mL min(-1). The most likely cause of initial renal impairment in our patient is uric and/or xanthine crystalluria. A missense and transition mutation 169A>G (57ATG>GTG, 57met>val) in exon 3 of the patient's HPRT gene was identified and the mother was the carrier of the mutation. As far as we are aware, the identified mutation has not previously been reported. We named the mutant HPRT Maribor.
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PMID:Eighteen-year follow-up of a patient with partial hypoxanthine phosphoribosyltransferase deficiency and a new mutation. 1596 71

Gouty arthritis, a common source of pain and disability, is the most common form of inflammatory arthritis affecting older people. The authors review the epidemiology and pathogenesis of hyperuricemia and gout, as well as the clinical forms of gouty arthritis. Gout is part of a clinical spectrum of conditions (obesity, diabetes mellitus, hyperlipidemia, coronary artery disease) and need for better patient education on management of these associated conditions is emphasized. The general algorithm of gout management is presented. Clinical particularities of gout presentation in older patients (increased incidence in women, polyarticular onset with hand involvement, earlier development of tophi, association with use of diuretics) are reviewed. Barriers against an optimal control of gout include lack of patient education, presence of comorbid conditions, particularly renal impairment, use of multiple drugs such as diuretics, and cognitive decline. Gout management in older adults remains unsatisfactory.
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PMID:Gouty arthritis. A primer on late-onset gout. 1602 79

Gout is one of the best understood among the rheumatological disorders and one of the most satisfying to treat. Even non-specialists should be able to diagnose and treat most patients provided some important principles are appreciated. Management of a minority of patients, including those with renal impairment is difficult and often unsatisfactory, because of restricted treatment options. In this paper, the basic principles underlying the diagnosis and management of gout are discussed first, followed by practical approaches.
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PMID:Diagnosis and management of gout: a rational approach. 1614 87

Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor. Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined. Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with renal failure, solid organ transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is essential for patients taking benzbromarone. Physicians should carefully consider therapeutic options for the management of hypertension and hyperlipidaemia, which are common in transplant recipients. While loop and thiazide diuretics increase serum urate, amlodipine and losartan have the same antihypertensive effect with the additional benefit of lowering serum urate. Atorvastatin, but not simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it has been associated with a decline in renal function. Gout in solid organ transplantation is an increasing and challenging clinical problem; it impacts adversely on patients' quality of life. Recognition and, if possible, alleviation of risk factors, prompt treatment of acute attacks and early introduction of hypouricaemic therapy with careful monitoring are the keys to successful management.
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PMID:Gout in solid organ transplantation: a challenging clinical problem. 1639 75

Gout is one of the oldest and better understood among rheumatic diseases. It is characterized by chronic hyperuricemia and recurrent attacks of acute arthritis provoked by release of sodium urate crystals into joints. The manifestations of Gout can be abolished by lifelong urate-lowering therapy maintainine serum urate levels under 360 mmol/l. The management of a minority of patients, including those with renal impairment, is difficult and often unsatisfactory because of restricted treatment options. In this paper; the current options for treating hyperuricemia are first discussed then followed by new approches.
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PMID:[Treatment of gout in 2006]. 1726 96

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

Elderly-onset gout (EOG), defined as a disease with onset at age 65 years or over, shows relevant epidemiological, clinical and therapeutic differences from the typical middle-age form. The main differences are the more frequent subacute/chronic polyarticular onset with hand involvement, the unusual localization of tophi on ostheoarthritis (OA) nodes, the increased female/male ratio and the frequent association with drugs that decrease renal urate excretion (diuretics and low-dose aspirin) and/or with primitive renal impairment. EOG has recently been confirmed as the most common inflammatory arthropathy in older people, with important demographic implications and substantial impact on daily clinical practice. Despite the high prevalence, gout, in the elderly, often remains misdiagnosed or diagnosed late in its clinical course. Even when correctly recognized, its treatment is often difficult or unsatisfactory.
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PMID:Elderly-onset gout: a review. 1765 19

Allopurinol is the drug most widely used to lower the blood concentrations of urate and, therefore, to decrease the number of repeated attacks of gout. Allopurinol is rapidly and extensively metabolised to oxypurinol (oxipurinol), and the hypouricaemic efficacy of allopurinol is due very largely to this metabolite. The pharmacokinetic parameters of allopurinol after oral dosage include oral bioavailability of 79 +/- 20% (mean +/- SD), an elimination half-life (t((1/2))) of 1.2 +/- 0.3 hours, apparent oral clearance (CL/F) of 15.8 +/- 5.2 mL/min/kg and an apparent volume of distribution after oral administration (V(d)/F) of 1.31 +/- 0.41 L/kg. Assuming that 90 mg of oxypurinol is formed from every 100mg of allopurinol, the pharmacokinetic parameters of oxypurinol in subjects with normal renal function are a t((1/2)) of 23.3 +/- 6.0 hours, CL/F of 0.31 +/- 0.07 mL/min/kg, V(d)/F of 0.59 +/- 0.16 L/kg, and renal clearance (CL(R)) relative to creatinine clearance of 0.19 +/- 0.06. Oxypurinol is cleared almost entirely by urinary excretion and, for many years, it has been recommended that the dosage of allopurinol should be reduced in renal impairment. A reduced initial target dosage in renal impairment is still reasonable, but recent data on the toxicity of allopurinol indicate that the dosage may be increased above the present guidelines if the reduction in plasma urate concentrations is inadequate. Measurement of plasma concentrations of oxypurinol in selected patients, particularly those with renal impairment, may help to decrease the risk of toxicity and improve the hypouricaemic response. Monitoring of plasma concentrations of oxypurinol should also help to identify patients with poor adherence. Uricosuric drugs, such as probenecid, have potentially opposing effects on the hypouricaemic efficacy of allopurinol. Their uricosuric effect lowers the plasma concentrations of urate; however, they increase the CL(R) of oxypurinol, thus potentially decreasing the influence of allopurinol. The net effect is an increased degree of hypouricaemia, but the interaction is probably limited to patients with normal renal function or only moderate impairment.
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PMID:Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. 1765 71

Allopurinol is the mainstay of urate-lowering therapy for patients with gout and impaired renal function. Although rare, a life-threatening hypersensitivity syndrome may occur with this drug. The risk of this allopurinol hypersensitivity syndrome (AHS) is increased in renal impairment. The recognition that AHS may be because of delayed-type hypersensitivity to oxypurinol, the main metabolite of allopurinol, and that oxypurinol concentrations are frequently elevated in patients with renal impairment prescribed standard doses of allopurinol has led to the widespread adoption of allopurinol-dosing guidelines. These guidelines advocate allopurinol dose reduction according to creatinine clearance in patients with renal impairment. However, recent studies have challenged the role of these guidelines, suggesting that AHS may occur even at low doses of allopurinol, and that these guidelines lead to under-treatment of hyperuricemia, a key therapeutic target in gout. Based on current data, we advocate gradual introduction of allopurinol according to current treatment guidelines, with close monitoring of serum uric acid concentrations. In patients with severe disease and persistent hyperuricemia, allopurinol dose escalation above those recommended by the guidelines should be considered, with careful evaluation of the benefits and risks of therapy. Further work is needed to clarify the safety and efficacy of allopurinol dose escalation, particularly in patients with renal impairment.
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PMID:Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events. 1789 42


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