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)

We report a case of myopathy induced by daily administration of colchicine. A 65-year-old man with gout and renal dysfunction had taken 1 mg of colchicine daily for 3 years. The dose was raised to 2 mg per day and two months later, he developed progressive weakness of the proximal limbs and had difficulty in rising from squatting and climbing stairs. Five months after the development of weakness, neurological examination showed proximal muscle weakness without wasting, generalized hyporeflexia and mild sensory loss and dysesthesia of the toes. Serum creatine kinase level was elevated to 788 IU/L and creatinine level was 2.1 mg/dl. Electromyography demonstrated myogenic changes with spontaneous activity. HE preparations of biceps muscle biopsy showed mild increase of variation in fiber size, small vacuoles with and without basophilic rims in some fibers and a few fibers with unevenly stained sarcoplasm. NADH-TR preparations showed numerous moth-eaten and targetoid fibers. The small rimmed vacuoles stained positively for acid phosphatase. Electron microscopy showed accumulation of lysosomes and autophagic vacuoles, and architectural changes and disruptions of myofibrils. After the discontinuation of colchicine, his strength and serum CK level normalized within two masquerading as polymyositis, may occur when customary doses of colchicine are given daily to patients with renal dysfunction.
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PMID:[Chronic human colchicine myopathy]. 226 97

Although colchicine has been used for centuries, its neuromuscular toxicity in humans is largely unrecognized. In this report we describe a characteristic syndrome of myopathy and neuropathy and present 12 new cases of the condition. Colchicine myopathy may occur in patients with gout who take customary doses of the drug but who have elevated plasma drug levels because of altered renal function. It usually presents with proximal weakness and always presents with elevation of serum creatine kinase; both features remit within three to four weeks after the drug is discontinued. The accompanying axonal polyneuropathy is mild and resolves slowly. Electromyography of proximal muscles shows a myopathy that is marked by abnormal spontaneous activity. Because of these features, colchicine myoneuropathy is usually misdiagnosed initially, either as probable polymyositis or as uremic neuropathy. The myopathy is vacuolar, marked by accumulation of lysosomes and autophagic vacuoles unrelated to necrosis or to the mild denervation in distal muscles. The morphologic changes in muscle suggest that the pathogenesis involves disruption of a microtubule-dependent cytoskeletal network that interacts with lysosomes. Correct diagnosis may save patients with this disorder from inappropriate therapy.
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PMID:Colchicine myopathy and neuropathy. 303 72

The presented case concerns a 77-year old man who had been chronically taking colchicine for treatment of gout. He was admitted because of a transient ischemic cerebrovascular attack with motor aphasia and complained of preexisting paraesthesias in the lower extremities. Neurological examination revealed a global muscular weakness, absent myotatic reflexes and a diminished sensation. Serum creatine kinase (CK) levels were increased and electromyography showed spontaneous fibrillations in deltoid muscles, positive spikewaves in deltoids and anterior tibial muscles. Motor and sensory conduction velocities were mildly reduced. Nerve biopsy findings were compatible with a chronic axonal neuropathy having produced a significant loss of myelinated axons and also denervation features of unmyelinated axons. In muscle, combined neurogenic and myogenic features were found. The former result from the axonal neuropathy. The latter were mainly characterized by focal myofibrillar disorganisation and accumulation of autophagic vacuoles in muscle fibres. The presented neuromuscular symptoms and signs, the increased CK values, the electromyographic and nerve conduction velocity findings as well as nerve and muscle biopsy observations, are consistent with the diagnosis of colchicine-induced myopathy and neuropathy. Furthermore, the disappearance of paraesthesias, normalisation of CK values, and disappearance of fibrillations and positive spike waves in deltoid and anterior tibial muscles on electromyography, after stopping of the colchicine therapy, supported the diagnosis.
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PMID:Chronic colchicine-induced myopathy and neuropathy. 772 94

Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints.
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PMID:Currently available hypolipidaemic drugs and future therapeutic developments. 859 27

Colchicine causes both muscle and peripheral nerve toxicity of subacute onset in patients with renal insufficiency. We report three cardiac transplant recipients, treated with colchicine for cyclosporin A (CyA)-induced gout, who developed acute weakness due to colchicine myoneuropathy. The onset of disabling weakness occurred over a 1-2 week period. All three patients had concomitant renal insufficiency and an elevated serum creatine kinase and two elevated CyA levels at the time of presentation. Electromyography revealed features of myopathy and motor axonal neuropathy in all three patients. Two underwent muscle biopsy which confirmed the presence of sarcoplasmic vacuoles characteristic of colchicine-induced myopathy. All patients rapidly improved with either colchicine dose reduction or drug discontinuation. In conclusion, cardiac transplant recipients treated with CyA and colchicine may be at increased risk of developing colchicine-induced myoneuropathy especially in the setting of concurrent renal insufficiency. In patients with post-transplantation gouty arthritis, other treatment modalities are suggested; and if colchicine is administered, the dose should be reduced, CyA levels should be monitored closely and patients should be assessed for signs of neuromuscular toxicity.
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PMID:Acute onset of colchicine myoneuropathy in cardiac transplant recipients: case studies of three patients. 949 3

Colchicine is widely employed for the treatment of gout in renal transplant patients where NSAIDs are contra-indicated and allopurinol prophylaxis is often avoided due to concomitant azathioprine immunosuppression. We report here a case of colchicine-induced myoneuropathy in a renal transplant recipient. Our patient had myalgia, muscle weakness, elevated creatine kinase levels, myopathic changes on electromyography and peripheral neuropathy. Withdrawal of colchicine resulted in recovery within 4 weeks. Renal transplant recipients are likely to be at greater risk of colchicine-induced myoneuropathy due to the unique concurrence of risk factors predisposing to toxicity in such patients. These risk factors include the high incidence of gout in this population, widespread use of colchicine as first-line therapy, impaired renal function and concomitant cyclosporin treatment. The diagnosis should be considered in any renal transplant recipient receiving the drug who develops myopathy. Prompt withdrawal of colchicine therapy should result in rapid clinical and biochemical improvement.
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PMID:Colchicine myoneuropathy in a renal transplant patient. 1212 15

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

We report a fatal case of toxic myopathy in a patient with a transplanted heart for severe ischemic coronary artery disease. He was on long-term cyclosporine, prednisone, and mycofenolate. Four months before the development of proximal muscle weakness, his simvastatin dose was doubled, and he was also started on colchicine for acute exacerbation of gout. He developed progressive muscle weakness leading to shortness of breath and hospitalization for respiratory failure. Colchicine and simvastatin were stopped on admission. He received high-dose methylprednisolone for continued muscle weakness while he was sedated with propofol. These changes led to a marked elevation of creatine kinase, peaking at 33,580 U/ml. The muscle biopsy revealed toxic vacuolization, mitochondrial damage, and no evidence of inflammation. Based on the timing of events, the combination of propofol, high-dose methylprednisolone, and cyclosporine have triggered rhabdomyolysis, which may have been facilitated by prior administration of colchicine and simvastatin.
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PMID:Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin. 1762 39

A case of colchicine-induced rhabdomyolysis is reported. A 48 year old African-American male with history of hypertension and chronic gout on colchicine 0.6 mg daily presented with symptoms of a community acquired pneumonia. The patient was started on 500 mg of clarithromycin orally twice daily and represented to the emergency room after 3 days complaining of severe muscle pain. His liver panel showed elevations in the serum aminotransferases; AST 513 mU/ml (nl 15-41) and ALT 182 mU/ml (nl 17-63). His complete blood count showed an elevated white blood cell count of 18,800/ml (nl 4,000-10,000/ml). Urine analysis was positive for myoglobin with no red cells present. Serum creatine kinase (CK) was 22,996 mU/ml (nl 31-221) with a normal troponin I 0.18 (nl <0.4).Investigations confirmed the presence of rhabdomyolysis and discontinuation of colchicine and clarithromycin resulted in resolution of clinical and biochemical features of rhabdomyolysis. By hospital day four, his muscle soreness had improved markedly. His serum CK improved to 3,389 mU/ml (nl 31-221 mU/ml) and serum creatinine improved to 1.5 mg/dl (nl 0.8-1.2). On hospital day five, the patient was discharged on oral anti-hypertensive medication and a ten-day course of doxycycline. Metabolism of colchicine by the cytochrome P450 3A4 system has been previously described, but this is the first published report of colchicine associated rhabdomyolysis secondary to drug metabolism interactions with an antibiotic. A review of medications that are metabolized via the cytochrome 3A4 and A-SLAVED-LIVER (Amiodarone, Simvastatin, Lovastatin, Atorvastatin, Verapamil, Erythromycin, Diltiazem, cLarithromycin, Itraconazole, Voriconazole, colchicinE, Ritonavir) pneumonic was established.
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PMID:Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis. 2541 92

A 67-year old man was hospitalized due to an aorto-coronary bypass and cecal perforation. After administration of atorvastatin, amiodarone, and fluconazole, rhabdomyolysis developed with electrolyte disturbances (hyperphosphatemia, hyopcalcemia) and a massive increase in creatine kinase and myoglobin. In the clinical course, other complications manifested such as acute renal failure, critical illness myopathy, acute gout on the knee, and sternal infection with coagulase-negative staphylococci. After stopping the assumed causal agents and treating the complications, the patient could be transferred for rehabilitation after a more than two months hospital stay. We discuss the causes and symptoms of muscle diseases as well as the epidemiology, mechanisms, treatment, and prevention of drug-induced myopathies with a focus on statins.
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PMID:[Rhabdomyolysis associated with atorvastatin combined with amiodarone and fluconazole]. 2136 57


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