Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The files of 122 patients treated for at least 6 months with bezafibrate, a second generation fibric acid derivative, were reviewed. Our indications for bezafibrate treatment included cases of type IIb, IV and V hyperlipidemia which did not respond to a serious dietetic trial. Mean decrease in plasma triglycerides was 45% and in cholesterol 1012%, while in HDL-cholesterol there was a mean increase of 8%. The drug was usually well tolerated. Thorough review of patient files for side effects revealed gastrointestinal disturbances in 6.5%. There was a decrease in libido in 4%. 2 patients developed gynecomastia, 1 abnormal liver function tests and 1 severe myositis. All side effects were fully reversed on discontinuing the drug. Bezafibrate seems to be well-tolerated and suitable for treating type IIb, IV and V hyperlipidemia unresponsive to diet.
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PMID:[Long-term bezafibrate treatment in a lipid clinic]. 152 40

The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias. 849 94

Hyperlipidemia is common in patients with glomerular proteinuria. It may contribute to atherosclerotic complications and accelerate glomerular damage. Early trials of the fibric acid derivative clofibrate led to a myositis syndrome causing many nephrologists to abandon attempts at treatment of nephrotic hyperlipidemia. Recent trials with lipid-lowering medications have been successful without major side effects. The bile acid sequestrants colestipol and cholestyramine bind bile acids in the gut and deplete the hepatic cholesterol pool, thus inducing LDL hepatocyte receptors. Recent studies showed a reduction of total cholesterol of 8-20% and LDL cholesterol of 19-31% without significant changes in HDL cholesterol. Probucol has reduced total cholesterol 23-30% and LDL cholesterol 23-25% in nephrotic patients. Although HDL cholesterol was reduced, the LDL/HDL ratio remains favorably changed. The fibric acid derivative gemfibrozil inhibits adipose lipolysis and enhances lipoprotein lipase activity thus decreasing LDL synthesis and increasing its removal. It caused a large decrease in triglycerides with a 13-15% decrease in total and LDL cholesterol in a recent trial. HDL cholesterol increased 18%. The HMG-CoA reductase inhibitors inhibit the rate-limiting step in cholesterol biosynthesis hence inducing an increase in LDL receptors on hepatocytes. Trials have shown decreases of 18-36% in total cholesterol and 18-47% in LDL cholesterol, while HDL cholesterol was either increased or unchanged. The use of lipid-lowering agents of several classes has been effective in ameliorating the progression of glomerular damage in a number of different models of glomerulosclerosis. Nevertheless, so far in humans lipid lowering drugs have not been established to have an effect on either the degree of proteinuria or the progression of glomerulosclerosis.
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PMID:Lipid-lowering agents in proteinuric diseases. 225 70

A 49-year-old woman with chronic renal failure was given gemfibrozil for hyperlipidemia. She developed gemfibrozil-induced myositis which precipitated an acute compartment syndrome, necessitating emergency fasciotomy. The muscle biopsy showed prominent degeneration of the skeletal muscle fibers, associated with moderate chronic inflammatory infiltration. Electron microscopy revealed myofibrillary fragmentation and mitochondrial disorganization. The clinicopathologic features of gemfibrozil-induced myositis appear to be distinct from those of clofibrate-induced muscular syndrome. Extreme caution should be exercised in the use of gemfibrozil in patients with impaired renal function.
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PMID:Gemfibrozil induced myositis: a case report with light microscopic and ultrastructural study. 800 60

The purpose of this study was to investigate the triglyceride-lowering effect of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in the combined hyperlipidemia of non-insulin-dependent diabetes mellitus (NIDDM). In this double-blind trial, 66 patients with NIDDM (24 men and 42 women, age 37-71), with low-density lipoprotein cholesterol (LDL-C) levels of 130-300 mg/dL (3.4-7.8 mmol/L) and triglyceride (TG) levels of 200-1,000 mg/dL (2.3-11.3 mmol/L) despite an 8-week period of diet modification, were randomized to receive either fluvastatin at 20 mg once daily (at night) or placebo for 6 weeks, followed by an increase of fluvastatin to 20 mg twice daily for an additional 6 weeks of treatment. After 12 weeks, fluvastatin decreased plasma levels of total cholesterol by 19.9% (p < 0.001), LDL-C by 24.3% (p < 0.001), TG by 15.3% (p < 0.01), very low-density lipoprotein cholesterol (VLDL-C) by 19.7% (p < 0.001), apolipoprotein (apo) B by 21.3% (p < 0.001), and apo E by 18.1% (p < 0.05), whereas high-density lipoprotein cholesterol (HDL-C) levels were increased by 4.6% (p < 0.05). Within the intermediate-density lipoprotein cholesterol (IDL-C) fraction, a constituent analysis revealed a total cholesterol reduction of 35% (p < 0.01). Greater decreases in TG were seen in patients who had higher levels of TG at baseline. Slight increases in glycemic indices and body weight were seen in both treatment groups. The occurrence of clinical and laboratory abnormalities was similar with both active treatment and placebo, and no myositis was observed. Slight increases in aspartate (ASAT; mean 5.6 U/L at the higher dose) and alanine (ALAT; mean 5.1 U/L at the higher dose) aminotransferases were not clinically significant. In this first, parallel-group placebo-controlled trial of a reductase inhibitor in a free-living NIDDM population, fluvastatin safely improved the combined TG, VLDL-C, IDL-C, LDL-C, and HDL-C abnormalities associated with NIDDM.
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PMID:Efficacy and safety of fluvastatin in patients with non-insulin-dependent diabetes mellitus and hyperlipidemia. 801 70

Hyperlipidemia is an important cardiovascular risk factor. Lipid-lowering therapy has been shown to decrease morbidity and mortality in these patients. Combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and a fibric-acid derivative has been reported to be more efficacious to reduce low-density lipoprotein (LDL) cholesterol and triglycerides but may be associated with an increased risk of myositis. The aim of this study was to investigate the efficacy and tolerability of fluvastatin, an HMG-CoA reductase inhibitor, alone and in combination with bezafibrate, a fibric-acid derivative. In a randomized controlled trial with 454 hypercholesterolemic patients (mean cholesterol, 8.6 +/- 1.6 mM), fluvastatin (20 mg/day) significantly lowered total plasma cholesterol levels (-12.5%; p < 0.0001 vs. placebo), LDL cholesterol (-14%; p < 0.0001), and triglycerides (-4%; p = 0.05). A small increase in high-density lipoprotein (HDL) cholesterol levels (3%, NS) also was observed. Combination therapy with fluvastatin and bezafibrate (400 mg/day) in 71 patients with persistent hypertriglyceridemia during treatment with the statin resulted in a more pronounced reduction in triglyceride (-47%; p < 0.0001) and total cholesterol levels (-15%; p < 0.0001) than did fluvastatin alone. Furthermore, the additional bezafibrate significantly increased HDL cholesterol (+5%; p < 0.001). No significant increases in creatine phosphokinase levels or in frequency of myalgia were observed. In summary, fluvastatin decreases both cholesterol and triglyceride levels. In patients with persistent hypertriglyceridemia, combination therapy with fluvastatin and bezafibrate may be safely used to lower triglyceride and cholesterol levels more efficiently.
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PMID:Efficacy and tolerability of fluvastatin and bezafibrate in patients with hyperlipidemia and persistently high triglyceride levels. 1071 Jan 19

Fibric acid derivatives are a class of hypolipidaemic drugs used in the treatment of patients with hypertriglyceridaemia, mixed hyperlipidaemia and diabetic dyslipidaemia. Fibrate therapy results in a significant decrease in serum triglycerides and an increase in high-density lipoprotein (HDL) cholesterol levels. The latest drugs of this class are also effective in lowering low-density (LDL) cholesterol levels and can change the distribution of LDL towards higher and larger particles. The effects of fibrates on lipid metabolism are mostly mediated through the activation of peroxisome proliferator-activated receptors (PPARalpha). A number of angiographic and clinical trials have confirmed that fibrates can slow the progression of atherosclerotic disease and decrease cardiovascular morbidity and mortality. Recently published data suggest that the ability of fibrates to prevent atherosclerosis is not related only to their hypolipidaemic effects but also to other 'pleiotropic effects', such as their anti-inflammatory, antioxidant and antithrombotic effects, as well as their ability to improve endothelial function. Interestingly, fibrates may favourably influence the thrombotic/fibrinolytic system. In fact, most of these drugs can significantly decrease plasma fibrinogen levels and inhibit tissue factor expression and activity in human monocytes and macrophages. Some studies have shown that fibrates can improve carbohydrate metabolism in patients with dyslipidaemia, including diabetic patients. Among fibrates only fenofibrate can significantly decrease serum uric acid levels by increasing renal urate excretion. Fibrates, with the possible exception of gemfibrozil, can significantly increase serum creatinine and homocysteine levels. Finally, a reduction in serum alkaline phosphatase and gamma glutamyltranspeptidase (gammaGT) activity is a well-documented effect of therapy with fibrates. The fibrates are generally well-tolerated drugs with few side-effects. The most important side-effect is myositis, which is observed in patients with impaired renal function or when statins are given concomitantly.
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PMID:Effects of fibrates on serum metabolic parameters. 1274 Jan 59

Obesity is a heterogeneous condition of variable aetiology, generally associated with pathologies such as arterial hypertension, hyperlipidaemia, diabetes and cardiac disease. These conditions, either themselves or because of the various treatments used, may further modify blood rheology in an arbitrary manner. Therefore, analyses of changes in the blood rheology induced by obesity in humans have had differing and controversial results. In our laboratory, a model of hypertriglyceridaemic obesity is provided by an inbred rat strain; the beta genotype from the IIMb/Fm strain, presenting a syndrome of moderate obesity with apparent peripubertal onset, associated with hypertriglyceridaemia and glucose intolerance that turns into diabetes. The alpha genotype, originated from the same IIM/Fm stock, represents the control. The present study describes a comparative analysis of the variables determining the rheological behaviour of the blood in obese and control strains. Our results, agreeing with some other studies performed in humans, confirmed the haemorheological changes associated with obesity, and the fact that these changes became more evident in the presence of pathologies such as diabetes. It appears that triglyceridaemia. cholesterolaemia and hyperglycaemia may influence the rheological behaviour of the cell membrane and this damage may provoke a decrease in erythrocyte deformability and, consequently, hyperviscosity of the blood.
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PMID:Haemorheological variables in a rat model of hypertriglyceridaemic obesity and diabetes. 1250 37

This retrospective study was carried out to assess the effectiveness of statin-gemfibrozil combination therapy in a community practice lipid clinic and to review safety data from published literature. Forty-six consecutive patients received a statin and gemfibrozil combination for resistant hyperlipidemia to either agent therapy. Fasting total cholesterol (mg/dL), high-density lipoprotein cholesterol (mg/dL), and triglycerides (mg/dL) were measured. Low-density lipoprotein cholesterol (mg/dL) was calculated using the Friedewald formula if triglycerides were <400 mg/dL. Combination therapy reduced total cholesterol, low-density lipoprotein cholesterol, and triglycerides by 11% (p=0.02), 22% (p=0.049), and 39% (p=0.0002), respectively, and raised high-density lipoprotein cholesterol by 5% (p=0.3). A pooled analysis of 838 patients from the literature on statin-gemfibrozil combination therapy revealed an incidence of myositis and severe myopathy of 0.7% and 0.6%, respectively (excluding cerivastatin). We conclude that statin-gemfibrozil combination therapy is effective in significantly reducing total cholesterol, low-density lipoprotein cholesterol, and triglycerides with a trend toward raising high-density lipoprotein cholesterol in patients with hyperlipidemia resistant to either agent alone. Myositis and severe myopathy are infrequent, but not rare side effects which may be statin-specific regarding the incidence of occurrence.
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PMID:Effectiveness of statin-gemfibrozil combination therapy in patients with mixed hyperlipidemia: experience of a community lipid clinic and safety review from the literature. 1460 12

Statin therapy (3-hydroxy-3methylglutaryl coenzyme A reductase inhibitor) is beneficial for primary prevention of cardiovascular events in patients younger than age 65 years with hyperlipidemia, yet there is uncertainty about using these agents for primary prevention in octogenarians. We present the case that can be made for not treating octogenarians with statins for the primary prevention of cardiovascular disease. This case is built on three points: 1) cholesterol levels are not associated with cardiovascular disease events in octogenarians without overt coronary artery disease; 2) no randomized, controlled trials have assessed the role of statins in reducing events in octogenarians without coronary artery disease; and 3) statins may increase risks of myositis, rhabdomyolysis, and cancer in the elderly. In view of gaps in the current evidence and the resulting clinical uncertainty, it is unclear whether the balance of risk and benefit favors treatment for the primary prevention of coronary artery disease in octogenarians. The use of statins in this age group should be based on patient preference.
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PMID:Are statins indicated for the primary prevention of CAD in octogenarians? antagonist viewpoint. 1461 Mar 84


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