Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dyslipidemia of chronic renal failure is of multifactorial origin. Decreased activity of lipoprotein lipase and hepatic triglyceride lipase, peripheral insulin resistance, hyperparathyroidism and L-carnitine deficiency are the contributing factors. This results in a disturbed catabolism of chylomicron, accumulation of very-low-density (VLDL) and intermediate-density (IDL) lipoproteins as well as incompletely cleared remnant particles, whereas low-density lipoprotein (LDL) levels are diminished. There is current debate as to whether cardiovascular disease is accelerated and whether hyperlipidemia should specifically be treated. In addition, there have been few means of influencing these metabolic alterations. Drug incompatibility and consequently side effects render treatment difficult. The drugs that have been most tested for lipid lowering in chronic renal failure are the fibric acids. By their mode of action, they are the logical choice. Dose reduction overcomes major side effects such as myopathy and rhabdomyolysis. The second generation of fibric acid derivatives (gemfibrozil and beclobrate) show several advantages over formerly used derivatives. Treatment with lovastatin and simvastatin appears to be safe and is recommended in a minority of patients with predominantly elevations of LDL. HMG-CoA reductase inhibitors also lower remnant particles effectively in hemodialysis (HD) patients. L-Carnitine and low-molecular-weight heparin have been shown to influence VLDL rich in triglycerides in a subset of patients on HD. In posttransplant hyperlipidemia, diet remains the first course of action in all patients. When this approach fails, the new lipid-lowering agents, especially fibric acids, appear to be safe in short-term studies in azathioprine- and ciclosporin-treated patients. Lovastatin has been shown to be safe in stable renal transplant patients. Its toxicity seems to depend mainly on high ciclosporin whole blood through or plasma levels.
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PMID:Hyperlipoproteinemia in chronic renal failure: pathophysiological and therapeutic aspects. 186 98

Cholesterol-lowering drugs include three major pharmacological classes: a) fibrates, b) statines, HMG-CoA reductase inhibitors and c) cholestyramine. The late eighties were characterized by the introduction of HMG-CoA reductase inhibitors in therapeutics. For 12 months (1st January-31 December 1991), a prospective intensive program of pharmacovigilance investigated the occurrence of side effects among the three pharmacological classes of cholesterol-lowering drugs in a specialized unit for prevention of atherosclerosis and dyslipidemia. Among 3,506 out patients who received cholesterol-lowering drugs, 36 side effects were reported (i.e. 1 side effect for 98 out-patients). Most of the side effects were observed with statines (61%). The most frequently observed side effects were gastralgia (19.5%) observed with the three classes of drugs and hepatitis with HMG-CoA reductase inhibitors (8.5%) or fibrates (3%) whereas myopathy (12%) only occurred with statines. The other side effects were cutaneous (14%: eczema, skin rashes) or neuropsychiatric (11%: insomnia...) ones. This study emphasizes the low frequency of severe side effects (myopathy: 1 per 1,000 prescriptions, hepatitis: 1 per 1,000 prescriptions) with cholesterol-lowering drugs in current practice.
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PMID:[A one-year prospective and intensive pharmacovigilance of antilipemic drugs in an hospital consultation for prevention of risk factors]. 814 47

Statins effectively lower LDL-cholesterol and some members of this class have been shown to reduce the risk of major cardiovascular events and total mortality in patients with or at risk for coronary heart disease. Statins are in general well tolerated. Withdrawal rates related to adverse events are low (< or =3%). The most common adverse events are mild gastrointestinal symptoms. Elevated serum transaminase levels occur infrequently (< or = 1.5%). These are generally asymptomatic, reversible and rarely require drug withdrawal. Statins do not cause adverse endocrine effects, do not alter glycemic control in diabetic patients, and do not increase cancer risk. Dose-related myopathy and/or rhabdomyolysis also occurs very rarely, although the risk is increased by concomitant administration of cyclosporine, niacin, fibrates, or by CYP3A4 isoenzyme inhibitors (e.g. erythromycin, systemic azole antifungal agents etc.) with statins metabolized by this isoenzyme. The pharmacokinetics of the individual statin should be considered in patients receiving polypharmacological treatments, to minimize the risk of unfavorable drug interactions. Atorvastatin is well tolerated in long-term treatment of dyslipidemia and is characterized by a safety profile similar to the other available statins.
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PMID:Safety of HMG-CoA reductase inhibitors: focus on atorvastatin. 1171 88

Three categories of highly active antiretroviral therapy (HAART)-associated major toxic effects have been identified: nucleoside-related toxic effects (e.g., neuropathy, myopathy, pancreatitis, hepatic steatosis, lactic acidosis, and possibly lipoatrophy), metabolic complications (e.g., fat redistribution, insulin resistance, and hyperlipidemia), and bone disease (e.g., osteopenia and/or osteoporosis). The toxic effects caused by nucleosides are hypothesized to be a result of mitochondrial injury and include myopathy, pancreatitis, liver failure, and lactic acidosis. Alterations in lactic acid metabolism range from common instances of asymptomatic lactic acidemia to rare occurrences of life-threatening lactic acidosis with hepatic steatosis. A metabolic syndrome consisting of lipodystrophy (i.e., fat redistribution), hyperlipidemia and insulin resistance has been observed, particularly with protease inhibitor treatment. Some additive interaction between protease inhibitors and nucleosides has also been described. The potential relationship of these metabolic abnormalities to increased risk of cardiovascular disease and diabetes has broad implications on long-term patient management. Lipodystrophy associated with HAART is generally accompanied by potentially serious abnormalities, including dyslipidemia (i.e., hypercholesterolemia and hypertriglyceridemia) and altered glucose metabolism (i.e., insulin resistance). Regimens of HAART may have adverse effects on bone metabolism, as indicated by emerging reports of osteopenia, osteoporosis, and avascular necrosis.
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PMID:Long-term exposure to lifelong therapies. 1183 99

Advicor (lovastatin and extended-release niacin) is the first cholesterol-lowering combination product to become available for the management of hyperlipidemia. Lovastatin significantly lowers low-density lipoprotein cholesterol, whereas niacin significantly lowers triglycerides and lipoprotein (a) and markedly increases high-density lipoprotein cholesterol. These effects are ideal for managing a variety of lipid disorders, including metabolic syndrome. Lovastatin and niacin reduce coronary heart disease mortality in primary and secondary prevention patients, respectively. The extended-release niacin component uses a unique technology to minimize adverse effects (e.g., flushing and hepatotoxicity) while retaining the same lipid-altering effects as immediate-release niacin. The combination product appears to be well tolerated, with discontinuation due to adverse effects other than flushing occurring in a similar percent of patients as for lovastatin in clinical trials. Approximately 9% of patients discontinued the combination product due to flush. No confined cases of myopathy or hepatotoxicity have been reported with this product. Once-daily dosing provides ease of administration that should improve compliance and result in a greater proportion of patients meeting their low-density lipoprotein cholesterol goals. The nomenclature surrounding niacin products used to treat dyslipidemias is confusing. While only two types of niacin formulations exist (immediate-release formulations and formulations which dissolve more slowly than immediate-release formulations), government regulations allow for slowly dissolved niacin formulations to be divided into two types of niacin products; those that are available over-the-counter (OTC) and those that are available by prescription only. Over-the-counter slowly dissolved niacin preparations are not classified as OTC per se, but are considered "nutritional supplements". For this reason, they fall under the jurisdiction of the Federal Trade Commission and do not fall under the umbrella of the FDA branch that controls dyslipidemic products (Endocrine and Metabolic Division of the Center for Drug Evaluation and Research). The slowly dissolved niacin nutritional supplements have not been reviewed by the FDA for safety nor efficacy in the treatment of dyslipidemia nor are they required to meet generic drug rules (even though various brands are available). These brands are described on their labels as "sustained-release", "timed-release", and "slow-release" for example. Only two slowly absorbed niacin products have been approved by the FDA for the treatment of dyslipidemia; they are Niaspan (Kos Pharmaceuticals, Inc., Miami, FL) and Advicor (Kos Pharmaceuticals, Inc., Miami, FL). The term "extended-release" has been given to these two products to simplify the terminology and differentiate the products from immediate-release niacin. In this review, we will use "extended-release" to refer to the FDA approved slowly dissolving niacin preparation and "sustained-release" to refer to the nutritional supplements (not FDA approved).
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PMID:Lovastatin and extended-release niacin combination product: the first drug combination for the management of hyperlipidemia. 1197 44

Combined statin and fibrate therapy is often imperative for the improvement of the serum lipid profile in patients with mixed hyperlipidemia. However, the potential risk of myopathy has limited the widespread use of such therapy. Preferably this treatment should involve low optimally tolerable doses of hypolipidemic drugs. Thus, we undertook a study to determine the safety and efficacy of combination therapy with fibrates and small doses of atorvastatin. Twenty-two patients with mixed hyperlipidemia were started on a fibrate regimen (micronised fenofibrate 200mg/day or ciprofibrate 100 mg/day). Because after 12 weeks of therapy the fibrate failed to normalise the serum lipid profile, small doses of atorvastatin (5 mg/day) were added for a further 12 weeks. The administration of the fibrates resulted in a significant decrease in total and LDL-cholesterol levels, as well as in triglycerides, and an increase in HDL-cholesterol levels. The addition of atorvastatin (5 mg/day) resulted in a further decrease in total and LDL-cholesterol levels. Consequently, the hypolipidemic therapy target was achieved in most of the patents. Combination therapy was well tolerated and no significant increases in serum liver and muscle enzymes were noticed. We conclude that the careful administration of small doses of atorvastatin in patients with mixed dyslipidemia receiving fibrates is associated with a significant amelioration of lipid abnormalities.
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PMID:Combined treatment with fibrates and small doses of atorvastatin in patients with mixed hyperlipidemia. 1209 21

Patients with combined dyslipidemia are at high risk for coronary artery disease and often require combination drug therapy to achieve lipid levels recommended by the US National Cholesterol Education Program's third Adult Treatment Panel (ATP III). In addition to recommendations for low-density lipoprotein (LDL) cholesterol and triglyceride levels, ATP III established non-high-density lipoprotein (HDL) cholesterol goals for individuals with triglycerides >or=2.26 mmol/L (>or=200 mg/dL). It also introduced certain criteria for the diagnosis of the metabolic syndrome, a clustering of risk factors (abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure, impaired fasting glucose) that increases cardiovascular risk and is common in patients with combined dyslipidemia. Statin monotherapy has been shown to benefit these patients, and additional benefit may be obtained by combination therapy that provides greater reductions in both LDL cholesterol and triglycerides as well as greater increases in HDL cholesterol. However, combining a statin with either niacin or a fibrate may increase the risk for myopathy and therefore requires careful monitoring and evaluation of the risk-benefit ratio for each patient. Moreover, combination therapy may be associated with increased drug costs and decreased patient compliance. Recently developed agents that may improve the effectiveness of combination therapy include ezetimibe-a cholesterol absorption inhibitor-and a formulation that combines extended-release niacin and lovastatin in a single pill. Clinical trials are needed to determine the optimal treatment in patients with combined dyslipidemia.
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PMID:Combination therapy for combined dyslipidemia. 1246 37

Nephrotic dyslipidemia is a risk factor for the development of systemic atherosclerosis, and may aggravate glomerulosclerosis and enhance progression of glomerular disease. The greatest and most consistent reductions in LDL-cholesterol are achieved with HMG-CoA reductase inhibitors but their efficacy and safety in long-term therapy need to be evaluated. In this study, we gave fluvastatin to 21 nephrotic patients and followed then up clinically, neurophysiologically and by laboratory tests. There was an improvement in the lipogram, with reductions of triglycerides (TG) (33%) and LDL (35%) at three months. There was no clinical manifestation of myopathy and CPK was normal. Electromyographic data showed significant decreases in the amplitude and duration of motor unit action potentials in the proximal muscles with statin therapy, but these changes did not amount to classic myopathy. We conclude that fluvastatin is a safe drug for long-term use in dyslipidemic nephrotic patients. However, we suggest further studies to verify whether the early electromyography (EMG) changes observed in this study may progress or not on its longer term use.
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PMID:Neuromuscular toxicity in nephrotic patients treated with fluvastatin. 1249 86

The significant age-adjusted decline in cardiovascular mortality that has occurred over the past three decades is multifactorial. However, the advent of statin therapy has markedly facilitated the optimization of dyslipidemia in patients at risk for coronary events. Statin therapy has proven to be effective in reducing morbidity and mortality in large-scale primary and secondary prevention trials. As with all therapies, the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co A) reductase inhibitors is not without clinical risks. Myopathy, albeit uncommon, was one of the earliest clinical problems associated with statin therapy. Recent data from the large-scale statin mega-trials have clarified the quantitative clinical risk-benefit relationship of reductase inhibitors relative to the induction of muscle toxicity. Histopathologic studies have clarified the potential role of statins in the syndrome of myalgias and normal creatine kinase levels. However, the precise mechanism of statin-associated muscle toxicity remains unclear and is potentially related to genetically mediated muscle enzyme defects, drug interactions, intracellular depletion of metabolic intermediates, and intrinsic properties of the statins per se.
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PMID:Statins and myotoxicity. 1257 93

Updated guidelines from the National Cholesterol Education Program give greater emphasis to lipoproteins other than low-density lipoprotein cholesterol (LDL) than previous guidelines. Although statins remain first-line therapy for most patients to lower LDL, combination therapy is the next logical step in achieving goals in patients with mixed dyslipidemia or elevated LDL despite statin therapy. As the prevalence of diabetes, metabolic syndrome, and atherogenic dyslipidemia rises, the importance of treating the total lipid profile becomes even more crucial. Niacin, fibrates, and bile acid sequestrants are effective in combination with statins in lowering LDL, triglycerides, and total cholesterol levels and increasing high-density lipoprotein cholesterol (HDL). Although combination therapies may increase the risk of myopathy, both fibrate-statin and niacin-statin combinations are considered safe. In addition, niacin-statin therapy reduces atherosclerotic progression and coronary events. New pharmacologic formulations exist that will further affect treatment: a single-tablet combination of lovastatin and extended-release niacin is available, as is ezetimibe, a cholesterol-absorption inhibitor. In all, both HDL and triglyceride levels correlate with cardiovascular risk and should be considered secondary targets of therapy. Combination therapy can be safe and effective and can be constructed to affect all lipoprotein parameters.
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PMID:Treating dyslipidemic patients with lipid-modifying and combination therapies. 1274 37


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