Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study describes the efficacy of the drug simvastatin. It is likely to be the first HMG CoA reductase inhibitor in Australia and New Zealand available for the treatment of hyperlipidemia. Twenty-four patients, 12 men and 12 women with primary hypercholesterolemia were randomly allocated to treatment by cholestyramine (eight patients) or to simvastatin (16 patients) for a 12-week period. With simvastatin, total cholesterol levels decreased by 37.5% from a baseline mean of 10.33 mmol/L to 6.4 mmol/L after 12 weeks. Low density lipoprotein (LDL) cholesterol concentration decreased by 48.2% from 8.40 mmol/L to 4.39 mmol/L. These effects were better than observed for cholestyramine alone where cholesterol and LDL-cholesterol reductions were 24.9% and 33.1% respectively. Thirteen patients, however, did not achieve target LDL levels of 3.62 mmol/L, or below, and therefore were treated with a combination of cholestyramine and simvastatin, resulting in a decrease of total cholesterol and LDL-cholesterol by 45.5% and 53.5% of baseline values studied over an eight-week period. No major clinical side-effects were encountered. One patient appeared to have had a change in colour vision at the end of the study at 20 weeks, without loss of visual acuity.
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PMID:Simvastatin (MK 733): an effective treatment for hypercholesterolemia. 267 12

There are indications that treatment of hypercholesterolemia by means of drugs reduce risk of atherosclerosis in patients with increased concentrations of atherogenic lipoproteins. Such therapy should be initiated only after satisfactory exclusion of secondary causes of hyperlipoproteinemia, and should be regarded as an adjunct to appropriate dietary therapy. Drug therapy should be strongly considered in patients with total cholesterol above 8-9 mmol/l on diet therapy only. Drug therapy should be considered at even lower concentrations of cholesterol when coronary heart disease is present and in familial forms of hyperlipidemia when increased risk of atherosclerosis has been documented. In patients with increased plasma concentrations of total cholesterol the drugs of choice are agents which enhance the rate of LDL catabolism (resins) or reduce the rate of LDL synthesis (nicotinic acid). Fibrates should be used when triglycerides and cholesterol are both increased. HMG CoA reductase inhibitors offer considerable promise in the therapy of patients with primary hypercholesterolemia. Probucol may be used in combination with other drugs, particularly when xanthomas are present in patients with familial hypercholesterolemia.
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PMID:[Drug therapy of hypercholesterolemia. Treatment of hypercholesterolemia in adults--a Norwegian therapeutic program 1988]. 270 70

The aim of this study was to characterize the plasma lipoprotein pattern and some aspects of cholesterol metabolism in a line of hyperlipemic male rats. Plasma cholesterol and triglycerides were increased about 3-fold as compared to control animals (238 vs. 75 and 185 vs. 59 mg/dl respectively). The plasma lipoprotein distribution and the chemical composition of the isolated lipoproteins was unaffected. Plasma triglyceride production rate was increased (40%, P less than 0.01) and post-heparin lipoprotein lipase activity in plasma decreased (-28%, P less than 0.01) in the hyperlipemic rat. The activity of 3 enzymes involved in cholesterol metabolism (HMG-CoA reductase, cholesterol 7 alpha-hydroxylase, and acyl-CoA cholesterol-acyltransferase) did not differ from control values. 3H2O incorporation into digitonin-precipitable sterols, however, was significantly higher than in controls. This finding was due, in part, to an increased liver weight in the hyperlipemic animals. Furthermore kinetic data using 125I-LDL showed that the fractional catabolic rate of lipoprotein was within the normal range, while the synthetic rate of LDL protein was increased (0.67 vs. 0.3 mg/kg/h, P less than 0.01) in the hyperlipemic rat. These observations suggest that multiple metabolic defects underline the hyperlipemia observed in this animal model.
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PMID:Plasma lipoproteins and cholesterol metabolism in spontaneously hyperlipemic rats. 273 Jul 13

Lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit HMG-CoA reductase. This new drug decreases cholesterol synthesis and apolipoprotein B concentrations, and increases LDL receptor activity without adverse effects on other products in the cholesterol pathway. In patients with heterozygous familial or polygenic (non-familial) hypercholesterolaemia, oral lovastatin 20 to 40 mg twice daily reduces plasma total cholesterol and LDL-cholesterol concentrations by 25 to 40% over a period of several weeks. Lovastatin also produces decreases in plasma triglyceride and VLDL-cholesterol concentrations, although to a lesser extent. In addition, small though significant increases in HDL-cholesterol concentrations have been observed. Combined administration of lovastatin with other lipid-lowering drugs results in further reductions in plasma total and LDL-cholesterol concentrations beyond those seen with either drug alone. From findings in short term studies, lovastatin appears to be well tolerated with a low incidence of side effects. However, liver function tests and eye examinations for possible lens opacities are advised, and further long term studies in larger groups of patients are necessary before the side effect profile of lovastatin will be clearly established. As would be expected at this relatively early stage of its clinical 'life,' lovastatin has not yet been studied in a manner that would determine its effect on cardiovascular mortality during long term administration. Nevertheless, if the substantial improvements to patients' lipid and lipoprotein profiles observed in short term studies are maintained during long term administration, then lovastatin will have an important role in the pharmacological management of hyperlipidaemia.
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PMID:Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidaemia. 306 36

Atherosclerosis can be defined in terms of the processes involved rather than in morphological terms, and there is evidence for possible roles of the macrophage in atherogenesis. The relevance of hyperlipidaemia to the morphogenesis of the atherosclerotic plaque is important, and this has been described in animal models including a strain of rabbit with a genetically determined hyperlipidaemia resembling familial combined hyperlipidaemia. Treatment of these animals with the HMG CoA reductase inhibitor lovastatin from the time of weaning results in a significant degree of inhibition of lesion formation.
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PMID:Interaction of lipoproteins with the artery wall. 307 20

The long term use of lipid-lowering drugs in the treatment of patients with hyperlipoproteinaemia is aimed at reducing plasma concentrations of known atherogenic lipoproteins with a favourable effect on lipid deposition in the arterial wall. A less common aim is to prevent the adverse sequelae of hyperchylomicronaemia in patients with severe hypertriglyceridaemia. The decision to begin drug therapy should be made only after the exclusion of secondary factors and after an adequate trial of diet has failed to produce acceptable concentrations of plasma lipids and lipoproteins. The bile acid sequestrants (cholestyramine and colestipol), nicotinic acid, fenofibrate and inhibitors of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase (e.g. lovastatin or simvastatin) are the most effective drugs for use in patients with primary hypercholesterolaemia; these agents reduce plasma concentrations of total and LDL-cholesterol by 15 to 45%. For those patients with concurrent hypertriglyceridaemia, nicotinic acid, lovastatin or simvastatin, or fenofibrate are the preferred drugs for initial use; bile acid sequestrants frequently exacerbate hypertriglyceridaemia in these patients. Fibric acid derivatives (e.g. clofibrate, gemfibrozil, bezafibrate or fenofibrate) are all effective in the therapy of patients with type III hyperlipoproteinaemia, as is nicotinic acid and I have found lovastatin to be effective also. Gemfibrozil or nicotinic acid are the most effective agents to use in the treatment of patients with severe hypertriglyceridaemia who are at increased risk of abdominal pain and pancreatitis. Combined therapy with drugs which have different mechanisms of action can be effectively used in the treatment of patients with severe hypercholesterolaemia or combined hyperlipidaemia; for the former group, combinations which use bile acid sequestrants, HMG CoA reductase inhibitors and nicotinic acid are the most effective.
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PMID:An overview of lipid-lowering drugs. 307 24

The plasma lipoprotein and liver lipid composition, and the lipid, cholesterol and apolipoprotein synthesis have been studied in normal and diet-induced hyperlipidemic rats, receiving ciprofibrate (2.5 mg/kg body weight) or fenofibrate (50 mg/kg b.w.) for 8 days. Ciprofibrate is about 25-fold more active than fenofibrate in reducing plasma triglyceride and cholesterol concentrations both in normolipemic and in hyperlipemic rats. In normolipemic rats ciprofibrate reduced the concentration and the lipid content of all lipoprotein classes. The incorporation of [14C]palmitate and [3H]leucine into the lipoproteins was reduced by ciprofibrate and fenofibrate. The reduction in lipoprotein production was confirmed by prevention of Triton-induced hyperlipemia. Liver and plasma cholesterol synthesis estimated by 3H2O and [14C]mevalonate incorporation indicated an inhibitory effect on HMG-CoA reductase. Administration of ciprofibrate or fenofibrate to rats fed a fat and cholesterol-rich diet partially prevented liver steatosis and hyperlipemia. Both drugs reduced the overproduction of lower density lipoproteins. The ratio of (VLDL + LDL)-cholesterol/HDL-cholesterol which was increased by the diet alone from 0.4 (normal) to 11 remained close to the normal value in the animals receiving ciprofibrate. In the hyperlipemic animals, ciprofibrate reduced the incorporation of [3H]oleate into the liver and plasma glycerolipid and increased cholesterol esterification. Ciprofibrate efficiently reduces plasma levels of cholesterol, triglyceride and phospholipid. Cholesterol and glycerolipid synthesis in the liver were significantly reduced leading to a lower lipoprotein secretion rate in both normolipidemic and diet-induced hyperlipidemic rats.
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PMID:Effects of ciprofibrate and fenofibrate on liver lipids and lipoprotein synthesis in normo- and hyperlipidemic rats. 324 Mar 33

A brief description has been given of the major processes involved in the genesis of atherosclerosis, and of the morphological features of fatty streaks, gelatinous elevations and fibrolipid plaques. The effects of hyperlipidaemia, genetically and dietarily determined, are described, with special reference to the possible role of macrophages in the development of arterial lesions caused by such hyperlipidaemias. The administration of a competitive inhibitor of HMG-CoA reductase (lovastatin) to genetically hyperlipidaemic rabbits markedly reduced the extent of intimal surface involvement by lipid-rich lesions.
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PMID:The pathology of atherosclerosis with particular reference to the effects of hyperlipidaemia. 331 74

In the past history of the pharmaceutical industry, secondary metabolites have been screened almost exclusively for antimicrobial activities. This biased and narrow view has severely limited the potential application of microbial metabolites. Fortunately, this situation is changing and we are now entering into a new era in which microbial metabolites are being applied to diseases heretofore only subjected to synthetic compounds. This new approach is the application of microbial secondary metabolites to diseases that are not caused by other bacteria or fungi. For years, major drugs such as hypotensive and anti-inflammatory agents that are used for non-infectious diseases have been strictly synthetic products. Similarly, major therapeutics for parasitic diseases in animals (for example, coccidiostats and anthelminthics) resulted strictly from screens of chemically synthesized compounds followed by molecular modification. However, today fermentation products such as monensin and lasalocid dominate the coccidiostat market. The avermectins, another group of streptomycete products, have high activity against helminths and arthropods. Indeed, their activity appears to be an order of magnitude greater than previously discovered anthelminthic agents, the vast majority of which are synthetic compounds. Umezawa's group in Japan has isolated many microbial products with important pharmacological activities by screening with simple enzymic assays. There is much interest in a natural inhibitor of intestinal glucosidase, which is produced by an actinomycete of the genus Actinoplanes. The aim is to decrease hyperglycaemia and triacylglycerol synthesis in adipose tissue, liver and the intestinal wall of patients with diabetes, obesity and type IV hyperlipidaemia. Another natural compound of interest is mevinolin, a fungal product which acts as a cholesterol-lowering agent in animals. Mevinolin is produced by Aspergillus terreus. In its hydroxyacid form (mevinolinic acid), mevinolin is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from liver. It is clear that, although the microbe has contributed greatly to the benefit of mankind, we have merely scratched the surface of the potential of microbial activity.
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PMID:A new era of exploitation of microbial metabolites. 640 Apr 79

The hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin is used to treat hyperlipidaemia. This agent prevents the isoprenylation of some proteins involved in signal transduction processes and inhibits IgE-receptor-linked mediator release from RBL-2H3 cells. In this study the effect of in vivo and in vitro administration of lovastatin on histamine release from rat peritoneal mast cells was examined. Lovastatin (4 mg/kg/day for 2 weeks) inhibited histamine release induced by concanavalin A (con A) from rat peritoneal mast cells of Hooded-Lister rats and both homozygous lean and obese Zucker rats. In contrast, release induced by antirat IgE (anti-IgE) was only significantly inhibited in cells derived from Hooded-Lister rats and that induced by compound 48/80 was not altered. Lovastatin (20 microM, 24 h, in vitro) caused a significant inhibition of the subsequent histamine release to con A, anti-IgE and compound 48/80 but not to the calcium ionophore A 23187. It is important to determine whether such inhibitory effects are also observed after the chronic, clinical administration of lovastatin and other HMG CoA reductase inhibitors.
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PMID:Effect of in vivo and in vitro lovastatin treatment on mast cell activation. 758 Feb 88


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