Currently available hypolipidaemic drugs and future therapeutic developments.
Article Details
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Farmer JA, Gotto AM Jr
Currently available hypolipidaemic drugs and future therapeutic developments.
Baillieres Clin Endocrinol Metab. 1995 Oct;9(4):825-47.
- PubMed ID
- 8593127 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Colestipol Bile acids Group Humans YesBinderDetails - Pharmaco-metabolomics
Drug Drug Groups Metabolite Change Description Fluvastatin Approved LDL cholesterol decreased Fluvastatin decreases the level of LDL cholesterol in the blood Niacin Approved Investigational Nutraceutical LDL cholesterol decreased Niacin decreases the level of LDL cholesterol in the blood Niacin Approved Investigational Nutraceutical Glucose increased Niacin increases the level of Glucose in the blood Niacin Approved Investigational Nutraceutical Triglycerides decreased Niacin decreases the level of Triglycerides in the blood Clofibrate Approved Investigational Triglycerides decreased Clofibrate decreases the level of Triglycerides in the blood Lovastatin Approved Investigational LDL cholesterol decreased Lovastatin decreases the level of LDL cholesterol in the blood Cholestyramine Approved Investigational LDL cholesterol decreased Cholestyramine decreases the level of LDL cholesterol in the blood Gemfibrozil Approved Triglycerides decreased Gemfibrozil decreases the level of Triglycerides in the blood Ciprofibrate Approved Investigational Triglycerides decreased Ciprofibrate decreases the level of Triglycerides in the blood Colestipol Approved LDL cholesterol decreased Colestipol decreases the level of LDL cholesterol in the blood Niacin Approved Investigational Nutraceutical Triglycerides decreased Niacin decreases the level of Triglycerides in the blood Bezafibrate Approved Investigational Triglycerides decreased Bezafibrate decreases the level of Triglycerides in the blood Fenofibrate Approved Triglycerides decreased Fenofibrate decreases the level of Triglycerides in the blood Niacin Approved Investigational Nutraceutical LDL cholesterol decreased Niacin decreases the level of LDL cholesterol in the blood Simvastatin Approved LDL cholesterol decreased Simvastatin decreases the level of LDL cholesterol in the blood