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Antihyperlipidemic Agents
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Hyperlipidemia Hyperlipidemia is the most prevalent indicator for susceptibility to atherosclerotic heart disease. it is a term used to describe elevated plasma levels of lipids that are usually in the form of lipoproteins.
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Lipoproteins Metabolism
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Lipid-lowering drugs can be classified into: Sequestering agents (Bile acids sequestrants) Inhibitor of de novo cholesterol biosynthesis. (HMG-CoA Reductase inhibitors) Alteration of cholesterol metabolism Inhibition of lipoprotein synthesis. Miscellaneous.
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1-Sequestering agents (Bile acids sequestrants)
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Cholestyramine Resin (Questran) It is a styrene copolymer with divinylbenzene with quaternary ammonium functional groups.
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Colestipol HCl (Colestid) It is a high-molecular-weight, insoluble, granular copolymer. It reduces cholesterol levels without affecting triglycerides.
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Colesevelam (Welchol) It does not possess Cl- ion (as in Cholestyramine and colestipol) and is not an anion-exchange resin.
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2-Inhibitor of de novo cholesterol biosynthesis (HMG-CoA Reductase inhibitors).
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Lovastatin (Mevacor) It is a potent inhibitor of HMG-CoA reductase. For inhibitory effect on HMG-CoA reductase, the lactone ring must be hydrolyzed to the open-ring heptanoic acid
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Simevastatin (Zocor) It is an analogue of Lovastatin.
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3-Alteration of cholesterol metabolism
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Dextrothyroxine sodium (Choloxin) O-(4-Hydroxy-3,5-diiodsophenyl)-3,5-diiodo-D- tyrosine monosodium hydrate.
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Clofibrate (Atromid-S) Ethyl 2-(p-chlorophenoxy)-2-methylpropionate
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Clofibrate is prepared by Williamson synthesis.
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Gemfibrozil (Lopid) 5-(2,5-Dimethylphenoxy)-2,2-dimethyl pentanoic acid It is structurally similar to clofibrate. Its mechanism of action and use are similar to those of clofibrate.
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Finofibrate (Tricor) 2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid 1- methylethyl ester. It has structural features represented in clofibrate.
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Structure-activity relationship of fibrates
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4-Inhibition of lipoprotein synthesis.
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Probucol (Lorelco) 4,4-[(1-Methylethyliden)-bis thio-[2,6-bis(1,1- dimethyethyl)] phenol. Probucol has high lipophilic characters with strong antioxidant properties.
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Nicotinic acid, Niacin 3-Pyridine carboxylic acid. It has the ability to inhibit lipolysis (i.e. prevent the release of free fatty acids and glycerol from fatty tissues).
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Pentaerthritol tetranicotinate Pentaerthritol tetranicotinate is an example of molecular association in which a tetra- replicate of nicotinic acid was developed (Molecular replication).
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5-Miscellaneous.
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β-Sitosterol Sitosterol is a plant sterol, whose structure is identical with that of cholesterol, except for the substituted ethyl group on C-24 of its side chain. The drug inhibits the absorption of dietary cholesterol from the gastrointestinal tact.
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