Antihyperlipidemic Agents

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.

Lipoproteins Metabolism

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.

1-Sequestering agents (Bile acids sequestrants)

Cholestyramine Resin (Questran)  It is a styrene copolymer with divinylbenzene with quaternary ammonium functional groups.

Colestipol HCl (Colestid)  It is a high-molecular-weight, insoluble, granular copolymer.  It reduces cholesterol levels without affecting triglycerides.

Colesevelam (Welchol)  It does not possess Cl- ion (as in Cholestyramine and colestipol) and is not an anion-exchange resin.

2-Inhibitor of de novo cholesterol biosynthesis (HMG-CoA Reductase inhibitors).

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

Simevastatin (Zocor)  It is an analogue of Lovastatin.

3-Alteration of cholesterol metabolism

Dextrothyroxine sodium (Choloxin) O-(4-Hydroxy-3,5-diiodsophenyl)-3,5-diiodo-D- tyrosine monosodium hydrate.

Clofibrate (Atromid-S) Ethyl 2-(p-chlorophenoxy)-2-methylpropionate

Clofibrate is prepared by Williamson synthesis.

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.

Finofibrate (Tricor) 2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid 1- methylethyl ester.  It has structural features represented in clofibrate.

Structure-activity relationship of fibrates

4-Inhibition of lipoprotein synthesis.

Probucol (Lorelco) 4,4-[(1-Methylethyliden)-bis thio-[2,6-bis(1,1- dimethyethyl)] phenol.  Probucol has high lipophilic characters with strong antioxidant properties.

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).

Pentaerthritol tetranicotinate  Pentaerthritol tetranicotinate is an example of molecular association in which a tetra- replicate of nicotinic acid was developed (Molecular replication).

5-Miscellaneous.

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.