Antihyperlipidemic drugs (hypolipidemic drugs; lipidlowering drugs) are used in patients with hyperlipoproteinemia. They are the essential components of the complex therapy used to prevent and treat atherosclerosis and its complications (ischemic disease of the heart, stroke, etc.). Their main effect includes the reduction of elevated levels of atherogenic lipoproteins in the plasma. Some of them also increase the levels of antiatherogenic lipoproteins. These principles of action are based on the fact that atherogenic dislipoproteinaemia is known to be one of the main risk factors for the development of atherosclerosis.
Lipoproteins circulating in the plasma are composed of lipids and proteins. These particles have different sizes and densities. The latter is determined by the ratio between proteins and lipids in the particles. There are several groups of plasma lipoproteins (Fig. 22.1; 22.2).
The largest particles (with the lowest density) are chylomicrons (CM). They are formed in the epithelial cells of the small intestine. Chylomicrons contain mainly exogenic (dietary) triglycerides, which they transport; they also include cholesterol. Under the effect of the lipoprotein lipase of the vascular endothelium, triglycerides release fatty acids and glycerol. Free fatty acids are either taken up by the myocardium and sceletal muscles where they are oxidized and act as an energy source, or they participate in the resynthesis of triglycerides in the adipose tissue where they are stored. Residual chylomicrons containing cholesterol bind to lipoprotein receptors in the liver and are then catabolized in hepatocytes (see Fig. 22.2). Very low density lipoproteins (VLDL; pre-β-lipoproteins) mainly include endogenous triglycerides. They are formed in the liver. Under the influence of the endothelial lipoprotein lipase some of the VLDL triglycerides are metabolised and converted into «short-living» intermediate density lipoproteins (IDL). 50% of IDL clearance results from their uptake (endocytosis) by the liver, regulated by LDL receptors. They also undergo lipolysis and readily transform into low density lipoproteins (LDL; β-lipoproteins). IDLs have approximately equal