Mechanisms of lipid-lowering agents.
Lipid-lowering agents are used with the purpose of ameliorating hyperlipoproteinemias, in order to prevent arterial disease. Lipid-lowering drugs can be classified into absorbable agents and into nonabsorbable compounds, acting within the gastrointestinal lumen. Absorbable drugs (fibric acids, nicotinic acid, probucol, HMG-CoA reductase inhibitors) reduce plasma very-low-density lipoproteins (VLDL) and/or low-density lipoproteins (LDL) by a variety of mechanisms. Fibric acids, in particular, act by stimulating the catabolism of VLDL and also, as a consequence, improving LDL delipidation, thus favoring receptor uptake. Nicotinic acid and acipimox interfere with the biosynthesis of LDL and can also improve the clearance of VLDL/LDL. Probucol acts by a newly described mechanism, i.e. accelerating reverse transport of cholesteryl esters from high-density lipoproteins to lower-density lipoproteins. Finally, HMG-CoA reductase inhibitors, interfering with the biosynthesis of cholesterol, can induce an increased expression of liver high-affinity lipoprotein receptors. Nonabsorbable agents (anion-exchange resins, neomycin, beta-sitosterol) interrupt the recirculation of bile acids and/or reduce the absorption of cholesterol with the gut. They display a selective activity on hypercholesterolemia, again by increasing LDL receptor expression. The choice of one or more lipid-lowering agents will depend upon the patient's phenotype, determining responsiveness to the pharmacological treatment.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-Y GENE-N GENE-N CHEMICAL GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
Nicotinic acid Probucol cholesteryl esters HMG-CoA cholesterol lipoprotein receptors LDL receptor HMG-CoA reductase plasma very-low-density lipoproteins VLDL neomycin low-density lipoproteins LDL VLDL LDL LDL VLDL LDL high-density lipoproteins lower-density lipoproteins HMG-CoA reductase beta-sitosterol bile acids cholesterol fibric acids nicotinic acid probucol HMG-CoA Fibric acids