Bile acid sequestrants, cholesterol-lowering effects

A combination of bile acid sequestrants with nicotinic acid or probucol or an HMG-CoA reductase inhibitor can be used to produce synergistic effects in lowering plasma lipoprotein levels, particularly LDL. The efficacy of drug treatment was shown in a recent study in which lovas-tatin and colestipol were used to reduce cholesterol levels in men with CHD. The rate of progression of coronary lesions was decreased and that of regression increased. These changes also were associated with reduced cardiovascular abnormalities. 

Cholestyramine and colestipol are bile acid sequestrants that enhance cholesterol loss into the feces, thereby stimulating new bile salt synthesis, which lowers liver cholesterol levels and consequently plasma LDL levels. Their adverse effects are also listed. 

MECHANISM OF ACTION The bUe-acid sequestrants are highly positively charged and bind negatively charged bile acids. The resins are not absorbed, and the bound bile acids are excreted in the stool. Since >95% of bile acids are normally reabsorbed, interruption of this process depletes the pool of bile acids and increases hepatic bile-acid synthesis. As a result, hepatic cholesterol content declines, stimulating the production of LDL receptors. The increase in hepatic LDL receptors increases LDL clearance and lowers LDL-C levels, but this effect is partially offset by the enhanced cholesterol synthesis caused by upregulation of HMG-CoA reductase. Inhibition of reductase activity by a statin substantially increases the effectiveness of the resins. 

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