Originally, cholestyramine was used to treat pruritis secondary to cholestasis, but its main use today is to treat hypercholesterolemia with concomitant hypertriglyceridemia. Cholestyramine also has been used to treat Clostridium difficile enterocolitis, although traditional antibiotics are more effective. Since cholestyramine and the related agent colestipol are not absorbed orally, they are the drugs of choice for treating hyperlipidemia in pregnant women. Cholestyramine was approved by the FDA in 1966. Cholestyramine resin releases chloride and combines with bile acids in the intestine to form insoluble, nonabsorbable complexes that are excreted in the feces along with unchanged resin.
Bile acids undergo enterohepatic circulation.
Since cholesterol is the precursor of bile acids, interference with reuptake of bile acids actually stimulates cholesterol synthesis via an increase in the activity of HMG-CoA reductase. Plasma cholesterol levels do not rise, however, since the newly formed cholesterol is shunted into the bile acid- synthesis pathway. Plasma cholesterol and LDL concentrations fall in patients with primary type II hyperlipoproteinemia. Reduction of plasma cholesterol usually is seen within the first month of therapy and returns to pretreatment levels within 1 month of discontinuation. Relief of pruritus associated with biliary stasis usually takes 1-3 weeks.