Cholestyramine is a bile acid sequestrant used as an adjunct in the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia, and for the relief of pruritus associated with partial biliary obstruction. Cholesterol is probably the sole precursor of bile acids. During normal digestion, bile acids are secreted into the intestines. A major portion of the bile acids is absorbed from the intestinal tract and returned to the liver via the enterohepatic circulation. Only very small amounts of bile acids are found in normal serum. Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the feces. This results in a partial removal of bile acids from the enterohepatic circulation by preventing their absorption. Cholestyramine resin is a strong anion exchange resin, allowing it to exchange its chloride anions with anionic bile acids present in the gastrointestinal tract and form a strong resin matrix. Since bile acid reabsorption and recycling is reduced, the liver has to synthesize new bile acid. This is done by increasing plasma LDL uptake. LDL is metabolized to form cholesterol. There is enhanced conversion of cholesterol to bile acids in the liver via 7a-hydroxylation. LDL receptors are upregulated in the liver to accommodate higher LDL uptake to replace the bile acids. Common adverse effects are dyspepsia and bloating. These symptoms can be decreased if cholestyramine is completely suspended in liquid several hours before ingestion. Constipation is a common side effect that is preventable with adequate water and fiber intake. Cholestyramine is considered a safe medication since it is not systemically absorbed.

Cholestyramine Pathway (New) References