Bile acid resins/sequestrants

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Information about Bile acid resins/sequestrants

The bile acid resins or sequestrants are the oldest and safest lipid lowering agents, but are less potent than other classes now available and are not always well tolerated.

Mechanism of action of Bile acid resins/sequestrants

The bile acid sequestrants are highly positively charged molecules that bind to the negatively charged bile acids in the intestine, inhibiting their lipid solubilizing activity and thus blocking cholesterol absorption. They also inhibit the reabsorption of bile acids (which is typically 95%) and thus cause a contraction of the bile acid pool which leads to increased bile acid synthesis that competes with cholesterol synthesis in the liver, which also contributes to the lowering of serum cholesterol levels.

FDA approval information for Bile acid resins/sequestrants

Three bile acid sequestrants are available in the United States (common brand name and year of approval): cholestyramine (Questran, 1973), colesevelam (Welchol, 2000) and colestipol (Colestid, 1977). These agents are also used for therapy of pruritus for their activity in lowering the “pruritogens” that accumulate in cholestatic forms of liver disease.

Liver safety of Bile acid resins/sequestrants

The bile acid resins are not absorbed and thus have not been linked to clinically apparent drug induced liver injury. They have the potential to bind to vitamins, hormones or medications in the intestine and result in subtherapeutic serum levels.

The bile acid resins have not been associated with clinically apparent acute liver injury, which is probably because of their lack of absorption. For unexplained reasons, however, therapy with these agents is associated with a low rate of mild (1 to 3 fold) serum aminotransferase and alkaline phosphatase elevations which are self-limited and not associated with symptoms or jaundice and resolve rapidly with stopping therapy.

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