cholestyramine

Cholestyramine is a bile acid sequestrant (resin) that binds bile acids in the intestinal lumen, forming a non-absorbable complex that is excreted in feces. This interrupts enterohepatic circulation of bile acids, forcing the liver to convert more cholesterol into bile acids, which depletes intracellular cholesterol and upregulates LDL receptor expression on hepatocytes, thereby lowering plasma LDL cholesterol levels. However, it can cause a compensatory increase in HMG-CoA reductase activity and may raise triglycerides, so it's often used with statins for synergistic effect. Clinically, it's used for hypercholesterolemia (adjunct to statins), pruritus due to bile acid accumulation in cholestatic liver disease, and to treat bile acid diarrhea (e.g., after ileal resection or in Crohn's disease). Adverse effects include GI disturbances (bloating, constipation, nausea), and importantly, it can impair absorption of fat-soluble vitamins (A, D, E, K) and other drugs (e.g., warfarin, thyroxine, statins) due to its binding capacity, so other medications should be taken 1 hour before or 4-6 hours after cholestyramine. It is not systemically absorbed, making it safe in pregnancy and for patients with hepatic impairment concerns related to systemic drug toxicity. Contraindicated in complete biliary obstruction since bile acids are needed for its mechanism of action.