Learning Objective

By the end of this section, learners should be able to describe the mechanism of action of bile acid sequestrants, explain their effects on lipid metabolism, recognize common adverse effects and drug interactions, and identify situations in which their use is contraindicated.

Drugs: Common agents

• Cholestyramine,
• Colestipol

Mechanism of Action

• Bind bile acids in the gut, forming insoluble complexes → ↓ enterohepatic recirculation of bile salts
• ↓ hepatic cholesterol → liver increases bile acid synthesis
• ↑ LDL receptor expression → ↓ plasma LDL cholesterol
• Modest effect on triglycerides; may ↑ increase VLDL in some patients

Clinical Effects

• ↓ LDL cholesterol
• Useful in patients who cannot tolerate statins or as adjunct therapy

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Side Effects

• Hypertriglyceridemia: may increase VLDL and triglyceride levels
• Gastrointestinal: constipation, bloating, dyspepsia
• Malabsorption: fat-soluble vitamins (A, D, E, K)

Drug Interactions

• Can bind and reduce the absorption of orally administered drugs:
  • Warfarin
  • Thiazide diuretics
  • Digoxin
• Recommendation: Take other medications 1 hour before or 4–6 hours after bile acid sequestrants

Contraindications

• Patients with hypertriglyceridemia are at risk of worsening triglyceride levels

Clinical Correlate

Nonstatin drugs have not been shown to improve cardiovascular outcomes when added to statin therapy. These drugs are most often used in patients who cannot tolerate a statin.

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