Antihyperlipidemic Drugs: Resins (Bile Acid Sequesterants)

Resins (Bile Acid Sequesterants)

Mechanism of Action (MOA)

  • Resins bind bile acids in the intestine through anion exchange.

  • This process reduces the enterohepatic recirculation (biliary recycling) of bile acids, which releases feedback regulation on the conversion of cholesterol to bile acids in the liver.

Examples of Bile Acid Sequesterants

  • Examples include (3C):

    • Cholestyramine

    • Colestipol (Colestid)

    • Colesevelam (WelChol)

Indication

  • They are primarily useful for isolated increases in LDL cholesterol.

  • These agents are large non-absorbable polymers that bind bile acids and similar steroids in the intestine, thus preventing their absorption.

Main Mechanism of Action (MOA)

  • By preventing bile acids from being reabsorbed in the liver, the resins inhibit cholesterol re-formation.

    • This action promotes the enhanced secretion of bile acids through feces.

  • Bile acid-binding resins can increase a patient’s triglyceride and VLDL cholesterol concentrations when used as monotherapy, necessitating their combination with other medications for effective lipid-lowering action.

  • By preventing the recycling of bile acids, bile acid-binding resins redirect hepatic cholesterol synthesis towards producing new bile acids, which reduces the cholesterol content in stool.

  • The main compensatory mechanism that occurs is the synthesis of high-affinity LDL receptors, which increases the removal of LDL from the bloodstream.

Other Uses

  • Treating digitalis toxicity (with the exception of colesevelam), as these agents bind to digoxin, thereby preventing its absorption.

  • Managing pruritis in patients experiencing cholestasis and bile salt accumulation.

Advantages

  • They have a strong safety record since they are not absorbed from the gastrointestinal tract, resulting in a lack of systemic toxicity.

Disadvantages

  • Older powder resins like Cholestyramine and Colestipol have an unpleasant granulated texture and can cause gastrointestinal discomfort.

  • Newer resins, such as Colesevelam, exhibit fewer gastrointestinal side effects and come in tablet and suspension forms but are larger in size (625mg).

Adverse Effects

  • Common gastrointestinal side effects include (CBENF):

    • Constipation

    • Bloating

    • Epigastric fullness

    • Nausea

    • Flatulence (particularly with older resins)

      • To manage bloating, dietary fibers and psyllium can be recommended to prevent constipation and bloating.

Drug Interactions

  • Bile acid or gastrointestinal binding can reduce the absorption of anionic drugs (WTDBT) such as warfarin, thyroxin, digitoxin, beta-blockers, and thiazide diuretics, as well as fat-soluble vitamins (Vit. A, D, E, and K).

    • This interference can potentially lead to malnutrition if not properly monitored, due to the impaired absorption of fat-soluble vitamins crucial for various bodily functions.