What is the key step to prevent bile acids from being re-absorbed once they are secreted into the small bowel?

Bile Acid Sequestrants: The Key Step to Prevent Bile Acid Reabsorption in the Small Bowel

The key step that prevents bile acids from being reabsorbed once they are secreted into the small bowel is the use of bile acid sequestrants (such as cholestyramine, colestipol, or colesevelam), which bind to bile acids in the intestinal lumen to form insoluble complexes that are excreted in the feces. 1, 2, 3

Mechanism of Action of Bile Acid Sequestrants

Bile acid sequestrants work through a specific mechanism:

1. Binding action: These positively charged, non-digestible resins bind to negatively charged bile acids in the intestinal lumen 4
2. Complex formation: They form an insoluble complex with bile acids 2, 3
3. Fecal excretion: The bound complex cannot be absorbed and is excreted in the feces 2
4. Interruption of enterohepatic circulation: This prevents bile acid reabsorption from the intestine, interrupting the normal enterohepatic cycle 3

Clinical Applications

Bile acid sequestrants are particularly important in several clinical scenarios:

• Bile acid malabsorption: Common after ileal resection or with terminal ileal disease in Crohn's disease 1
• Cholestatic pruritus: Used to reduce excess bile acids deposited in dermal tissue 3
• Hypercholesterolemia: Primary FDA-approved indication 2, 3
• Chronic diarrhea: Particularly effective in diarrhea caused by bile acid malabsorption 1, 5

Available Bile Acid Sequestrants

Three main bile acid sequestrants are clinically available:

1. Cholestyramine: Most commonly used, though may be unpalatable for some patients 1
2. Colestipol: Alternative option with similar mechanism of action 2
3. Colesevelam: Newer agent, may be better tolerated but more expensive 1

Physiological Impact

When bile acid sequestrants are administered:

• They prevent the reabsorption of bile acids in the terminal ileum
• This leads to increased fecal loss of bile acids
• The liver responds by increasing conversion of cholesterol to bile acids
• This results in decreased serum cholesterol levels 2, 3
• In patients with bile acid malabsorption, this reduces diarrhea by preventing excess bile acids from reaching the colon 1

Clinical Considerations and Cautions

Important clinical considerations when using bile acid sequestrants include:

• Dosing timing: Most effective when administered about 30 minutes before meals 1
• Potential worsening of steatorrhea: In severe bile acid malabsorption, sequestrants may worsen fat malabsorption 1
• Contraindication in short bowel syndrome: Should generally be avoided in short bowel syndrome as they may worsen steatorrhea and fat-soluble vitamin losses 1
• Drug interactions: Can bind to and reduce absorption of many medications; should be administered at different times 1

Diagnostic Considerations

When bile acid malabsorption is suspected:

• SeHCAT scan: Gold standard where available (values <15% suggest bile acid malabsorption) 1
• Empirical trial: A therapeutic trial of bile acid sequestrants is often used when diagnostic tests are unavailable 1
• Serum 7α-hydroxy-4-cholesten-3-one: Alternative diagnostic method 1, 5

By binding bile acids in the intestinal lumen and preventing their reabsorption, bile acid sequestrants represent the key pharmacological intervention to interrupt the enterohepatic circulation of bile acids, making them essential in managing conditions associated with bile acid malabsorption.