Antidiarrheals

Introduction

Diarrhea is defined as the passage of abnormally loose or frequent stools, often accompanied by increased fluid and electrolyte loss. It may be acute (often infectious and self-limiting) or chronic (associated with inflammatory bowel disease, irritable bowel syndrome, malabsorption, or systemic illness).

Management includes fluid and electrolyte replacement as the cornerstone, with antidiarrheal agents used for symptom control or as specific therapy when underlying causes have been identified.

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Classification of Antidiarrheals

1. Opioid Agonists (Motility Inhibitors)

• Mechanism: Act on μ-opioid receptors in the intestinal wall, slowing peristalsis and prolonging transit time, allowing increased absorption of water and electrolytes.

• Generic Names:

  • Loperamide

  • Diphenoxylate (usually combined with atropine to discourage abuse)

  • Codeine (rarely used today due to dependence risk)

• Uses: Symptomatic treatment of acute nonspecific diarrhea, traveler’s diarrhea (with antimicrobials if bacterial), chronic diarrhea in irritable bowel syndrome.

• Adverse Effects: Constipation, abdominal cramps, paralytic ileus (overuse), CNS depression (at high doses, esp. with diphenoxylate).

• Contraindications: Infectious diarrhea (e.g., C. difficile, dysentery), children <2 years, severe colitis.

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2. Adsorbents and Bulk-Forming Agents

• Mechanism: Bind water, toxins, or microorganisms; increase stool consistency by bulking action.

• Generic Names:

  • Kaolin

  • Pectin

  • Polycarbophil

  • Attapulgite (less commonly used today)

• Uses: Mild acute diarrhea, adjunctive therapy in chronic diarrhea, irritable bowel syndrome with diarrhea (IBS-D).

• Adverse Effects: Constipation, bloating, interference with absorption of other drugs.

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3. Bismuth Compounds

• Mechanism: Antisecretory, anti-inflammatory, and antimicrobial activity; binds enterotoxins.

• Generic Names: bismuth subsalicylate, bismuth subcitrate.

• Uses: Traveler’s diarrhea, nonspecific acute diarrhea, dyspepsia, Helicobacter pylori eradication regimens.

• Adverse Effects: Black stool and tongue discoloration, salicylate toxicity with high doses.

• Contraindications: Aspirin allergy, children with viral illness (risk of Reye’s syndrome), renal insufficiency.

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4. Anticholinergics and Antispasmodics

• Mechanism: Inhibit muscarinic receptors, reducing GI motility and spasms.

• Generic Names: atropine, hyoscyamine, dicyclomine, propantheline.

• Uses: Adjunctive in functional diarrhea and IBS with diarrhea.

• Adverse Effects: Dry mouth, blurred vision, urinary retention, constipation, confusion (esp. in elderly).

• Contraindications: Narrow-angle glaucoma, obstructive uropathy, paralytic ileus.

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5. Somatostatin Analogues

• Mechanism: Inhibit intestinal secretion, motility, and hormone release.

• Generic Names: octreotide, lanreotide.

• Uses: Severe secretory diarrhea (carcinoid syndrome, VIPoma, AIDS-related diarrhea, chemotherapy-induced diarrhea).

• Adverse Effects: Gallstones, steatorrhea, abdominal pain, glucose metabolism disturbance.

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6. Probiotics and Microflora Restoratives

• Mechanism: Restore normal gut flora balance, inhibit pathogenic bacteria.

• Generic Names: Lactobacillus species, Saccharomyces boulardii, Bifidobacterium species.

• Uses: Antibiotic-associated diarrhea, traveler’s diarrhea, mild infectious diarrhea, prevention of Clostridioides difficile recurrence (as adjunct).

• Adverse Effects: Rare systemic infection in immunocompromised patients.

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7. Miscellaneous Agents

• Racecadotril (Enkephalinase Inhibitor): Inhibits degradation of endogenous enkephalins → reduces intestinal hypersecretion of water and electrolytes. Used in acute diarrhea (especially in children in some countries).

• Crofelemer: Chloride channel inhibitor, used in HIV/AIDS-associated diarrhea.

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Therapeutic Indications

1. Acute nonspecific diarrhea: Loperamide, bismuth subsalicylate.

2. Traveler’s diarrhea: Bismuth compounds, loperamide (with antibiotics if severe/bacterial).

3. Chronic functional diarrhea / IBS-D: Loperamide, antispasmodics, probiotics.

4. Secretory diarrhea (tumor-related, AIDS, chemotherapy): Octreotide.

5. Diarrhea associated with antibiotic use: Probiotics, supportive therapy.

6. H. pylori eradication therapy: Bismuth-containing regimens.

7. Pediatric acute diarrhea (selected regions): Racecadotril as adjunct to oral rehydration.

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Contraindications

• General Contraindications for Antidiarrheals:

  • Infectious diarrhea with systemic symptoms (fever, bloody stools, C. difficile colitis).

  • Severe inflammatory bowel disease (risk of toxic megacolon).

  • Children under 2 years (especially with opioid agonists).

• Class-Specific:

  • Bismuth: salicylate allergy, viral illness in children.

  • Anticholinergics: glaucoma, obstructive uropathy.

  • Octreotide: gallbladder disease, uncontrolled diabetes.

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Adverse Effects (Summary)

• Opioid agonists: Constipation, abdominal cramps, drowsiness, risk of abuse (diphenoxylate).

• Adsorbents: Constipation, bloating, drug binding interactions.

• Bismuth compounds: Black stool, salicylate toxicity, tinnitus.

• Anticholinergics: Antimuscarinic side effects (dry mouth, blurred vision, urinary retention).

• Octreotide: Steatorrhea, gallstones, abdominal pain.

• Probiotics: Rare fungemia/bacteremia in immunocompromised patients.

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Clinical Considerations

1. First priority is rehydration therapy (oral or IV), especially in children and elderly.

2. Symptomatic control vs. underlying cause: Antidiarrheals should not mask symptoms of infectious or inflammatory diarrhea.

3. Combination therapy: Loperamide with antibiotics is effective in traveler’s diarrhea caused by invasive bacteria.

4. Pediatric caution: Avoid loperamide in children under 2; use racecadotril in select settings.

5. Chronic diarrhea management: Requires ruling out organic causes (IBD, celiac disease, malabsorption).