Pharmacology of Laxatives and Antidiarrheal

Laxatives

• Laxatives are used to accelerate the movement of food through the GI tract, treating constipation
• Classification of laxatives is based on their mechanism of action
• Risks of laxatives include:
  • Loss of pharmacologic effect of poorly absorbed, delayed-acting, and extended-release oral preparations
  • Electrolyte imbalances with chronic use
  • Dependency risk for the user

Types of Laxatives

• Purgatives: stronger than laxatives, used for full cleaning of the GI tract, e.g., in radiological and endoscopic procedures
• Irritants and Stimulants:
  • Senna: a widely used stimulant laxative, causes evacuation of the bowels within 8-10 hours
  • Bisacodyl: a potent stimulant of the colon, available as suppositories and enteric-coated tablets
  • Castor oil: broken down in the small intestine to ricinoleic acid, irritating the stomach and increasing peristalsis
• Saline and Osmotic Laxatives:
  • Saline cathartics, e.g., magnesium citrate and magnesium hydroxide, hold water in the intestine by osmosis
  • Electrolyte solutions containing polyethylene glycol (PEG) used for colonic lavage and as an oral laxative
  • Lactulose: a semisynthetic disaccharide sugar, acting as an osmotic laxative, also used for hepatic encephalopathy treatment
• Stool Softeners:
  • Emollient laxatives or surfactants, e.g., docusate sodium and docusate calcium, produce softer feces and ease passage
• Lubricant Laxatives:
  • Mineral oil and glycerin suppositories facilitate the passage of hard stools
• Chloride Channel Activators:
  • Lubiprostone: increases fluid secretion in the intestinal lumen, easing stool passage with minimal electrolyte imbalance and no tolerance or dependency issues

Antidiarrheals

• Major Factors in Diarrhea:
  • Increased motility of the GI tract
  • Decreased absorption of fluid
• Antidiarrheal Drugs:
  • Antimotility Agents:
    • Diphenoxylate and Loperamide: opioid-like actions on the gut, inhibit acetylcholine release and decrease peristalsis
  • Adsorbents:
    • Aluminum hydroxide and methylcellulose: adsorb intestinal toxins or microorganisms and/or coat or protect the intestinal mucosa
  • Agents that Modify Fluid and Electrolyte Transport:
    • Bismuth subsalicylate: decreases fluid secretion in the bowel, used for traveler's diarrhea