Gastrointestinal Motility and Laxatives

Lesson 21: Gastrointestinal Motility

• Gastrointestinal system motility is affected by a variety of medications.
• Drugs that alter GI tract motility include purgatives, which accelerate food passage through the intestines; this may include prokinetic drugs, which increase motility without causing purgation; antidiarrheal drugs, which reduce motility; and antispasmodic/spasmolytic drugs, which reduce smooth muscle tone.

Laxative Agents

• Purgatives or laxatives include bulk laxatives (e.g., ispaghula husk), osmotic laxatives (e.g., lactulose), faecal softeners (e.g., docusate), and stimulant purgatives (e.g., senna).
• Bulk laxatives work by increasing fecal volume and consistency, promoting peristalsis, taking 1-3 days to act.
• Osmotic laxatives work by retaining fluid in the intestine, speeding up transit and causing distension, which has an effect within one hour.
• Faecal softeners act similarly to detergents in the gut, promoting soft stool production and a weak stimulant laxative activity. They can affect the absorption of fat-soluble vitamins (A,D,E).
• Stimulant laxatives (bisacodyl, sodium picosulfate, senna, and dantron) increase electrolyte and water secretion and peristalsis via stimulation of enteric nerves. Bisacodyl is often administered rectally. Senna and dantron are anthraquinone derivatives.
• Overuse of laxatives can cause dependence and lead to an atonic colon.

Prokinetic Drugs

• Prokinetic drugs stimulate GI cholinergic activation, increasing stomach emptying rate and peristalsis/transit rate.
• These drugs may include serotonin agonists (e.g., prucalopride, tegaserod), dopamine decreasers (e.g., antidopaminergics).
• D₂ antagonists (e.g., domperidone, metoclopramide). Some are antiemetics (prevent nausea & vomiting). Some may cross the blood-brain barrier.
• Other agents (e.g., lubiprostone) stimulate chloride and fluid secretion for softer stools.
• Naloxegol and methylnaltrexone are opioid receptor antagonists that combat opioid-induced constipation but generally don't affect pain management.

Antidiarrheal Agents

• Antidiarrheal agents can include inhibitors of intestinal motility
• Opioids (loperamide) have a selective and local effect in the GI tract, reducing abdominal cramps and passage of feces. They have enterohepatic cycling.
• Muscarinic antagonists (e.g., atropine, hyoscine, propantheline, dicycloverine) are rarely used due to anticholinergic side effects.
• Absorbents (e.g., kaolin, pectin, chalk, charcoal) are believed to adsorb microorganisms or toxins.
• Other agents (e.g., racecadotril) inhibit enkephalinase, reducing intestinal secretion.
• Anandamide is a cannabinoid receptor agonist that reduces intestinal motility and diarrhea.

Treatment of Chronic Bowel Disease

• Chronic bowel disease comprises irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).
  • IBS includes diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), and mixed-symptom (IBS-M). Aetiology is uncertain but may involve gut-brain axis, visceral hypersensitivity, and stress.
    • Treatment includes a low-residue diet, loperamide for diarrhea, and laxatives if needed for constipation.
  • 5-HT treatments include antagonists (alosetron, ramosetron), which decrease gut motility, and agonists (tegaserod) which stimulate motility.
  • Other treatments such as eluxadoline, a mixed μ/κ opioid receptor agonist and δ-receptor antagonist, act on peripheral receptors to reduce colonic motility but improve pain/diarrhea. Linaclotide stimulates secretion leading to rapid intestinal transit.
• IBD subtypes include ulcerative colitis or Crohn's disease.
  • Treatment includes glucocorticoids (prednisolone or budesonide), or via suppositories or enemas; aminosalicyates (sulfasalazine) to inhibit inflammation; and immunomodulators or biologics like infliximab, vedolizumab or ustekinumab.

This quiz explores the factors affecting gastrointestinal motility and the different types of laxative agents. Learn about purgatives, prokinetic drugs, and other medications that influence the digestive system. Test your knowledge on how these agents work and their effects on the GI tract.