Gastrointestinal Motility Disorders Quiz

Gastrointestinal Motility Disorders: Pharmacotherapy

• Nausea and Vomiting:

  • Vomiting is a complex physiological process involving the GI tract and nervous system, often preceded by nausea and retching.
  • Vomiting center (VC) is located in the medulla, interacting with chemoreceptor trigger zone (CTZ), afferent nerves from the gut, the vestibular system, and intracranial pressure receptors.
  • Vomiting is preceded by a prodrome, including nausea, cold sweats, pupillary dilation, tachycardia, and salivation.
  • Vomiting action involves relaxation of the proximal stomach, longitudinal contraction of the esophagus, and pulling the proximal stomach into the thorax, evacuating the upper small intestine into the stomach via retrograde giant contraction, while emptying the lower intestines into the colon. This is caused by the compression of the stomach through simultaneous contraction of the diaphragm and abdominal muscles.
  • Conditions related to vomiting include motion sickness, pregnancy, CNS infection, radiation/chemotherapy, post-operative conditions, GI irritation, and other GI problems, psychiatric disorders, and chemical substances.
  • Prolonged or severe vomiting can lead to hypochloremia, hypokalemia, alkalosis, and dehydration, which are dangerous, especially in vulnerable populations.

• Emetic Drugs:

  • Ipecac syrup irritates the gastric mucosa and causes emesis.
  • Apomorphine is a dopamine-like drug that stimulates D2 receptors in the CTZ to cause emesis.
  • Hypertonic salt solutions, antimon potassium, copper sulfate, and zinc sulfate have emetic effects but are less commonly used due to side effects.

• Drugs used in the treatment of Nausea and Vomiting:

  • Muscarinic receptor antagonists (e.g., scopolamine)
  • Histamine H1 receptor antagonists (e.g., cyclizine, diphenhydramine, dimenhydrinate, cinnarizine, doxylamine ,meclizine , promethazine)
  • Dopamine receptor antagonists (e.g., phenothiazines, butyrophenones, domperidone, metoclopramide )
  • Serotonin 5HT3 receptor antagonists (e.g., ondansetron, granisetron, tropisetron)
  • Cannabinoids (e.g., tetrahydrocannabinol, nabilone)
  • Pyridoxine
  • Corticosteroids (e.g., dexamethasone)
  • Benzodiazepines (e.g., lorazepam)
  • Substance P/Neurokinin-1 receptor antagonists (e.g., aprepitant)

• Prokinetic Agents:

  • Drugs that stimulate gut motor function, useful in hypermotility patients.
  • Increase lower esophageal sphincter pressures, helpful for Gastroesophageal Reflux Disease.
  • Reduce gastric fluid volume, decreasing risk of aspiration pneumonitis.

• Gastric Hypomotility:

  • Delayed emptying of stomach contents in conditions like diabetic neuropathy, anorexia nervosa, achlorhydria, and post-operative gastric surgery.
  • Conditions like emergency surgery, full stomach, hiatus hernia, and esophageal reflux require increased gastric motility.

• Diarrhea:

  • Diarrhea is an abnormal increase in stool frequency, weight, and liquidity caused by many GI disorders (infectious or non-infectious).
  • Common types include malabsorptive, maldigestive, and secretory diarrhea.
  • Acute diarrhea is usually infectious and self-limiting; drug therapy is rarely needed. Treatment involves electrolyte replacement.
  • Chronic diarrhea may be caused by conditions like irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) .
  • Use of antidiarrheals may be safe in mild-to-moderate acute diarrhea, but should not be used in bloody diarrhea, high fever, or systemic toxicity, as they can worsen underlying conditions.

• Antidiarrheal Agents:

  • Antimotility agents (e.g., opioids, diphenoxylate with atropine, loperamide)
  • Adsorbents (e.g., kaolin, pectin, aluminum silicate, methylcellulose)
  • Agents that modify fluid and electrolyte transport (e.g., NSAIDs, bismuth subsalicylate)
  • Octreotide, a synthetic somatostatin analogue, is effective in higher doses for treating diarrhea due to GI neuroendocrine tumors, vagotomy, dumping syndrome, short bowel syndrome, and AIDS.
  • Other agents like antimicrobial drugs and bacterial replacement (e.g., Lactobacillus acidophilus, Saccharomyces boulardii) may be useful in specific cases.

• Constipation:

  • Inability to have stool frequently, sensation of incomplete evacuation, hard stool, difficulty defecating, flatulence, bloating, and abdominal pain.
  • Factors like diet, physical activity, and use of certain medications affect constipation.
  • Laxatives should be used judiciously and for a limited duration.
  • Analgesics, antacids, anticholinergics, antidiarrheals, antiparkinsonian drugs, barium sulfate, clonidine, diuretics, antihistamines, and ganglion-blocking agents can cause constipation.

• Laxative Drugs:

  • Bulk-forming agents (e.g., psyllium seed, methylcellulose) swell in the intestine to increase stool bulk and soften stools.
  • Stool surfactant agents (e.g., docusate sodium, docusate potassium) promote water absorption into stool, softening it.
  • Stimulant laxatives (e.g., bisacodyl, senna glycosides) stimulate bowel movements through increased intestinal motility, sometimes causing abdominal cramps.
  • Osmotic laxatives (e.g., lactulose, magnesium hydroxide, sodium phosphate) retain water in the intestine, increasing stool volume.

• Treatment of Irritable Bowel Syndrome (IBS):

  • IBS is an idiopathic, chronic, relapsing disorder characterized by abdominal discomfort and alterations in bowel habits (diarrhea, constipation, or both).
  • Pharmacotherapies for IBS focus on relieving abdominal pain and improving bowel function.
  • Antidiarrheals (e.g., loperamide) are helpful for patients with predominant diarrhea.
  • Fiber supplements may soften stools and reduce straining in constipation-predominant IBS.
  • Low doses of tricyclic antidepressants (e.g., amitriptyline, desipramine) may be helpful for chronic abdominal pain.
  • Other agents, including anticholinergics, 5-HT3 & 5-HT4 receptor antagonists, may be used.