L2- Anti emetics/Diarrhoea/Crohns

Introduction to Intestinal Pharmacology

• Focus areas: vomiting, anti-nausea medications, constipation, Crohn's disease.

• Suggested reading: Rang and Dale, Chapter 30 for gastrointestinal tract information.

Control of Vomiting

• The vomiting reflex is complex, involving brain, gut, and muscles.

• Key areas in the brain:

  • Chemoreceptor Trigger Zone (CTZ): Located in the medulla; serves as a sensor for toxins, drugs, and metabolic disturbances.

  • Vomiting Center (VC): Receives signals from the CTZ and integrates various inputs (gastrointestinal tract, vestibular system, emotional responses).

Key Neurotransmitters Involved in Vomiting

• Dopamine D2 receptors: In CTZ; antagonists used to treat nausea.

• Serotonin 5-HT3 receptors: Major factor in chemotherapy-induced nausea; antagonists can be effective.

• Histamine H1 receptors: Involved in motion sickness; antagonists used to manage nausea in travel sickness.

• Substance P (NK-1 receptors): Associated with delayed phase vomiting; antagonists can help block this response.

Drug Classes for Nausea and Vomiting

1. H1 Receptor Antagonists (e.g., Promethazine, Cinnarizine)

   • Mechanism: Block histamine receptors in VC and vestibular system.

   • Uses: Motion sickness, vertigo, morning sickness.

   • Side effects: Drowsiness, sedation.

2. Muscarinic Receptor Antagonists (e.g., Hyoscine)

   • Mechanism: Block M1 receptors, preventing nausea signals.

   • Commonly used in travel sickness; relaxes stomach muscles.

   • Side effects: Dry mouth, blurred vision.

3. 5-HT3 Receptor Antagonists (e.g., Granisetron, Ondansetron)

   • Mechanism: Block receptors in the peripheral vagus nerve and CTZ.

   • Generally used pre-chemotherapy to prevent nausea.

   • Important for comfort during cancer treatment.

4. NK-1 Receptor Antagonists (e.g., Aprepitant, Fosaprepitant)

   • Mechanism: Block substance P receptor, inhibiting emetic response.

   • Used for chemotherapy-induced nausea and postoperative nausea.

   • Side effects: Diarrhea, fatigue, headaches.

5. Dopamine D2 Receptor Antagonists (e.g., Domperidone, Metoclopramide)

   • Mechanism: Block D2 receptors, increasing acetylcholine activity.

   • Effective for postoperative nausea and delayed gastric emptying.

   • Side effects: Dry mouth, dizziness, blurred vision.

Constipation Treatments

• Types of laxatives: Bulk-forming, stimulant, and fecal softeners.

1. Bulk-Forming Laxatives

• Mechanism: Absorb water, increase stool bulk, stimulating bowel movement.

• Must be taken with adequate fluids to prevent worsening constipation.

2. Stimulant Laxatives

• Mechanism: Accumulate water & electrolytes, irritate bowel nerves for increased motility.

• Commonly used for bowel prep before surgeries but can cause cramping and electrolyte imbalances.

3. Fecal Softeners (e.g., Docusate)

• Mechanism: Detergent action to soften stool by mixing water and fats.

• Commonly used after bowel surgery to prevent strain.

Brief Overview of Crohn's Disease

• Crohn's disease is a chronic inflammatory bowel disease affecting any GI tract part.

• Causes: Environmental factors, immune dysregulation, genetics, altered gut microbiome.

Symptoms and Treatment

• Symptoms: Abdominal pain, diarrhea, mucus or blood in stools.

• Treatment focuses on reducing inflammation and managing symptoms:

  • 5-ASA drugs: For mild cases, reduce gut inflammation.

  • Corticosteroids: For moderate to severe cases but caution for long-term use.

  • Immunosuppressants: Control overactive immune response.

  • Biologics: Target specific inflammatory proteins (TNF inhibitors).

Biologics in Crohn's Treatment

1. Infliximab: Targets TNF alpha, preventing inflammation cascade.

2. Vedolizumab: Blocks integrin to reduce T lymphocyte migration into inflamed tissues.

3. Ustekinumab: Targets interleukin-12 and -23 to reduce inflammatory responses.

Conclusion

• Summarized concepts:

  • Control of vomiting and mechanisms behind antiemetic drugs.

  • Drug types for treating constipation and their actions.

  • Overview of Crohn's disease management with a focus on biologics.

• Study Tips: Focus on understanding mechanisms, utilize visual aids, and practice clinical scenarios to enhance learning and comprehension.