Emesis and Anti-Emetic Drugs Overview

Overview of Emesis and Anti-Emetic Drugs

What is Emesis?

  • Definition: Emesis is the forceful expulsion of gastrointestinal contents through the mouth, commonly known as vomiting.
  • Function: Acts as a physiological defense mechanism to expel poisons, toxins, and foreign organisms.
  • Causes:
    • Emotional distress (e.g., fear, disgust)
    • Pain
    • Vestibular disturbances (e.g., motion sickness)
    • Pregnancy
    • Gastric irritation
    • Cancer treatments (e.g., radiotherapy, chemotherapy)

Physiological Process of Vomiting

  • Symptoms:
    • Nausea, excess salivation
    • Cold sweat, increased pulse rate, respiration (sympathetic ANS activation)
    • Closure of the glottis, relaxation of diaphragm, contraction of abdominal muscles
    • Giant retrograde contraction of the gastrointestinal tract, mainly from the proximal jejunum
  • Central Coordination: Controlled by the "vomiting center" located in the brainstem.

Central Control of Vomiting

  • Location: Medulla oblongata, particularly the lateral reticular formation.
  • Involved Structures:
    • Chemoreceptor trigger zone (CTZ)
    • Area postrema, Nucleus tractus solitarius (NTS)
  • Receptors: Rich expression of muscarinic M1, histamine H1, neurokinin NK1, and serotonin 5-HT3 receptors involved in coordinating visceral and somatic responses.

Chemoreceptor Trigger Zone (CTZ)

  • Location: Floor of the 4th ventricle of the brain; has a lack of effective blood-brain barrier.
  • Function: Receives input from vestibular nuclei; links to the vomiting center and considered a major site for sensing blood-borne toxins.
  • Receptors: Abundant in serotonin 5-HT3, dopamine D2, and neurokinin NK1 receptors.

Pathways Involved in Vomiting

  • The vomiting center integrates signals from:
    • Higher cortical centers (emotional and sensory inputs)
    • Afferents from the vagus nerve (visceral inputs)
    • Chemoreceptor trigger zone (blood-borne stimuli)
  • Physiology includes multiple receptor types that facilitate the vomiting reflex:
    • 5-HT3, NK1, and D2 receptors play crucial roles in this process.

Types of Anti-Emetic Drugs

  • Antihistamines:
    • Drugs: Diphenhydramine, cyclizine, promethazine
    • Mechanism: Target H1 receptors; effective for motion sickness and morning sickness; promethazine preferred for morning sickness.
  • Muscarinic Antagonists:
    • Drug: Hyoscine
    • Usage: Primarily for motion sickness and post-operative nausea.
  • Dopamine Antagonists:
    • Drugs: Chlorpromazine, domperidone, metoclopramide
    • Mechanism: Block D2 receptors in CTZ; effective in severe nausea from cancer treatment.
  • Serotonin Antagonists:
    • Drugs: Ondansetron, granisetron
    • Mechanism: Block 5-HT3 receptors; highly effective for chemotherapy-induced nausea.
  • Neurokinin Antagonists:
    • Drugs: Aprepitant, fosaprepitant
    • Usage: Useful in chemotherapy-induced vomiting; often combined with other agents.
  • Cannabinoids:
    • Drug: Nabilone
    • Mechanism: Agonizes CB1 receptors to prevent vomiting; used when other drugs are ineffective.

Drug Indications for Vomiting

  • Motion Sickness: Hyoscine, cyclizine, promethazine.
  • Morning Sickness: Promethazine, metoclopramide.
  • Post-Operative Pain: Hyoscine, metoclopramide, ondansetron.
  • Chemotherapy Induced Vomiting: Metoclopramide, ondansetron, aprepitant.
  • Drug-Induced Vomiting: Metoclopramide, cyclizine.

Conclusion

  • Emesis is a complex physiological response managed by multiple pathways in the CNS.
  • Anti-emetic drugs work on various receptors including histamine, muscarinic, dopamine, serotonin amongst others to prevent vomiting and manage associated nausea effectively.
  • Prophylactic use is common for anticipated nausea during surgeries or chemotherapy treatments.