Emesis and Anti-emetics Notes

Overview of Emesis and Anti-emetics

  • Emesis refers to the act of vomiting, regulated by specific neurological pathways.
  • Main goals of studying emesis:
    • Understand the physiology of vomiting and its causes.
    • Identify neurotransmitters involved in emesis.
    • Learn about anti-emetic drugs and their mechanisms.
    • Recognize side effects associated with anti-emetic medications.

Physiology of Vomiting

  • Vomiting Center: Located in the medulla, coordinating the act of vomiting through:
    • Cranial and spinal nerves controlling abdominal and diaphragm muscles.
    • Reverse peristalsis moving gastric contents upward.
    • Closure of the epiglottis to protect airways.
  • Chemoreceptor Trigger Zone (CTZ):
    • Located in the area postrema, outside the Blood-Brain Barrier (BBB).
    • Sensitive to circulating toxins and drugs, primarily activating vomit reflexes.

Causes of Emesis

  • Physiological responses:
    • Can be beneficial (e.g., to expel toxins) or a side effect of drugs/diseases.
  • Main Causes:
    • Drugs: Cytotoxic medications, opioids, anesthetics, alcohol.
    • Diseases: Ménière’s disease, labyrinthitis, gastroenteritis.
    • Conditions: Pregnancy, motion sickness, food poisoning.

Neurotransmitters Involved in Emesis

  • Key Neurotransmitters:
    • Acetylcholine (ACh)
    • Histamine
    • Serotonin (5-HT)
    • Dopamine (DA)
  • Receptors:
    • 5-HT3, D2, NK1, m-opioid receptors are crucial for emetic responses.
  • Stimulation of these pathways can lead to nausea and vomiting, especially in response to CTZ activity.

Anti-emetic Drugs

  • Categories of Anti-emetics:
    • Dopamine D2 Antagonists:
    • Examples: Prochlorperazine, Metoclopramide, Domperidone.
    • Effective for severe emesis (cytotoxic drug-induced).
    • Side effects (especially in antipsychotics): Dystonia, fatigue, sedation.
    • 5-HT3 Antagonists:
    • Examples: Ondansetron, Granisetron.
    • Effective in postoperative and chemotherapy-induced vomiting.
    • Side effects: Headache, constipation.
    • Antihistamines:
    • Examples: Cinnarizine (motion sickness), Promethazine (severe morning sickness).
    • Side effects: Drowsiness.
    • Muscarinic Antagonists:
    • Example: Hyoscine for motion sickness.
    • Side effects include dry mouth, blurred vision.
    • Cannabinoids:
    • Example: Nabilone, a CB1 agonist.
    • Side effects: Drowsiness, dry mouth.
    • Neurokinin-1 Antagonists:
    • Example: Aprepitant, effective against Substance P-induced vomiting.

Side Effects of Anti-emetics

  • Common Side Effects:
    • Drowsiness, dizziness, dry mouth, postural hypotension, and constipation.
  • Specific side effects based on drug classification include:
    • Dopamine Antagonists: Move to movement disorders, dyskinesia, endocrine effects like galactorrhea.
    • 5-HT3 Antagonists: Risks of headache and constipation.

Conditions Associated with Emesis

  • Vestibular Disorders:
    • Motion sickness, Ménière’s disease, labyrinthitis leading to nausea and vomiting due to imbalance signals.
    • Treatments include antihistamines for symptom management.
  • Pregnancy:
    • Nausea and vomiting common especially in the first trimester, affecting many women but tends to lead to better pregnancy outcomes.
    • Treatment usually avoided, except in severe cases with antihistamines.

Summary of Key Points

  • Vomiting is controlled by a coordinated effort from the vomiting center in the brain, which responds to various stimuli.
  • Understanding neurotransmitters and anti-emetics provides insight into treatments available for different causes of emesis.