Antiemetics

Vomiting Vexations - The Why & How

Vomiting (emesis): Protective reflex via Vomiting Center (VC) in medulla, integrating multiple inputs.

• Key Trigger Zones & Neurotransmitters:
  • Chemoreceptor Trigger Zone (CTZ):
    • Area Postrema (outside BBB). Detects blood/CSF toxins.
    • Receptors: Dopamine (D2), Serotonin (5-HT3), Neurokinin-1 (NK1). 📌 Mnemonic: "Don't Say No" (D2, Serotonin, NK1).
  • Vestibular System:
    • Motion sickness. Receptors: Histamine (H1), Muscarinic (M1).
  • GIT (Vagal Afferents):
    • Irritation/distension. Receptors: Serotonin (5-HT3).
  • Higher CNS Centers:
    • Psychological triggers (stress, sight, smell).

⭐ The CTZ is located in the area postrema, which lacks a true blood-brain barrier, making it directly accessible to emetogenic substances in the blood.

Drug Arsenal Overview - Classy Combatants

• 5-HT3 Antagonists: Ondansetron, Granisetron, Palonosetron.
  • MoA: Block 5-HT3 (CTZ, GIT).
  • Uses: CINV, PONV, RINV.
  • SE: Headache, constipation, QT↑.

  ⭐ Palonosetron: Longest t½ (~40 hrs) & highest affinity; effective for delayed CINV.

• D2 Antagonists:
  • Prochlorperazine: CTZ D2 block. SE: EPS, sedation.
  • Prokinetics:
    • Metoclopramide: D2 block (CTZ), 5-HT4 agonist. SE: EPS.
    • Domperidone: Peripheral D2 block. SE: ↑Prolactin, QT risk ⚠️.
• H1 Antihistaminics: Promethazine, Cyclizine, Meclizine.
  • MoA: H1 block (vomiting center, vestibular).
  • Uses: Motion/morning sickness. SE: Sedation.
• Anticholinergics: Hyoscine (Scopolamine).
  • MoA: M1 block (vestibular). Uses: Motion sickness (patch).
• NK1 Receptor Antagonists: Aprepitant, Fosaprepitant.
  • MoA: NK1 (Substance P) block. Uses: Delayed CINV.
• Adjuvants: Dexamethasone (CINV), Lorazepam (anticipatory N/V).

Star Players Spotlight - Med Champs

• 5-HT₃ Antagonists (Setrons)
  • Examples: Ondansetron, Granisetron, Palonosetron (longest $t_{1/2}$).
  • MOA: Block central & peripheral 5-HT₃ receptors (CTZ, vagal afferents).
  • Uses: CINV, PONV, radiotherapy-induced emesis.
  • SE: Headache, constipation, dizziness, QT prolongation (⚠️ with Ondansetron).
• D₂ Antagonists
  • Metoclopramide
    • MOA: Central D₂ block (CTZ); prokinetic (5-HT₄ agonism).
    • Uses: GERD, gastroparesis, antiemetic.
    • SE: EPS (⚠️), drowsiness, hyperprolactinemia. Crosses BBB.
  • Domperidone
    • MOA: Peripheral D₂ block.
    • Uses: Similar to metoclopramide; less EPS.
    • SE: Hyperprolactinemia, cardiac arrhythmias (QT prolongation ⚠️).
• NK₁ Receptor Antagonists (Pitants)
  • Examples: Aprepitant, Fosaprepitant.
  • MOA: Block Substance P at NK₁ receptors in brainstem.
  • Uses: Delayed CINV (often with 5-HT₃ antag. + steroid).
  • SE: Fatigue, hiccups, CYP3A4 interactions.

  ⭐ Aprepitant is highly effective for delayed CINV, typically occurring >24 hours post-chemotherapy.

Clinical Combat Zones - Strategic Strikes

• CINV (Chemotherapy-Induced Nausea & Vomiting)
  • Acute (<24h): 5-HT3 antagonists (Ondansetron), NK1-R antagonists (Aprepitant), Dexamethasone.
  • Delayed (>24h): Aprepitant, Dexamethasone, Olanzapine (especially for highly emetogenic chemo).
  • Anticipatory: Benzodiazepines (Lorazepam) pre-chemo.
• PONV (Post-Operative Nausea & Vomiting)
  • Risk assessment crucial. Multimodal: Ondansetron, Dexamethasone, Droperidol.
• Motion Sickness
  • Prophylaxis key: Antihistaminics (Promethazine), Hyoscine (transdermal patch).
• Pregnancy (NVP)
  • 1st line: Doxylamine + Pyridoxine. 📌 "Morning Sickness? Don't Puke!"
  • Refractory (Hyperemesis Gravidarum): Ondansetron cautiously.

⭐ Aprepitant (NK1-R antagonist) significantly improves control of both acute and delayed CINV, especially with highly emetogenic chemotherapy.

High‑Yield Points - ⚡ Biggest Takeaways

• Ondansetron (5-HT3 antagonist) is first-line for CINV & PONV; watch for QT prolongation.
• Metoclopramide (D2 antagonist) is prokinetic; risk of EPS. Domperidone has fewer CNS effects.
• Aprepitant (NK1 antagonist) is crucial for delayed CINV, often combined with other antiemetics.
• Antihistamines (e.g., promethazine) and anticholinergics (e.g., scopolamine) treat motion sickness.
• Dexamethasone acts as a potent antiemetic adjunct, especially in CINV.
• Olanzapine offers broad-spectrum antiemesis for refractory CINV.