Classification of Antiemetics

Nausea and vomiting are common symptoms caused by various physiological and pathological triggers such as motion sickness, drug toxicity, pregnancy, and gastrointestinal infections. Antiemetic drugs are used to suppress nausea and vomiting by acting on the central and peripheral pathways involved in the vomiting reflex.

This blog from Pharmacy Freak explains the classification, mechanisms, uses, and drug of choice guidelines for antiemetic drugs based on trusted sources like KDT, Sparsh Gupta, and Goodman & Gilman.

What is Antiemetics?

Antiemetic drugs are agents that prevent or relieve nausea and vomiting. They act on specific receptors in the vomiting center, chemoreceptor trigger zone (CTZ), vestibular system, and gastrointestinal tract.

Antiemetics Classifications (KD Tripathi)

  • Anticholinergics: Hyoscine, Dicyclomine
  • Neuroleptics (D2 blockers): Chlorpromazine, Triflupromazine, Prochlorperazine, others
  • Prokinetic drugs: Metoclopramide, Domperidone, Cisapride, Mosapride, Itopride
  • NK₁ receptor antagonists: Aprepitant, Fosaprepitant
  • H₁ antihistaminics: Promethazine, Diphenhydramine, Dimenhydrinate, Doxylamine, Meclozine (Meclizine)
  • 5-HT₃ antagonists: Ondansetron, Granisetron, Palonosetron, Ramosetron
  • Adjuvant antiemetics: Dexamethasone, Benzodiazepines, Dronabinol, Nabilone

Classification (General)

  1. 5-HT3 Receptor Antagonists
    Mechanism: Block serotonin (5-HT3) receptors in the CTZ and GI tract
    Drugs: Ondansetron, Granisetron, Palonosetron, Tropisetron
    Uses: Chemotherapy-induced nausea and vomiting (CINV), postoperative and radiation-induced vomiting
  2. D2 Receptor Antagonists (Dopamine Antagonists)
    Mechanism: Block dopamine receptors in the CTZ
    Drugs: Metoclopramide, Domperidone, Prochlorperazine, Promethazine
    Uses: Drug-induced vomiting, GI disorders, postoperative nausea
    Note: Metoclopramide also has prokinetic properties
  3. H1 Receptor Antagonists (Antihistamines)
    Mechanism: Block histamine receptors in the vestibular system
    Drugs: Cyclizine, Meclizine, Dimenhydrinate, Promethazine
    Uses: Motion sickness, vestibular disorders, pregnancy-induced nausea
  4. Muscarinic Antagonists
    Mechanism: Inhibit muscarinic (M1) receptors in the vestibular apparatus
    Drug: Hyoscine (Scopolamine)
    Uses: Motion sickness (prophylactic use)
  5. NK1 Receptor Antagonists
    Mechanism: Block substance P neurokinin-1 receptors in the CNS
    Drugs: Aprepitant, Fosaprepitant, Netupitant
    Uses: Delayed-phase chemotherapy-induced vomiting (in combination with 5-HT3 antagonists and corticosteroids)
  6. Corticosteroids
    Mechanism: Unclear; possibly reduce inflammation and prostaglandin activity in CNS
    Drugs: Dexamethasone, Methylprednisolone
    Uses: CINV (especially delayed phase), postoperative nausea (as adjunct)
  7. Cannabinoids
    Mechanism: Act on cannabinoid receptors in the CNS
    Drugs: Dronabinol, Nabilone
    Uses: Refractory CINV, appetite stimulation in cancer or AIDS patients
  8. Benzodiazepines
    Mechanism: Act on GABA-A receptors; reduce anticipatory nausea
    Drugs: Lorazepam, Diazepam
    Uses: Anxiety-related nausea, anticipatory vomiting in chemotherapy

Uses

Antiemetics are used in the management of:

  • Chemotherapy-induced nausea and vomiting (acute and delayed)
  • Radiation and postoperative vomiting
  • Motion sickness
  • Vertigo and vestibular disorders
  • Gastrointestinal disorders (gastritis, gastroenteritis)
  • Pregnancy-induced nausea
  • Drug-induced vomiting (opioids, digoxin, levodopa)

Drug of Choice Highlights

Motion sickness – Hyoscine or Promethazine
Chemotherapy-induced vomiting (acute) – Ondansetron
Delayed chemotherapy vomiting – Aprepitant + Dexamethasone
Postoperative nausea – Ondansetron or Metoclopramide
Pregnancy-induced vomiting – Doxylamine + Pyridoxine (Sparsh Gupta)
Drug-induced vomiting – Metoclopramide
Vertigo – Meclizine or Promethazine
Anticipatory vomiting – Lorazepam

Side Effects

  • 5-HT3 antagonists – Headache, constipation, QT prolongation
  • D2 antagonists – Extrapyramidal symptoms (EPS), sedation, hyperprolactinemia
  • H1 blockers – Drowsiness, dry mouth, blurred vision
  • Muscarinic blockers – Dry mouth, dizziness, blurred vision, urinary retention
  • NK1 antagonists – Fatigue, hiccups, drug interactions (CYP3A4)
  • Corticosteroids – Hyperglycemia, insomnia, mood changes
  • Cannabinoids – Euphoria, dizziness, hypotension, abuse potential
  • Benzodiazepines – Sedation, dependence

Updated Clinical Pearls

  • Ondansetron is the most commonly used antiemetic across hospital and outpatient settings.
  • Metoclopramide should be used cautiously due to risk of extrapyramidal effects, especially in children and elderly.
  • Aprepitant is reserved for high-emetogenic chemotherapy regimens and should be used in combination with dexamethasone and 5-HT3 blockers.
  • Doxylamine combined with pyridoxine is the preferred option in pregnancy-related nausea and vomiting.
  • Cannabinoids are not first-line and are used only in refractory cases due to their psychotropic side effects.

References

  1. Tripathi KD. Essentials of Medical Pharmacology. 7th ed. New Delhi: Jaypee Brothers Medical Publishers; 2013. p. 964–968.
  2. Gupta S, Garg A. Review of Pharmacology. 15th ed. New Delhi: Jaypee Brothers Medical Publishers; 2023. p. 292–294.
  3. Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Education; 2011. p. 1065–1072.

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