16A23: Exam Report

Classify anti-emetic agents by describing their mechanism of action and provide examples.

52% of candidates passed this question.

Successful candidates were those who discussed the multiple locations in the vomiting pathway where a drug acts, the receptors involved and discussed 5 or more classes. Several approaches can be taken to this topic. Classification by drug group works well and then allows more detail to be provided about possible receptor activity.
For example:
Anithistamines: Promethazine H1 ++++ M ++ D2 ++ 5-HT3
Anitcholinergics: Scopalamine H1 + M ++++ D2 + 5-HT3
Benzamines: Metoclopromide H1 + M — D2 +++ 5-HT3 ++,
Neuroleptics: Droperidol H1 + M – D2 +++ 5-HT3 +,
5-HT3 Antagonists: Ondansetron H1 – M – D2 – 5-HT3 ++++, Granisetron H1 ++++ M ++
D2 ++ 5-HT3 ; Glucocorticoids: Dexamethasone H1 – M – D2 – 5-HT3 -,
Propofol: GABBA
Cannabinoids: direct on vomiting center.
An alternative approach involves a discussion of the distribution of receptor sites: nucleus
vestibularis H1 M, area postrema (chemoreceptor trigger zone) 5-HT3 D2 M1 H1, nucleus tractus solitarius 5-HT3 D2 M H2 and then discuss which drugs act where. This material has also been previously covered in the viva examination and knowledge of both drug properties and receptor distribution is often required.

Few answers detailed relative activity at various receptors types – “+” scale illustrated above would be sufficient to convey an understanding to the examiners.

O2iii / 16A23: Classify antiemetic agents by describing their mechanism of action and provide examples

  • Antiemetics can be classified at their receptor site of action in the vomiting pathway
  • Vomiting Centre = cluster of neurons in medulla which receive input from:
    • CTZ: D2, 5HT3
    • Viscera: D2, 5HT3, mAChR
    • Cerebral cortex: D2, 5HT3, mAChR
    • Vestibular centre: mAChR

Dopamine Antagonists

  • Block D2 receptors in CTZ ∴↓activation of vomit centre
  • Act peripherally on D2 receptors of gut to ↑motility
  • 3 classes of D2 antagonists:
    • Phenothiazines → prochlorperazine, chlorpromazine
    • Benzamides → metoclopramide
    • Butyrophenones → droperidol, domperidone, haloperidol

5HT3 Antagonists

  • Block 5HT3 receptors
    • Peripherally: in stomach to ↓afferent signals to CTZ & VC
    • Centrally: act in CTZ to ↓activation of VC (vomit centre)
  • E.g. Ondansetron, granisetron


  • Peripheral: blocks vagal afferents & ↓GI secretions
  • Peripheral ear: blocks M1 receptors on labyrinth ∴↓CTZ activation
  • Centrally: mAChR blocked to ↓VC activation
  • E.g. atropine, glycopyrrolate, hyoscine

H1 Antagonists

  • Inhibits H1-mediated activation of VC
  • Useful to block off signals from labyrinth in motion sickness
  • E.g. cyclizine, promethazine


  • Benzodiazepines via GABAA modulation ↓inputs to VC → lorazepam
  • Steroids ?act directly on VC to ↓activation → useful prophylactically pre-op → dexamethasone
  • Cannabinoids blocks cannabinoid receptors from CTZ → VC → cannabis
  • Propofol ?GABAA modulation ↓VC activation
  • Acupuncture

Notes on GI Effects of Metaclopramide (12A23)


  • Dopamine antagonist anti-emetic
  • Acts as a GI prokinetic by stimulating different receptors in the GI tract
  • Although classified as anti-dopaminergic, the PROKINETIC effects of metoclopramide are due to ↑ cholinergic activity
  • ∴requires background cholinergic activity to be effective


  1. Inhibits presynaptic + postsynaptic D2 receptor
  2. Stimulates 5HT4 receptor
  3. Antagonises presynaptic inhibition of muscarinic receptors

  1. ↑LES & gastric tone
  2. ↑gastric P
  3. Acceleration of gastric emptying


  1. Direct gut relaxation by activating D2 receptors on LES & stomach
  2. Inhibits ACh release by activating pre-junctional D2 receptors which leads to indirect inhibition of musculature