Question 14

Describe the neural integration of vomiting, highlighting the site and mechanism of action of antiemetics.

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College Answer

The examiners commented that a well-drawn and labelled diagram was a very useful adjunct to answering this question. Consideration of stimulus, sensors, integrators/processors, and effectors was also useful to ensure that all components of the question were covered by a candidate’s answer. Incorrect facts or a lack of detail about the various receptors and their locations was a common theme in answers that scored poorly. Classes of antiemetics, with specific drugs given as examples, were expected to gain marks.


Neurology of nausea and vomiting:

  • Stimuli:
    • Bloodstream toxins
    • Sensory stimuli (any of the senses!)
    • Gut distension or noxious chemical content
    • Psychological stimuli
  • Sensors: Chemoreceptor trigger zone, sense organs (eg. visual, olfactory and gustatory), vestibular labyrinth, mechanoreceptors in the GIT.
  • Afferents: vagus, sensory tracts, vestibulocochlear nerve, central descending
    • Main receptors involved are 5-HT3, D2, H1 and muscarinic.
  • Central processors: Nucleus of the solitary tract and chemoreceptor trigger zone both feed into the "central pattern generator" which coordinates the mechanical act of vomiting
    • Neurotransmission in these centres is mediated by:
      • Muscarinic acetylcholine receptors
      • Dopamine receptors
      • 5-HT3 serotonin receptors
  • Efferents: Vagus (to stomach and small intestine), lower cranial nerves (to face and oropharynx), somatic motor fibres (to chest/abdominal muscles), sympathetic nervous system (tachycardia, vasoconstriction, sweating)

Antiemetic classes acting on these receptors:

  • Dopamine (D2) antagonists:
    • Phenothiazines (promethazine), which also have potent activity against muscarinic, H1, 5-HTand dopamine receptors
    • Butyrophenones (droperidol), which have slightly less potent anticholinergic and antihistamine effects 
    • Benzamides (metoclopramide), which have a prokinetic effect related to indirect cholinergic activity
  • Anticholinergic (antimuscarinic): 
    • Hyoscine, atropine (purely antimuscarinic)
    • Phenothiazines and butyrophenones also have strong antimuscarinic effect
  • 5-HT3 antagonists: 
    • ondansetron and granisetron are pure, high-affinity 5-HT3 antagonists
    • Phenothiazines and butyrophenones also have strong 5-HT3 antagonist effects
  • Antihistamines: 
    • Cyclizine and prochlorperazine have mainly anti-H1 effects
    • Most centrally acting H1 antagonists also have potent antimuscarinic activity
  • NK-1 antagonists: 
    • aprepitant 


Lyons, Samantha, and Ben Ballisat. "Antiemetic drugs: pharmacology and an
overview of their clinical use"
 Update in Anaesthesia 31 (2016).

Flake, Zachary A., Robert Scalley, and Austin G. Bailey. "Practical selection of antiemetics." American family physician 69.5 (2004): 1169-1174.

Sanger, Gareth J., and Paul LR Andrews. "A history of drug discovery for treatment of nausea and vomiting and the implications for future research." Frontiers in pharmacology 9 (2018): 913.

Horn, Charles C. "The physiology of vomiting." Nausea and Vomiting. Springer, Cham, 2017. 15-25.

Parkes J.D. (1986) A Neurologist’s View of Nausea and Vomiting. In: Davis C.J., Lake-Bakaar G.V., Grahame-Smith D.G. (eds) Nausea and Vomiting: Mechanisms and Treatment. Advances in Applied Neurological Sciences, vol 3. Springer, Berlin, Heidelberg.

Singh, Prashant, Sonia S. Yoon, and Braden Kuo. "Nausea: a review of pathophysiology and therapeutics." Therapeutic advances in gastroenterology 9.1 (2016): 98-112.