Describe the neural integration of vomiting, highlighting the site and mechanism of action of antiemetics.
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:
- 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-HT3 and 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
- Cyclizine and prochlorperazine have mainly anti-H1 effects
- Most centrally acting H1 antagonists also have potent antimuscarinic activity
- NK-1 antagonists:
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