Physiology of vomiting

Vomiting is controlled by the emetic centre which is situated in the floor of the fourth ventricle. The emetic centre represents the final common pathway for stimuli from several sites included the chemoreceptor trigger zone - CTZ - located on the surface of the fourth ventricle, the meninges, cerebral cortex, vestibular apparatus and the gastrointestinal tract via vagus and sympathetic afferents. In the emetic centre and the CTZ there are high concentrations of dopamine receptors with associated cholinergic and H1 receptors.

Metoclopramide, phenothiazines, butyrophenones, and domperidone act mainly by antagonism at the dopamine receptors to reduce vomiting stimuli. Domperidone crosses the blood-brain barrier poorly and has mainly a peripheral action. Metoclopramide also has a peripheral action and increases gastro-oesophageal tone and increases stomach emptying due to a cholinergic effect. Serotonin antagonists such as Ondansetron probably have peripheral effects in the gut and a central action.

Note - although not routinely used, Olanzapine may be of use in patients who are not responding to standard antiemetics. at a dose of 10mg stat then days 2 to 4. (An unlicensed indication for delayed nausea and vomiting). Nabilone (a synthetic cannabinoid) is licensed for nausea and vomiting caused by cytotoxic chemotherapy, unresponsive to conventional antiemetics at a dose of 1-2mg b.d. orally. NICE state that the evidence is limited, and of low quality using outdated antiemetics but that it could be an option as an add on where patients have nausea and vomiting despite optimised conventional antiemetics.) (1,2)

Reference

1. Roila F et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Annals of Oncology 27 (Supplement 5): v119–v133, 2016
2. NICE. Cannabis-based medicinal products. NICE guideline NG144. Published November 2019, last updated March 2021