Q: What anti-emetic drugs are used for the treatment of vomiting in pregnancy and how do they act?

A: Histamine H1-receptor antagonists and antimuscarinics

Nausea and vomiting are triggered by a number of factors and stimuli are channelled via neurological centres in the brain to the vomiting centre in the medulla. Histamine H1 and acetylcholine (muscarinic) receptors predominate in the vomiting centre. Histamine H1 antagonists (‘sedating antihistamines’) and antimuscarinics, eg, hyoscine, block both of these receptors. The BNF suggests the antihistamine promethazine as a possible treatment for vomiting during pregnancy.

Neurotransmitter antagonists acting in the chemoreceptor trigger zone (CTZ)

One of the neurological centres that feeds into the vomiting centre is the CTZ. Dopamine is the main neurotransmitter in the CTZ and the D2 receptor is the main receptor. D2 receptor antagonists are therefore effective against nausea and vomiting caused by CTZ stimulation. Metoclopramide is a drug of this type suggested in the BNF for vomiting in pregnancy. Phenothiazines also exert an anti-emetic effect via the same mechanism. Prochlorperazine is a phenothiazine suggested in the BNF as a possible treatment for vomiting in pregnancy.

There is also a high density of serotonin (5-hydroxytryptamine, 5-HT3) receptors in the CTZ. Serotonin is the key neurotransmitter released by the gut in response to emetogenic stimuli. Thus, 5-HT3-receptor antagonists also counteract nausea and vomiting due to CTZ stimulation. Ondansetron is an anti-emetic drug in this group. It is not specifically licensed for use in pregnancy but is used as a second-line treatment, and evidence suggests there is no significant risk of adverse foetal outcome when used in pregnancy.¹