TeacherOfMedicine: Antiemetics, serotonin 5-HT3-receptor antagonists

Prophylaxis and treatment of nausea and vomiting, particularly in the context of general anaesthesia and chemotherapy.

Nausea and vomiting are triggered by a variety of factors, including gut irritation, drugs, motion and vestibular disorders, as well as higher stimuli (sights, smells, emotions). The various pathways converge on a ‘vomiting centre’ in the medulla, which receives inputs from the chemoreceptor trigger zone (CTZ), the solitary tract nucleus (which is innervated by the vagus nerve), the vestibular system and higher neurological centres. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in two of these pathways. First, there is a high density of 5-HT3 receptors in the CTZ, which are responsible for sensing emetogenic substances in the blood (e.g. drugs). Second, serotonin is the key neurotransmitter released by the gut in response to emetogenic stimuli. Acting on 5-HT3 receptors, it stimulates the vagus nerve, which in turn activates the vomiting centre via the solitary tract nucleus. Of note, serotonin is not involved in communication between the vestibular system and the vomiting centre. Thus 5-HT3 antagonists are effective against nausea and vomiting due to CTZ stimulation (e.g. drugs) and visceral stimuli (gut infection, radiotherapy), but not in motion sickness.

Adverse effects are rare with these medications, although constipation, diarrhoea and headaches can occur.

There is a small risk that 5-HT3 antagonists may prolong the QT interval, although this is usually evident only at high doses (e.g. >16 mg ondansetron). Nevertheless, they should be avoided in patients with a prolonged QT interval. If in doubt, review an ECG before prescribing.

Avoid 5-HT3 antagonists when patients are taking drugs that prolong the QT interval, such as antipsychotics, quinine and selective serotonin reuptake inhibitors. If in doubt, check the BNF.

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