Antiemetics

Question 1

Example of an antiemetics

Answer 1

Metoclopramide

Question 2

How does Metoclopramide work?

dopamine D2-receptor antagonists

Answer 2

Nausea and vomiting are triggered by a variety of factors, including gut irritation, drugs, motion and vestibular disorders, as well as higher stimuli.

The various pathways converge on a ‘vomiting centre’ in the medulla, which receives inputs from the chemoreceptor trigger zone, the solitary tract nucleus ( innervated by the vagus nerve), the vestibular system and higher neurological centres.

The D2 receptor is the main receptor in the chemoreceptor trigger zone (CTZ), which is the area responsible for sensing emetogenic substances in the blood (e.g. drugs). Dopamine is an important neurotransmitter in the gut, where it promotes relaxation of the stomach and lower oesophageal sphincter and inhibits gastroduodenal coordination.

Drugs that block D2 receptors therefore have a prokinetic effect – promoting gastric emptying – which contributes to their antiemetic action. They are effective in nausea and vomiting due to CTZ stimulation (e.g. due to drugs) and reduced gut motility (e.g. due to opioids or diabetic gastroparesis).

Question 3

Indications of metoclopramide

Answer 3

Nausea and vomiting

Question 4

Contraindications of metoclopramide

Answer 4

Extrapyramidal side effects are more common in children and young adults so its use should be avoided in these groups.

Contraindicated in patients with gastrointestinal obstruction and perforation.

Question 5

Side effects of metoclopramide

Answer 5

Diarrhoea is probably the most common side effect of D2-blocking antiemetics.

Metoclopramide can induce extrapyramidal syndromes (movement abnormalities) In the context of short-term treatment for nausea and vomiting, this is most likely to take the form of an acute dystonic reaction such as an oculogyric crisis (characterized by a prolonged involuntary upward deviation of the eyes).

Domperidone tends not to cause extrapyramidal symptoms because it does not cross the blood–brain barrier (note that the chemoreceptor trigger zone is largely outside the blood–brain barrier)

Question 6

Elimination of metoclopramide

Answer 6

Renal

Question 7

Patient Information

Answer 7

Starting dose: 10 mg, up to three times daily
available for injection.

Explain that you are offering an anti-sickness medicine. Most people are able to take it without any significant side effects. If you are prescribing outside hospital, it is prudent to mention the possibility of muscle spasms and abnormal movements with metoclopramide. Ask your patient to stop taking the medicine and seek medical attention if they notice any side effects of this type.

Question 8

Possible interactions

Answer 8

The risk of extrapyramidal side effects is increased when metoclopramide is prescribed with antipsychotics. It should not be combined with dopaminergic agents for Parkinson’s disease, as it will antagonise their effects.

Domperidone is not subject to these interactions.