Antiemetics

Question 1

John is a 67-year-old man with hepatocellular carcinoma, currently admitted to a hospice for end of life care. He is complaining of nausea without vomiting and would like something to help relieve this.

On examination, he appears jaundiced and there is a large amount of ascites present. He is feeling bloated and has not opened his bowels in 2 days, but is passing wind.

Which of the following medications would be most suited to treat his nausea?

A) Cyclizine
B) Haloperidol
C) Metoclopramide
D) Morphine
E) Ondansetron

Answer 1

C) Metoclopramide

Dopamine (D2) receptor antagonists should be used in palliative care for nausea and vomiting that is due to gastric dysmotility and stasis.

The symptoms John is experiencing is suggestive of gastric stasis. In this situation, a prokinetic drug such as metoclopramide (D2 antagonist) will help ease his symptoms.

Question 2

The choice of an antiemetic in a palliative care setting is dependant on the cause of nausea.

What are the six broad causes of nausea and vomiting? What treatment is recommended for each?

Answer 2

1) Reduced gastric motility
- Opioids
- Related to serotonin (5HT4) and dopamine (D2) receptors
» Metoclopramide (pro kinetic) and domperidone

2) Chemically mediated
- Secondary to hypercalcaemia, opioids or chemotherapy
- Correct the disturbance
» Ondansetron, haloperidol and levomepromazine

3) Visceral/serosal
- Due to constipation
- Oral candidiasis
» Cyclizine and levomepromazine

4) Raised ICP
- Usually in the context of cerebral metastases
» Cyclizine, or dexamethasone if related to cerebral oedema

5) Vestibular
- Related to activation of acetylcholine and histamine (H1) receptors
- Can be motion related, or due to base of skull tumours
- Frequently opioid-related
» Cyclizine, metoclopramide or prochlorperazine

6) Cortical
- Anxiety, pain, fear, anticipatory
- Related to GABA and histamine (H1) receptors in the cerebral cortex
» Short-acting benzodiazepine (e.g. lorazepam) for anticipatory, alternatively cyclizine, ondansetron or metoclopramide

Question 3

What receptor does ondansetron work on?

Answer 3

5HT3 antagonist

Question 4

What are the options for patients on chemotherapy who are at low or high-risk of nausea and vomiting?

Answer 4

For patients at low-risk of symptoms then drugs such as metoclopramide may be used first-line. For high-risk patients then 5HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone.