Anti-Emetics

These drugs principally act by in inhibiting the chemoreceptor trigger zone, thereby blocking the activation of the vomiting centre in the medulla. Three of the most common first line anti-emetics are Metoclopramide + Cyclizine + Haloperidol. 

D₂ receptor antagonists

These block dopaminergic receptors in the CTZ which blocks activation of the vomiting centre.

Haloperidol

This is effective at stopping vomiting due to chemical reasons e.g. drugs (like opioids), hypercalcaemia.

Metoclopromide

This is used to stop all types of nausea except motion sickness

It also inhibits the dopamine break which usually inhibits the cholinergic neurones in gut, so aids bowel motility

It acts as a prokinetic gut agent, helping to increase lower oesophageal tone and it increases rate of food transit

Hence it is also used for reflux disease and helps treat gastroparesis secondary to diabetic neuropathy

Must be avoided in bowel obstruction with colic as it increases bowel contractions.

Domperidone

Unlike the drugs before, this does not cross the blood brain barrier and so it is safe to give in Parkinson’s disease.

H₁ antagonists – Cyclizine, promethazine

These reduce histaminergic and cholinergic signalling, particularly in the vomiting centre of the vestibular apparatus.

Cyclizine is also used to treat nausea due to raised intracranial pressure as it directly inhibits the vomiting centre.

Cyclizine is a non-sedating drug, whereas promethazine is sedating. 

5-HT₃ antagonists – Ondansetron

This blocks 5-HT3 receptors in the CTZ, reducing stimulation of the vomiting centre.

It is used first-line to treat nausea due to chemotherapy, radiation-induced emesis, and post-operative nausea.

It is often combined with corticosteroids to produce an enhanced anti-mimetic effect.

AchR antagonists – Scopolamine (Hyoscine Hydrobromide)

This is a muscarinic antagonist which blocks M1 receptors in the vomiting centre and decreases the excitability of labyrinth receptors.

It is a very effective treatment for motion sickness.

There is another form of hyoscine called Hyoscine Butylbromide (Buscopan), not used as an anti-emetic:

This is used to reduce crampy abdominal pain, spasms and improves respiratory secretions at the end of life.

Levomapromazine

This is an antipsychotic which blocks multiple receptors e.g., D2, H1 and AchR.

It can therefore be used for multiple causes of nausea.

It also acts as a potent anxiolytic, so it is especially useful for young patients, as well as in palliative care medicine for nausea and agitation at the end of life. 

Dexamethasone

This is a corticosteroid which is effective for prevention of nausea in patients who have had surgery, received epidural spinal opioids and chemotherapy.

It can potentiate the effect of ondansetron.

It is also used as an anti-emetic in people who have intracranial tumours.

Aprepitant

This is a neurokinin-1 antagonist which is used to treat emesis caused by chemotherapy, often in combination with 5-HT3 antagonists and steroids.

Some anti-emetics can be used in combination if they have complimentary actions:

i) Drugs which can be combined:

Cyclizine and Haloperidol (different mechanisms of action)

ii) Cannot combine:

Cyclizine (anti-kinetic) and Metoclopramide (pro-kinetic) as it gives opposing actions

Metoclopramide and Haloperidol (too much dopaminergic antagonism) 

Disclaimer