11/13/24, 7\:43 PM Guide | Prescribing antiemetics

Prescribing antiemetics

Table of contents

Introduction

Nausea and vomiting are common symptoms that have many causes, such as adverse e
raised intracranial pressure. Although vomiting can be a protective re
prescribing antiemetics is extremely useful.
The main classes of antiemetics include antagonists of the dopamine, muscarinic, histamine, serotonin and neurokinin
systems, corticosteroids, benzodiazepines and medications for speci

Causes of nausea and vomiting

The two main areas of the brain associated with the nausea and vomiting re
the base of the 4th ventricle, and the vomiting centre in the medulla.
The vomiting centre is responsible for most of the coordination of nausea and vomiting and receives input from the nucleus
tractus solitarium and vagus nerve. It can be directly stimulated by stimuli or indirectly by the CTZ.
Visceral stimulation is one way the vomiting centre can be stimulated. This is mostly through a
gastrointestinal tract (mechanical and chemosensory receptors). These are triggered by direct visceral irritation or distension,
and the impulse is conducted by the vagus nerve. The neurotransmitters involved are serotonin (5HT) and dopamine. This is
the mechanism for nausea and vomiting from illnesses such as gastroenteritis.
Gastric stasis, radiotherapy and chemotherapy stimulate 5HT3, 5HT4 and D2 receptors within the peripheral gastrointestinal
tract, as well as chemoreceptors and mechanoreceptors within the liver and gastrointestinal tract. This directly stimulates the
vomiting centre and also indirectly via CTZ.
The vomiting centre can also be stimulated by inputs from other neurological centres, for example through di
nerves. The vestibular component of CN VIII is commonly implicated in nausea. There can often be a psychological
component to nausea and common triggers that act via this mechanism include emotions, smells, vertigo, taste and
anticipatory nausea (for example, following repeat cycles of chemotherapy). Common neurotransmitters involved in this
pathway are acetylcholine, histamine and serotonin.
Anxiety and raised intracranial pressure interact with GABA and H1 receptors within the cerebral cortex which directly
stimulates the vomiting centre.
The CTZ lies outside the blood-brain barrier and is therefore exposed to more "systemic" causes of nausea and vomiting, such
as medication or metabolic disturbances. It can be stimulated directly by hypercalcaemia or opioids in the blood or by
peripheral receptors in the gastrointestinal tract or vestibular input. Common neurotransmitters involved in this are serotonin
and dopamine.
After the vomiting centre is stimulated, vomiting may occur by the following steps\:
A deep breath is taken
Relaxation of the upper oesophageal sphincter
Closure of the glottis and elevation of the soft palate
Contraction of the diaphragm and abdominal wall muscles
Relaxation of the lower oesophageal sphincter

Prescribing antiemetics

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Key prescribing points for antiemetic drugs\:
2
When prescribing, always follow basic prescribing principles.
Ask for allergies and other medications being taken.
Why are they nauseated? The aetiology of nausea and vomiting guides the choice of anti-emetic.
Any other medical conditions that will inParkinson’s disease or pregnancy.
Describe what route is suitable for the patient and document on the prescription.
Document a clinical review and decision date and rationale.

Route

The route of antiemetics is important in practice to achieve optimum therapeutic e
vomiting, then an oral antiemetic is unlikely to be e
The available routes for speci
subcutaneous (SC), rectal (PR), and buccal.

Choice of antiemetic

While, in theory, any antiemetic can be prescribed for any cause of nausea and vomiting, certain classes will be more e
for some causes than others.
When considering indications for the classes of antiemetic medication in this article, the most common situations in which each
medication is used will be listed.

Antihistamines

Examples of antihistamine antiemetics include cyclizine, promethazine hydrochloride, and doxylamine with pyridoxine.

Common indications

Antihistamines are generally used for nausea and vomiting caused by\:
Vertigo
Labyrinthine disorders
Meniere’s disease
Pregnancy
Motion sickness
Post-operative nausea and vomiting
Cyclizine is also used to treat nausea and vomiting in bowel obstruction and in raised intracranial pressure (for example, in
patients with brain metastases).

Contraindications

Cyclizine is contraindicated in heart failure as it can worsen cardiac oedema.
Antihistamine antiemetics should be used with caution in people with a higher risk of urinary retention, such as benign
prostatic hypertrophy or bladder outlet obstruction due to the central anticholinergic e

Mechanism of action

Antihistamines work on H1 receptors, which directly act on the vestibular system and the CTZ.
Doxylamine with pyridoxine is o
which selectively binds H1 receptors at the CTZ. Pyridoxine is vitamin B6 and is a water-soluble vitamin which is given as there
could be a de

Side e

Antihistamines are usually well tolerated; however, the most common side e
patients. This can cause reduced coordination, reaction speed, and judgement if they drive or operate heavy machinery.
Anticholinergic side e
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There is an increased antimuscarinic and sedative e
oxidase inhibitors, so this should be avoided if possible.

Phenothiazines and related drugs

Examples of phenothiazines are metoclopramide and prochlorperazine (can be given as buccal).
Other antipsychotics which are commonly used as antiemetics include haloperidol (unlicensed use), levomepromazine and
domperidone.

Common indications

Phenothiazines and antipsychotics are often used for\:
Chemotherapy-induced nausea and vomiting
Radiotherapy-induced nausea and vomiting
Prevention and treatment of acute nausea and vomiting
Labyrinthine disorders
Migraine-related nausea and vomiting
Nausea and vomiting in palliative care
Metoclopramide speci
Levomepromazine and haloperidol are often used for nausea and vomiting associated with hypercalcaemia, non-
chemotherapy drugs and metabolic causes, e.g. hyponatraemia.

Contraindications

Metoclopramide is contraindicated in bowel obstruction due to its prokinetic e
perforation. It can be useful to con
abdominal x-ray may be indicated.
This class of antiemetics should also be avoided in Parkinson's disease, as the mechanism of action can worsen Parkinsonian
symptoms.
Domperidone should not be used in patients with disorders of cardiac conduction, arrhythmias and congestive cardiac failure,
as there is a small risk of cardiac side e

Mechanism of action

These are dopamine (D2) antagonists and work on D2 receptors within the CTZ.
Levomepromazine is a broad-spectrum anti-emetic working at multiple receptor sites, including dopamine type 2 (D2)
antagonist, H1, 5HT-2 receptors and serotonergic sites. This makes it useful in situations such as palliative care as it can cover
many aetiologies of nausea and vomiting and works secondarily as a sedative.
Domperidone is less likely to cause central e
because it does not readily cross the blood-brain barrier.

Side e

Due to their action at dopamine (D2) receptors, movement disorders can be a side e
precipitate acute dystonic reactions even in patients without underlying dopaminergic disorders like Parkinson's disease. This
side e
Other common side e
urinary retention, and weight gain.
Levomepromazine can cause a prolonged QT interval so you should be cautious prescribing this alongside other medications
that can a
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5HT3 receptor antagonists

Examples of 5HT3 antagonists are ondansetron and granisetron.

Common indications

5HT3 receptor antagonists are commonly used in\:
Patients receiving chemotherapy
Post-operative patients
Patients with Parkinson’s disease\: due to other drug classes being associated with worsening of Parkinson's symptoms such
as bradykinesia, shu
Acute gastroenteritis

Contraindications

Due to the speci
There has also been shown to be a “small increased risk of oral clefts following use in the
2020)”
9

Mechanism of action

These work on 5HT3 receptors found in the vomiting centre within the medulla and the CTZ, blockade of these receptors
suppresses the vomiting re

Side e

The side e

Antiemetics in speci

Parkinson's disease10,11
Consider using low-dose domperidone (does not cross the blood-brain barrier), cyclizine or ondansetron.
Metoclopramide and prochlorperazine are contraindicated due to the risk of exacerbation of parkinsonism.
Pregnancy12,13
The only drug o
However, prochlorperazine, promethazine, metoclopramide, cyclizine, ondansetron, and chlorpromazine have established use
in practice.
Meniere’s disease6
Antihistamines and phenothiazines are recommended due to the vestibular disruption.

Motion sickness

Hyoscine hydrobromide (an anti-muscarinic) is licensed to prevent motion sickness-induced nausea, vomiting and vertigo, and
less sedating antihistamines such as cyclizine can also be used.
Post-operative nausea and vomiting (PONV)6,14
Antiemetic therapy after surgical procedures is an important part of enhanced recovery programs (ERPs) and helps prevent
and manage postoperative ileus.
5HT3 receptor antagonists such as ondansetron are often used
(D2) receptor antagonists can also be used.
Within the GI tract, 5-HT3 receptors are found on macrophages. During gastrointestinal (GI) surgery, in
when the viscera is mobilised, reducing intestinal motility and leading to postoperative ileus. Ondansetron, which is a 5-HT3
receptor antagonist, helps improve GI motility by preventing in
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Palliative care15
It is more likely to see medications for end-of-life symptoms, including nausea and vomiting, to be given through continuous
subcutaneous infusion as patients may no longer be able to manage medications orally, and this prevents having to put the
patient through multiple injections and needles.
Levomepromazine is a typical antipsychotic drug that acts by mainly blocking dopamine type 2 (D ) receptors in the brain.
2
Adverse e
with cardiovascular disease, therefore an echocardiogram may be required.

Summary

Table 1. Summary of commonly prescribed antiemetics.
Examples Route Indications Notes
Antihistamine\: H1 antagonists
Cyclizine
PO, IV, SC,
PR
Vertigo
Labyrinthine disorders
Meniere's disease
Can precipitate cardiac failure
Sedating
Promethazine
hydrochloride
PO
Motion sickness
Dopamine antagonists
Prochlorperazine
PO,
buccal
Labyrinthine disorders.
Migraine-related nausea and vomiting
Haloperidol PO, IM, SC Postoperative nausea and vomiting Contraindicated in Parkinson's disease
Metoclopramide
hydrochloride
PO, IM,
slow IV
Migraine-associated nausea and
vomiting
Delayed (but not acute)
chemotherapy-induced nausea and
vomiting
Radiotherapy-induced nausea and
vomiting
Prevention of postoperative nausea
and vomiting
Prokinetic side e
Metoclopramide can induce acute
dystonic reactions involving facial and
skeletal muscle spasms and
oculogyric crises
Contraindicated in Parkinson’s disease
and bowel obstruction
Domperidone PO
Levomepromazine SC, IM, IV
Nausea and vomiting in palliative care
Multifactorial nausea and vomiting
Contraindicated in bowel obstruction
and impaired cardiac conduction
Does not readily cross blood-brain
barrier
Sedation
Dose-dependent postural hypotension
Antimuscarinic adverse e
Can help with confusion/restlessness
Neurokinin 1 receptor antagonists
Aprepitant PO
Adjunct to prevent nausea and
vomiting in moderately-highly
emetogenic chemotherapy
Expensive
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Dexamethasone PO
Adjunct in nausea and vomiting in
palliative care
Useful for nausea and vomiting in
raised intracranial pressure
Appetite stimulant
Increases blood glucose
5HT -receptor antagonists
3
Ondansetron
PO, IM,
slow IV
Prevention and treatment of
postoperative nausea and vomiting
Acute gastroenteritis
Chemotherapy/radiotherapy-induced
nausea and vomiting
Constipating

Reviewer

Dr Amir Guirguis

References

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