Important factors to consider when prescribing anti-emetics include:

mechanism of action of anti-emetic drugs (, & )8655,27
response to anti-emetics already given
when more than one anti-emetic drug is needed, a combination of drugs with different actions should be used (e.g. cyclizine and haloperidol)
combinations with antagonistic actions should not be used (e.g. cyclizine and metoclopramide)
levomepromazine (methotrimeprazine) has multiple receptor effects and is sometimes more effective than drug combinations
effects of anti-emetics on gastro-intestinal motility, i.e.
- prokinetic (metoclopramide, domperidone, cisapride)
- antikinetic (antimuscarinics)
adjuvant use of antisecretory drugs (e.g. hyoscine butylbromide, glycopyrronium, octreotide)
adjuvant use of corticosteroids (e.g. dexamethasone, prednisolone)
undesirable effects of drugs
cost of drugs (5HT₃-receptor antagonists and octreotide are expensive)
role of non-drug treatments.

Generally, the initial choice of an anti-emetic in palliative care lies between three drugs, namely metoclopramide, haloperidol and cyclizine.68 One of these should be prescribed both regularly and as needed ().
In bowel obstruction with large volume vomiting or associated intestinal colic, an antisecretory agent (which acts partly by reducing the volume of gastro-intestinal secretions) may be used either alone as a first-line manoeuvre, e.g. hyoscine butylbromide 60–120mg/24h CSCI, or in conjunction with cyclizine. If this proves inadequate, a trial of octreotide should be considered.

Diagram of the neural mechanisms controlling vomiting^a

a. Based on Twycross et al., 1997.68 Abbreviations refer to receptor types: ACh_m = muscarinic cholinergic; α₂ = α₂-adrenergic; D₂ = dopamine type 2; GABA = gamma-aminobutyric acid; 5HT, 5HT₂, 5HT₃ = 5-hydroxytryptamine (serotonin) type undefined, type 2, type 3; H₁ = histamine type 1. Anti-emetics act as antagonists at these receptors, whereas the central anti-emetic effects of clonidine and opioids are agonistic.

Classification of drugs used to control nausea and vomiting

Putative site of action	Class	Example
Central nervous system
Vomiting centre	Antimuscarinic	Hyoscine hydrobromide
	Antihistaminic antimuscarinic^a	Cyclizine, dimenhydrinate, prochlorperazine
	5-HT₂-receptor antagonist	Levomepromazine (methotrimeprazine)
Area postrema	D₂-receptor antagonist	Haloperidol, prochlorperazine, metoclopramide, domperidone
	5HT₃-receptor antagonist	Granisetron, ondansetron, tropisetron
Cerebral cortex	Benzodiazepine	Lorazepam
	Cannabinoid	Nabilone
	Corticosteroid	Dexamethasone
Gastro-intestinal tract
Prokinetic	5-HT₄-receptor agonist	Metoclopramide, cisapride
	D₂-receptor antagonist	Metoclopramide, domperidone
Antisecretory	Antimuscarinic	Hyoscine butylbromide, glycopyrronium
	Somatostatin analogue	Octreotide, vapreotide
Vagal 5-HT₃-receptor blockade	5-HT₃-receptor antagonist	Granisetron, ondansetron, tropisetron
Anti-inflammatory	Corticosteroid	Dexamethasone

a. antihistamine and phenothiazines both have H₁-receptor antagonist and antimuscarinic properties (see Table 4.11).

Corticosteroids and levomepromazine (methotrimeprazine) are both useful options when first-line anti-emetics fail to relieve nausea and vomiting satisfactorily. Dexamethasone is normally added to an existing regimen, whereas levomepromazine is normally substituted. Sometimes it is necessary to use dexamethasone and levomepromazine concurrently. Other phenothiazines are still often used as anti-emetics, notably promethazine, prochlorperazine and chlorpromazine. Promethazine is used as an alternative to cyclizine and haloperidol in some countries, in doses similar to cyclizine both PO and CSCI.

Prochlorperazine is often effective against moderate chemical emetogenic stimuli in a dose of 5–10mg t.d.s. PO; suppositories and injections are also available. Chlorpromazine has an even broader spectrum of receptor affinity (Table 4.11) but does not share the potent 5HT₂ antagonism of levomepromazine which should be used in preference to chlorpromazine when a broad-spectrum drug is indicated.

5HT₃-receptor antagonists, developed primarily to control chemotherapeutic vomiting, have a definite but limited role in palliative care. Drug-induced nausea and vomiting can be problematic. It may be caused by several different mechanisms (), each of which calls for a distinct therapeutic response.

Guidelines for the management of nausea and vomiting

After clinical evaluation, document the most likely causes of the nausea and vomiting in the patient's case notes.
Ask the patient to record symptoms and response to treatment, preferably using a diary.
Correct correctable causes/exacerbating factors, e.g. drugs, severe pain, infection, cough, hypercalcaemia. (Correction of hypercalcaemia is not always appropriate in a dying patient.) Anxiety exacerbates nausea and vomiting from any cause and may need specific treatment.
Prescribe the most appropriate anti-emetic stat. regularly and p.r.n. (). Give by SC injection if continuous nausea or frequent vomiting, preferably by CSCI.
Review anti-emetic dose every 24h, taking note of p.r.n. use and the patient's diary.
If little benefit despite optimising the dose, have you got the cause right?
- if no, change to an alternative anti-emetic and optimise
- if yes, provided the antiemetic has been optimised, add or substitute a second anti-emetic.
Anti-emetics for inoperable bowel obstruction are best given byCSCI: levomepromazine (methotrimeprazine) is the exception; it can be given as a single SC dose o.n.
In patients who fail to respond to the commonly used anti-emetics, consider other drugs for nausea and vomiting.
Some patients with nausea and vomiting need more than one anti-emetic.
Antimuscarinic drugs block the cholinergic pathway through which prokinetics act; concurrent use antagonises the prokinetic effect of metoclopramide and is best avoided.
Continue antiemetics unless the cause is self-limiting.
Except in organic bowel obstruction, consider changing to PO after 72h of good control with CSCI.

Commonly used anti-emetics

Prokinetic anti-emetic (about 50% of prescriptions)

For gastritis, gastric stasis, functional bowel obstruction (peristaltic failure); metoclopramide 10mg PO (orally) stat & q.d.s. or 10mg SC stat & 40-100mg/24h CSCI. & 10mg p.r.n.up to q.d.s.

Anti-emetic acting principally in chemoreceptor trigger zone (about 25% of prescriptions)
For most chemical causes of vomiting. e.g. morphine, hypercalcaemia, renal failure;
haloperidol 1.5-3mg PO stat & o.n. or 2.5-5mg SC stat & 2.5-10mg/24h CSCI, & 2.5-5mg p.r.n. up to q.d.s.
Metoclopramide also has a central action.

Antispasmodic and antisecretory antiemetic
If bowel colic and/or need to reduce gut secretions:
hyoscine butylbromide 20mg SC stat, 80-200mg/24h CSCI. & 20mg SC hourly p.r.n.

Anti-emetic acting principally in the vomiting centre
For raised intracranial pressure (in conjunction with dexamethasone), motion sickness and in organic bowel obstruction:
cyclizine 50mg PO stat & b.d.-t.d.s. or 50mg SC stat & 100-150mg/24h CSCI. & 50mg p.r.n. up to q.d.s.

Broad-spectrum antiemetic
For organic bowel obstruction, add when other anti emetics are unsatisfactory: levomepromazine (methotrimeprazine) 6-12.5mg PO/SC stat. o.n. & p.r.n. up to q.d.s.

Nausea & vomiting ladder

		Hyoscine butylbromide^c + levomepromazine^d
	Hyoscine butylbromide^c ± cyclizine or haloperidol	Step 3
Metoclopramide^a	Step 2
Step 1
	± dexamethasone^b

a. if colic. omit step 1
b. the place of dexamethasone is inoperable bowel obstruction is controversial - for dose see below
c. alternatively use glycopyrronium 600-1200microgram/24h
d. if levomepromazine is too sedative, consider using olanzapine 1.25-2.5mg o.d. PO instead: or revert to step 2 but give both cyclizine and haloperidol.

Other drugs for nausea and vomiting

Corticosteroid

Adjuvant anti-emetic, for bowel obstruction and when all else fails: dexamethasone 8-16mg PO/SC stat & o.d.: consider reducing the dose after days.

5HT₃-receptor antagonist
Use when massive release of 5HT (Serotonin) from enterochromaffin cells or platelets.e.g. chemotherapy. abdominal radiation. bowel obstruction (distension), renal failure:
tropisetron 5mg PO/SC stat & o.d.

Somatostatin analogue
An anti-secretory agent without antispasmodic effects: use in obstruction if hyoscine inadequate:
octreotide 100microgram stat. 300-600microgram/24h CSCI, & 100microgram p.r.n. up to q.d.s.

Receptor site affinities of selected anti-emetics68,8655

	D₂-receptor antagonist	H₁-receptor antagonist	Muscarinic antagonist	5HT₂-receptor antagonist	5HT₃-receptor antagonist	5HT₄-receptor agonist
Metoclopramide	++	0	0	0	+	++
Domperidone	++	0	0	0	0	0
Cisapride	0	0	0	0	0	+++
Ondansetron^b	0	0	0	0	+++	0
Cyclizine	0	++	++	0	0	0
Hyoscine hydrobromide	0	0	+++	0	0	0
Haloperidol	+++	0	0	0	0	0
Prochlorperazine	++	+	0	0	0	0
Chlorpromazine	++	++	+	0	0	0
Levomepromazine (methotrimeprazine)	++	+++	++	+++	0	0

Pharmacological activity: 0 none or insignificant; + slight; ++ moderate; +++ marked.

a. domperidone does not cross the blood brain barrier and therefore does not cause extrapyramidal effects.

b. other 5HT₃-receptor antagonists e.g. granisetron and tropisetron have comparable receptor affinity.