A Textbook of Clinical Pharmacology and Therapeutics

ANTI-EMETICS

Complex processes underlie nausea and vomiting. Nausea is
associated with autonomic effects (sweating, bradycardia, pal-
lor and profuse salivary secretion). Vomiting is preceded by
rhythmic muscular contractions of the ‘respiratory’ muscles of
the abdomen (retching) and is a somatic rather than an auto-
nomic function. Central co-ordination of these processes
occurs in a group of cells in the dorsolateral reticular formation
in the floor of the fourth ventricle of the medulla oblongata in
close proximity to the cardiovascular and respiratory centres
with which it has synaptic connections. This vomiting centre
(Figure 34.2) is not directly responsive to chemical emetic stim-
uli, but is activated by one or more inputs. The major efferent
pathways from the vomiting centre are the phrenic nerve, the
visceral efferent of the vagus to the stomach and oesophagus,
and the spinal nerves to the abdominal musculature.
An important receptor area for emetic stimuli, namely the
chemoreceptor trigger zone (CTZ), is a group of neurones in
the area postrema of the fourth ventricle which is sensitive to
emetic stimuli such as radiation, bacterial toxins and uraemia.
Dopamineexcites CTZ neurones, which in turn activate the
vomiting centre and cause emesis. Emetic stimuli originating
in the pharynx, oesophagus and gut are transmitted directly
to the vomiting centre via the vagus and glossopharyngeal
nerves. Those from the vestibular organs (in travel sickness
and Ménière’s disease) act indirectly via the CTZ. A histamine
pathway is apparently involved in labyrinthine vomiting.
Anti-emetic drugs can be classified pharmacologically as
shown in Table 34.3. They should only be used when the cause
of nausea or vomiting is known, otherwise the symptomatic
relief produced could delay diagnosis of a remediable and

serious cause. Nausea and sickness during the first trimester

of pregnancy will respond to most anti-emetics, but are rarely

treated with drugs because of the possible dangers (currently

unquantifiable) of teratogenesis.

ANTI-EMETICS 253

Vestibular stimulation

? via cerebellum

Circulating emetic agents

(e.g. opiates, apomorphine)

Vagal and sympathetic

afferents from

gastrointestinal

tract

Higher centres

Act of vomiting

(somatic and autonomic)

CTZ

(dopamine is

major transmitter)

Vomiting centre

(acetylcholine is

major transmitter)

Figure 34.2:The central mechanisms of vomiting.
Key points
Use of anti-emetics

• The cause of vomiting should be diagnosed.


• Symptomatic relief may delay investigation of the
  underlying cause.


• Treatment of the cause (e.g. diabetic ketoacidosis,
  intestinal obstruction, intracerebral space-occupying
  lesion) usually cures the vomiting.


• The choice of drug depends on the aetiology.

MUSCARINIC RECEPTOR ANTAGONISTS

These act partly by their antimuscarinic action on the gut, as

well as by some central action. Hyoscine(0.3 mg) is effective

in preventing motion sickness and is useful in single doses for

short journeys, as the anticholinergic side effects make it

unsuitable for chronic use. Hyoscineis an alternative to anti-

histamines and phenothiazines for the treatment of vertigo

and nausea associated with Ménière’s disease and middle ear

surgery. Drowsiness, blurred vision, dry mouth and urinary

retention are more common at therapeutic doses than is the

case with antihistamines.

ANTIHISTAMINES (H 1 -BLOCKERS)

These are most effective in preventing motion sickness and treat-

ing vertigo and vomiting caused by labyrinthine disorders.

They have additional anticholinergic actions, and these con-

tribute to their anti-emetic effect. They include cyclizine,

promethazine,betahistineandcinnarizine. The main limita-

tions of these drugs are their modest efficacy and common dose-

related adverse effects, in addition to antimuscarinic effects.

Table 34.3:Classification of anti-emetics

Anticholinergics (e.g. hyoscine)

Antihistamines (H 1 -blockers) (e.g. promethazine)

Dopamine antagonists (e.g. metoclopramide)

Phenothiazines (e.g. prochlorperazine)

5-Hydroxytryptamine (5HT 3 )-receptor antagonists (e.g.

ondansetron)

Neurokinin antagonists (e.g. aprepitant)

Cannabinoids (e.g. nabilone)

Miscellaneous:

Glucocorticosteroids

Benzodiazepines