Antiemetics, phenothiazines

Key examples

• Prochlorperazine
• Chlorpromazine

 

Common indications

1. Prophylaxis and treatment of nausea and vomiting in a wide range of conditions, particularly when due to vertigo. However, due to their side effect profile, other antiemetic classes are usually preferable.
2. Psychotic disorders, such as schizophrenia, where they are used as first-generation (typical) antipsychotics.

 

Mechanisms of action

• Nausea and vomiting are triggered by a variety of factors, including gut irritation, drugs, motion and vestibular disorders, as well as higher stimuli (sights, smells, emotions). 
• The various pathways converge on a ‘vomiting centre’ in the medulla, which receives inputs from the chemoreceptor trigger zone (CTZ), the solitary tract nucleus (which is innervated by the vagus nerve), the vestibular system and higher neurological centres. 
• The antiemetic properties of phenothiazines arise from blockade of various receptors, including dopamine (D2) receptors in the CTZ and gut (see Antiemetics, dopamine D2-receptor antagonists) and, to a lesser extent, histamine (H1) and acetylcholine (muscarinic) receptors in the vomiting centre and vestibular system (see Antiemetics, histamine H1-receptor antagonists). 
• This makes them effective for nausea and vomiting in a wide range of situations, including chemotherapy, radiotherapy and vertigo.

 

Important adverse effects

• Drowsiness and postural hypotension are relatively common with phenothiazines. 
• Movement abnormalities, termed extrapyramidal syndromes, are a major drawback of their use. They arise from D2 receptor blockade via the same mechanism as for other first-generation (typical) antipsychotics. 
• In the context of short-term treatment for nausea and vomiting, this is most likely to take the form of an acute dystonic reaction such as oculogyric crisis. 
• In longer-term treatment (which is more likely when they are used as an antipsychotic), other extrapyramidal syndromes such as tardive dyskinesia may occur (see Antipsychotics, first-generation [typical]). 
• Like all antipsychotics, phenothiazines can cause QT-interval prolongation.

 

Warnings

• Due to their sedative effect and potential for hepatotoxicity, these drugs should be avoided in patients with severe liver disease.
• They should also be avoided in patients susceptible to anticholinergic side effects, such as those with prostatic hypertrophy (who may develop urinary retention). 
• Doses should be reduced in the elderly.

 

Important interactions

• You should consult the BNF when prescribing for a patient taking these drugs as there is an extensive list of interactions. 
• Prominent among these are drugs that prolong the QT interval, such as antipsychotics, amiodarone, ciprofloxacin, macrolides, quinine and SSRIs.