Antiemetics, histamine H1-receptor antagonists

Key examples

• Cyclizine 
• Cinnarizine
• Promethazine

 

Common indications

• Prophylaxis and treatment of nausea and vomiting, particularly in the context of motion sickness or vertigo.

 

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. Histamine (H1) and acetylcholine (muscarinic) receptors predominate in the vomiting centre and in its communication with the vestibular system. 
• Drugs such as cyclizine block both of these receptors. 
• This makes them useful treatments for nausea and vomiting in a wide range of conditions (e.g. drug-induced, post-operative, radiotherapy), but most particularly when associated with motion or vertigo.

 

Important adverse effects

• The most common adverse effect is drowsiness. Cyclizine is the least sedating drug in this class and is therefore usually preferred. 
• Due to their anticholinergic effects they may cause dry throat and mouth. This is usually undesirable, but in patients with copious mucosal secretions it may be beneficial. 
• After IV injection they may cause transient tachycardia, which the patient may notice as palpitations. Along with their central anticholinergic effects (excitation or depression) this may make for a rather unpleasant experience.

 

Warnings

• Due to their sedating effect, these drugs should be avoided in patients at risk of hepatic encephalopathy. 
• They should also be avoided in patients susceptible to anticholinergic side effects, such as those with prostatic hypertrophy (who may develop urinary retention). 
• Use with caution in severe heart failure—may cause fall in cardiac output and associated increase in heart rate.

 

Important interactions

• Sedation may be greater when combined with other sedative drugs (e.g. benzodiazepines, opioids). 
• Anticholinergic effects may be more pronounced in patients taking ipratropium or tiotropium.