Antiemetics

Regarding antiemetics, which one of the following statements is TRUE?

a) Dexamethasone has been shown to downregulate 5-HT3 receptors in the

chemoreceptor trigger zone

b) As an anticholinergic, glycopyrrolate has useful antiemetic properties

c) Cyclizine acts as an antiemetic by antagonism of muscarinic acetylcholine receptors

d) Ondansetron exerts antagonism at 5-HT3 receptors only in the chemoreceptor

trigger zone and the nucleus tractus solitarius

e) Nabilone is an antagonist at endogenous cannabinoid receptors

Answer: c

Explanation

The mechanism via which steroids prevent and treat nausea and vomiting remains

unknown. They may act by reducing central and peripheral prostaglandin production,

or via an anti-inflammatory process that may reduce stimulation from an operative

site, or block 5-HT3 production from the gut. Muscarinic acetylcholine receptors are

found in the nucleus ambiguous, nucleus tractus solitarius and the dorsal motor

nucleus of the vagus. Central receptors are also involved in the vestibular initiation

of motion sickness. As all these target sites are within the blood–brain barrier only

tertiary amine anticholinergics reduce nausea and vomiting. The quaternary ammonium

compound glycopyrrolate does not cross the barrier and has no antiemetic

properties. Cyclizine is an H1-antagonist (antihistamine) and blocks centrally located

H1 receptors; however, a significant proportion of its antiemetic properties are due to

an anticholinergic action. Ondansetron antagonises central and peripheral (mainly gut)

5-HT3 receptors. Nabilone is a novel agent, which is an agonist at endogenous cannabinoid

receptors – amechanism not previously employed pharmaceutically. The pharmacology

of antiemetics is best recalled by learning the physiological pathways, anatomical

sites and neurotransmitters involved in the induction of vomiting then considering

where each of these pathways may be interrupted with appropriate antagonists.

Reference

Forrest K, Simpson K. Physiology and pharmacology of nausea and vomiting. In:

Hemmings J, Hopkins P (eds) Foundations of Anesthesia: Basic Sciences for Clinical

Practice, 2nd edn. Philadelphia: Mosby-Elsevier, 2006; pp. 763–72.