2009B03 Discuss classes of drugs that influence post-operative nausea and vomiting (PONV)
including mechanisms where known.

Drug

Mechanism of anti-emesis

Dexamethasone

·   Not well understood

·   For PONV prevention, not rescue

·   (onset 2 hours)

·   Receptor: transcription factor in cytosol;
? action in nucleus tractus solitarius (NTS)

·   Affects 25% of the genome

5-HT₃ antagonist

e.g. ondansetron

·   Central: ↓afferent CTZ -> VC

·   Peripheral: ↓CNX afferent to CTZ via NTS

DA₂ antagonist:

-Butyrophenone

e.g. droperidol

e.g. droperidol

·   ↓Afferent CTZ -> VC

DA₂ antagonist:

-Phenothiazine

e.g. prochlorperazine

·   ↓Afferent CTZ -> VC

DA₂ antagonist:

-Benzamide

Metoclopramide

·   Central: DA₂i, 5HT₃i (↓afferent from CTZ toVC)

·   Peripheral: DA₂i, 5HT₄a (↓afferent CNX to CTZ via NTS)

·   Anti-emetic and prokinetic

Anti-histamine: first generation

e.g. cyclizine

·   ↓Afferent CTZ to VC

·   ↓Afferent vestibular apparatus to CTZ

·   Strong anti-muscarinic

·   Weak anti-DA

Anti-muscarinic

e.g. atropine

·   mAChRi

·   Central: CTZ, vestibular

·   Peripheral: CNX afferent

Propofol

·   Central 5HT₃i

·   ↓Afferent from CTZ to VC

Benzodiazepines

e.g. midazolam

·   Positive allosteric modulator at GABA-A

·   ? ↓cortical afferent to CTZ

Cannabinoids

·   Agonist at cannabinoid receptor in GIT

·   Esp cancer-associated nausea and vomiting

NK-1 antagonist

e.g. aprepitant

e.g. aprepitant

·   Substance P antagonist at NK-1R

·   Peripheral: ↓CNX afferent to CTZ via NTS

·   Esp cancer N&V. Long duration.

Opioids

·   Mu receptor agonist in CTZ

Halogenated ethers

·   5-HT agonist in CTZ

Nitrous oxide

·   NMDA antagonism

IV induction agents

·   Ketamine: NMDA antagonism, 5HT reuptake inhibition, opioid agonism

·   Barbiturates

·   Etomdiate

Ergometrine

·   5-HT agonist in CTZ