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

 

List:

·     Diagramme

·     Anti-emetic drugs

·     Pro-emetic drugs

 

Diagramme:

 

Anti-emetics:

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.

 

Pro-emetic drugs:

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