Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

Kinetics

Cyclizine is well absorbed orally and has a high oral bioavailability (approximately

75%). Surprisingly little is known regarding the rest of the kinetics of this drug.

Promethazine

Promethazine has traditionally been used in combination with pethidine for intra-

muscular premedication. However, it may also be used as an oral premed for children.

Ithas significant anticholinergic properties and sedative effects. It is well absorbed

from the gut but is subject to a significant first-pass hepatic metabolism so that its

oral bioavailability is 25%. It has a duration of action of 3–6 hours and its metabolites

are eliminated entirely in the urine.

5-HT 3 antagonists

Ondansetron

Ondansetron is a carbazole.

Presentation

Ondansetron is available as tablets (4–8 mg), a strawberry-flavoured lyophilisate

(4–8 mg) to dissolve on the tongue, a suppository (16 mg) and as a clear solution

containing 2 mg.ml−^1 for slow intravenous injection.

Uses

Ondansetron is indicated for the treatment of nausea and vomiting associated with

chemo- or radiotherapy and in the peri-operative period. It is ineffective for vomiting

induced by motion sickness or dopamine agonists. It is licensed for children above

2years of age.

Mechanism of action

The activation of 5-HT 3 receptors peripherally and centrally appears to induce vom-

iting. Chemo- and radiotherapy may cause the release of 5-HT from enterochro-

maffin cells. Peripheral 5-HT 3 receptors in the gut are then activated and stimulate

vagal afferent neurones that connect to the VC, again via 5-HT 3 receptors. Thus

ondansetron may antagonize 5-HT 3 both peripherally and centrally.

Effects

Ondansetron is well tolerated and its other effects are limited to headache, flushing,

constipation and bradycardia following rapid intravenous administration.

Kinetics

Ondansetron is well absorbed from the gut with an oral bioavailability of about

60%. It is 75% protein bound and undergoes significant hepatic metabolism by