Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

Dihydrocodeine

Dihydrocodeine is a synthetic opioid, which is structurally similar to codeine but

is approximately twice as potent. Like codeine its metabolism is subject to genetic

polymorphism by virtue of the cytochrome P450 (CYP2D6).

Pethidine

Pethidine is a synthetic phenylpiperidine derivative originally designed as an anti-

cholinergic agent but was subsequently shown to have analgesic properties.

Presentation

Pethidine is available as tablets and as a solution for injection containing 10–50

mg.ml−^1 .The intravenous and intramuscular dose is 0.5–1.0 mg.kg−^1 and may be

repeated 2–3 hourly. In common with all opioids the dose should be titrated to

effect.

Uses

Pethidine is often used during labour. Its high lipid solubility enables significant

amounts to cross the placenta and reach the foetus. Following its metabolism, the less

lipid-soluble norpethidine accumulates in the foetus, levels peaking about 4 hours

after the initial maternal intramuscular dose. Owing to reduced foetal clearance,

the half-lives of both pethidine and norpethidine are prolonged by a factor of

three.

Effects

Pethidine shares the common opioid effects with morphine. However, differences

are seen:


Anticholinergic effects – it produces less marked meiosis and possibly a degree of

mydriasis, a dry mouth and sometimes tachycardia.


Gut–itissaid to produce less biliary tract spasm than morphine but the clinical

significance of this is unclear.


Interactions – pethidine may produce a serious interaction if administered with

monoamine oxidase inhibitors (MAOI). This is probably due to central sero-

toninenergic hyperactivity caused by pethidine inhibition of serotonin re-uptake

in combination with an MAOI induced reduction in amine breakdown. Effects

include coma, labile circulation, convulsions and hyperpyrexia. Other opioids are

safe.

Kinetics

Pethidine is more lipid-soluble than morphine resulting in a faster onset of action. It

has an oral bioavailability of 50%. It is metabolized in the liver by ester hydrolysis to

the inactive pethidinic acid and by N-demethylation to norpethidine, which has half

the analgesic activity of pethidine. Norpethidine has a longer elimination half-life