FRCA Notes

Pethidine

Pethidine is a synthetic phenylpiperidine derivative

Pethidine chemical structure

Presentation

Tablets
Solution containing between 10mg/ml and 50mg/ml for IV, SC or IM use

Typical dose 0.5-1.0mg/kg (i.e. usually 25-100mg)

Uses

Often used as a labour analgesic

It is highly lipid soluble therefore significant amounts cross the placenta and reach the foetus
Its less lipid soluble metabolite norpethidine accumulates in the foetus
Foetal levels peak 4hrs post-maternal IM dose
There is reduced foetal clearance and therefore a 3x increased half life of both pethidine and norpethidine

Absorption

pKa 8.7
Therefore only 5% unionised at physiological pH
Relative lipid solubility of 30x morphine, therefore faster onset of action
Oral bioavailability 50%

Distribution

Volume of distribution 4L/kg
60% protein bound
More lipid soluble than morphine, so crosses BBB rapidly

Metabolism & excretion

Hepatic metabolism via:

Ester hydrolysis to pethidinic acid
N-demethylation to norpethidine (active metabolite with 50% analgesic activity of pethidine)

Elimination half life 210mins

Norpethidine has a much longer half life (14-24hrs)
Accumulates in renal failure and may cause hallucinations and grand-mal seizures
Norpethidine is not reversed by naloxone

Norpethidine, pethidinic acid and (small amounts of unchanged) pethidine are excreted in the urine

Shares the common opioid effects with morphine

Neurological

Has some LA-like actions

Anticholinergic properties

Less marked meiosis than morphine and possibly a degree of mydriasis
Dry mouth
Tachycardia

Gastrointestinal

Less biliary tract spasm than morphine although clinical significance of this unclear

Interactions

Interaction with MAO-I's (e.g. tranycypromine) causes central serotonergic hyperactivity

Pethidine blocks serotonin re-uptake
MAO-I's block/reduce amine breakdown
The combined effect can cause hyperpyrexia, labile circulation, convulsions and coma