Pethidine Chlorpromazine

Verbeeck RK, Cardinal J (1985) Plasma protein binding of salicylic acid, phenytoin, chlorpromazine, propranolol and pethidine using equilibrium dialysis and ultracentrifugation. Arzneimittelforschung 35 903... 

Pethidine Chlorpromazine Increased toxicity of pethidine Altered metabolism... 

A 2-month-old boy had a cardiac arrest when he was given a combination of pethidine, promethazine, and chlorpromazine in 10 times the recommended dose by the wrong route (intravenously rather than intramuscularly). Within seconds he became apneic and stiff. Cardiopulmonary resuscitation was instituted, including two intravenous doses of adrenaline 0.06 mg and naloxone 0.6 mg, with recovery 7 minutes after the incident and complete resolution 24 hours later. 

Chlorpromazine has been reported to increase the analgesic effect of pethidine, but increased respiratory depression, sedation, CNS toxicity and hypotension can also occur. Other phenothiazines such as levomepromazine, promethazine, prochlorperazine, pro-piomazine and thioridazine may also interact with pethidine to cause some of these effects. Additive CNS depressant effects would be expected when opioids are given with phenothiazines. 

There is evidence that chlorpromazine can increase the activity of the liver microsomal enzymes so that the metabolism of pethidine to norpethidine and norpethidinic acid are increased. These metabolites are toxic and probably account for the lethargy and hypotension seen in one study. The effects of the phenothiazines on pethidine-induced respiratory depression may be related. Both the opioids and the phenothiazines are CNS depressants, and their effects may be additive. 

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