Respiratory depression chlorpromazine

Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when combined with other sedatives, such as alcohol or barbiturates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such as diazepam. 

Chlorpromazine increases the respiratory-depressant effects of meperidine, as do tricyclic antidepressants this is not true of diazepam. Concurrent administration of drugs such as promethazine or chlorpromazine also may greatly enhance meperidine-induced sedation without slowing clearance of the drug. Treatment with phenobar-bital or phenytoin increases systemic clearance and decreases oral bioavailability of meperidine this is associated with an elevation of the concentration of normeperidine in plasma. As with morphine, concomitant administration of an amphetamine has been reported to enhance the analgesic effects of meperidine and its congeners while counteracting sedation. 

A phenothiazine structural analogue, very intimately related to chlorpromazine, and exhibits extremely potent analgesie aetivity. Importantly, it is devoid of any dependence liability, besides it does not produee respiratory depression. It is specifically of some extent of advantage in such patients for whom addiction as well as respiratory depression are serious problems. 

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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