Morphine MAOIs

Injection - Heart failure secondary to chronic lung disease cardiac arrhythmias brain tumor acute alcoholism delirium tremens idiosyncrasy to the drug increased intracranial or CSF pressure head injuries acute bronchial asthma upper airway obstruction. Because of its stimulating effect on the spinal cord, morphine should not be used in convulsive states (eg, status epilepticus, tetanus, strychnine poisoning) concomitantly with MAOIs or in those who have received such agents within 14 days. 

The combination of MAOIs with meperidine, and perhaps with other phenylpiperidine analgesics, also has been implicated in fatal reactions attributed to the serotonin syndrome. Aspirin, nonsteroidal anti-inflammatory drugs, and acetaminophen should be used for mild to moderate pain. Of the narcotic agents, codeine and morphine are safe in combination with MAOIs, although doses may need to be lower than usual. 

Hyperpyrexia and hypertension have been observed with the use of pethidine and MAO inhibitors. Pethidine is the opioid most commonly associated with an adverse reaction with MAOIs. Although only a small proportion of patients taking MAOIs will react adversely to pethidine, there is no sure way of predicting those in whom the combination could produce severe, life-threatening reactions. These can present in two distinct forms. The excitatory form is characterised by sudden agitation, delirium, headache, hypotension or hypertension, rigidity, hyperpyrexia, convulsions and coma. It is possibly caused by an increase in cerebral 5-HT concentrations due to inhibition of MAO. This is potentiated by pethidine, which blocks neuronal uptake of 5-HT. The depressive form, which is frequently severe and fatal, presents as respiratoiy and cardiovascular depression and coma. It is the result of a reduced breakdown of pethidine due to the inhibition of hepatic /V-demethylase by MAOIs, leading to accumulation of pethidine. The risk of adverse reactions to pethidine may be less likely with the newer, specific MAO-A inhibitors. Interactions with other opioids, such as morphine and pentazocine, have been reported, but are less common. Other opioids appear to be safe in combination with MAOIs, with the possible exception of phenoperidine, which is metabolised to pethidine, norpethidine and pethidinic acid. 

MAOIs PETHIDINE, MORPHINE, PHENOPERIDINE, DEXTROMETHORPHAN Two types of reaction are reported 1. Risk of serotonin syndrome with dextromethorphan, pethidine or tramadol and MAOIs 2. Depressive - respiratory depression, hypotension, coma Type 1 reactions are attributed to inhibition of reuptake of serotonin -more common with pethidine, phenoperidine, dextromethorphan. Type II reactions are attributed to MAOI inhibition of metabolism of opioids - more common with morphine Avoid co-administration do not give dextromethorphan, pethidine or tramadol for at least 2 weeks after cessation of MAOI... 

Other nonreceptor site of action interactions include MAOIs - pethidine (acute dystonias), ethanol - benzodiazepines (synergisitic sedation and respiratory depression), cocaine - amphetamines (hypertensive crisis) and dihydrocodeine -morphine (the former is a partial agonist and reduces the efficacy of the full agonist). 

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