Pethidine MAOIs

Irreversible MAOIs + pethidine — severe excitation, hypertension and coma that can lead to death. This is a very hazardous combination. 

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). 

This serious MAOI/pethidine interaction also casts a shadow over morphine, which probably accounts for its inclusion in a number of lists and charts of drugs said to interact with the MAOIs. However, there is some limited evidence that patients on MAOIs who had reacted adversely with pethidine did not do so when given morphine, and quite a number of reports of its safe use. The few hypotensive reactions cited here "- are of a different character and appear to be rare. There would therefore seem to be no good reason for avoiding morphine in patients taking MAOIs, but be alert for the rare adverse response. However, several manufaeturers have contraindicated concurrent use of morphine in patients taking MAOIs or within 2 weeks of stopping an MAOI, " because they can cause CNS adverse effects with hyper- or hypotension.A similar sit-... 

Dmg-induced serotonin syndrome is generally mild and resolves when the offending drugs are stopped. However, it can be severe and deaths have occurred. A large number of drugs have been implicated including tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), selective serotonin re-uptake inhibitors (SSRIs), pethidine, lithium, and dextromethorphan. The most severe type of reaction has occurred with the combination of selective serotonin re-uptake inhibitors and monoamine oxidase inhibitors. Both non-selective MAOIs such as phenelzine and selective MAOIs such as moclobemide and selegiline have been implicated. 

The combination of pethidine with monoamine oxidase inhibitors (MAOIs) can cause serious adverse reaction, which can present in two distinct forms. The excitatory form is characterised by sudden agitation, delirium, headache, hypo- or hypertension, rigidity, hyperpyrexia, convulsions and coma. It is thought to be caused by an increase in cerebral 5-HT concentrations because of inhibition of monoamine oxidase. This is potentiated by pethidine, which blocks neuronal uptake of 5-HT. The depressive form, which is frequently severe and fatal, consists of respiratory and cardiovascular depression and coma. It is the result of the inhibition of hepatic microsomal enzymes by the MAOI, leading to accumulation of pethidine. Phenoperidine should also be avoided in patients taking MAOI drugs but other opioids appear to be safe. 

Pethidine MAOI drugs (see text) Dangerous interaction (see... 

Pethidine and MAOIs show fatal reactions when coadministered. Phenoth-iozine, pethidine, and retonavir should be avoided. 

Monoamine oxidase inhibitors (MAOI) are not completely selective for MAO and impair the metabolism of tricyclic antidepressants, of some sympathomimetics, e.g. phenylpropanolamine, amfetamine, of opioid analgesics, especially pethidine, and of mercaptopurine. 

Pethidine has a rapid onset of action but its short duration (3 hours) makes it unsuitable for the control of prolonged pain. Pethidine is metabolized in the liver and at high doses a toxic metabolite (norpeiht-dine) can accumulate and cause convulsions. Pethidine interacts seriously with MAOIs (diapier 28) causing delirium, hyperpyrexia and convulsions or respiratory depression. 

It is generally recommended that MAOIs should be withdrawn at least 2 weeks before anaesthesia. Individual cases of both hypo-and hypertension have been seen and MAOIs can interact dangerously with other drugs sometimes used during surgery (particularly pethidine (meperidine) and ephedrine). 

Because sibutramine inhibits serotonin uptake, and because the serious serotonin syndrome has been seen when serotonergic drugs were taken with SSRIs, the manufacturers say that sibutramine should not be taken with any serotonergic drugs. They name dextromethorphan, dihydroergot-amine, fentanyl, pentazocine, pethidine (meperidine), SSRIs, sumatriptan, and tryptophan. Possible cases have been reported for sibutramine and SSMs , (below).The US manufacturers also include lithium in their list. Note that this list is not exhaustive (see MAOIs under (d) above) and a case of the serotonin syndrome has been seen when venla-faxine was given with sibutramine. ... 

The UK manufacturer of linezolid (a drug with weak, reversible, non-selective MAOI activity) contraindicates its use with pethidine, unless facilities are available for close observation and monitoring of blood pressure, because of the possibility of serious reactions, as have occurred with classical MAOIs and pethidine, see MAOIs or RIMAs -I- Opioids Pethidine (Meperidine) , p.1140. 

A case of fluctuating stupor and agitation, with muscie rigidity, sweating and a raised temperature has been reported when pethidine was used with seiegiline. This case is simiiar to cases reported with the older non-selective MAOIs or RlMAs and pethidine. The manufacturers say that selegiline and rasagiline should not be used with pethidine. 

Apart from these two isolated reports, there seems to be no other clinical evidence of adverse interactions between MAOIs and dextropropoxyphene. For reports of the serotonin syndrome seen with pethidine (meperidine) and MAOIs, see MAOIs or RIMAs + Opioids Pethidine (Meperidine) , p.ll40. 

The concurrent use of pethidine and MAOIs has resulted in a serious and potentiaiiy iife-threatening reaction in several patients, and one possibie case has been reported with mociobemide. Excitement, muscie rigidity, hyperpyrexia, flushing, sweating and unconsciousness can occur very rapidiy. Respiratory depression and hypertension or hypotension have aiso been seen. Pethidine shouid not be given to patients taking any MAOI or RIMA. 

The interaction between pethidine and the MAOIs, which was first observed in the mid-1950s, is based on case reports. One case has been reported with RIMA mociobemide. It is serious and potentially fatal. Its incidence is unknown, but it is probably quite low, because one study that attempted to produce the interaction by giving increasing test doses of pethidine to 15 patients taking various MAOIs did not show the interaction. It may therefore be an idiosyncratic reaction. Nevertheless, it would be imprudent to give pethidine to any patients on an MAOI or RIMA. Bear in mind that the older MAOIs are all essentially irreversible so that an interaction is possible for many days after their withdrawal (at least 2 weeks is the official advice), whereas the newer RIMAs (e.g. mociobemide) are reversible and unlikely still to interact 48 hours after they have been stopped. 

A sensitivity test has been suggested, but given the fact that there are many alternatives to pethidine and MAOIs readily available, and given that a drop in systolic blood pressure of 30 mmHg has been reported even with the first step of the test dose (5 mg of pethidine) it would seem prudent to avoid the combination. Also, the test dose procedure is unlikely to be suitable when opioids are required in an emergency situation. 

---