Tranylcypromine drug interactions with

The pharmacological inhibition of the serotonin eliminating enzyme MAO is used in the therapy of depression and hypertension. Tranylcypromine is an irreversible unselective MAO inhibitor which displays numerous interactions with amine-containing food and monoamine-related drugs, resulting in evenmally fatal hypertensive crisis, cranial hemorrhage, arrhythmias and seizure can occur. The coadministration with speciflc serotonin reuptake inhibitors (SSRI) can result in similar effects and is therefore contraindicated. Moclobemide, on the other hand, is a reversible inhibitor of MAOa, one of the two enzyme subtyppes (MAOa, MAOb) which is void of most interactions see with tranylcypromine. 

Monoamine oxidase inhibitors (eg, tranylcypromine, phenelzine) are older antidepressants that are occasionally used for resistant depression. They can cause severe hypertensive reactions when interacting foods or drugs are taken (see Chapters 9 and 30), and they can interact with the selective serotonin reuptake inhibitors (SSRIs). 

These two classes of drugs are subject to life-threatening interactions (e.g., mania, convulsions, hypertension, heart arrythmias) with monoamine oxidase (MAO) inhibitors, such as isocarboxazide, phenelzine, selegiline, and tranylcypromine, because they inhibit the metabolism of serotonin and sympathomimetic amines (19,120). This interaction is one of the earliest toxic drug-drug interactions to be recognized however, these interactions are not often observed because the MAO inhibitors are now used sparingly. 

The monoamine oxidase inhibitors epitomize cyclical fashions in drug use and the impact of adverse effects. They were the first psychotropic drugs for which a clear biochemical action was defined. Early excitement was quickly tempered by reports of liver toxicity with the hydrazine derivatives, leading to synthesis of the cyclopropylamine drug, tranylcypromine, which in turn elicited the food and drug interactions that led to an overall decline in popularity. 

Tranylcypromine Cyclopropylamine Most amphetamine-like High propensity for interactions with foods and drugs... 

Clinically important, potentially hazardous interactions with dihydroergotamine, ergot-containing drugs, isocarboxazid, MAO inhibitors, methysergide, naratriptan, phenelzine, propanolol, sibutramine, St John s wort, sumatriptan, tranylcypromine, zolmitriptan... 

MAO INHIBITORS (isocarboxazid, phenelzine, tranylcypromine) Hypotension restlessness insomnia daytime sleepiness mania urinary retention tremors sexual disturbances paresthesias dry mouth nausea constipation anorexia weight gain edema rash hepatitis tinnitus muscle spasm lupus-like reaction leukopenia hyperthermia hypertension interactions with other drugs or foods may be severe MAPROTILINE... 

MAO inhibitors (MAOIs) These drugs (eg, phenelzine, tranylcypromine, isocarboxazid) are stmcturally related to amphetamines and are orally active. They inhibit both MAO-A (which metabolizes norepinephrine, serotonin, and tyramine) and MAO-B (which metabolizes dopamine). Tranylcypromine is the fastest in onset of effect but has a shorter duration of action (about a week) than do other MAO inhibitors (with durations of 2-3 weeks). In spite of these prolonged actions, the MAO inhibitors are given daily. These drugs are inhibitors of hepatic drug-metabolizing enzymes and cause many drug interactions. 

A hyperthermic reaction has been reported in some animals given tranylcypromine or nialamide with procyclidine or benzatropine. It was considered that this might be due to an exaggerated dopamine response. However, there do not appear to be any reports of such an interaction occurring clinically. Nevertheless, some manufacturers of irreversible non-selective MAOIs and antimuscarinics issue cautions about the possibility of increased effects of antimuscarinics when given with MAOIs. This is presumably because, in theory, inhibition of drug-metabolising enzymes by MAOIs may possibly enhance the effects of antimuscarinics. 

Atomoxetine, bupropion, and TCAs are second-line alternatives to the stimulants for treatment of ADHD in children, teens, and adults. The potential benefits of these agents in comparison with stimulants include reduced risk of abuse and somewhat lower potential for sleep disturbance. TCAs are the most dangerous in overdose and pose the greatest risk for cardiovascular side effects. The monoamine oxidase inhibitor tranylcypromine is effective but used infrequently due to the potential for dangerous drug and dietary interactions. Selective serotonin reuptake inhibitors (SSRIs) are not effective for ADHD. ... 

The antihypertensive effects of guanethidine may be partially or totally reversed by the mixed-acting sympathomi-metics. Halogenated hydrocarbon anesthetics may sensitize the myocardium to the effects of catecholamines. Use of vasopressors may lead to serious arrhythmias. MAO inhibitors, such as tranylcypromine, increase the pressor response to mixed-acting vasopressors. Possible hypertensive crisis and intracranial hemorrhage may occur. This interaction may also occur with furazolidone, an antimicrobial with MAO inhibitor activity. In obstetrics, if vasopressor drugs are used either to correct hypotension or are added to the local anesthetic solution, some oxytocics may cause severe persistent hypertension in the presence of mephenteramine. The pressor response of mephenteramine may be attenuated by tricyclic antidepressants, which block the uptake of norepinephrine. 

Tranylcypromine, phenelzine, clomipramine and imipramine appear to be high on the list of drugs that have interacted adversely. Combination of clomipramine with tranyleypromine is particularly dangerous. Amitriptyline, trimipramine and isocarboxazid are possibly safer. 

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