Phenylpropanolamine MAOIs

Ephedrine —contraindicated with MAOIs Pseudoephedrine —contraindicated with MAOIs Phenylephrine —contraindicated with MAOIs Phenylpropanolamine —contraindicated with MAOIs Seriously elevated blood pressure (hypertensive crisis), elevated temperature, seizures, cerebral hemorrhage, death... 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

The main limitation to the clinical use of the MAOIs is due to their interaction with amine-containing foods such as cheeses, red wine, beers (including non-alcoholic beers), fermented and processed meat products, yeast products, soya and some vegetables. Some proprietary medicines such as cold cures contain phenylpropanolamine, ephedrine, etc. and will also interact with MAOIs. Such an interaction (termed the "cheese effect"), is attributed to the dramatic rise in blood pressure due to the sudden release of noradrenaline from peripheral sympathetic terminals, an event due to the displacement of noradrenaline from its mtraneuronal vesicles by the primary amine (usually tyramine). Under normal circumstances, any dietary amines would be metabolized by MAO in the wall of the gastrointestinal tract, in the liver, platelets, etc. The occurrence of hypertensive crises, and occasionally strokes, therefore limited the use of the MAOIs, despite their proven clinical efficacy, to the treatment of atypical depression and occasionally panic disorder. 

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. 

Monoamine oxidase inhibitors and many pharmacological agents are synergistic, sometimes resulting in a hypertensive crisis. The agents with which the MAOIs may be synergistic include amphetamine, dextroamphetamine, methyl amphetamine, ephedrine, procaine preparations (which usually contain norepinephrine), epinephrine, methyldopa, and phenylpropanolamine (over-the-counter cold preparations). 

Interactions of MAOIs with other sympathomimetic drugs are well known. The increased neuronal stores of NE represent a booby-trap hazard that can easily be triggered by indirectly acting adrenergic agents such as the amphetamines found in many antiobesity preparations. Drugs such as ephedrine, phenylpropanolamine, and phenylephrine are potentially more dangerous because of their ready availability to the public in over-the-counter medications such as cold medicines and nose drops. 

Sympathomimetics (indirectly acting) Combining MAOis with agents such as amphetamines, cocaine, ephedrine, methylphenidate, pemoline, pseudoephedrine, phenylpropanolamine, and others (including many cold and allergy medications) can cause a potentially fatal hypertensive crisis. 

After 5 to 10 days of use furazolidone has MAO-inhibitory activity about equivalent to that of the non-selective MAOIs. The concurrent use of furazolidone with indirectly-acting sympathomimetic amines (amfetamines, phenylpropanolamine, ephedrine, etc.) or with tyramine-rich foods and drinks may be expected to result in a potentially serious rise in blood pressure. However, direct evidence of accidental adverse reactions of this kind does not seem to have been reported. The pressor effects of noradrenaline (norepinephrine) are unchanged by furazolidone. 

The manufaeturers eontraindieate the use of sympathomimetics (including adrenergic bronchodilators, pseudoephedrine, phenylpropanolamine, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, dob-utamine) with linezolid unless there are faeilities available for close observation of the patient and monitoring of blood pressure. Some indirectly-aeting sympathomimetics occur in cough and cold remedies, whieh can be bought without prescription. To keep in line with the manufaeturers recommendations, patients should be told to avoid these preparations. However, it should be said that the evidenee available indicates that blood pressure rises are unlikely to be of the proportions seen with the antidepressant MAOIs, which result in hypertensive crises. Consider also MAOIs or RIMAs + Sympathomimetics Indirectly-acting , p.l 147. 

A single report describes a woman taking an MAOI who developed a severe occipital headache after taking 30 mL of a paediatric cough linctus. Initially this interaction was attributed to promethazine, but it is now known that the linctus in question contained phenylpropanolamine, which is much more likely to have been the cause. See N OIs or RIMAs + Sympathomimetics Indirectly-acting , p.ll47 for the interaction with phenylpropanolamine. 

A very well-documented, serious, and potentially fatal interaction. Patients taking any of the MAOIs should not normally take any sympathomimetic amine with indirect activity. These include ephedrine, isometheptene mucate, mephentermine, metaraminol, phenylpropanolamine and pseudoephedrine. Direct evidence implicating methylephe-drine and pholedrine seems not to have been documented, but on the basis of their known pharmacology their concurrent use with the MAOIs should be avoided. 

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