Tranylcypromine Sympathomimetics

Phenelzine and tranylcypromine are both effective in the treatment of social phobia. Many practitioners continue to be hesitant to use this class of medications, given the dietary restrictions required of patients and the potential risk of hypertensive crises when combined with dietary tyramine and sympathomimetic medications. However, the proven effectiveness of this class makes it an important option in the treatment of social phobia. 

If a patient does not respond to one MAO I, or if there appears to be a loss of efficacy over time, it may be reasonable to try a second. When switching from a hydrazine-based MAOl (e.g., phenelzine or isocarboxazid) to a nonhydrazine MAOl (e.g., tranylcypromine), one should wait at least 2 weeks. This is because the nonhydrazine MAOl, tranylcypromine, produces NE uptake inhibitory and sympathomimetic effects similar to dextroamphetamine and may cause a toxic reaction if initiated within 2 weeks following MAO inhibition by another agent (261). 

Monoamine oxidase inhibitors (eg, tranylcypromine, phenelzine) are a group of older antidepressants that are occasionally used for resistant depression. They can cause severe hypertensive reactions when interacting foods or drugs are taken (see Chapter 9 Adrenoceptor-Activating Other Sympathomimetic Drugs) 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. 

Clinically important, potentially hazardous interactions with alcohol, amprenavir, arbutamine, cholestyramine, clonidine, CNS depressants, epinephrine, formoterol, guanethidine, isocarboxazid, linezolid, MAO inhibitors, phenelzine, QT interval prolonging agents, quinolones, selegiline, sparfloxacin, sympathomimetics, tranylcypromine... 

Clinically important, potentially hazardous interactions with albuterol, alpha-blockers, amitriptyline, amoxapine, atenolol, beta-blockers, carteolol, chlorpromazine, clomipramine, cocaine, desipramine, doxepin, ephedra, ergotamine, furazolidone, halothane, imipramine, insulin detemir, MAO inhibitors, metoprolol, nadolol, nortriptyline, oxprenolol, penbutolol, phenelzine, phenoxybenzamine, phenylephrine, pindolol, prazosin, propranolol, protriptyline, sympathomimetics, terbutaline, thioridazine, timolol, tranylcypromine, tricyclic antidepressants, trimipramine, vasopressors... 

Clinically important, potentially hazardous interactions with alprazolam, amphetamines, astemizole, clarithromycin, clozapine, desipramine, dexibuprofen, dextroamphetamine, diethylpropion, droperidol, duloxetine, erythromycin, haloperidol, imipramine, isocarboxazid, linezolid, lithium, MAO inhibitors, mazindol, meperidine, methamphetamine, midazolam, moclobemide, nortriptyline, phendimetrazine, phenelzine, phentermine, phenylpropanolamine, phenytoin, pimozide, pseudoephedrine, selegiline, serotonin agonists, sibutramine, St John s wort, sumatriptan, sympathomimetics, tramadol, tranylcypromine, trazodone, tricyclic antidepressants, troleandomycin, tryptophan, zolmitriptan... 

Considerable interest has recently been aroused by reports that patients treated with monoamine oxidtise inhibitors may suffer severe hypertensive attacks after taking certain foods, notably cheese - , beans and extracts of yeast . Some of these attacks have proved fatal. The hypertensive crises arise as a result of pressor substances in the offending foods (such as tyramine in cheese) which are absorbed unchanged into the blood stream when intestinal and liver monoamine oxidase is inhibited . Some of the inhibitors (tranylcypromine is an example) also have sympathomimetic actions which will contribute to the hypertensive effect. The administration of sympathomimetic substances—such as adrenaline in a local anaesthetic—to patients treated with monoamine oxidase inhibitor also creates a dangerous situation. The possibility of hypertensive crises clearly constitutes a serious hazard of therapy with these enzyme inhibitors. In many instances their limited effectiveness would not justify the exposure of patients to these hazards. 

SELECTIVE MAO-B INHIBITORS Two isozymes of MAO (MAO-A and MAO-B) oxidize monoamines and both are present in the periphery and GI tract MAO-B is the predominant form in the striatum and is responsible for most of the oxidative metabolism of dopamine in the brain. At low-to-moderate doses (10 mg/day or less), selegiline (eldepryl) selectively and irreversibly inhibits MAO-B. Unlike nonspecific inhibitors of MAO (e.g., phenelzine, tranylcypromine, isocarboxazid), selegiline does not inhibit peripheral metabolism of catecholamines and can be taken safely with levodopa. Selegihne does not cause the lethal potentiation of indirectly acting sympathomimetic amines such as dietary tyramine. Doses of selegiline higher than 10 mg daily can produce inhibition of MAO-A and should be avoided. 

Monoamine oxidase inhibitors used in depressive disorders (phenelzine, tranylcypromine) increase the stores of norepinephrine in sympathetic nerve endings. They also inhibit the metabolism of tyramine, which at high levels in the blood can act as an indirect sympathomimetic to release norepinephrine. The answer is (L). 

Switching from iproniazid to tranylcypromine/triftuoperazine may have been the cause of a fatal reaction (fever, shivering, sweating, cyanosis) in a patient also given ephedrine (see also MAOIs or RIMAs -i-Sympathomimetics Indirectly-acting , p. 1147). 

An extremely well-documented, well-established, serious interaction. A potentially fatal hypertensive reaction can occur between the irreversible, non-selective MAOIs (see Table 32.1 , (p.ll30)) and tyramine-rich foods. Tranylcypromine is more likely to cause the reaction than phenelzine. The incidence is uncertain, but early estimates of hypertensive reactions to tranylcypromine (before restrictions in its use with indirectly-acting sympathomimetics and foods) range from 0.03% to 20%. Patients taking any of the non-selective MAOIs (isocarboxazid, niaiamide. 

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