Phenelzine 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). 

Phenelzine Blockade of MAO-A and MAO-B (phenelzine, nonselective) MAO-B irreversible selective MAO-B inhibition (low dose selegiline) Transdermal absorption of selegiline achieves levels that inhibit MAO-A Major depression unresponsive to other drugs Very slow elimination Toxicity Hypotension, insomnia Interactions Hypertensive crisis with tyramine, other indirect sympathomimetics serotonin syndrome with serotonergic agents, meperidine... 

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. 

Q14 MAOIs, such as phenelzine and isocarboxazid, affect the sympathetic nervous system by inhibiting one or both forms of brain monoamine oxidase. Their sympathomimetic effects can produce a feeling of well-being and increased energy, which is helpful for depressed patients. However, psychosis may occur in a susceptible individual or may follow over-administration of these agents. An increase in sympathomimetic action (such as occurs with use of amphetamines, which increase the release of noradrenaline) can result in a lethal hypertensive crisis. In addition, a hypertensive crisis can also be initiated if the patient consumes a diet rich in amines foods with a high amine content include cheese, pickles, broad beans and wine. 

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... 

The starting dose of phenelzine is 15 mg/day. It can be increased weekly by 15 mg/day to a maximum of dose of 90 mg (in divided doses). Patients must avoid tyramine-containing foods and sympathomimetic drugs to prevent hypertensive crisis. If a patient is switched from another antidepressant to phenelzine, an appropriate washout period should be followed. 

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). 

A 15-year-old girl taking phenelzine 15 mg three times daily (as well as thioridazine, procyclidine and metronidazole) took 13 capsules of Romilar CF (containing dextromethorphan hydrobromide 15 mg, phenindamine tartrate 6.25 mg, phenylephrine hydrochloride 5 mg and paracetamol (acetaminophen) 120 mg in each capsule). She became comatose, hyper-pyrexic (lOS F), had a blood pressure of 100/60 mmHg, a pulse of 160 bpm and later died ofa cardiac arrest. This case is complicated by the overdosage and multiplicity of drugs present, particularly the phenylephrine. See MAOIs or RIMAs + Sympathomimetics Phenylephrine , p.1148. 

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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