Interactions at Receptor Sites

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The enzyme monoamine oxidase (MAO) metabolizes catecholamines (eg, norepinephrine). MAO inhibitors (eg, phenelzine, tranylcypromine) cause norepinephrine to accumulate within adrenergic neurons. Drugs that release the stored norepinephrine (eg, indirectly acting sympathomimetic amines) can produce exaggerated responses, including severe headache, hypertension (possibly a hypertensive crisis), and cardiac arrythmias. Although most sympathomimetic amines (eg, amphetamine) are available only by prescription, others (eg, phenylpropanolamine), know to interact with MAO inhibitors, are present in many popular OTC cold, allergy, and diet products. Patients taking MAO inhibitors should avoid such products.

Hypertensive crises have occurred in patients taking MAO inhibitors after they have ingested foods and beverages with a high tyramine content (eg, certain cheeses, alcoholic beverages, concentrated yeast, extracts, broad-ban pods, pickled herring). This effect has been called the "cheese reaction" (see discussion of MAO inhibitors in Ch, 189). Tyramine is normally metabolized by MAO in the intestinal wall and liver. When MAO is inhibited unmetabolized tyramine can accumulate, releasing more norepinephrine from adrenergic neuron.

The antineoplastic drug procarbazine and the anti-infective drug furazolidone (or probably its metabolite) can also inhibit MAO, causing similar interactions. However, furazolidone usually does not inhibit MAO within the first 5 days of therapy, and the course of treatment is often completed within that time. The antiparkinsonian drug selegiline selectively inhibits MAO type B. When used as recommended (not exceeding 10 mg/day), selegiline is less likely than MAO inhibitor antidepressants to interact with other drugs and tyramine-containing foods. However, it may interact with antidepressants, selective serotonin reuptake inhibitors (eg, fluoxetine), and meperidine and should not be used with these drugs. If the dose of selegeline is >10 mg/day, its selectivity diminishes, and the risk of interactions increases.

pp. 2581-2582 The Merck Manual: Seventeenth Edition edited by Keryn A.G. Lane (1999)

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