Tyramine is an exogenous dietary amine that is normally metabolized by intestinal and hepatic MAO enzymes.8 In patients taking a nonselective MAOI, a greater amount of tyramine is able to reach the systemic circulation. Tranylcypromine is more frequently associated with tyramine reactions than phenelzine or isocarboxazid. Selegiline (MAO-B selective) is unlikely to produce a tyramine reaction if taken at therapeutic doses. Tyramine is classified as an indirect sympathomimetic and is structurally similar to amphetamine. Like most indirect sympathomimetics, tyramine enters the presynaptic neuron through amine uptake pumps. Once inside the neuron, indirect sympathomimetics are capable of releasing presynaptic stores of norepinephrine and to a lesser degree serotonin and dopamine. Tyramine can also displace epinephrine from the adrenal gland. This action produces the "cheese" reaction since aged cheese contains a large amount of tyramine. In similar fashion, broad (fava) beans contains large quantities of dopamine.
Tyramine is found in over 70 foods and beverages, and any one of these sources may trigger such a reaction. 9 It has been reported that less than 30 percent of patients comply with a MAOI-restrictive diet. In addition, approximately 4 to 8 percent of compliant patients will experience a tyramine reaction during their course of therapy. Nonetheless, newer guidelines call for avoiding only a few high-risk food groups such as meat or fish that is not fresh, sauerkraut, aged meats and cheeses, alcohol (Chianti wine and vermouth), pickled fish (herring), concentrated yeast extracts, and broad beans.
The tyramine reaction is typically of rapid onset, occurring within 15 to 90 min after the dietary amine is ingested. The severity of this reaction is highly variable and partially related to the total amount of tyramine ingested. The hallmark symptom of the tyramine reaction is a severe occipital or temporal headache. Other associated symptoms include hypertension, diaphoresis, mydriasis, neck stiffness, pallor, neuromuscular excitation, palpitations, and/or chest pain. Most symptoms gradually resolve over 6 h without specific therapy but fatalities have been rarely reported, usually due to intracranial hemorrhage or myocardial infarction. Therefore, an electrocardiogram should be obtained on all patients with tyramine-associated chest pain. Focal neurologic findings or a persistent severe headache warrants investigation with a computed tomography (CT) scan of the head.
In cases of severe hypertension the drug of choice remains phentolamine (Regitine), which is given intravenously in 2.5- to 5-mg doses every 5 to 15 min until the blood pressure is controlled. The half-life of phentolamine is approximately 20 min, and its duration of action less than 1 h. Nitroprusside (Nipride) is another rapidly acting direct vasodilator, which is always administered as a continuous infusion (1 to 4 pg/kg per minute). In cases of moderate hypertension, nifedipine (Procardia) and prazosin (Minipress) have been reported to be effective. Newer recommendations for the treatment of accelerated chronic hypertension discourage the use of nifedipine due to concerns of excessive blood pressure reduction. These concerns may not apply to the acute hypertension seen in tyramine reactions. Beta-adrenergic blockers should be considered contraindicated due to unopposed alpha-receptor stimulation. Hospital admission should be strongly considered for patients whose symptoms do not completely resolve within 6 h after onset.
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