Monoamine oxidase inhibitors cheese effect

Monoamine oxidase inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

The monoamine oxidase inhibitors are associated with a number of undesirable side effects including weight gain, postural hypotension, sexual dysfunction, and insomnia. The most serious side effect is the risk of tyramine-re-lated hypertensive crisis, often referred to as the "cheese effect," which can be fatal. To avoid this situation patients taking MAOIs must limit their tyramine intake, and the restrictive diet required to accomplish this leads to low patient compliance. A similar interaction occurs when switching patients from MAOI to SSRI therapy, and a minimum 2-week washout period before commencement of SSRI therapy is essential to allow MAO levels to return to normal. The therapeutic effects of the TCAs derive from their inhibition of serotonin and norepinephrine uptake, al-... 

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. 

Desmethylselegiline is also an irreversible inhibitor of monoamine oxidase B in humans. There is evidence that the 1-stereoisomers of 1-amphetamine and 1-methamphetamine may have some qualitatively different actions from their d-isomer counterparts, which might result in beneficial clinical effects and could complement any beneficial clinical actions of selegiline itself. Food has no effect on the pharmacokinetics of desmethylselegiline, methamphetamine, and amphetamine. At a dose of 10 mg per day, selegiline is devoid of the cheese effect that is, it does not cause hypertension when taken with tyramine-containing foods such as cheese. 

Figure 10.22. Hypothetical mechanism of the antihypertensive effect of monoamine inhibitors. This mechanism does not fit the observation of the cheese reaction , in which tyramine contained in fermented food causes hypertensive episodes in patients receiving monoamine oxidase blockers.

Piperonyl butoxide, isoniazid, and SKF 525A and related chemicals are inhibitors of various xenobiot-ic-metabolizing enzymes. For instance, piperonyl butoxide increases the toxicity of pyrethrum (an insecticide) by inhibiting MFO activity in insects that detoxifies this agent. Isoniazid, when taken along with phenytoin, lengthens the plasma half-life of the antiepileptic drug and increases its toxicity. Iproniazid inhibits monoamine oxidase and increases the cardiovascular effects of tyramine, which is found in cheese and which is normally readily metabolized by the oxidase. 

Elsworth JD, Glover V, Reynolds GP, Sandler M, Lees AJ, Phuapradit P, Shaw KM, Stern GM, Kumar P (1978) Deprenyl administration in man a selective monoamine oxidase B inhibitor without the cheese effect . Psychopharmacology 57 33-38... 

Monoamine oxidases (both MAO-A and MAO-B) also exist in peripheral tissue, specifically the gastrointestinal tract (GIT). In the GIT, they inhibit the first-pass metabolism of exogenous tyramine. Because of this property, treatment with non-selective irreversible MAOIs can result in the accumulation of tyramine and have the potential to precipitate a dangerous hypertensive crisis, the so-called cheese effect. This effect may occur more frequently in elderly than in younger patients, because the cardiovascular systems of the elderly are already compromised by age. Selective MAO-B inhibitors and reversible MAO-A inhibitors are free from this potentially fatal interaction. 

---