Cheese, monoamine oxidase inhibitors

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). 

Catecholamine neurotransmitters are subsequently inactivated by enzymic methylation of the 3-hydroxyl (via catechol-O-methyltransferase) or by oxidative removal of the amine group via monoamine oxidase. Monoamine oxidase inhibitors are sometimes used to treat depression, and these drugs cause an accumulation of amine neurotransmitters. Under such drug treatment, simple amines such as tyramine in cheese, beans, fish, and yeast extracts are also not metabolized and can cause dangerous potentiation of neurotransmitter activity. 

When explaining possible medication and/or food interactions, for example the importance of avoiding alcohol with certain drugs such metronidazole or cheese with monoamine oxidase inhibitors (MAOIs). 

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-... 

Administered as a single, daily dose on an empty stomach Monoamine oxidase inhibitors drug-food interactions with tyramine-rich foods such as red wines, dark beers, aged cheeses, yogurt may precipitate hypertensive crisis drug interactions tricyclic antidepressants and SSRIs, sympathomimetics disulfiram-like reaction with alcohol... 

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. 

Procarbazine can cause a disulfiram-like reaction and is a monoamine oxidase inhibitor. Thus, ingestion of alcohol, foods containing tyramine (e.g., cheese), drugs that increase sympathetic activity, and MAOl-type antidepressants (e.g., tranylcypromine) should be avoided. 

Horwitz D, Lovenberg W, Engelman K, Sjoerdsma A. Monoamine oxidase inhibitors, tyramine and cheese. JAMA (1964) 188, 1108-10. 

Metabolic inactivation, whether taking place in the e,r, or at other sites, is often accidentally inhibited by other drugs. Thus many patients have died as a result of the simultaneous administration of an inhibitor of monoamine oxidase (an enzyme present in mitochondria) and an amine drug which is not toxic on its own. These monoamine oxidase inhibitors, such as tranylcypromine 9,47), are prescribed as mood-elevators in depressive illnesses. Until their synergistic properties were realized, they caused many deaths after usually safe doses of amphetamine, pethidine, and amitriptyline, or after the patient had consumed food rich in pressor amines such as tyramine such foods are red wine, meat-extract, yeast-extract, broad beans, and particularly cheese. These are examples of unfortunate synergism, but many favourable cases are known, examples of which will now be given. 

Several of these amines are found in animals and some are involved in nerve transmission see Chapter 27). When plant amines are consumed by animals, they can be quite toxic. For example, phenylethylamine (8) in Acacia berlan-dieri is poisonous to livestock (Smith, 1977b). The presence of amines in foods consumed by humans also has been noted. Catecholamines, indoleamines, and histamine (11) fulfill important metabolic functions, especially in the nervous system and in the control of blood pressure. The occasional presence of greater than usual amounts of tyramine in cheese can cause severe episodes of hypertension, especially in the presence of monoamine oxidase inhibitors, which often are used in the treatment of depression (Smith, 1981). Amines can be formed from bacterial activity in foods (Smith, 1981). 

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. 

Monoamine oxidase (MAO) inhibitors Foods containing tyramine (liver, pickled herring, cheese, bananas, avocados, soup, beer, wine, yogurt, sour cream, yeast, nuts) Palpitations, headache, hypertensive crises... 

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. 

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