Tyramine cheese effect

The main limitation to the clinical use of the MAOIs is due to their interaction with amine-containing foods such as cheeses, red wine, beers (including non-alcoholic beers), fermented and processed meat products, yeast products, soya and some vegetables. Some proprietary medicines such as cold cures contain phenylpropanolamine, ephedrine, etc. and will also interact with MAOIs. Such an interaction (termed the "cheese effect"), is attributed to the dramatic rise in blood pressure due to the sudden release of noradrenaline from peripheral sympathetic terminals, an event due to the displacement of noradrenaline from its mtraneuronal vesicles by the primary amine (usually tyramine). Under normal circumstances, any dietary amines would be metabolized by MAO in the wall of the gastrointestinal tract, in the liver, platelets, etc. The occurrence of hypertensive crises, and occasionally strokes, therefore limited the use of the MAOIs, despite their proven clinical efficacy, to the treatment of atypical depression and occasionally panic disorder. 

The "cheese effect" is a well-established phenomenon whereby an amine-rich food is consumed while the patient is being treated with an irreversible MAOI. Foods which cause such an effect include cheeses, pickled fish, yeast products (red wines and beers, including non-alcoholic varieties), chocolate and pulses such as broad beans (which contain dopa). It appears that foods containing more than 10 mg of tyramine must be consumed in order to produce a significant rise in blood pressure. Furthermore, it is now apparent that there is considerable variation in the tyramine content of many of these foods even when they are produced by the same manufacturer. Therefore it is essential that all patients on MAOIs should be provided with a list of foods and drinks that should be avoided. 

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). 

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. 

Irreversible MAOIs + sympathomimetic amines, tyramine-containing foods ("cheese effect") and buspirone — hypertension, possibly leading to stroke. 

The search for selective inhibitors for the two forms of MAO (MAO A and MAO B) remains an important area of medicinal chemistry223. Mood-elevating effects of MAO inhibitors make them useful drugs for the treatment of depressive illness. Complications of MAO treatment include elevation of blood pressure due to blockade of the oxidative metabolism of tyramine, a pressor amine present in many foods (the cheese effect ). Since this inhibition has been attributed to the action of intestinal MAO A, the search for selective MAO B inhibitors has been particularly intense. 

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-... 

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. 

Chlorgyline, like many other nonspecific and MAO A inhibitors, potentiates the pressor effect of tyramine on the cardiovascular system in humans and rodents and may result in hypertensive crises. This effect is probably due to inhibition of MAO A activity in the intestines which normally detoxify monoamines in food and beverages such as cheese and winei id 2 jg believed that only MAO A inhibitors (and mixed inhibitors) have this so-called cheese effect ... 

There are two issues of concern which are associated with irreversible MAOIs involving the display of liver toxicity, particularly with hydrazines, and the permanent inactivation of both MAO-A and -B isoforms. The replacement of MAOs requires protein synthesis which may take up to 14 days. From the antidepressant viewpoint, only a selective blockage of serotonin metabolism may be of interest in order to increase serotonin availability. However, this long-term effect significantly reduces metabolism of a variety of other biogenic amines, which leads to their accumulation, which is not necessarily desired. This leads to an excessive availability of tyramine and others, which ultimately leads to increased release of noradrenaline that may result in the stimulation of cardiovascular sympathetic nervous system activity. As a consequence, potentially fatal hypertensive crises and cerebral haemorrhage can occur (Fig. 18.22). This phenomenon has often been termed the cheese effect, in order to reflect the fact that tyramine is present in a variety of foods such as wine, cheese and other fermented food and drink products. It would appear, however, that under carefully controlled and restricted dietary conditions such a risk can be minimised. 

As of the mid-1990s, use of MAOIs for the treatment of depression is severely restricted because of potential side effects, the most serious of which is hypertensive crisis, which results primarily from the presence of dietary tyramine. Tyramine, a naturally occurring amine present in cheese, beer, wine, and other foods, is an indirecdy acting sympathomimetic, that is, it potently causes the release of norepinephrine from sympathetic neurons. The norepinephrine that is released interacts with adrenoceptors and, by interacting with a-adrenoceptors, causes a marked increase in blood pressure the resultant hypertension may be so severe as to cause death. 

A direct effect of vasoactive amines on the organism which are not degraded in GI tracts due to the lack of mono- and diaminooxidase (MAO and DAO) or their blockade by medicines or alcohol. This group of amines includes tyramine (in Cheddar, emmental, roquefort cheeses, pickled fish, and walnuts), phenylethylamine (in chocolate), serotonin (in bananas), octopamine (in lemons), and histamine (in fermented foods, e.g., blue cheeses, but also in strawberries, tomatoes, wines, and in mackerel that have not been stored properly [scombrotoxin illness]). 

Tyramine acts as an indirect sympathomimetic to cause release of catecholamines from nerve terminals. It is present in a number of foods mature cheese, yeast extracts, some red wines, hung game, pickled herrings, broad bean pods. Normally, MAO-A in the intestinal mucosa will metabolise tyramine absorbed from the gut. In patients on the older MAOls, considerable amounts of tyramine will enter the circulation and this will lead to increased release of catecholamines stored in nerve terminals because the MAOI prevents their metabolism. For patients on RIMA drugs, high concentrations of tyramine can compete for MAO-A, thus mitigating some of the effects, and MAO-B is still available to metabolise noradrenaline (norepinephrine). MAO-B, however, has relatively much less effect on 5-HT and thus 5-HT function is still enhanced. 

Enter the reversible MAO inhibitors. If someone eats cheese, tyramine will still release sympathomimetic amines, but these amines will chase the reversible inhibitor off the MAO enzyme, allowing the dangerous amines to be destroyed (Fig. 6—24). This is sort of like having your cake—or cheese—and eating it, too. The reversible MAO inhibitors have the same therapeutic effects as the suicide inhibitors of MAO, but without the likelihood of a cheese reaction if a patient inadvertently takes in otherwise dangerous dietary tyramine. 

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