A Type of Drug-Food Interaction 4
October 3rd 2009 06:51
Mode of Action of MAO Inhibitors
MAO Inhibitors act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. Such concept aids a patient in depression by prolonging the effect of the monoamines in the effector organs or tissues, since they will not easily be degraded. MAO inhibitors usually act irreversibly and so the effect is long-lasting. When they react with monoamine oxidase, they permanently deactivate it, and the enzyme cannot function until it has been replaced by the body, which can take about two weeks. MAO inhibitors can also be non-selective or selective, depending whether they inhibit any of the two isoforms of MAO or both. In our case, iproniazid is of non-selective type.
Why Did the Patient Had Headache and Hypertension Crisis Upon Intake of Wine and Cheese?
Wine and cheese are fermented products containing considerable amounts of tyramine. In humans, if monoamine metabolism is compromised by the use of monoamine oxidase inhibitors (MAO Inhibitors) and foods high in tyramine are ingested, a hypertensive crisis can result as tyramine can cause the release of stored monoamines, such as dopamine, norepinephrine, epinephrine.
Tyramine causes displacement of norepinephrine from the storage vesicles to the synapses. This will therefore magnify the adrenergic reactions, especially in a state of MAO inhibition. To begin with, inhibiting MAO already increases monoamine-adrenergic effects. And then tyramine further adding to such will definitely trigger adrenergic overstimulation. This will lead to “pressor response”-which includes vasoconstriction, increased heart rate, and increased blood pressure.
Tyramine also directly plays a role in vasopressor response. Tyramine can bind to G-protein coupled receptors (TA1), inducing chemical processes that will constrict blood vessels.
Another event that largely contributes to the pressor response occurs in the liver. With intake of MAO inhibitors, the MAO in the liver is NOT SPARED. Hepatic MAO (MAO-A) is also inhibited. Usually tyramine undergoes deamination in the liver to make it an inactive metabolite. This happens under a normally functioning hepatic MAO. But because of MAO inhibition, the first pass clearance of tyramine is blocked, and the concentration of circulating tyramine goes up. This further amplifies severity of pressor response.
MAO Inhibitors act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. Such concept aids a patient in depression by prolonging the effect of the monoamines in the effector organs or tissues, since they will not easily be degraded. MAO inhibitors usually act irreversibly and so the effect is long-lasting. When they react with monoamine oxidase, they permanently deactivate it, and the enzyme cannot function until it has been replaced by the body, which can take about two weeks. MAO inhibitors can also be non-selective or selective, depending whether they inhibit any of the two isoforms of MAO or both. In our case, iproniazid is of non-selective type.
Why Did the Patient Had Headache and Hypertension Crisis Upon Intake of Wine and Cheese?
Wine and cheese are fermented products containing considerable amounts of tyramine. In humans, if monoamine metabolism is compromised by the use of monoamine oxidase inhibitors (MAO Inhibitors) and foods high in tyramine are ingested, a hypertensive crisis can result as tyramine can cause the release of stored monoamines, such as dopamine, norepinephrine, epinephrine.
Tyramine causes displacement of norepinephrine from the storage vesicles to the synapses. This will therefore magnify the adrenergic reactions, especially in a state of MAO inhibition. To begin with, inhibiting MAO already increases monoamine-adrenergic effects. And then tyramine further adding to such will definitely trigger adrenergic overstimulation. This will lead to “pressor response”-which includes vasoconstriction, increased heart rate, and increased blood pressure.
Tyramine also directly plays a role in vasopressor response. Tyramine can bind to G-protein coupled receptors (TA1), inducing chemical processes that will constrict blood vessels.
Another event that largely contributes to the pressor response occurs in the liver. With intake of MAO inhibitors, the MAO in the liver is NOT SPARED. Hepatic MAO (MAO-A) is also inhibited. Usually tyramine undergoes deamination in the liver to make it an inactive metabolite. This happens under a normally functioning hepatic MAO. But because of MAO inhibition, the first pass clearance of tyramine is blocked, and the concentration of circulating tyramine goes up. This further amplifies severity of pressor response.
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