Pharmacology
Summary
Monoamine oxidase enzymes, MAO-A and MAO-B, play pivotal roles in neurotransmitter metabolism. The enzyme MAO-A primarily degrades neurotransmitters such as serotonin, norepinephrine, and dopamine, while MAO-B predominantly metabolizes dopamine. MAO inhibitors, which include drugs like tranylcypromine, phenelzine, and isocarboxazid, irreversibly inhibit these enzymes. Their primary clinical utility is in the treatment of depression, especially in atypical and treatment-resistant cases. However, they are not considered first-line agents due to their potential for severe side effects and dietary restrictions. Selegiline, a selective MAO-B inhibitor, increases dopamine levels in the CNS, making it an invaluable agent in managing Parkinson's disease.
MAO-A is also responsible for metabolizing tyramine in the GI tract. MAO inhibitors can lead to increased circulating levels of this tyramine if tyramine-rich foods such as aged meats, wine and cheese are consumed. The excess tyramine can exert sympathomimetic effects, potentially triggering hypertensive crisis. Furthermore, the combination of MAO inhibitors with drugs that increase serotonin, such as TCAs, SSRIs, and SNRIs, can precipitate serotonin syndrome. Phentolamine, an alpha-1 and alpha-2 blocker, can be administered to manage the hypertensive symptoms arising from tyramine toxicity.
Lesson Outline
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FAQs
MAO-A and MAO-B are enzymes that metabolize neurotransmitters. Specifically, MAO-A degrades serotonin, norepinephrine, and dopamine, while MAO-B is more focused on dopamine. MAO inhibitors, such as tranylcypromine, phenelzine, and isocarboxazid, irreversibly block these enzymes, leading to increased neurotransmitter levels in the brain.
MAO inhibitors serve as therapeutic agents for depression, especially in instances of treatment-resistant depression or certain cases of atypical depression. Notably, selegiline, a selective MAO-B inhibitor, boosts dopamine levels in the CNS, making it a valuable treatment option for Parkinson's disease.
In the presence of MAO inhibitors, tyramine, found in specific foods, isn't adequately metabolized by MAO-A in the GI tract. Consequently, elevated tyramine levels in the bloodstream can act as a sympathomimetic agent, which can precipitate a hypertensive crisis. Further, combining MAO inhibitors with medications that enhance serotonin, such as TCAs, SSRIs, or SNRIs, heightens the risk of serotonin syndrome.
Patients on MAO inhibitors who ingest tyramine-rich foods might experience tyramine toxicity. This condition arises from increased tyramine absorption into the circulation due to MAO-A inhibition, manifesting as hypertension, blurry vision, and diaphoresis. Administration of phentolamine, an alpha-1 and alpha-2 receptor antagonist, can effectively mitigate the hypertensive symptoms associated with this toxicity.
One of the notable side effects of MAO inhibitors is serotonin syndrome, which encompasses symptoms ranging from restlessness and tachycardia to neuromuscular dysfunction and seizures. MAO inhibitors can also cause tyramine toxicity if tyramine-rich foods like wine and cheese are consumed. Tyramine toxicity can precepitate hypertensive crisis, which can be managed using the alpha-1 and alpha-2 blocker phentolamine.
