Drug interactions involving MAOIs can be grouped into three categories: pharmacodynamic, pharmacokinetic, and idiosyncratic. The most common pharmacodynamic reaction involves indirect-acting sympathomimetics. They have the potential to produce a hyperadrenergic condition similar to the tyramine reaction (see above) and can be found in over-the-counter preparations, drugs of abuse, and some prescription products. Pharmacokinetic drug interactions have been noted with MAOIs because they are metabolized through the cytochrome oxidase enzyme system and thus can inhibit the metabolism of other drugs. The potentiation of opiate and sedative-hypnotic drugs is an example of this type of enzyme inhibition. Tranylcypromine and phenelzine have been shown to increase insulin release and predispose to hypoglycemia, especially in patients taking oral sulfonylureas agents. Insulin dosage may also warrant reduction. Serotonin syndrome is a rare, potentially life-threatening idiosyncratic reaction. It most commonly occurs when MAOIs are combined with other serotonergic agents. A complete description of serotonin syndrome as well as a listing of serotonergic medications can be found in Chap 153, on newer antidepressants. However, specific emphasis pertaining to emergency physicians is placed on the avoidance of using meperidine (Demerol),11 dextromethorphan, or tramadol (Ultram) in combination with MAOIs. Even after a patient discontinues MAOI therapy, it still takes 2 weeks before 50 percent of MAO enzyme activity returns. Consequently, there should always be at least a 2-week abstinence period between the time of MAOI discontinuation and the time that any contraindicated drug is administered. This recommendation is particularly important to prevent the development of serotonin syndrome.
It is also important to note which medications are generally considered safe in patients on MAOIs ( Table 15.4-2.). Aspirin, acetaminophen, ibuprofen, and morphine have been used in combination with MAOIs without complications. Morphine should be given in decreased doses due to impaired morphine metabolism and enhanced opiate effects. Direct-acting sympathomimetic agents (e.g., norepinephrine) can be used with caution, utilizing the lowest possible effective dose. Direct sympathomimetics do not rely on the release of neurotransmitters for their activity and they are inactivated by the enzyme COMT, which is unaffected by MAOIs.
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