Adverse Effects

The potential for toxicity that is associated with the administration of the MAOIs restricts their use in major depression. Hepatotoxicity is likely to occur with iso-carboxazid or phenelzine, since hydrazine compounds can cause damage to hepatic parenchymal cells. This is true particularly for patients identified as slow acetyla-tors (see Chapter 4) of hydrazine compounds. Fortunately, the incidence of hepatotoxicity is low with the available agents.

A greater concern is the potentially lethal cardiovascular effects that can occur in patients who do not comply with their dietary restrictions. Patients who take a MAOI should not eat food rich in tyramine or other biologically active amines. Normally, these amines are rapidly metabolized by MAO-A during gastric absorption by the mucosal cells of the intestinal wall and by MAO-A and MAO-B during passage through the liver parenchyma. If both isozymes of MAO are inhibited, elevated circulating levels of tyramine will be free to interact with the sympathetic noradrenergic nerve terminals innervating cardiac and vascular smooth muscle tissue to produce a pressor effect (see Chapter 10). In these conditions, tyramine can cause an acute elevation in blood pressure, sometimes leading to a hypertensive crisis. Cheeses, wine, and a whole host of other foods rich in tyramine must be avoided. A number of other bothersome side effects, such as tremors, orthostatic hypotension, ejaculatory delay, dry mouth, fatigue, and weight gain, are common at therapeutic doses of MAOIs (Table 33.2).

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