severe toxicity, even in the patient who takes them in appropriate doses There are three important clinical pictures of MAOI toxicity First, because GI tract activity of monoamine oxidase is inhibited, patients who take them appropriately and then ingest foods that contain biogenic amines (e.g., tyramine in wines, cheeses, or soy sauce) may develop severe hypertension with subsequent headache, seizures, or stroke The second picture of MAOI toxicity appears when those who take the drug therapeutically are given certain sympathomimetic or serotonergic agents causing the serotonin syndrome Important examples of such drugs include common agents in OTC cough and cold preparations (e.g., dextromethorphan), analgesics (e.g., meperidine), and psychotropic medications (e.g., clomipramine, fluoxetine, other SSRIs) This drug combination may quickly lead to hyperpyrexia, skeletal muscle rigidity, cardiac arrhythmias, and death Finally, those with acute MAOI overdoses develop a clinical syndrome that includes blood pressure instability, hyperpyrexia, skeletal muscle rigidity, opsoclonus, seizures, and death Clinical Considerations Because of the toxicity of these agents and the frequent delay in their onset of activity (up to 24 hours), all patients with a history of MAOI ingestion, regardless of symptoms, should be admitted to the hospital for 24 hours Management of the patient with MAOI toxicity is largely dictated by the specific toxic manifestations In those with hypertensive reactions, treatment consists of the immediate administration of an antihypertensive The ideal agent may be nitroprusside because its brief duration of action permits titration of effect In the treatment of hyperpyrexia, institute cooling measures promptly Because hyperpyrexia is often accompanied by skeletal muscle rigidity and rhabdomyolysis, monitor serum creatine kinase levels and urine for myoglobinuria Benzodiazepines are often helpful in this situation and neuromuscular blockade may be beneficial in patients with severe muscle rigidity with hyperthermia In the patient with acute overdose, treatment is directed to hemodynamic stability Because blood pressure changes occur quickly and consist of hypotension and hypertension, hypertension should be treated with short-acting agents and hypotension with fluid and vasopressor support Intensive care unit admission is mandatory for these patients because of their clinical instability Phenothiazine Antipsychotics CLINICAL PEARL