Monoamine oxidase inhibitors are oral anti-hypertensive and antidepressant agents.
- Pharmaceutical preparations include selegiline (Deprenyl), clorgyline, nialimide, isocarboxazid (Marplan), pargyline (Eutonyl), phenelzine (Nardil), moclobemide, tranylcypromine (Parnate), furazolidone (Furoxone), and procarbazine (Matulane).
- Selegiline (Deprenyl), isocarboxazid, pargyline, phenelzine, and tranylcypromine are approved for use in treating anxiety, phobias, bulimia, treatment-resistant or atypical depression, migraines, obsessive-compulsive disorders, narcolepsy, and Parkinson's disease.
- Approved indications for furazolidone include bacterial or protozoal diarrhea and enteritis caused by the majority of gastrointestinal pathogens.
- Tranylcypromine. Adult dosage, 10 to 30 mg/day orally.
- Phenelzine. Adult dosage, 15 to 90 mg/day orally.
- Moclobemide. Adult dosage, 300 to 450 mg, given in two to three divided doses orally.
- Furazolidone. Adult dosage, one tablet four times per day or 2 tablespoons four times per day; children 5 years of age or older, 25 to 50 mg four times per day; children 1 to 4 years of age, 1 to 1½ tablespoons four times per day orally.
Ingestion of 2 to 3 mg/kg of any MAO inhibitor may produce serious toxicity.
- Inhibition of the enzyme monoamine oxidase results in the increase of norepinephrine, dopamine, and serotonin in the synapse, producing an antidepressant effect.
- In overdose, overstimulation of the postsynaptic receptors results in toxicity.
- Toxicity from MAO inhibitors is uncommon.
- Toxic effects are typically mild to moderate.
- Death occurs infrequently, related to a large overdose or an adverse drug interaction.
- Overdose is usually the result of intentional ingestion.
- Child neglect should be considered if the patient is under 1 year of age; attempted suicide should be considered in patients over 6 years of age.
MAO inhibitors may interact with many drugs or foods to produce life-threatening hypertension, neuroleptic malignant syndrome (NMS), or serotonin syndrome (SS).
- All sympathomimetic agents
- Opioids
- Tricyclic antidepressants
- Lithium
- Selective serotonin reuptake inhibitors (SSRIs)
- Levodopa, methyldopa, and tryptophan
- Guanethidine
- Theophylline, caffeine
- Various foods, including chocolate, aged cheese, chianti, vermouth, pickled fish, and concentrated yeast extracts
- US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
- Abruptio placentae may occur if severe hypertension develops.
- Toxic causes of hypertension include stimulants (amphetamine, cocaine, etc.), and theophylline, among others.
- Primary causes of hypertension associated with hyperthermia and altered mental status are NMS (phenothiazines, many other drugs), SS, SSRIs, stimulants, hallucinogens, and many other drugs.
- Nontoxic causes include hypertensive crisis, noncompliance with antihypertensive medications, and alcohol or sedative-hypnotic withdrawal, among others.
The primary effects associated with overdose are hyperadrenergic and include agitation and hypertension; severe cases may involve multiple organ failure.
- Hypertension is followed by hypotension in serious cases.
- Hyperthermia should raise concern for NMS or SS.
Headaches, dilated pupils, blurry vision or tinnitus may occur.
Tachypnea and pulmonary edema may develop in severe cases.
Hypertension may cause myocardial ischemia and dysrhythmias.
Nausea, diarrhea, abdominal pain, and constipation may occur.
Hepatitis occurs rarely.
Renal failure and syndrome of inappropriate antidiuretic hormone secretion have been reported.
- Weakness, muscle spasm, and myoclonic jerks have been reported.
- If stiffness or rhabdomyolysis develop, diagnosis of NMS or SS should be considered.
- Tinnitus, numbness, paresthesia, akinesia, restlessness or insomnia occur.
- Weakness and drowsiness may progress to agitation, confusion, seizures, and coma.
- Headache and focal neurologic deficits may indicate intracranial hemorrhage.
Urinary retention, retarded ejaculation, and impotence may occur.
Anemia, leukopenia, thrombocytopenia, and agranulocytosis have been reported.
PROCEDURES AND LABORATORY TESTS
No tests may be needed in asymptomatic patients.
- Serum electrolytes, BUN, creatinine, and urinalysis are recommended to assess acidosis, renal injury, and electrolyte abnormalities.
- Serum creatine kinase and liver enzyme tests may be done to assess rhabdomyolysis and chest pain.
- An ECG should be performed if symptoms of myocardial ischemia occur.
- Arterial blood gases may show respiratory alkalosis, respiratory acidosis, or metabolic acidosis.
- A complete blood count often reveals leukocytosis.
- Serum acetaminophen and aspirin levels in overdose setting to detect occult ingestion.
- Head CT, lumbar puncture, and bacterial cultures should be ordered as needed to evaluate patients with altered mental status of unknown etiology.
Drug levels are not clinically useful.