Monoamine oxidase inhibitor toxicity

Background

• MonoAmine Oxidase Inhibitors (MAOI)
• Used to treat depression and Parkinsonism
• MAOI drugs available in the US include:
  • Isocarboxazid, phenelzine (Nardil), tranylcypromine (Parnate)
  • Selegiline (Deprenyl, Eldepryl, Emsam, Zelapar)--> MAO-B at lower doses, MAO-A at higher doses, rasagiline (Azilect), safinamide (Xadago)
  • Linezolid is a reversible inhibitor of MAO and produces significant inhibition of MAO-A
  • Methylene blue
• Lead to increased norepinephrine, serotonin, dopamine, tyramine

Toxicity Mechanisms

• Intentional overdose
  • Symptoms often delayed 6-24 hours after ingestion
• Food-drug interactions
  • Taking MAOI at therapeutic doses, but inadvertently eating foods rich in tyramine (aged cheese, red wine, aged meats)
  • Symptoms are generally acute
• Drug-drug interactions
  • Many prescription and OTC medications interact with MAOI

Types

• MAO-A
  • Primarily deaminates serotonin and norepinephrine
• MOA-B
  • Primarily deaminates phenylethylamine

Clinical Features

• Similar to hyperadrenergic state (tachycardia, hypertension, hyperthermia)
• Severe toxicity accompanied by coma, seizure, bradycardia, hypotension, worsening hyperthermia, rhabdomyolysis

Differential Diagnosis

• Intoxications
  • Amphetamines
  • Antimuscarinics
  • Methylxanthine toxicity (theophylline, caffeine)
  • St. John's Wort
• Withdrawal states
  • Ethanol
  • Benzodiazepine withdrawal
  • Clonidine
  • Beta-blockers
• Medical conditions
  • Heat stroke
  • Hypoglycemia
  • Hyperthyroidism
  • Meningitis
  • Encephalitis
  • Pheochromocytoma
  • Carcinoid syndrome
• Adverse drug reactions
  • Malignant Hyperthermia
  • Serotonin Syndrome
  • Tyramine Reaction
  • Neuroleptic Malignant Syndrome (NMS)

Movement Disorders and Other Abnormal Contractions

• Chorea
  • Sydenham's chorea
• Neuroleptic malignant syndrome
• Serotonin syndrome
• Hypocalcemia
• Strychnine toxicity
• Acute tetanus
• Parkinson's disease
• Mono amine oxidase inhibitor toxicity
• Phencyclidine toxicity
• Anti-NMDA receptor encephalitis
• Huntington disease
• Wilson's disease
• CVA
• Schizophrenia
• Psychotic agitation
• Dementia
  • Lewy body dementia
  • Vascular dementia
  • Frontotemporal dementia
• Dystonic reaction
• Extrapyramidal reaction
• Torticollis
• Idiopathic movement disorder

Evaluation

• Asymptomatic period followed by delayed toxicity can suggest MAO-I toxicity
• urine immunoassays and mass spectroscopy can fail to detect MAOI (patients taking selegiline will test positive for methamphetamine)
• consider ECG and chemistry panel in MAOI overdose patients who are obtunded

Management

1. Gastric decontamination
   • Activated charcoal PO x 1
   • Consider gastric lavage, if can be performed <1 hour after ingestion
2. Supportive care
   • Hypertension
     • Treat only with short-acting agents: may develop precipitous hypotension
     • Phentolamine: 2.5-5mg IV bolus q15-15min; can also give as infusion 0.2-0.5mg/min
     • Nitroprusside: 1mcg/kg/min and titrate up
   • Hypotension: intravenous fluid +/- norepinephrine
   • CNS excitation and Seizures: benzodiazepines are 1st line
   • Hyperthermia
     • Routine cooling measures
     • Consider paralysis if patient has persistent muscle rigidity

Prevention

• Do not prescribe the following medications if a patient is taking a MAOI: meperidine, dextromethorphan, tramadol, propoxyphene, or cyclobenzaprine

Medication Dosing

Phentolamine 2.5-5mg IV bolus q10-15min; or infusion 0.2-0.5mg/min IV Nitroprusside 1mcg/kg/min IV, titrate up IV

Disposition

• Admit all patients for 24 hour observation to monitored setting (risk of delayed hyperadrenergic symptoms)

See Also

• Tyramine Reaction
• Toxidromes

References

• Rosen's