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[1]
  • 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

Differential Diagnosis

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
  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

Disposition

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


See Also

References

  • Rosen's
  • Petzer A, Harvey BH, Wegener G, Petzer JP (February 2012). "Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase". Toxicology and Applied Pharmacology. 258 (3): 403–9.