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
- 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
- Adverse drug reactions
- Malignant Hyperthermia
- Serotonin Syndrome
- Tyramine Reaction
- Neuroleptic Malignant Syndrome (NMS)
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
- Gastric decontamination
- Activated charcoal PO x 1
- Consider gastric lavage, if can be performed <1 hour after ingestion
- 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
- Hypertension
Prevention
- Do not prescribe the following medications if a patient is taking a MAOI: meperidine, dextromethorphan, tramadol, propoxyphene, or cyclobenzaprine
Disposition
- Admit all patients for 24 hour observation to monitored setting (risk of delayed hyperadrenergic symptoms)
See Also
- Tyramine Reaction
- Toxidromes
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.
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