Monoamine oxidase inhibitor toxicity: Difference between revisions

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==Background==
==Background==
*Mono Amine Oxidase Inhibitors
*MonoAmine Oxidase Inhibitors (MAOI)
*Used to treat depression and Parkinsonism (e.g. selegiline)
*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]]<ref>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. </ref>
*Lead to increased norepinephrine, serotonin, dopamine, tyramine
*Lead to increased norepinephrine, serotonin, dopamine, tyramine
*Toxicity often delayed 6-24 hours after ingestion


==Clinical Features of Overdose==
===Toxicity Mechanisms===
*Similar to hyperadrenergic state
*Intentional overdose
*Severe toxicity accompanied by coma, seizure, bradycardia, hypotension, worsening hyperthermia
**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==
==Differential Diagnosis==
#Intoxications
*Intoxications
##Amphetamines
**[[Amphetamines]]
##Antimuscarinics
**[[Anticholinergic toxicity|Antimuscarinics]]
#Withdrawal states
**Methylxanthine toxicity ([[theophylline toxicity|theophylline]], [[caffeine toxicity|caffeine]])
##Ethanol
**St. John's Wort
##Clonidine
*Withdrawal states
##Beta-blockers
**[[Ethanol withdrawal|Ethanol]]
#Medical conditions
**[[Benzodiazepine withdrawal]]
##Heat stroke
**[[Clonidine]]
##Hypoglycemia
**[[Beta-blockers]]
##Hyperthyroidism
*Medical conditions
#Adverse drug reactions
**[[Heat stroke]]
##[[Malignant Hyperthermia]]
**[[Hypoglycemia]]
##[[Serotonin Syndrome]]
**[[Hyperthyroidism]]
##[[Tyramine Reaction]]
**[[Meningitis]]
##[[Neuroleptic Malignant Syndrome (NMS)]]
**[[Encephalitis]]
**[[Pheochromocytoma]]
**[[Carcinoid syndrome]]
*Adverse drug reactions
**[[Malignant Hyperthermia]]
**[[Serotonin Syndrome]]
**[[Tyramine Reaction]]
**[[Neuroleptic Malignant Syndrome (NMS)]]
 
{{Movement disorder DDX}}
 
==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


==Treatment==
==Management==
#Gastric decontamination
#Gastric decontamination
##Lavage indicated if can be performed <1 hour after ingestion
#*[[Activated charcoal]] PO x 1
##Activated charcoal x 1
#*Consider [[gastric lavage]], if can be performed <1 hour after ingestion
#Supportive care
#Supportive care
##Hypertension
#*Hypertension
###Treat only with short-acting agents: may develop precipitous hypotension
#**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
#**[[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
#**[[Nitroprusside]]: 1mcg/kg/min and titrate up
##Hypotension: intravenous fluid / +/- norepinephrine
#*Hypotension: intravenous fluid +/- [[norepinephrine]]
##Seizures: benzodiazepines are 1st line
#*CNS excitation and [[Seizures]]: [[benzodiazepines]] are 1st line
##Hyperthermia
#*Hyperthermia
###Routine cooling measures
#**Routine cooling measures
###Consider paralysis if patient has persistent muscle rigidity
#**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]]


==Disposition==
==Disposition==
*Admit all patients for 24 hour obsservation
*Admit all patients for 24 hour observation to monitored setting (risk of delayed hyperadrenergic symptoms)


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


==See Also==
==See Also==
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*[[Toxidromes]]
*[[Toxidromes]]


==Source==
==References==
*Tintinalli
*Rosen's


[[Category:Tox]]
[[Category:Toxicology]]

Latest revision as of 13:45, 14 November 2020

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

Movement Disorders and Other Abnormal Contractions

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
  1. ↑ 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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