Monoamine oxidase inhibitor toxicity: Difference between revisions

(Created page with "==Background== *MAOIs are used for depression and Parkinson's (e.g. selegiline) *Lead to increased norepi, serotonin, dopamine, tyramine *Toxicity often delayed 6-24hr after inge...")
 
 
(32 intermediate revisions by 11 users not shown)
Line 1: Line 1:
==Background==
==Background==
*MAOIs are used for depression and Parkinson's (e.g. selegiline)
*MonoAmine Oxidase Inhibitors (MAOI)
*Lead to increased norepi, serotonin, dopamine, tyramine
*Used to treat depression and Parkinsonism
*Toxicity often delayed 6-24hr after ingestion
*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
 
===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==
==Clinical Features==
*Similar to a hyperadrenergic state
*Similar to hyperadrenergic state ([[tachycardia]], [[hypertension]], [[hyperthermia]])
*Severe toxicity is accompanied by:
*Severe toxicity accompanied by [[coma]], [[seizure]], [[bradycardia]], [[hypotension]], worsening [[hyperthermia]], [[rhabdomyolysis]]
**Coma, seizure, bradycardia, hypotension, worsening hyperthermia


==DDX==
==Differential Diagnosis==
#Intoxications
*Intoxications
##Amphetamines, antimuscarinics
**[[Amphetamines]]
#Withdrawal states
**[[Anticholinergic toxicity|Antimuscarinics]]
##ETOH, clonidine, B-blockers
**Methylxanthine toxicity ([[theophylline toxicity|theophylline]], [[caffeine toxicity|caffeine]])
#Medical conditions
**St. John's Wort
##Heat stroke, hypoglycemia, hyperthyroidism
*Withdrawal states
#Adverse drug reactions
**[[Ethanol withdrawal|Ethanol]]
##[[Malignant Hyperthermia]]
**[[Benzodiazepine withdrawal]]
##[[Serotonin Syndrome]]
**[[Clonidine]]
##[[Tyramine Reaction]]
**[[Beta-blockers]]
##[[Neuroleptic Malignant Syndrome (NMS)]]
*Medical conditions
**[[Heat stroke]]
**[[Hypoglycemia]]
**[[Hyperthyroidism]]
**[[Meningitis]]
**[[Encephalitis]]
**[[Pheochromocytoma]]
**[[Carcinoid syndrome]]
*Adverse drug reactions
**[[Malignant Hyperthermia]]
**[[Serotonin Syndrome]]
**[[Tyramine Reaction]]
**[[Neuroleptic Malignant Syndrome (NMS)]]


==Treatment==
{{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
 
==Management==
#Gastric decontamination
#Gastric decontamination
##Gastric lavage indicated if can be performed <1hr after ingestion
#*[[Activated charcoal]] PO x 1
##Activated charcoal x1
#*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
#**[[Phentolamine]]: 2.5-5mg IV bolus q15-15min; can also give as infusion 0.2-0.5mg/min
####Give 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
#*Hypotension: intravenous fluid +/- [[norepinephrine]]
####Give 1mcg/kg/min and titrate up
#*CNS excitation and [[Seizures]]: [[benzodiazepines]] are 1st line
##Hypotension
#*Hyperthermia
###IVF
#**Routine cooling measures
###Norepi
#**Consider paralysis if patient has persistent muscle rigidity
##Seizures
 
###Benzos are 1st line
 
##Hyperthermia
==Prevention==
###Routine cooling measures
*Do ''not'' prescribe the following medications if a patient is taking a MAOI: [[meperidine]], [[dextromethorphan]], [[tramadol]], propoxyphene, or [[cyclobenzaprine]]
###Consider paralysis if pt has persistent muscle rigidity


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


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


==See Also==
==See Also==
*[[Tyramine Reaction]]
*[[Tyramine Reaction]]
*[[Toxidromes]]


==References==
*Rosen's


==Source==
[[Category:Toxicology]]
*Tintinalli
 
[[Category:Tox]]

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.
Retrieved from "https://www.wikem.org/w/index.php?title=Monoamine_oxidase_inhibitor_toxicity&oldid=284091"