Monoamine oxidase inhibitor toxicity: Difference between revisions

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==Background==
==Background==
*MonoAmine Oxidase Inhibitors (MAOI)
*MonoAmine Oxidase Inhibitors (MAOI)
*Used to treat depression and Parkinsonism (e.g. selegiline -> MAO-B at lower doses, MAO-A at higher doses)
*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
*Linezolid is a reversible inhibitor of MAO and produces significant inhibition of MAO-A


===Toxicity Mechanisms===
===Toxicity Mechanisms===
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==Clinical Features==
==Clinical Features==
*Similar to hyperadrenergic state (tachycardia, hypertension, hyperthermia)
*Similar to hyperadrenergic state ([[tachycardia]], [[hypertension]], [[hyperthermia]])
*Severe toxicity accompanied by [[coma]], [[seizure]], [[bradycardia]], [[hypotension]], worsening [[hyperthermia]], [[rhabdomyolysis]]
*Severe toxicity accompanied by [[coma]], [[seizure]], [[bradycardia]], [[hypotension]], worsening [[hyperthermia]], [[rhabdomyolysis]]


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**[[Amphetamines]]
**[[Amphetamines]]
**[[Antimuscarinics]]
**[[Antimuscarinics]]
**Methylxanthine toxicity (theophylline, caffeine)
**Methylxanthine toxicity ([[theophylline toxicity|theophylline]], [[caffeine toxicity|caffeine]])
**St. John's Wort
**St. John's Wort
*Withdrawal states
*Withdrawal states
**[[Ethanol withdrawal|Ethanol]]
**[[Ethanol withdrawal|Ethanol]]
**[[Benzodiazepine withdrawal]]
**[[Benzodiazepine withdrawal]]
**Clonidine
**[[Clonidine]]
**Beta-blockers
**[[Beta-blockers]]
*Medical conditions
*Medical conditions
**[[Heat stroke]]
**[[Heat stroke]]
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==Evaluation==
==Evaluation==
*asymptomatic period followed by delayed toxicity can suggest MAO-I toxicity
*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 metamphetamine)
*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
*consider ECG and chemistry panel in MAOI overdose patients who are obtunded


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#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]]
#*CNS excitation and [[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 observation to monitored setting (risk of delayed hyperadrenergic symptoms)
*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==

Revision as of 14:11, 1 September 2019

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
  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.