Monoamine Oxidase Inhibitor Poisoning

Basics

Description

  • Primarily for depression
  • Selegiline, a selective monoamine oxidase B inhibitor, is sometimes used to treat Parkinson disease, and also comes in a transdermal preparation
  • Monoamine oxidase inhibitor (MAOI) pharmacologic actions:
    • Disruption of equilibrium between endogenous monoamine synthesis and degradation, resulting in:
      • Increased neural norepinephrine levels
      • Downregulation of several receptor types
    • Inhibition of irreversible (noncompetitive) enzyme
    • Inhibition of other B6-containing enzymes
  • MAO: Principal inactivator of neural bioactive amines:
    • MAO A:
      • Present in the gut and liver
      • Protects against dietary bioactive amines
    • MAO B:
      • Present in neuron terminals and platelets
      • Sympathomimetic amines: Types of bioactive amines

Etiology

  • MAOI overdose:
    • Toxicopharmacology poorly understood
    • MAO inhibitors: Amphetamine-like in structure:
      • Early: Indirect sympathomimetic effect
      • Late: Sympatholytic response (hypotension)
  • MAOI hypertensive crisis syndrome:
    • Results from impaired norepinephrine degradation and large norepinephrine release precipitated by an indirect- or mixed-acting sympathomimetic agent
    • Common precipitants: Tyramine, cocaine, amphetamines
  • Serotonin syndrome (SS):
    • Commonly results from exposure to combinations of agents that affect serotonin metabolism or action
    • Increases serotonin synthesis: Tryptophan
    • Increase serotonin release:
      • Indirect- and mixed-acting sympathomimetic agents and dopamine receptor agonists
    • Decrease serotonin reuptake:
      • Selective serotonin reuptake inhibitors
      • Tricyclic antidepressants
      • Newer antidepressants: Trazodone, nefazodone, venlafaxine
      • Phenylpiperidine opioids: Meperidine, dextromethorphan, tramadol, methadone, propoxyphene
    • Direct serotonin receptor agonists:
      • Buspirone, sumatriptan, lysergic acid diethylamide
    • Decrease serotonin breakdown:
      • MAOIs
    • Increases nonspecific serotonin activity:
      • Lithium

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