MAO Inhibitors

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MAOIs: Intro & MOA - Enzyme Blockers

  • Monoamine Oxidase (MAO): Mitochondrial enzymes that catabolize monoamine neurotransmitters.
    • MAO-A: Metabolizes Serotonin (5-HT), Norepinephrine (NE), Dopamine (DA), Tyramine. Found in brain, gut, liver.
    • MAO-B: Metabolizes Dopamine (DA), Tyramine, Phenylethylamine. Found in brain, platelets.
  • Mechanism of Action (MOA): MAOIs inhibit MAO enzyme activity, leading to ↑ intraneuronal concentrations of 5-HT, NE, and DA.
    • Irreversible: Form stable covalent bonds (e.g., Phenelzine). Effect lasts ~2 weeks.
    • Reversible (RIMA): Bind non-covalently (e.g., Moclobemide for MAO-A). Shorter duration of action. MAO-A inhibition mechanism for 5-HT and Noradrenaline

⭐ MAO-A primarily metabolizes serotonin and norepinephrine; MAO-B primarily metabolizes dopamine and phenylethylamine.

MAOIs: Classification & Drugs - The Lineup

MAOIs: Classified by MAO-A/B selectivity & reversibility.

DrugTypeReversibilityKey Notes
PhenelzineNon-selective (A+B)Irreversible📌 'PIT' group (Phenelzine, Isocarboxazid, Tranylcypromine)
IsocarboxazidNon-selective (A+B)Irreversible
TranylcypromineNon-selective (A+B)IrreversibleAmphetamine-like structure
SelegilineSelective MAO-BIrreversibleParkinson's; dose-dependent selectivity
RasagilineSelective MAO-BIrreversibleParkinson's; potent
MoclobemideSelective MAO-A (RIMA)ReversibleSafer profile; less cheese reaction
BrofaromineSelective MAO-A (RIMA)ReversibleLimited use

MAOIs: Clinical Uses & PK - When & How

  • Clinical Uses:
    • Atypical Depression (core indication, often with mood reactivity)
    • Treatment-Resistant Depression (TRD)
    • Anxiety Disorders: Panic disorder, Social phobia
    • Parkinson's Disease (adjunctive with L-DOPA; MAO-B specific: Selegiline, Rasagiline)
  • Pharmacokinetics (PK):
    • Oral absorption: Generally good.
    • Metabolism: Hepatic; e.g., Phenelzine via acetylation (genetic variability).
    • Duration: Irreversible MAOIs have a long duration; enzyme regeneration takes ~2 weeks (crucial for washout).

      ⭐ MAOIs are particularly effective for atypical depression characterized by hypersomnia, hyperphagia, leaden paralysis, and rejection sensitivity.

MAOIs: Adverse Effects & CIs - Danger Zone

  • Common Side Effects:
    • Postural hypotension (most common)
    • Weight gain
    • Sexual dysfunction
    • Insomnia, edema
    • Anticholinergic effects (less common)
  • ⚠️ Hypertensive Crisis ('Cheese Reaction'):
    • Interaction with tyramine-rich foods (aged cheese, cured meats, red wine).
    • Symptoms: Severe headache, hypertension, tachycardia.

    ⭐ The 'Cheese Reaction' is a medical emergency requiring immediate BP management, often with phentolamine.

  • ⚠️ Serotonin Syndrome:
    • Risk with serotonergic agents (SSRIs, triptans).
    • Symptoms: Hyperthermia, muscle rigidity, myoclonus, autonomic instability, mental status changes.
  • Contraindications:
    • Pheochromocytoma
    • Severe liver disease
    • Significant cardiovascular disease (CHF, recent MI)
    • Concomitant use of: sympathomimetics, other MAOIs, TCAs, SSRIs, SNRIs, meperidine, dextromethorphan.

Serotonin Syndrome Symptoms, Causes, and Treatment

MAOIs: Drug Interactions - Mixer Mayhem

  • Food (Tyramine "Cheese Reaction"):
    • Avoid: Aged cheese, cured/fermented meats, red wine, beer, soy.
    • Risk: Hypertensive crisis.
  • Drug Interactions (Potentially Fatal):
    • Serotonin Syndrome: SSRIs, SNRIs, TCAs, pethidine, dextromethorphan.
    • Hypertensive Crisis: Sympathomimetics (e.g., pseudoephedrine, amphetamines).
  • Washout Period:
    • General: 2 weeks before/after antidepressants.
    • Fluoxetine: 5 weeks (long half-life).

⭐ A washout period of at least 14 days is crucial when switching to/from MAOIs to prevent serious interactions.

High‑Yield Points - ⚡ Biggest Takeaways

  • Irreversibly inhibit MAO-A & MAO-B, ↑ levels of serotonin, norepinephrine, dopamine.
  • Used for atypical depression and resistant depression; examples: Phenelzine, Tranylcypromine.
  • Hypertensive crisis ("cheese reaction") with tyramine-rich foods (aged cheese, red wine) is a critical adverse effect.
  • Risk of Serotonin Syndrome with SSRIs, TCAs, pethidine; requires a 2-week washout period (5 weeks for fluoxetine).
  • Moclobemide (RIMA) is reversible, with lower risk of cheese reaction. Selegiline is MAO-B selective for Parkinson's disease at low doses.

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