MAO Inhibitors

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 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.

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.

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.