Tricyclic Antidepressants

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Tricyclic Antidepressants - Mood Menders

  • Three-ring structure drugs.
  • MoA: Inhibit reuptake of Norepinephrine (NE) & Serotonin (5-HT).
  • Also block muscarinic (M1), histamine (H1), & α1-adrenergic receptors, leading to side effects.
  • Examples: Imipramine, Amitriptyline, Nortriptyline, Clomipramine.
  • Uses: Major depression, neuropathic pain, nocturnal enuresis (Imipramine).
  • Side Effects: Anticholinergic (dry mouth, blurred vision), sedation, weight gain (H1), postural hypotension (α1).
  • ⚠️ Toxicity: 📌 "Tri-C's": Coma, Convulsions, Cardiotoxicity.

    ⭐ Clomipramine is highly serotonin-selective; a key drug for Obsessive-Compulsive Disorder (OCD). Tricyclic Antidepressant Mechanism of Action

Tricyclic Antidepressants - Antidepressant Army

  • Mechanism: Block reuptake of Norepinephrine (NE) & Serotonin (5-HT).
  • Side effects: Anticholinergic (dry mouth, constipation), antihistaminic (sedation, weight gain), α1-block (orthostatic hypotension), cardiac toxicity (arrhythmias, QRS prolongation).
  • Classified by amine structure:
FeatureTertiary AminesSecondary Amines
ExamplesImipramine, Amitriptyline, Clomipramine, DoxepinNortriptyline, Desipramine, Protriptyline
Predominant Action↑ 5-HT > NE↑ NE > 5-HT
Side EffectsMore pronouncedLess pronounced

Tricyclic Antidepressants - Beyond Blues

  • Psychiatric Indications:
    • MDD (severe/SSRI-resistant).
    • Obsessive-Compulsive Disorder (OCD) - Clomipramine highly effective.
    • Panic Disorder, Generalized Anxiety Disorder (GAD).
    • Post-Traumatic Stress Disorder (PTSD).
    • ADHD (Desipramine, Nortriptyline).
  • Non-Psychiatric Applications:
    • Neuropathic pain: Diabetic neuropathy, postherpetic neuralgia (Amitriptyline).
    • Migraine prophylaxis (Amitriptyline).
    • Nocturnal enuresis in children >6 years (Imipramine).
    • Insomnia (low-dose Doxepin, Amitriptyline).
    • IBS (pain predominant).
    • Peptic Ulcer Disease (Doxepin - H2 blockade).

⭐ Imipramine is a TCA approved for childhood enuresis (bedwetting).

Tricyclic Antidepressants - Caution Crew

  • Adverse Effects (AEs): 📌 Mnemonic: "Tri-C's & A's"
    • Cardiotoxicity: Arrhythmias (QT prolongation), orthostatic hypotension. ECG: QRS >100ms in toxicity.
    • Convulsions: Lower seizure threshold (esp. Maprotiline).
    • Coma: In overdose.
    • Anticholinergic: Dry mouth, blurred vision, urinary retention, constipation. (Amitriptyline > Desipramine).
    • Antihistaminic (H1): Sedation, weight gain.
    • Anti-α1-adrenergic: Postural hypotension.
  • Contraindications (CIs):
    • Acute recovery post-MI, arrhythmias.
    • Narrow-angle glaucoma.
    • MAOI use (within 14 days).
  • Drug Interactions:
    • MAOIs, SSRIs: Serotonin syndrome.
    • CNS depressants: Additive sedation.
    • Warfarin: ↑ Anticoagulant effect.

ECG showing QRS prolongation in TCA toxicity

⭐ TCA overdose is highly lethal; QRS duration >100ms is a critical sign. Mainstay of treatment: Sodium Bicarbonate.

Tricyclic Antidepressants - Overdose Alert

  • 📌 3 C's of Toxicity: Coma, Convulsions, Cardiotoxicity.
  • Cardiotoxicity: Sinus tachycardia, ↑PR/QRS/QT intervals. QRS >100ms indicates severe toxicity; QRS >160ms predicts ventricular arrhythmias.
  • Anticholinergic effects: Mydriasis, dry mouth, urinary retention, ileus.
  • Hypotension: Due to α1-adrenergic blockade.

⭐ Sodium bicarbonate is the mainstay of treatment for TCA cardiotoxicity, aiming to narrow QRS and reverse hypotension by increasing extracellular sodium and pH.

High‑Yield Points - ⚡ Biggest Takeaways

  • TCAs inhibit norepinephrine (NE) and serotonin (5-HT) reuptake.
  • Adverse effects: anticholinergic symptoms, sedation (H1 blockade), orthostatic hypotension (α1 blockade).
  • Cardiotoxicity (arrhythmias, QT prolongation) is life-threatening, from Na+ channel blockade.
  • Sodium bicarbonate is key for managing TCA-induced cardiotoxicity.
  • Uses: Depression (second-line), neuropathic pain, migraine prophylaxis, enuresis (imipramine).
  • Risk of serotonin syndrome or hypertensive crisis with MAOIs.
  • Examples: Amitriptyline, Imipramine, Nortriptyline.

Practice Questions: Tricyclic Antidepressants

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A patient with nocturnal enuresis and depressive symptoms was started on an antidepressant. What is the drug?

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Flashcards: Tricyclic Antidepressants

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Main mechanism of antidepressant action is to change the neurotransmitter _____

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Main mechanism of antidepressant action is to change the neurotransmitter _____

receptor sensitivity

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