tricyclic antidepressants (tca)

The "Dirty Drug"

A “dirty drug” with multiple receptor effects. Classic triad: Anticholinergic Toxidrome + Hypotension + Wide QRS. Common agents: Amitriptyline, Nortriptyline.

mechanism

The “Dirty Drug” blockade profile:

  • Na-channel blockade: QRS widening, arrhythmias.
  • -blockade: Hypotension (vasodilation).
  • Anticholinergic: Tachycardia, delirium, hyperthermia.
  • GABA antagonism: Seizures.
  • Antihistamine: Sedation.
  • Reuptake Inhibition: Serotonin/Norepinephrine effects.

diagnosis

  • Triad: History of Ingestion + Anticholinergic Toxidrome + ECG Findings.
  • Urine Tox: Not reliable for diagnosis.
    • False Positives: Diphenhydramine (Benadryl), Quetiapine, Carbamazepine, Cyclobenzaprine.

clinical features

cardiovascular

  • Sinus Tachycardia: Most common finding.
  • QRS Widening:
    • : 26% risk of seizures.
    • : 50% risk of ventricular arrhythmias (VT/VF).
  • Terminal R wave in aVR: Specific sign of Na-channel blockade.

cns

  • LOC, Agitation, Psychosis, Delirium.
  • Seizures: Can be refractory.

management

1. stabilisation & airway

  • Intubation: Early for GCS < 8 or seizures.
  • Hyperventilation: If intubated, maintain pH 7.50–7.55 (alkalaemia reduces drug toxicity).

2. decontamination

  • Activated Charcoal: 1g/kg (max 50g).
    • Indication: Ingestion within 1–2 hours.
    • Contraindication: Unprotected airway (risk of aspiration with rapid LOC), ileus.
  • Enhanced Elimination: No role (drug is highly protein bound and lipophilic).

3. symptom specific management

a. hypotension

  1. IV Fluids: Bolus 10–20 mL/kg (Saline or Sodium Bicarbonate).
  2. Vasopressors: Norepinephrine (preferred) or Phenylephrine (Neo-Synephrine).
  3. Refractory: Consider Hypertonic Saline (100 mL 3% NaCl).

b. seizures

  1. Benzodiazepines: First line (Lorazepam/Diazepam).
  2. Propofol: Second line infusion.
  3. Barbiturates: Third line.

    contraindication: phenytoin Do NOT use Phenytoin. It blocks Na-channels and will enhance cardiotoxicity.

c. arrhythmias / qrs widening

Goal: Narrow the QRS and maintain perfusion.

  1. Sodium Bicarbonate (First Line):
    • Indication: QRS > 100 ms, Ventricular Arrhythmia, or Hypotension.
    • Bolus: 1–2 mEq/kg IV. Repeat until QRS narrows.
    • Maintenance: 150 mEq (3 amps) in 1L D5W at 250 mL/hr (roughly 2x maintenance).
    • Target: Serum pH 7.50–7.55. (Alkalaemia increases protein binding of TCA).
  2. Magnesium Sulfate: If Torsades/polymorphic VT.
  3. Lidocaine (Class IB): 1.5 mg/kg bolus. (Competitive binding may displace TCA).
  4. Lipid Emulsion: Rescue for unstable refractory arrest/shock.
  5. ECMO: V-A ECMO for refractory shock.

4. contraindications

  • Physostigmine: Strictly contraindicated (causes asystole).
  • Class IA (Procainamide) & IC (Flecainide): Worsen Na-channel blockade.
  • Class III (Amiodarone): QT prolongation risk.

exam pearl

A patient with “anticholinergic toxidrome” + wide QRS is TCA until proven otherwise.