Neuropharmacology — TCA Overdose

TCA (e.g. amitryptilline and imipramine)

• Toxic dose of amitrytilline
  • >10mg/kg

Mechanism of Action

• Act via central inhibition of noradrenaline reuptake (via inhibition of NET) and serotonin reuptake (via inhibition of SERT) but not dopamine transfer
• Also Na channel blockade
• Agonist at α₁ and to a lesser extent α₂ receptors
• Decreases sensitivity of muscarinic receptors
• Antagonist at H₁ receptors
• Downregulates expression of GABA_b and NMDA receptors

Physiological effects

CNS

• Agitation
• Seizures
• Coma and respiratory depression

CVS

• Sinus tachycardia
• Hypertension
• Na channel blockade
  • Prolonged QT
  • Widened QRS
  • RBBB

Anticholinergic

• Dry mouth
• Dry, warm skin
• Urinary retention
• Tachycardia

Management

• Maintain airway patency
• Support ventilation
• Support organ perfusion
  • Fluids, vasopressors as needed
• ABGs, blood tests, ECG
• Activated charcoal early
  • However TCA rapidly absorbed
• Sodium bicarbonate
  • 100mmol boluses
  • Target pH >7.45
  • Alkalinization promotes protein binding and limits free fraction of drug
  • Alkalinization promotes dissociation of TCA and Na channel
• Consider intralipid, hypertonic saline for refractory cases