2007 Second Sitting Paper 1 Question 3

2007-2-3 Describe the physiological effects and principals of management of

tricyclic antidepressant 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 GABAb 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

2007 Second Sitting Paper 1 Question 3

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