Anaesthesia: Tricyclic antidepressant poisoning

Which of the following is NOT a recognised cause of the toxic effects of tricyclic

antidepressant drugs taken in overdose?

a) Inhibition of noradrenaline reuptake at nerve terminals

b) A myocardial membrane stabilising effect

c) An anticholinergic action

d) Indirect activation of GABAA receptors

e) Direct alpha adrenergic action

Answer: d

Tricyclic antidepressant drugs are among the most commonly ingested substances in

self-poisoning along with benzodiazepines, paracetamol and alcohol. They are rapidly

absorbed from the GI tract, are highly protein bound, have a large volume of distribution

and therefore have a long elimination half-life. The toxic effects are mediated in

four main ways, direct alpha adrenergic blockade, an anticholinergic action, a membrane

stabilising effect on the myocardium and inhibition of noradrenaline reuptake at

nerve terminals. The clinical features of overdose may be divided into effects on the

cardiovascular system, central nervous system (mainly sedative but also proconvulsant)

and anticholinergic effects. The latter effects are common and include

pyrexia, urinary retention, absent bowel sounds and dilated pupils. Sinus tachycardia

and hypotension are the commonest cardiovascular effects but the major toxic effect is

related to the slowing of depolarisation of the cardiac action potential by sodium

current inhibition. Treatment following overdose is, in the main, supportive. Specific

treatments include alkalinisation with intravenous sodium bicarbonate. This works by

reducing the pharmacologically active unbound proportion of the drug by raising pH.

Anti-arrhythmic treatment should be avoided where possible but there may be a role

for magnesium in the treatment of ventricular arrhythmias. Tricyclic-specific antibody

fragments have been developed but their use is limited by cost and the potential renal

toxicity due to the large dose required.

Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg

Med J 2001; 18(4) 236–41.

Anaesthesia