Tricyclic anti-depressants

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Updated June 2006

Pharmacology

Generally high protein binding (85-95%)
- pH dependent, increased by alkalosis and decreased by acidosis
Large volume of distribution (10-20 L/kg)
Elimination half life ranges from 10-20 hours
Anticholinergic properties of tricyclic antidepressants ⇒ delayed absorption
CNS and CVS toxicity
- CNS effects due to anticholinergic effects and inhibition of neural re-uptake of norepinephrine and/or serotonin
- CVS effects due to:
  - anticholinergic effects
  - inhibition of neural re-uptake of norepinephrine and/or serotonin
  - peripheral alpha blockade
  - sodium channel blockade ⇒membrane depressant effects

Clinical features

Toxicity is expected within 6 hours after ingestion

"Hot as a hare, dry as a bone, red as a beet, mad as a hatter"

ECG at 4-6 h can be used to predict severity:
- QRS <0.1 sec, no significant toxicity
- QRS of 0.1 sec or more indicates risk of seizures
- QRS >0.16 sec associated with ventricular arrhythmias
- amoxapine is an exception to the rule. Status epilepticus occurs in the setting of normal QRS duration
- absence of QRS prolongation not a sensitive predictor of low risk of toxicity
duration of ECG monitoring is arbitrary. Monitoring for 12h after normalization of ECG suggested

gastric lavage (NB tricyclics cause gastroparesis)
activated charcoal (but beware vomiting and aspiration). No role for multiple doses, particularly because anticholinergic induced ileus increases risk of causing intestinal obstruction
in severe cases and in cases with prolonged QRS aim for alkalosis (by hyperventilation and/or IV bicarbonate) to increase protein binding. Sodium bicarbonate may also have membrane stabilizing effects via a Na mechanism. Bicarbonate drug of choice for all CVS haemodynamic abnormalities
indications for sodium bicarbonate (dose – 1-2 mEq/kg, repeated boluses titrated to clinical effects):
- QRS prolongation (even in the absence of acidosis)
- malignant arrhythmia
- hypotension
- metabolic acidosis
lignocaine drug of choice for refractory ventricular arrhythmias. Anecdotal reports supporting use of phenytoin but no longer recommended. Other anti-arrhythmics contraindicated (Class IA, IC), potentially lethal (Class II), and of unproven efficacy.
benzodiazepines for seizures. Phenytoin for refractory cases
ineffective treatment includes calcium chloride, as may worsen both CVS and CNS toxicity. Physiostigmine can provoke malignant arrhythmia.
haemodialysis and haemoperfusion are of no benefits as the kinetic properties of TCA do not favor their elimination