Tricyclic antidepressant overdose

• What are tricyclic antidepressants used to manage now?

  Neuropathic pain and migraine prophylaxis.
• Give an example of a tricyclic antidepressant

  Amitriptyline
• What are the two main mechanisms of action of tricyclic antidepressants?

  1. Re-uptake inhibition of serotonin and noradrenaline
  2. Postsynaptic receptor antagonism of H1, A1-adrenoreceptors and acetylcholine receptors
• Which 2 neurotransmitted are continually activated by TCAs and what are the related clinical manifestations?

  Serotonin - nausea, GI upset, sexual dysfunction

  Noradrenaline - Tachycardia, tremors
• Which 3 receptors are antagonised by TCAs and what are the related clinical manifestations?

  1. H1 receptor - antihistamine - sedation and weight gain
  2. Acetylcholine receptors - anticholinergic - dry mouth, blurred vision, confusion, constipation, tachycardia, urinary retention
  3. A1-adrenoreceptors - alpha-1-adrenergic - postural hypotension, drowsiness, dizziness
• Which channel is blocked by TCAs and what are the related clinical manifestations?

  Sodium channels in myocardial cells - cardiac arrhythmias, convulsions, coma
• Do TCAs have a broad or narrow therapeutic window?

  Narrow
• How long after ingestion do the clinical manifestations of TCAs become apparent?

  6 hours
• What would you likely see on ECG in TCA overdose?

  1. Widened QRS
  2. Prolonged QTc which could lead to VT or VF
• What is a major risk of TCA overdose?

  Serotonin syndrome
• Give the 3 hallmarks of Serotonin syndrome

  Altered mental state

  Neuromuscular hyperactivity

  Autonomic hyperactivity
• Give 2 examples of neuromuscular hyperactivity in serotonin syndrome

  Myoclonus

  Hyperreflexia
• Give 3 examples of autonomic activity in serotonin syndrome

  Hypertension

  Tachycardia

  Diaphoresis
• In severe cases of serotonin syndrome, what are a couple of clinical manifestations?

  Muscle rigidity and hyperthermia
• What may you see on a blood gas in TCA overdose? And how would you treat it?

  Mixed acidosis

  Sodium bicarbonate
• How do you manage TCA overdose?

  Supportive management as there is no antidote. You can give activated charcoal if presenting within 1 hour of ingestion, sodium bicarbonate for acidosis and arrhythmias, benzodiazepines for seizures and cooling measures for hyperpyrexia.