Background
- Largely superseded by newer antidepressants
- Classic TCAs (e.g. Imipramine, Amitriptyline) have greatest toxicity
- Rapidly absorbed from GIT
- Peak plasma concentration in 2 to 8 hours
- Delayed gastric emptying in overdose (anti-muscarinic effect) prolongs the time to peak plasma concentration
Pharmacokinetics
- TCAs inhibit:
- Pre-synaptic neurotransmitter uptake
- Cholinergic receptors
- Cardiac fast Sodium Channels
- Alpha-1 adrenergic receptors
- Metabolised by liver
- Half life is from 7 to 8 hours depending on the agent
- 70% excreted by the kidney
- Acidosis increases the amount of active drug in plasma by decreasing protein binding
Clinical effects
Cardiovascular
- Tachycardia
- Hypotension (cause of mortality)
- Arrhythmia-SVT/VT
- VT in 4% of cases approx)
CNS
- Ataxia
- Nystagmus
- Sedation, coma
- Seizures (about 5% of cases)
- Amblyopia
Anticholinergic
- Mydriasis
- Dry mouth
- Absent bowel sounds
- Urinary retention
- Agitation
ECG changes
- Tall R in avR
- RAD
- PR prolongation
- QRS complex > 100 msec (26 % risk of seizure)
- QRS complex > 160 msec (50 % risk of ventricular arrhythmia)
- Deep S in 1, avL
Diagnosis
Based on the history, clinical signs and ECG changes as above. Additional Invx include:
- ABG's
- Paracetamol/salicylate levels
- Urine test for TCAs ( beware false positives)
- Lab testing for TCAs not indicated
- Consider concomitant drug / alcohol ingestion
Management
- Secure Airway, Breathing, Circulation
- Check blood glucose if decreased level of consciousness/seizure
- Consider activated charcoal (50g) if more than 4mg/Kg have been ingested within 1 hour.
- There is no convincing evidence for the use of charcoal [BestBets] or gastric lavage [BestBets]
- Treat hypotension with normal saline initially.
- Consider Noradrenaline if vasopressor required
- In patients with dysrhythmias following TCAD overdose, treatment should include alkalinisation to a pH of 7.55 [BestBets]
- Use 50 - 100 mmol of Sodium Bicarbonate ( 50 - 100 mls of 8.4% Na Bic) as "IV push"
- Aim for pH of 7.45-7.5. Consider infusion
- Avoid antiarrhythmics
- Control seizures with IV Lorazepam
- Consider RSI with Thiopentone (with anaesthetic back up) for status epilepticus
- Avoid phenytoin
- There is not enough evidence to support the routine use of glucagon in the treatment of TCAD overdose [BestBets]
Disposition
- Admit
- Consider ITU for significant poisoning