PharmacologyTier 1Medical Sciences concept

TCA overdose - sodium channel blockade and ECG predictors (QRS widening)

Core concept

TCAs block cardiac fast Na channels (open-state, use-dependent) -> slowed phase 0 -> QRS widening
- Also block K channels (QT), muscarinic (antimuscarinic toxidrome), alpha-1 (hypotension), H1 (sedation), GABA-A (seizures) and monoamine reuptake
QRS duration is the single best predictor of major toxicity - not the dose, not the level, not the tachycardia
- Right-axis shift of the terminal 40 ms -> terminal R wave in aVR
Acidosis and hyperkalaemia worsen Na channel blockade; alkalosis and Na loading reverse it

QRS	Risk
<100 ms	Major toxicity unlikely
>100 ms	Seizure risk rises
>160 ms	Ventricular arrhythmia risk rises

Classic ECG: sinus tachycardia + wide QRS + terminal R in aVR (R >3 mm) + R/S ratio in aVR >0.7
- First-degree AV block, P waves buried in the T wave
- Rightward terminal axis -> deep S in I and aVL
Sodium bicarbonate 1-2 mmol/kg IV bolus, repeat to QRS narrowing
- Two mechanisms: inc extracellular Na (raises the electrochemical gradient) and alkalinisation to pH 7.45-7.55 (dec drug binding to the channel)
Hyperventilation alone gives alkalosis without the sodium load - inferior
Seizures -> benzodiazepines; phenytoin is contraindicated (also a Na channel blocker)
Hypotension -> fluids, bicarbonate, then noradrenaline (alpha-1 agonist counters alpha-1 blockade)
Avoid flumazenil, physostigmine, class Ia/Ic antiarrhythmics
Large Vd (~20 L/kg) and high protein binding -> not dialysable; activated charcoal within 1-2 h if airway secure
Intralipid and VA-ECMO for refractory cardiac arrest

A wide-complex tachycardia in an overdose is TCA toxicity until proven otherwise - treat with bicarbonate, not amiodarone
Serial ECGs are the monitoring tool; a normal ECG at 6 h with no anticholinergic signs allows discharge
Antimuscarinic features (dry, hot, dilated, delirious, urinary retention, absent bowel sounds) delay gastric emptying -> late deterioration
Same sodium channel mechanism, same treatment: amitriptyline, dosulepin, propranolol massive overdose, flecainide, quinine, carbamazepine, cocaine, local anaesthetics, hydroxychloroquine
Dosulepin is the most lethal of the TCAs (early seizures and arrhythmia)

Toxidrome recognition - anticholinergic
Drug-induced long QT syndrome; Vaughan Williams classification (class I sodium blockade)
Comparative anticholinergic potency of drugs
Dialysability of drugs in overdose - high Vd, high protein binding
Specific antidotes in poisoning; serotonin syndrome

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