19/10/2025
🔆 Digoxin Toxicity
A potentially life-threatening complication of digoxin therapy due to its narrow therapeutic index, accumulation, or drug interactions.
📍 Cause / Pathophysiology:
• Mechanism of action (therapeutic):
– Digoxin inhibits the Na⁺/K⁺-ATPase pump in cardiac myocytes → ↑ intracellular Na⁺ → ↓ Na⁺/Ca²⁺ exchanger activity → ↑ intracellular Ca²⁺ → ↑ myocardial contractility (positive inotropy).
– In the AV node, digoxin increases vagal tone → slows conduction and prolongs refractory period → negative chronotropy.
• Toxicity mechanism:
– Excess intracellular Ca²⁺ leads to delayed afterdepolarizations (DADs) → ectopy and arrhythmias.
– Enhanced vagal tone + direct myocardial irritability → bradyarrhythmias, AV block, or ventricular tachyarrhythmias.
• Predisposing factors: Renal failure, hypokalemia, hypomagnesemia, hypercalcemia, drug interactions (e.g., amiodarone, verapamil, macrolides).
⌛ Epidemiology:
• Narrow therapeutic window (therapeutic serum level: 0.5–2 ng/mL).
• More common in elderly patients, especially women, and those with renal impairment.
• Mortality remains significant in severe overdose without prompt recognition.
📈 Clinical Features:
• Cardiac: Any arrhythmia is possible! Classically: PVCs, atrial tachycardia with block, AV block, ventricular bigeminy, bidirectional VT.
• GI: Anorexia, nausea, vomiting, abdominal pain (often earliest symptoms).
• CNS/Neuro: Confusion, weakness, delirium, dizziness, seizures.
• Visual disturbances: Blurred vision, xanthopsia (“yellow-green halos around lights”).
📚 Investigations / Diagnosis:
• ECG:
– Scooped “hockey stick” ST depression (digoxin effect—not toxicity per se).
– Arrhythmias: atrial tachycardia with AV block, PVCs, bidirectional VT.
• Serum digoxin level: Helpful but correlation with clinical toxicity is imperfect.
• Electrolytes: Look for hypokalemia, hypomagnesemia, hypercalcemia.
• Renal function: Assess for impaired clearance.
🚨 Clinical Importance:
• Digoxin is one of the most common drugs tested in exams due to its paradoxical dual action:
– Heart failure: Used for positive inotropy to improve contractility.
– Atrial fibrillation: Used for rate control by vagal stimulation and AV nodal slowing.
• This dual action explains its utility but also why toxicity manifests with arrhythmias spanning brady- to tachyarrhythmias.
• Untreated severe toxicity → high mortality.
💊 Treatment / Management:
1. Immediate supportive care: ABCs, IV access, continuous cardiac monitoring.
2. Discontinue digoxin and any interacting medications.
3. Correct electrolytes:
– Hypokalemia and hypomagnesemia worsen toxicity.
– Avoid calcium (“stone heart” risk).
4. Antiarrhythmics:
– Atropine for bradyarrhythmias/AV block.
– Lidocaine or phenytoin for ventricular arrhythmias (avoid class IA/IC and amiodarone).
5. Definitive treatment:
– Digoxin-specific antibody fragments (Digibind/DigiFab): Indicated for life-threatening arrhythmias, severe hyperkalemia, or hemodynamic instability.
6. Hemodialysis is NOT useful (digoxin is tissue-bound, large Vd).
📊 Key Facts (High-Yield):
• Therapeutic window is very narrow.
• Earliest signs: GI upset → neuro/visual → cardiac arrhythmias (most lethal).
• Arrhythmias: atrial tachycardia with AV block, bidirectional VT are classic.
• Treatment: supportive, correct electrolytes, Digibind for severe cases.
• Dialysis is ineffective.
📝 Answer to the Question (High-Yield for Exams):
How does digoxin work in both HF and AF despite seeming contradictory?
• In Heart Failure: Digoxin’s inhibition of Na⁺/K⁺-ATPase increases intracellular Ca²⁺ → stronger myocardial contraction (positive inotropy) → improved cardiac output.
• In Atrial Fibrillation: Digoxin enhances parasympathetic (vagal) tone → slows AV nodal conduction and increases refractory period → better ventricular rate control.
👉 Thus, in HF it strengthens contraction, while in AF it slows conduction—different mechanisms in different tissues, not a contradiction.
