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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Therapeutic range: 1.0–2.0 ng/mL (1.3–2.6 nmol/L). Toxicity can occur within range if hypokalaemia, hypomagnesaemia, or hypothyroidism present
- Mechanism: inhibits Na+/K+ ATPase → increased intracellular calcium → increased contractility but also increased automaticity and delayed conduction
- Classic toxicity features: nausea/vomiting, visual disturbance (yellow-green halos, xanthopsia), confusion, and virtually ANY arrhythmia
- ECG in therapeutic use: "reverse tick" ST depression (not a sign of toxicity), prolonged PR interval
- Severe toxicity (life-threatening arrhythmias, K+ >5.5): Digoxin-specific antibody fragments (Digibind/DigiFab)
Overview
Digoxin is a cardiac glycoside used for rate control in atrial fibrillation and as a positive inotrope in heart failure. It inhibits the Na+/K+ ATPase pump, increasing intracellular calcium and thus cardiac contractility. In toxicity, the excessive intracellular calcium causes increased automaticity (ectopic beats, tachyarrhythmias) and decreased AV conduction (bradyarrhythmias, heart block). This combination of enhanced automaticity WITH impaired conduction is the hallmark of digoxin toxicity and can produce virtually any arrhythmia. Toxicity is potentiated by hypokalaemia (competes for same binding site on Na+/K+ ATPase), hypomagnesaemia, hypercalcaemia, renal impairment (reduced clearance), and hypothyroidism.
Epidemiology
Digoxin toxicity occurs in approximately 2–5% of patients taking the drug chronically. Risk factors include renal impairment (digoxin is primarily renally excreted), older age, low body weight, electrolyte disturbances (especially hypokalaemia from diuretics), hypothyroidism, and drug interactions (amiodarone, verapamil, and macrolides all increase digoxin levels).
Clinical Features
Symptoms
Nausea, vomiting, and anorexia — often earliest symptoms
Visual disturbances: yellow-green halos around lights (xanthopsia), blurred vision
Confusion, drowsiness, disorientation (particularly in elderly)
Diarrhoea and abdominal pain
Palpitations (from arrhythmias)
Signs
Bradycardia (especially in AF — new regularisation of an irregular rhythm = complete heart block)
Any arrhythmia: AV block, ventricular ectopics (bigeminy), ventricular tachycardia, AF with slow ventricular rate
Bidirectional VT (alternating QRS axis) is almost pathognomonic of digoxin toxicity
Hypotension
Investigations
First-line
Serum digoxin levelTake at least 6 hours post-dose (earlier samples overestimate). Therapeutic 1.0–2.0 ng/mL. But toxicity can occur at therapeutic levels with hypokalaemia
U&Es (especially potassium and magnesium)Hypokalaemia POTENTIATES digoxin toxicity — correct urgently. Check magnesium also
ECGTherapeutic: "reverse tick" ST depression (does NOT indicate toxicity). Toxicity: any arrhythmia — heart block, VEs, bidirectional VT
Second-line
Renal functionDigoxin is renally excreted — reduced eGFR increases toxicity risk
Calcium and TFTsHypercalcaemia and hypothyroidism increase sensitivity to digoxin
Management
TOXBASE + BNF1
Mild toxicity (no life-threatening arrhythmias)
- STOP digoxin
- Correct hypokalaemia (target K+ 4.0–5.0 mmol/L) — IV KCl if needed, with cardiac monitoring
- Correct hypomagnesaemia (IV magnesium sulphate 2 g)
- Monitor ECG, recheck digoxin level at 6–12 hours
- Withhold and restart at lower dose once resolved
2
Severe toxicity (life-threatening arrhythmias, K+ >5.5 mmol/L)
- Digoxin-specific antibody fragments (Digibind or DigiFab) — the definitive antidote
- Dose based on estimated total body digoxin load or empiric dosing
- Rapidly binds free digoxin — renders it inactive
- Atropine 500 mcg IV for symptomatic bradycardia (first-line while awaiting Digibind)
- Do NOT use calcium IV for hyperkalaemia in digoxin toxicity (may worsen arrhythmias)
- Temporary pacing if complete heart block unresponsive to atropine
3
Prevention
- Regular monitoring of digoxin levels (especially after dose changes or new interacting drugs)
- Monitor renal function and potassium (particularly if on concurrent diuretics)
- Drugs that increase digoxin levels: amiodarone (halve digoxin dose), verapamil, macrolides, ciclosporin
Complications
- Fatal arrhythmias: VF, complete heart block, asystole
- Hyperkalaemia: In acute massive overdose (Na+/K+ ATPase inhibition releases intracellular K+)
UKMLA Exam Tips
- 1"Reverse tick" ST depression on ECG is a THERAPEUTIC effect of digoxin — NOT a sign of toxicity
- 2Hypokalaemia POTENTIATES digoxin toxicity — always check K+ (diuretics are a common culprit)
- 3Bidirectional VT = virtually pathognomonic of digoxin toxicity
- 4Regularisation of an irregular pulse in AF = complete heart block from digoxin toxicity
- 5Yellow-green visual halos (xanthopsia) are the classic visual symptom
- 6Digibind (digoxin-specific antibodies) is the antidote for life-threatening toxicity
- 7Do NOT give IV calcium for hyperkalaemia if digoxin toxicity is present — may cause fatal arrhythmia ("stone heart")
- 8Amiodarone doubles digoxin levels — HALVE the digoxin dose if starting amiodarone
practicetest your knowledge on digoxin toxicityApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — clinical pharmacology and beyond.
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