Digoxin
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Direct answer
Digoxin inhibits the sodium-potassium ATPase of cardiac myocytes, indirectly raising intracellular calcium and producing positive inotropy plus vagally mediated atrioventricular nodal slowing. Its two surviving indications are rate control in atrial fibrillation (especially with heart failure, where it adds gentle inotropy) and chronic heart failure as add-on therapy; it has a narrow therapeutic index (0.5–2 nanogram/mL), renal excretion, and a classic toxicity triad of gastrointestinal upset, visual disturbance (yellow-green halos, xanthopsia) and arrhythmias, treated by stopping the drug, correcting potassium, and giving digoxin-specific antibody fragments in severe cases.
What you must remember
- Half-life 36–48 hours; maintenance 0.125–0.25 mg daily; nearly all excreted unchanged by the kidney, so dose reduces in renal impairment and in the elderly.
- Toxicity is precipitated by hypokalaemia, hypomagnesaemia and hypercalcaemia — the reason diuretic-treated patients are the classic victims.
- Verapamil, amiodarone and quinidine all raise digoxin levels (halve the digoxin dose when amiodarone is started).
- Arrhythmia repertoire: paroxysmal atrial tachycardia with block, ventricular ectopics, bidirectional ventricular tachycardia (nearly pathognomonic), and almost any bradyarrhythmia.
- Digoxin is contraindicated in Wolff-Parkinson-White syndrome with atrial fibrillation — it accelerates conduction down the accessory pathway.
- In the DIG trial digoxin did not reduce mortality in heart failure but reduced hospitalisations; target trough in heart failure is lower (0.5–0.9 ng/mL).
- Acute massive overdose causes hyperkalaemia (potassium is driven out of cells), and the potassium level itself predicts severity.
- Digoxin-specific Fab antibody (Digibind) is indicated for life-threatening arrhythmia, potassium above 5.5 mmol/L in acute poisoning, or massive ingestion.
A typical exam case
A 78-year-old woman on digoxin 0.25 mg and furosemide for heart failure with atrial fibrillation presents with a week of anorexia, vomiting, and a pulse of 44 with occasional dropped beats; she mentions that her vision has a yellow-green tinge. Stepwise: first, suspect toxicity from the combination — loop diuretic losses of potassium and magnesium sensitise the myocardium, and her creatinine has drifted upward. Second, obtain an ECG and a digoxin level plus electrolytes; levels above 2 ng/mL support the diagnosis, but in chronic toxicity the correlation with symptoms is loose, and a normal level with convincing signs still deserves a pause. Third, treatment in order: stop digoxin, hold the diuretic, correct potassium and magnesium, and observe — most chronic toxicity needs nothing more. Fourth, escalate to Digibind only for ventricular arrhythmia, symptomatic bradycardia unresponsive to atropine, hyperkalaemia above 5.5, or an acute ingestion of a large quantity. Fifth, cardioversion during toxicity is dangerous — it can trigger refractory ventricular fibrillation — so chemical rate control and patience win. Sixth, before discharge, ask why she was on digoxin at all: with an estimated glomerular filtration rate of 30, her maintenance dose should have been halved. The case teaches the whole chapter in one bedside.
Where students slip
The recurring viva trap is digoxin plus verapamil or digoxin plus amiodarone in a stem about new bradycardia — the candidate reaches for a pacemaker when the answer is a drug interaction that doubles digoxin levels. The second trap is physiology: in acute digoxin poisoning potassium rises (Na-K ATPase poisoning), while chronic toxicity usually rides on hypokalaemia — students merge the two and lose the mark. Third, the examinable ECG finding of "reverse tick" ST depression and the symptom of xanthopsia are quoted precisely because they are specific; diarrhoea and confusion are not. Finally, remember that hypocalcaemia does not protect and hypercalcaemia (for example in malignancy) predisposes to toxicity, since digoxin and calcium share intracellular signalling at the sarcoplasmic reticulum.
Frequently asked questions
What is the mechanism of digoxin's positive inotropic action?
Inhibition of Na-K ATPase raises intracellular sodium, reducing sodium-calcium exchange so more calcium is retained within the myocyte, augmenting contractile force.
Which arrhythmia is nearly diagnostic of digoxin toxicity?
Bidirectional ventricular tachycardia, alternating QRS axis beat to beat; paroxysmal atrial tachycardia with block is the other classic.
When is digoxin-specific antibody indicated?
Life-threatening arrhythmia or hyperkalaemia above 5.5 mmol/L in acute poisoning, ingestion of more than 10 mg in adults, or haemodynamic instability — the critical use criteria every final-year student must recite.
Why must digoxin be avoided in Wolff-Parkinson-White syndrome?
It shortens the refractory period of the accessory pathway, so atrial fibrillation can be conducted extremely rapidly to the ventricles, causing ventricular fibrillation.
How do amiodarone and verapamil interact with digoxin?
Both reduce its renal and non-renal clearance (amiodarone also inhibits P-glycoprotein), roughly doubling levels — the digoxin dose should be halved when either is added.