Generic Name

Digoxin

Mechanism

Digoxin exerts its effects primarily through inhibition of the Na⁺/K⁺‑ATPase pump in cardiac myocytes. The key downstream consequences are:
• Increased intracellular Na⁺ → reversal of the Na⁺/Ca²⁺ exchange → enhanced intracellular Ca²⁺ → stronger cardiac contractility (positive inotropy).
• Improved atrial contractility, preload, and stroke volume → reduced pulmonary congestion.
• Vagal influence on the atrioventricular node → slowed conduction and decreased ventricular rate in atrial fibrillation/flutter.
• Reduction of sympathetic nervous system activity → overall decrease in heart rate and myocardial oxygen demand.

These combined actions provide both hemodynamic and rhythm‑control benefits in heart‑failure and atrial arrhythmias.

Pharmacokinetics

• Absorption: 60–80 % oral bioavailability; best on an empty stomach; the presence of food or antacids can delay absorption.
• Distribution: Large volume (10–13 L/kg); significant protein binding (~50 %); lipophilic; can cross the placenta.
• Metabolism: Minimal hepatic metabolism; primarily unchanged drug.
• Excretion: 60–70 % renal (glomerular filtration and active secretion). Half‑life:
• Normal renal function: 36–48 h.
• Mild CKD (CrCl 50–80 mL/min): 36–84 h.
• Severe CKD (CrCl < 30 mL/min): 110–300 h.
• Drug interactions:
• Digoxin-binding drugs (cimetidine, ketoconazole) ↑ levels.
• Potassium‑cautious drugs (digitalis‑sensitive β‑blockers, lidocaine) ↑ toxicity risk.

Indications

Digoxin is indicated for:
• Atrial fibrillation or flutter with uncontrolled ventricular response (> 90 bpm) in the presence of heart failure or when β‑blockers are contraindicated.
• Systolic heart failure (NYHA classes II–III) as adjunctive therapy to reduce hospitalization and improve functional state.
• Ventricular arrhythmias in selected patients (e.g., idiopathic ventricular tachycardia) where antiarrhythmic drugs are less effective.

Contraindications

• Contraindications
• Severe bradyarrhythmias (HR  II°.
• Acute myocardial infarction (unless definitive reperfusion achieved > 12 h).
• Digitalis hypersensitivity or anaphylaxis.
• Hyperkalemia (K⁺ > 5.5 mmol/L) – risk of digitalis toxicity escalates rapidly.
• Warnings
• Renal impairment – dose reductions required; monitor trough levels.
• Electrolyte disturbances – hypokalemia and hypomagnesemia increase toxicity; hypocalcemia can potentiate arrhythmias.
• Drug interactions – caution with anticholinergics, calcium channel blockers, and inhaled β₂‑agonists (e.g., albuterol).

Dosing

• Administration: PO daily; for IV initiation, use a loading dose of 0.25 mg daily × 4–5 days (not in heart failure) then taper. Avoid bolus administration unless cardioversion is required.

Adverse Effects

• Common (≤ 5 %)
• Nausea, vomiting, anorexia
• Headache, dizziness
• Fatigue
• Serious (> 5 % or life‑threatening)
• Arrhythmias: ventricular ectopy, torsades de pointes, ventricular tachycardia
• AV block: 2° or 3° conduction delays
• Bradycardia (< 50 bpm) leading to syncope
• Visual disturbances: yellow, blurred vision; “halo” around light
• Neurologic: confusion, delirium, visual hallucinations

Monitoring

• Serum digoxin concentration: trough (predose) 0.5–2.0 ng/mL standard; lower targets (0.5–1.2 ng/mL) in CKD.
• Electrolytes: K⁺, Mg²⁺, Ca²⁺ – correct hypokalemia and hypomagnesemia before and during therapy.
• Renal function: serum creatinine, eGFR; repeat every 2–4 weeks until stabilization.
• Cardiac rhythm: ECG for QRS duration, QTc interval, heart rate; monitor for new arrhythmias.
• Toxicity signs: visual changes, nausea, vomiting, confusion.
• Therapeutic compliance: patient education on dosing interval and food interactions.

Clinical Pearls

• Start low, go slow: Even a single tablet can lead to profound toxicity in patients with impaired renal function or electrolyte imbalance.
• Potassium is a digitalis gatekeeper: Correct hypokalemia before initiation; avoid hyperkalemia, which can precipitate ventricular arrhythmias.
• Avoid grapefruit juice: It suppresses CYP450 enzymes and can increase digoxin exposure.
• Monitor the patient’s weight: In heart failure, fluid shifts can change volume distribution and therapeutic levels.
• Adwernberg note: In digoxin toxicity, give digoxin‑specific antibody fragments (digoxin‑Fab) in severe cases; consider supportive care for arrhythmias.
• Educate patients on “visual holo‑encephalopathy”: This classic sign often precedes full‑blown toxicity and prompts immediate re‑evaluation of drugs and electrolytes.

--
• *These concise data are intended for medical professionals and students and should complement clinical judgment through peer‑reviewed guidelines.*