Digoxin

 Class

  • Cardiac glycoside
  • Positive inotrope, negative chronotrope

Mechanism of Action

  • Inhibits Na⁺/K⁺-ATPase → ↑ intracellular Na⁺ → ↓ Na⁺/Ca²⁺ exchange → ↑ intracellular Ca²⁺ → stronger myocardial contraction (positive inotropy).
  • Enhances vagal tone → slows AV nodal conduction (negative chronotropy), useful in atrial fibrillation/flutter.

Indications

  • Heart failure (reduced EF) – improves symptoms, exercise tolerance, reduces hospitalizations (but no mortality benefit).
  • Atrial fibrillation/flutter – rate control, especially in patients with hypotension or HF (not first-line in stable patients; used if β-blockers or non-DHP CCBs are contraindicated).

Dosing

  • Adult oral dose: usually 0.125–0.25 mg once daily.
  • Elderly, renal impairment, or low lean body mass → start at lower dose (0.125 mg or every other day).
  • IV dose available (loading possible in AF).

Pharmacokinetics

  • Renally cleared (≈ 70% unchanged).
  • Half-life: ~36–48 hrs (longer in renal dysfunction).
  • Volume of distribution: large (binds tissue, esp. heart, skeletal muscle).

Therapeutic Drug Monitoring (TDM)

Narrow therapeutic index.

Goal serum concentration:

  • HF: 0.5–0.9 ng/mL
  • AF: up to 2 ng/mL may be used

Draw levels ≥6 hrs post-dose (distribution phase complete).

Toxicity & Adverse Effects

  • Cardiac: bradycardia, AV block, ventricular arrhythmias.
  • GI: anorexia, nausea, vomiting (early signs).
  • CNS/Visual: confusion, delirium, xanthopsia (yellow-green vision, halos).
  • Toxicity risk ↑ with: renal dysfunction, hypokalemia, hypomagnesemia, hypercalcemia, drug interactions.

Key Interactions

  • Increase digoxin levels: amiodarone, verapamil, diltiazem, dronedarone, clarithromycin, cyclosporine, itraconazole, quinidine.
  • Electrolytes: loop/thiazide diuretics (↓K⁺/Mg²⁺), ACEI/ARB/spironolactone (↑K⁺).
  • P-gp substrate: inhibitors raise levels.

Antidote

  • Digoxin immune Fab (DigiFab) for life-threatening arrhythmias, hyperkalemia, or massive overdose.

As a clinical pharmacist, main roles are:

  • Ensuring appropriate indication and dosing (esp. renal adjustment).
  • Monitoring serum levels, renal function, and electrolytes.
  • Screening for drug–drug interactions.
  • Educating on symptoms of toxicity.
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