Digoxin Therapy Notes

Comprehensive Notes on Digoxin Therapy 1. Introduction Digoxin is a cardiac glycoside derived from the foxglove plant (Digitalis lanata). It has been used for centuries in the management of heart diseases, particularly for its ability to increase myocardial contractility and regulate heart rate. Clinically, digoxin remains important for treating heart failure and atrial arrhythmias. 2. Pharmacology of Digoxin Mechanism of Action • Inotropic Effect: Increases the force of myocardial contraction by inhibiting the Na+/K+ ATPase pump, leading to increased intracellular calcium. • Chronotropic Effect: Reduces heart rate via enhanced vagal tone. • Dromotropic Effect: Slows conduction through the atrioventricular (AV) node. Pharmacokinetics • Absorption: Well absorbed orally (approx. 70-80%). Peak plasma concentrations occur 2-6 hours after ingestion. • Distribution: Widely distributed; volume of distribution is ~7 L/kg. Crosses the placenta. • Metabolism: Minimal hepatic metabolism; mostly excreted unchanged by kidneys. • Elimination: Half-life approximately 36-48 hours in patients with normal renal function. Pharmacodynamics • Dose-response relationship is narrow; small changes in plasma concentration may lead to therapeutic failure or toxicity. 3. Indications • Heart Failure (HF): Especially systolic HF to improve symptoms, exercise tolerance, and quality of life. • Atrial Fibrillation (AF): Rate control by slowing AV conduction. • Atrial Flutter: Similar mechanism as AF. • Off-label: Certain supraventricular tachyarrhythmias and pediatric congenital heart disease cases. 4. Contraindications Absolute • Ventricular fibrillation 1 • Hypersensitivity to digoxin Relative • AV block without pacemaker • Severe bradycardia • Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia) 5. Dosage and Administration Adult Dosing • Loading dose: 0.5–1 mg orally in divided doses over 24 hours. • Maintenance dose: 0.125–0.25 mg daily, adjusted based on response and serum levels. Pediatric Dosing • Based on weight; commonly 10–15 mcg/kg/day in divided doses. Renal Adjustment • Dose reductions are essential in renal impairment. Routes • Oral (tablets, elixir) • Intravenous (IV) Loading vs Maintenance • Loading doses achieve therapeutic levels quickly; maintenance doses maintain them. 6. Monitoring Parameters • Serum digoxin levels: Therapeutic range 0.5–2 ng/mL. • Renal function: Creatinine clearance, BUN, serum creatinine. • Electrolytes: Potassium, magnesium, calcium. • ECG monitoring: For arrhythmias or conduction abnormalities. 7. Adverse Effects Cardiac • Arrhythmias (PVCs, bradycardia, AV block, ventricular tachycardia/fibrillation) 2 Non-cardiac • Gastrointestinal: nausea, vomiting, diarrhea • CNS: fatigue, confusion, visual disturbances (yellow-green vision, halos) Risk Factors for Toxicity • Advanced age, renal impairment, hypokalemia, drug interactions 8. Drug Interactions • Pharmacokinetic: Amiodarone, verapamil, quinidine (increase digoxin levels) • Pharmacodynamic: Beta-blockers, calcium channel blockers (may enhance bradycardia) 9. Digoxin Toxicity Signs and Symptoms • Nausea, vomiting, anorexia • Fatigue, confusion, dizziness • Visual disturbances • Arrhythmias (various types) ECG Changes • AV block, atrial tachycardia with block, PVCs, ventricular tachycardia Management • Discontinue digoxin • Correct electrolyte abnormalities • Administer digoxin-specific antibody fragments if severe 10. Special Populations • Elderly: More sensitive; start at lower doses • Pediatrics: Careful dosing based on weight and monitoring • Pregnancy & Lactation: Crosses placenta; use only if benefit outweighs risk • Renal impairment: Dose reduction essential 11. Patient Education • Importance of adherence • Recognizing toxicity symptoms • Avoiding high-potassium foods if using potassium supplements • Regular monitoring and follow-up 3 12. Recent Advances • Optimized dosing algorithms • Combination therapy with beta-blockers and ACE inhibitors • Use of digital monitoring and telehealth for adherence and toxicity detection 13. Case Studies • Heart Failure: 68-year-old male, reduced EF, digoxin improves symptoms and exercise tolerance. • Atrial Fibrillation: 72-year-old female, rapid AF, digoxin for rate control. • Toxicity: 80-year-old female, renal impairment, develops nausea, arrhythmia, treated with antibody fragments. 14. Summary & Key Points • Digoxin is a cardiac glycoside with narrow therapeutic index. • Used primarily for HF and AF. • Requires careful dosing, monitoring, and patient education. • Toxicity can be life-threatening but manageable with early recognition. 15. References • Katzung BG. Basic and Clinical Pharmacology, 15th Edition. • Rang HP, Ritter JM. Rang & Dale's Pharmacology, 9th Edition. • Gheorghiade M, et al. Digoxin in heart failure and atrial fibrillation: Clinical use and controversies. Lancet, 2013. • UpToDate: Digoxin: Drug information and clinical guidelines. 4