What oral medications increase cardiac contractility?

Oral Medications That Increase Cardiac Contractility

Digoxin is the primary oral medication that increases cardiac contractility by inhibiting the sodium-potassium ATPase pump in myocardial cells, producing a transient increase in intracellular calcium that enhances myocardial contractility. 1

Mechanism of Action of Digoxin

• Digoxin works by inhibiting the sodium-potassium ATPase pump, leading to increased intracellular sodium and subsequently increased intracellular calcium through sodium-calcium exchange 2
• The increased intracellular calcium results in enhanced myocardial contractility (positive inotropic effect) 2
• Digoxin also has vagomimetic effects that slow heart rate and decrease conduction through the AV node, making it useful for rate control in atrial fibrillation 2
• It decreases activation of the sympathetic nervous system and renin-angiotensin system (neurohormonal deactivating effect) 2

Clinical Applications of Digoxin

• Primarily used in heart failure with reduced ejection fraction as an inotrope to improve symptoms, quality of life, and exercise tolerance 3
• Used as a rate-controlling agent in patients with atrial fibrillation 1
• Particularly beneficial in patients with both heart failure and atrial fibrillation 4
• Most effective in patients with severe heart failure, cardiomegaly, and a third heart sound 5

Pharmacokinetics of Digoxin

• Oral bioavailability is approximately 60-80% 2
• Onset of effect is observed within 1-3 hours after oral absorption 1
• Elimination half-life is 36-48 hours (longer in elderly patients at 69.6 hours) 1, 4
• Approximately 50-70% of the drug is excreted unchanged in the urine 1
• Metabolism is primarily by gut bacteria, not dependent on the CYP450 system 1

Dosing Considerations

• Standard dosage ranges from 0.125-0.25 mg daily for most patients 3
• Lower doses (0.125 mg daily) should be used in patients over 70 years, those with impaired renal function, or low lean body mass 3, 4
• Higher doses (0.375-0.50 mg daily) are rarely needed 3
• Loading doses are not necessary for chronic heart failure management 3

Monitoring and Safety

• Therapeutic serum levels should be monitored, especially in elderly patients 2, 4
• Digoxin toxicity is commonly associated with serum levels >2 ng/mL 3
• Regular monitoring of serum electrolytes and renal function is essential 2
• Risk of toxicity increases with hypokalemia, hypomagnesemia, or hypothyroidism 3

Drug Interactions with Digoxin

• Amiodarone, verapamil, propafenone, and quinidine can increase serum digoxin concentrations 2
• Calcium, particularly when administered rapidly intravenously, may produce serious arrhythmias in digitalized patients 2
• Hypocalcemia can nullify the effects of digoxin 2
• Concomitant use with beta-blockers or calcium channel blockers requires caution due to additive effects on AV node conduction 2
• Atorvastatin at high doses (80 mg) can increase digoxin levels by approximately 20% 1

Contraindications and Cautions

• Should not be administered to patients with significant sinus or atrioventricular block unless treated with a permanent pacemaker 3
• Use with caution in patients receiving other agents that depress sinus or AV nodal function 3
• Contraindicated in patients with Wolff-Parkinson-White syndrome and pre-excited atrial fibrillation 1
• Should be used cautiously in patients with acute myocardial infarction 2
• May need dose reduction 1-2 days prior to electrical cardioversion of atrial fibrillation 2

Clinical Positioning in Current Guidelines

• Recommended as a second-line drug after diuretics, ACE inhibitors, and beta-blockers in patients with heart failure in sinus rhythm 5
• Considered first-line for patients with congestive heart failure who are in atrial fibrillation 5
• In atrial fibrillation without heart failure, digoxin is recommended primarily for sedentary patients or those who cannot tolerate other rate-control agents 4, 6
• Often used in combination with beta-blockers for more effective rate control during exercise 1

Common Pitfalls

• Overreliance on digoxin as monotherapy for rate control in physically active patients with atrial fibrillation (less effective during exercise) 4
• Failure to adjust dosing in elderly patients, leading to increased risk of toxicity 4
• Not monitoring for drug interactions, especially with amiodarone and other medications that increase digoxin levels 3
• Inadequate monitoring of serum electrolytes, particularly potassium levels 2
• Using digoxin in patients with pre-excited atrial fibrillation (can be dangerous) 1

Digoxin remains the primary oral positive inotropic agent available for chronic use, with decades of clinical experience supporting its efficacy and safety when properly monitored.