How does digoxin (digitalis glycoside) affect blood pressure (BP) in patients?

Digoxin's Effects on Blood Pressure

Digoxin has a modest effect on blood pressure, primarily causing a reduction in diastolic blood pressure during overnight sleep, likely due to increased parasympathetic activity or decreased sympathetic activity. 1

Mechanism of Action and Hemodynamic Effects

• Digoxin inhibits sodium-potassium ATPase, leading to increased intracellular calcium concentration, which produces its cardiovascular effects 2
• The drug has both direct cardiac effects and indirect autonomic nervous system effects, including:
  • Positive inotropic action (increased force of myocardial contraction) 2
  • Vagomimetic action (slowing heart rate and decreasing AV node conduction) 2
  • Neurohormonal deactivation (decreased sympathetic nervous system activity) 2

Blood Pressure Effects in Different Patient Populations

Heart Failure Patients

• In patients with heart failure and reduced ejection fraction, digoxin increases cardiac output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure, and systemic vascular resistance 2
• These hemodynamic improvements are accompanied by an increase in left ventricular ejection fraction and decreased end-systolic and end-diastolic dimensions 2
• Digoxin can reduce circulating norepinephrine levels, which may contribute to its hemodynamic effects 3

Normotensive Individuals

• In healthy normotensive subjects, digoxin significantly decreases diastolic blood pressure (by approximately 8 mmHg) and heart rate during overnight sleep 1
• Similar effects are seen with digitoxin, which reduces diastolic blood pressure by 5-7 mmHg during overnight sleep 1
• Neither digoxin nor digitoxin significantly affects systolic blood pressure in normotensive individuals 1

Pulmonary Hypertension

• In patients with pulmonary hypertension and right ventricular dysfunction, digoxin produces a modest increase in cardiac output 3
• It also significantly reduces circulating norepinephrine levels in these patients 3

Vascular Effects

• Contrary to the traditional "Blaustein hypothesis" that suggested cardiac glycosides induce arterial vasoconstriction, recent evidence indicates digoxin may have vasodilatory effects 4
• This slight vasodilation of resistance vessels followed by a fall in diastolic blood pressure may contribute to the beneficial effects of cardiac glycosides in heart failure patients 4
• The vasodilation may be caused by central (neurohumoral) effects of digitalis glycosides 4
• Digoxin increases cutaneous vascular conductance and augments the vasoconstrictive effect of exogenous norepinephrine 5

Clinical Implications

• Digoxin is not primarily used for blood pressure management but for specific indications:
  • Rate control in atrial fibrillation, especially when ventricular rate at rest is >80 bpm or during exercise >110-120 bpm 6
  • As an adjunct therapy in symptomatic heart failure with reduced ejection fraction (LVEF <40%) 6
• When used for these indications, the blood pressure effects should be monitored, particularly in patients with:
  • Pre-existing hypotension 6
  • Electrolyte abnormalities (hypokalemia, hypomagnesemia) that may increase risk of digoxin toxicity 6

Dosing Considerations

• Initial dose should be 0.125-0.25 mg daily for most adults with normal renal function 7
• Lower doses (0.125 mg daily or every other day) should be used for patients over 70 years, those with impaired renal function, or low lean body mass 7
• Target serum concentration should be between 0.5-0.9 ng/mL, as concentrations above 1.0 ng/mL have not shown superior outcomes and may increase mortality risk 7

Monitoring and Precautions

• Regular monitoring of serum electrolytes and renal function is mandatory due to the risk of arrhythmias, particularly with hypokalemia 6
• Digoxin should be used with caution in patients taking medications that can increase digoxin levels (amiodarone, verapamil, quinidine, clarithromycin, etc.) 6
• Digoxin is contraindicated in patients with significant sinus or AV block without a permanent pacemaker 7

In summary, while digoxin is not primarily prescribed for its blood pressure effects, it does have modest effects on blood pressure, particularly reducing diastolic blood pressure during overnight sleep. These effects are part of its overall hemodynamic profile, which includes improved cardiac output in heart failure patients and reduced sympathetic activity.