INDICATIONS AND PHARMACOKINETICS
Digitalis is the genus of the foxglove plant group, a species from which cardiac glycosides are derived. Cardiac glycosides contain a primary sugar group (usually a polysaccharide) that is bound to a steroid nucleus. Digoxin is the most common form of digitalis used in cardiac patients today.
The primary indications for digoxin therapy are (1) ventricular rate control of chronic atrial fibrillation or flutter, especially in patients with compromised myocardial contractility; (2) treatment of narrow-complex paroxysmal supraventricular tachycardia (PSVT); and (3) treatment of congestive heart failure. Because of improved outcomes with first-line drugs like ACE inhibitors and angiotensin receptor blockers, digoxin is used much less frequently today in patients with congestive heart failure due to left ventricular systolic dysfunction.
Digoxin can be given as 0.5–1 mg IV bolus. It has a 5–30-minute onset time, achieves peak effect in 1–3 hours, and has a 36-hour elimination half-life if renal function is normal. Digoxin undergoes minimal hepatic metabolism and is mostly excreted unchanged by the kidneys. Patients with chronic renal insufficiency should have reduced doses and digoxin plasma levels should be closely monitored.
Digoxin’s mechanism of action on myocardial cell membranes is complex. Digoxin binds to and inhibits the sodium–potassium adenosine triphosphate pump, leading to increased cytosolic sodium concentrations. Without the normal electrochemical gradient for sodium, the sodium–calcium transporter cannot remove calcium in exchange for sodium, resulting in increased free intracellular calcium. Higher levels of calcium release from the sarcoplasmic reticulum promote sarcomere contraction and enhance myocardial contractility. This nonadrenergic mechanism of positive inotropy makes digoxin a unique vasopressor. Unlike sympathomimetic drugs such as epinephrine and dopamine, digoxin will not precipitate tachydysrhythmias. Patients taking beta-blockers benefit from digoxin’s independence from myocardial beta-1 receptors.
Digoxin directly affects cardiac pacemaker cells with negative chronotropy. In the atrioventricular (AV) node, inhibition of the Na+/K+ ATPase transporter alters the resting membrane potential, increases the absolute refractory period, and decreases action potential conduction velocity. Digoxin also increases vagal activity and enhances the AV node’s response to acetylcholine. Heart transplant patients, who lack vagal innervation, do not respond to the rate control effects of digoxin. At therapeutic levels, digoxin decreases pacemaker cell automaticity by prolonging phase 4 spontaneous depolarization of the cardiac action potential. The primary ECG effects of therapeutic levels of digoxin are prolonged PR interval, ST segment depression, T-wave flattening or inversion, and increased U-wave amplitude.
Digoxin has a narrow therapeutic index (0.5–2.5 ng/mL). Conditions that increase the risk of digoxin toxicity include hypoxemia, renal insufficiency, hypothyroidism, hypoglycemia, hypomagnesemia, and hypercalcemia. Since both digoxin and K+ compete for the same binding site on the Na+/K+ ATP pump, hypokalemia will augment the effects of digoxin, leading to toxicity. Patients receiving diuretic therapy should have potassium levels closely monitored.