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Digoxin is the primary cardiac glycoside in clinical use. Digoxin
is used for the treatment of congestive heart failure (CHF) because
of its inotropic effects on the myocardium and for the treatment
of atrial fibrillation because of its chronotropic effects on the
electrophysiological system of the heart. The role of digoxin in
the treatment of each of these disease states has changed in recent
years as a better understanding of the pathophysiology of these
conditions has been gained and new drug therapies have been developed.1,2 For
the treatment of chronic CHF, angiotensin I converting enzyme inhibitors
(ACE inhibitors) and diuretics are the primary pharmacotherapeutic
agents with angiotensin II receptor antagonists, spironolactone,
and β-blockers playing key roles.3 For
the treatment of acute or severe heart failure, agents that decrease
cardiac preload (diuretics, nitrates) or afterload (vasodilators)
and ACE inhibitors (decreases both preload and afterload) are used
in conjunction with potent intravenously administered inotropic
agents (dobutamine, dopamine, adrenergic agonists) to balance the
current cardiovascular status of the patient.3 In either
the acute or severe heart failure situations, digoxin can be used
when a mild inotropic or oral agent is needed.
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If a patient presents with severe cardiovascular symptoms due
to atrial fibrillation, direct-current cardioversion is a treatment
option.4 For the treatment of atrial fibrillation with
mild or no cardiovasuclar symptoms, many clinicians prefer to prescribe intravenous
calcium channel blockers (diltiazem or verapamil) for the control
ventricular rate.4 If atrial fibrillation is due to excessive
adrenergic tone, intravenous β-blockers can also
be used. Digoxin continues to be prescribed for the control of ventricular
rate in patients with atrial fibrillation with no accessory pathway
and can be an excellent choice if the patient is sedentary or has
heart failure or left ventricular dysfunction. It is also possible
to use digoxin in combination with a β-blocker
or a calcium channel blocker to treat atrial fibrillation.5 Once
ventricular rate is controlled, the patient’s heart may
spontaneously revert to normal sinus rhythm, or electrical or pharmacologic
cardioversion of atrial fibrillation may be necessary.
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The positive inotropic effect of digoxin is caused by binding
to sodium- and potassium-activated adenosine triphosphatase, also
known as Na,K-ATPase or the sodium pump.6 Digoxin-induced
inhibition of Na,K-ATPase leads to decreased transport of sodium
out of myocardial cells and increased intracellular sodium concentrations
that aid calcium entry and decrease calcium elimination via the
sodium-calcium exchanger. The increased intracellular calcium is
stored in the endoplasmic reticulum so that action potential–induced
calcium release is augmented causing enhanced myocardial contractility.
The chronotropic effects of digoxin are mediated via increased parasympathetic
activity and vagal tone.
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When given as oral or intravenous doses, the serum digoxin concentration–time
curve follows a two-compartment model and exhibits a long and large
distribution phase of 8–12 hours (Figure 6-1).7–9 During
the distribution phase, digoxin in the serum is not in equilibrium
with digoxin in the ...