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Digoxin

Digoxin is a cardiac glycoside extracted from the foxglove plant, digitalis. It is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and congestive heart failure that cannot be controlled by other medication. more...

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The main effects of digoxin are on the heart, its extracardiac effects are responsible for most of the side effects, i.e. nausea, vomiting, diarrhea and confusion.

Its main cardiac effects are:

  • A decrease of conduction of electrical impulses through the AV node, making it a commonly used drug in controlling the heart rate during atrial fibrillation or atrial flutter.
  • An increase of force of contraction via inhibition of the Na+/K+ ATPase pump (see below).

Mechanism of action

Digoxin binds to a site on the extracellular aspect of the α-subunit of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes). This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. The proposed mechanism is the following: inhibition of the Na+/K+ pump leads to increased Na+ levels, which in turn slows down the extrusion of Ca2+ via the Na+/Ca2+ exchange pump. Increased amounts of Ca2+ are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by digoxin. This is a different mechanism from that of catecholamines.

Digoxin also increases vagal activity via its central action on the central nervous system, thus decreasing the conduction of electrical impulses through the AV node. This is important for its clinical use in different arrhythmias (see below).

Clinical use

Today, the most common indications for digoxin are probably atrial fibrillation and atrial flutter with rapid ventricular response. High ventricular rate leads to insufficient diastolic filling time. By slowing down the conduction in the AV node and increasing its refractory period, digoxin can reduce the ventricular rate. The arrhythmia itself is not affected, but the pumping function of the heart improves owing to improved filling.

The use of digoxin in congestive heart failure during sinus rhythm is controversial. In theory the increased force of contraction should lead to improved pumping function of the heart, but its effect on prognosis is disputable and digoxin is no longer the first choice for congestive heart failure. However, it can still be useful in patients who remain symptomatic despite proper diuretic and ACE inhibitor treatment.

Digoxin is usually given by mouth, but can also be given by IV injection in urgent situations (the IV injection should be slow, heart rhythm should be monitored). The half life is about 36 hours, digoxin is given once daily, usually in 125μg or 250μg dosing. In patients with decreased kidney function the half life is considerably longer, calling for a reduction in dosing or a switch to a different glycoside (digitoxin).

Read more at Wikipedia.org


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Role of carvedilol and digoxin in heart failure
From American Family Physician, 7/15/04 by Karl E. Miller

In the treatment of heart failure and atrial fibrillation, digoxin has been a longstanding option. It is standard therapy in patients with heart failure and atrial fibrillation, but it is inadequate at rate control in these patients during exercise or times of increased sympathetic tone. Multiple studies have shown the benefit of beta-blocker therapy in the treatment of patients with heart failure. In addition, beta blockers have been shown to improve ventricular rate control in atrial fibrillation alone or in combination with digoxin. Despite these studies, no information demonstrates that beta blockers alone or in combination with digoxin improve outcomes in patients with heart failure and persistent atrial fibrillation. Khand and associates evaluated the use of digoxin, carvedilol, and their combination in the treatment of patients with heart failure and persistent atrial fibrillation.

The trial was a randomized, double-blind, placebo-controlled study of patients who met the standard criteria for heart failure and persistent atrial fibrillation for more then one month. All patients who entered the trial were taking digoxin. In phase 1 of the study, digoxin alone was compared with the combination of carvedilol and digoxin for four months. In phase 2, digoxin was withdrawn in a double-blinded fashion. Patients were assessed at the start of the study and at the end of each phase. Primary outcome measurements included assessment of left ventricular function, ventricular rate control, symptoms, and exercise tolerance.

There were 47 patients who participated in the study. The combination of digoxin and carvedilol, when compared with digoxin alone, provided a significantly lower ventricular rate on 24-hour monitoring and during submaximal exercise. In addition, combination therapy provided significantly better symptom control and improved left ventricular function compared with digoxin alone. When patients were changed to carvedilol alone, their mean ventricular rate rose, and the left ventricular ejection fraction declined. There was no difference in the six-minute walk distance between treatment arms.

The authors conclude that the combination of digoxin and carvedilol in the treatment of patients with heart failure and persistent atrial fibrillation is superior to either medication alone. They add that the combination provides better left ventricular function and ventricular rate control. In patients who were taking the combination, left ventricular function and rate control deteriorated after digoxin withdrawal. This study is the first to demonstrate the added benefit of digoxin in patients who are receiving beta-blocker therapy.

KARL E. MILLER, M.D.

Khand AU, et al. Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure? J Am Coll Cardiol December 3, 2003;42:1944-51.

COPYRIGHT 2004 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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