The common digoxin brand name for the lower dose Digoxin is relatively inexpensive — costing patients around 20 cents a tablet on the Pharmaceutical Benefits Scheme — and less expensive if a person has a concession card. Digoxin is a relatively common medicine for heart conditions. In the last 12 months, , prescriptions for digoxin were dispensed on the Pharmaceutical Benefits Scheme in Australia.
However, its use is declining since medications with greater proven effectiveness and safety are preferred. One of the interesting stories in the history of digoxin is the link with Vincent Van Gogh. Much has been written about the physical and mental health problems that Van Gogh had in his life and numerous diagnoses have been proposed. Among these diagnoses is the suspicion that he suffered from digitalis foxglove toxicity , which resulted in the frequent use of yellow halos in his paintings due to xanthopsia.
Supporting this hypothesis is the fact that when Vincent painted his personal physician in the Portrait of Doctor Gachet he was holding the foxglove plant. But it does make for an interesting story, and an even better painting! Portsmouth Climate Festival — Portsmouth, Portsmouth.
More calcium becomes available to the sarcoplasmic reticulum and myocyte contractility is enhanced. Equally important, though some might argue even more important, there are many effects on the autonomic nervous system. These become beneficial when managing both arrhythmias and heart failure. They also relate to digoxin side effects and toxicity. Digoxin has a vagomimetic effect on the sinoatrial and atrioventricular node. This contributes to a decrease in heart rate and slows atrioventricular conduction velocity, the former being important in congestive heart failure, and the later in atrial fibrillation with rapid ventricular response.
Baroreceptor sensitization also occurs with the result being an increased afferent inhibitory activity resulting in reduction of sympathetic nervous and renin-angiotensin-aldosterone signaling system activity. With high doses of digoxin resulting in high serum concentrations, one can demonstrate an increase in central nervous system sympathetic activity and this probably drives much of what we characterize as digoxin toxicity, particularly toxicity manifest as ventricular arrhythmias.
Of course the vagomimetic effects account for arrhythmia toxicity as well, with precipitation of profound bradycardia or atrioventricular nodal heart block. This fact must be remembered when using concomitant agents, which also have an effect on heart rate and atrioventricular nodal conduction such as beta-blockers, some calcium channel blockers, and amiodarone.
When using digoxin a focus on low doses and serum levels is important, as enhancing parasympathetic effects is likely more beneficial long term than increasing sympathetic activity.
Regulatory labeling of digoxin notes that the drug is indicated for treatment of patients with mild to moderate heart failure. Specifically noted is that digoxin increases left ventricular ejection fraction and improves the symptoms of heart failure and the latter is largely based on evidence from the previously mentioned PROVED, RADIANCE, and DIG trials where, collectively, exercise capacity was increased and heart failure related hospitalizations diminished.
For patients with atrial fibrillation the indication is control of the ventricular response rate. As alluded to, regulatory approval of digoxin for heart failure was driven primarily by the three clinical trials mentioned. These trials were not done in an era where beta-blockers were frequently used in these patients. In aggregate, the two trials noted that when participants were blindly withdrawn from digoxin drug replaced with placebo , exercise tolerance, a global symptomatic benchmark, decreased; NYHA functional classification deteriorated; and heart failure related hospitalizations and need for urgent care increased.
There were many ramifications and nuances of this study. Dose was adjusted for patient age, sex, lean body weight, and serum creatinine with a substudy of 1, subjects using a dosing algorithm and ending up with a mean serum digoxin level of 1. The median daily dose prescribed was mcg. Post hoc analyses suggested that patients with lower serum digoxin levels did better.
Thus, digoxin has some of the most convincing data supporting its use in patients with heart failure in a setting of more normal LVEF. Comprehensive heart failure practice guidelines have addressed use of digoxin and there appears to be consensus. Digoxin should not be given to patients with known hypersensitivity to the drug. Ventricular fibrillation and Wolff-Parkinson-White syndrome are contraindications as well. Some would argue that a patient at extremely high risk of developing an undesirable effect of the drug an elderly, frail, patient with multiple comorbidities, on many drugs, and in renal failure or having renal insufficiency should not be given digoxin.
Some believe this is actually trivial when compared to the other actions of the drug. Nonetheless, there are no other oral available agents that mimic the inotropic action of digoxin. In patients with heart failure, though not strictly alternatives, beta-blockers, ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists are essential agents to consider as adjunctive therapies to digoxin.
Indeed, these are core baseline drugs that are necessary in heart failure. Also, there are many alternatives that can achieve the antiarrhythmic effects of digoxin.
Some are much more effective. Undesirable effects of digoxin can be numerous and, arguably, the drug has a narrow therapeutic range. Despite that fact, when rationally prescribed and patients are watched closely, digoxin is very well tolerated, simple to take, inexpensive, and effective. One must use the drug with caution when sinus node disease or AV nodal conduction abnormalities present because of the risk of excessive bradycardia and advanced heart block. In the presence of Wolff-Parkinson-White syndrome, after intravenous administration of digoxin, because of the slowing of AV conduction that occurs, precipitous acceleration of heart rate can develop with supraventricular arrhythmias unless other agents have been used to block the accessory conduction pathway.
There is some evidence to suggest that digoxin toxicity is more likely in patients with restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, hypertrophic obstructive cardiomyopathy, and acute cor pulmonale. Undesirable effects are more likely in patients with renal insufficiency, and settings of hypokalemia, hypomagnesemia, and hypercalcemia. Hypocalcemia may make digoxin ineffective.
Atrial fibrillation associated with hyperthyroidism is difficult to control and sometimes clinicians are tempted to push the dose of digoxin to gain control over the ventricular response rate. There is an increased risk of digoxin toxicity when this tactic is used. Side effects that the clinicians using digoxin need to be aware of are those primarily centered on the gastrointestinal tract and central nervous system. One of the most feared complications of the drug is necrotic bowel syndrome due to intestinal ischemia.
In our experience, this is seen more often in older, frail patients with systemic atherosclerosis receiving the drug intravenously during digitalization for management of atrial fibrillation or significant congestive heart failure during a hospitalization. Emboli in a setting of atrial fibrillation is always a concern but rapid digitalization with higher serum levels does cause vascular resist ance to rise in the mesenteric circulation, setting the stage for bowel hypoperfusion.
The savvy clinician will know that and be able to take quick and appropriate action if abdominal pain develops in such a setting.
From the central nervous system perspective, digoxin can cause visual disturbance classically described as blurred or yellowed vision some have speculated that Vincent van Gogh was cardiac glycoside toxic , headache, dizziness, apathy, and depression. Delirium and hallucination has even been reported as side effects of digoxin.
Other side effects include gynecomastia, thrombocytopenia, and a maculopapular rash. Fortunately these side effects are infrequent but do occur more often when the digoxin levels rise, particularly over 2. Many of these side effects improve simply by stopping or reducing the dose of digoxin. The speed with which they dissipate relates to renal function and serum concentration of the drug. Life-threatening complications of digoxin can occur with massive overdoses or extremely high levels, particularly in the setting of acute renal failure.
Ventricular fibrillation or tachycardia can be dramatic, producing bizarre looking QRS complexes and electrocardiogram. Hyperkalemia can be seen and is a result of the drug effects on the sodium-potassium cell wall pump described above.
Patients with massive digoxin ingestion suicide attempt as an example should receive large doses of activated charcoal to prevent absorption. When hemodynamic compromise is evident, usually in the setting of problematic ventricular or supraventricular arrhythmias, and remembering that digoxin is not dialyzable, administration of Digibindshould be considered. Digoxin immune Fab binds to digoxin, making the molecule incapable of activating receptor sites on the myocyte cell wall.
Digoxin acts by inhibiting the sodium-potassium adenosine triphosphatase pump, promoting sodium-calcium exchange; this results in an upsurge of intracellular calcium, thereby increasing myocardial contractility. Digoxin also has parasympathomimetic properties.
By increasing vagal tone in the sinoatrial and atrioventricular AV nodes, it slows the heart rate and AV nodal conduction. Digoxin has been around for centuries, but its use has been limited by several factors. Because of its narrow therapeutic window, digoxin requires close monitoring.
Also, two major drawbacks of digoxin are its adverse effects AEs and multiple drug interactions. Despite these limitations, digoxin still plays a role in therapy for HF, AF, and several off-label uses. It is considered adjunctive therapy, rather than first-line therapy, for these indications.
It is used mainly as add-on therapy in AF patients whose heart rates are not adequately controlled on beta-blockers alone. In CHF, contractility is decreased, which in turn reduces cardiac output. Digoxin is effective in patients with CHF because of its positive inotropic properties. Although studies have shown that digoxin reduces hospitalizations and improves symptoms of HF, it has not been proven to decrease mortality.
One double-blind, controlled trial of digoxin for CHF treatment randomized subjects with cardiac dysfunction to digoxin or placebo for 7 weeks. Cardiac function, as measured by ejection fraction EF , was significantly improved in digoxin patients. Digoxin may also be considered in patients with stage C HF structural heart disease with prior or current symptoms of HF or stage D HF HF symptoms at rest and recurrent hospitalizations despite therapy.
Although digoxin is prescribed for patients with HF and AF, concomitant beta-blocker therapy is usually more effective at controlling ventricular response, particularly during exercise. The initial dosage of digoxin is 0. The target serum level of digoxin in HF is 0.
Digoxin has been shown effective for decreasing HF symptoms, and its effect on morbidity and mortality has been assessed as well.
The primary outcome was mortality; secondary outcomes were a composite of mortality from cardiovascular causes, death from worsening HF, and hospitalization for other causes digoxin toxicity.
In the intent-to-treat analysis, there were 1, deaths in the digoxin group and 1, deaths in the placebo group Fewer digoxin patients than placebo patients were hospitalized and 1,, respectively; risk ratio 0. Also, the risk associated with the combined outcome of death due to worsening HF or hospitalization was lower in the digoxin group 1, vs. The conclusion was that although digoxin had no effect on overall mortality, it significantly decreased the overall number of hospitalizations attributed to worsening HF.
AF is a common arrhythmia in which irregular electrical impulses are conducted through the heart. These irregular electrical impulses lead to uncoordinated and inefficient heart contractions. As a result, blood pools in the heart, increasing the likelihood of a blood clot, which may lead to serious consequences such as myocardial infarction or stroke. AF can be managed by utilizing either rate or rhythm control agents. Digoxin exhibits its benefit in AF by controlling the heart rate.
One multicenter, randomized, double-blind, crossover trial evaluated the benefit of digoxin versus placebo in 43 patients with paroxysmal AF.
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