Digoxin adverse effects
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Adverse Effects of Digoxin: A Comprehensive Overview
Introduction to Digoxin and Its Therapeutic Use
Digoxin is a cardiac glycoside widely used in the treatment of various heart conditions, including heart failure, atrial fibrillation, and atrial flutter. Despite its therapeutic benefits, digoxin has a narrow therapeutic window, making it prone to adverse effects and toxicity5 8.
Toxic Serum Digoxin Concentration and Risk Factors
One of the primary concerns with digoxin is its potential to reach toxic serum concentrations. Studies have shown that serum digoxin concentrations (SDC) above 2.0 ng/mL are considered toxic. In a study involving Chinese patients with acute heart failure, 50% of the patients reached toxic SDC, and 30% exhibited toxic effects. Key risk factors for toxicity included lower estimated glomerular filtration rate (eGFR), higher normalized dosage of digoxin (NDD), and ischemic cardiomyopathy1.
Drug Interactions and Their Impact on Digoxin Toxicity
Digoxin is often used in combination with other medications, which can significantly impact its plasma concentration and lead to adverse reactions. Traditional Chinese Medicine (TCM) formulations, for instance, can affect digoxin's pharmacology by influencing gastrointestinal motility, gastric juice pH, and P-glycoprotein levels. These interactions can enhance the sensitivity of the heart to digoxin, increasing the risk of toxicity2. Additionally, drugs like NSAIDs, ACE inhibitors, and amiodarone can exacerbate digoxin's cardiac adverse effects through pharmacokinetic interactions8.
Specific Adverse Effects of Digoxin
Cardiac Adverse Effects
Digoxin's most severe adverse effects are cardiac-related, including bradycardia, arrhythmias, and heart block. These effects are often potentiated by renal impairment and interactions with other medications that affect electrolyte balance or cardiac conduction8.
Gastrointestinal and Neuropsychological Disorders
Patients on digoxin therapy may also experience gastrointestinal issues such as nausea and vomiting, as well as neuropsychological disorders like confusion and dizziness. These symptoms often serve as early warning signs of digoxin toxicity8.
Erectile Dysfunction
Digoxin has been found to adversely affect male sexual function by inhibiting sodium/potassium adenosine triphosphatase activity in the corpus cavernosum, leading to reduced penile rigidity and erectile dysfunction3.
Age-Related Adverse Effects
The risk of adverse effects and mortality associated with digoxin increases with age. Older patients are more susceptible to digoxin toxicity and its associated complications, such as hospitalizations and withdrawal from therapy due to side effects. However, the beneficial effects of digoxin in reducing heart failure admissions and mortality are consistent across all age groups6.
Mortality Risk Associated with Digoxin
Meta-analyses have shown that digoxin use is associated with an increased risk of all-cause mortality, particularly in patients with atrial fibrillation and heart failure. The increased mortality risk underscores the need for careful monitoring and judicious use of digoxin in clinical practice4 10.
Conclusion
While digoxin remains a valuable medication for managing certain heart conditions, its narrow therapeutic window and potential for severe adverse effects necessitate careful monitoring and consideration of individual patient risk factors. Clinicians must be vigilant about drug interactions, renal function, and age-related susceptibilities to minimize the risk of digoxin toxicity and improve patient outcomes.
Sources and full results
Most relevant research papers on this topic
Safety profile of intravenous digoxin in Chinese patients with acute heart failure with reduced ejection fraction: a small-scale prospective cohort study
Intravenous digoxin 0.5 mg is safe for initial dose but not suitable for maintenance treatment in Chinese patients with acute heart failure with reduced ejection fraction.
Non-RCTInteraction between Chinese medicine and digoxin: Clinical and research update
TCM formulations may interact with digoxin, potentially causing adverse reactions and enhancing the efficacy and safety of the drug in clinical practice.
Systematic ReviewA possible mechanism for alteration of human erectile function by digoxin: inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity.
Digoxin alters human erectile function by inhibiting corporeal smooth muscle sodium pump activity, promoting contraction and preventing nitric oxide-induced relaxation.
RCTDigoxin for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and trial sequential analysis of randomised clinical trials
Digoxin is a safe and effective treatment for atrial fibrillation and atrial flutter, but its long-term safety and effectiveness remain unclear.
Meta-Analysis
Rigorous JournalDigoxin: Pharmacology and toxicology-A review.
Digoxin is a cardiac glycoside used for treating heart problems, but its pharmacology and toxicology require careful monitoring and appropriate therapy regimens.
Highly CitedEffect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study.
Increasing age worsens clinical outcomes in heart failure patients, but digoxin's beneficial effects in reducing all-cause and HF admissions remain independent of age.
RCT
Large Human TrialHighly CitedHigh doses of digoxin increase the myocardial nuclear factor-kB and CaV1.2 channels in healthy mice. A possible mechanism of digitalis toxicity.
High doses of digoxin increase myocardial nuclear factor-kB and CaV1.2 channels, potentially contributing to its toxicity through modulation of intracellular calcium homeostasis in the heart.
Non-RCT
Animal StudyRigorous JournalDigoxin: serious drug interactions.
Digoxin's cardiac adverse effects can be exacerbated by renal impairment, certain drugs, and interactions with other drugs.
Literature ReviewA randomized pilot study on the effectiveness and side-effect profiles of two doses of digoxin as fetocide when administered intraamniotically or intrafetally prior to second-trimester surgical abortion.
Intraamniotic or intrafetal injection of digoxin is safe and effective for inducing fetal death prior to second-trimester surgical abortion, with doses greater than 1.0 mg potentially not necessary.
RCTDigoxin-associated mortality: a systematic review and meta-analysis of the literature.
Digoxin use is associated with an increased mortality risk, particularly in patients with atrial fibrillation.
Meta-AnalysisRigorous JournalHighly Cited