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Annals of Medicine Dec 2021Atrial fibrillation (AF) is one of the main cardiac arrhythmias associated with higher risk of cardiovascular morbidity and mortality. AF can cause adverse symptoms and... (Review)
Review
Atrial fibrillation (AF) is one of the main cardiac arrhythmias associated with higher risk of cardiovascular morbidity and mortality. AF can cause adverse symptoms and reduced quality of life. One of the strategies for the management of AF is rate control, which can modulate ventricle rate, alleviate adverse associated symptoms and improve the quality of life. As primary management of AF through rate control or rhythm is a topic under debate, the purpose of this review is to explore the rationale for the rate control approach in managing AF by considering the guidelines, recommendations and determinants for the choice of rate control drugs, including beta blockers, digoxin and non- dihydropyridine calcium channel blockers for patients with AF and other comorbidities and atrioventricular nodal ablation and pacing. Despite the limitations of rate control treatment, which may not be effective in preventing disease progression or in reducing symptoms in highly symptomatic patients, it is widely used for almost all patients with atrial fibrillation. Although rate control is one of the first line management of all patient with atrial fibrillation, several issues remain debateable.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Rate; Humans; Quality of Life
PubMed: 34032538
DOI: 10.1080/07853890.2021.1930137 -
Tidsskrift For Den Norske Laegeforening... Oct 2018The withdrawal of digitoxin and subsequent substitution with digoxin around 2012 may have led to an increased health risk for patients. The aim of this study was to...
BACKGROUND
The withdrawal of digitoxin and subsequent substitution with digoxin around 2012 may have led to an increased health risk for patients. The aim of this study was to follow individual patients during the switch.
MATERIAL AND METHOD
Serum concentrations of digitoxin and digoxin, measured at the Department of Clinical Pharmacology at St Olavs University Hospital in the period 1 January 2011-31 December 2013 were reviewed. Patients who had switched from digitoxin to digoxin and whose serum concentrations of both drugs had been measured during this period were included.
RESULTS
A total of 304 patients, 1686 samples and 1858 serum concentration analyses were included in the study. Therapeutic serum concentrations were measured in 171 patients (56.3 %) before the switch and 176 (57.9 %) after this had taken place. Altogether 108 patients (35.5 %) had therapeutic concentrations both before and after the change. For 58.9 % of the patients, the change resulted in a reduction in serum concentration of digitalis, calculated as digoxin equivalents. The proportion of patients with assumed supratherapeutic concentrations fell from 43.1 % to 33.9 %; however, the proportion of patients with toxic serum concentrations rose from 0.3 % to 3.0 %.
INTERPRETATION
Although the switch led to a reduction in dose and serum concentration for many, a significant number of patients may have been put in harm's way.
Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Digitoxin; Digoxin; Drug Monitoring; Drug Substitution; Drug and Narcotic Control; Female; Humans; Male; Middle Aged; Norway
PubMed: 30277048
DOI: 10.4045/tidsskr.18.0093 -
The American Journal of Medicine Dec 2015The use of digoxin in the therapy of systolic heart failure and certain supraventricular tachycardias is controversial. This review of the art and science of digoxin... (Review)
Review
The use of digoxin in the therapy of systolic heart failure and certain supraventricular tachycardias is controversial. This review of the art and science of digoxin presents information needed by physicians considering digoxin therapy for these common cardiovascular disorders.
Topics: Aged; Cardiotonic Agents; Digoxin; Heart Failure, Systolic; Humans; Tachycardia, Supraventricular
PubMed: 26159635
DOI: 10.1016/j.amjmed.2015.06.016 -
Current Pharmaceutical Design 2022Heart failure (HF) is a common cause of morbimortality with different etiopathogenesis and prognosis between men and women. This review provides a brief overview of... (Review)
Review
Heart failure (HF) is a common cause of morbimortality with different etiopathogenesis and prognosis between men and women. This review provides a brief overview of gender-based differences in response to pharmacological therapies of heart failure with or without reduced ejection fraction (EF). It focuses on the differences in therapy outcomes with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), angiotensin neprilysin inhibitors (ARNI), beta-adrenergic blockers, mineralocorticoid/ aldosterone receptor antagonists, diuretics, ivabradine and digoxin. The baseline data originate from randomised controlled trials (RCTs) and large registries. We conclude that current guidelines recommending similar therapeutic approaches for both men and women are appropriate, while additional consideration should be given to different approaches regarding the use of ARBs, ACEi, and digoxin. Based on the available data, the ARBs might be considered a first-line therapy of HR for women instead of ACEi. Moreover, female patients should have stricter digoxin monitoring due to higher sensitivity and increased risk of complications. Finally, women are underrepresented in current clinical trials, and therefore future trials should aim to balance the gender recruitment disparity allowing sub-group analysis and comparisons between genders to guide individualised therapeutic strategies and appropriately targeted preventative steps.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Sex Characteristics; Stroke Volume
PubMed: 35232346
DOI: 10.2174/1381612828666220301125514 -
Emergencias : Revista de La Sociedad... Oct 2023
Topics: Humans; Digoxin
PubMed: 37801413
DOI: 10.55633/s3me/E022.2023 -
Journal of Pharmacy Practice Aug 2017Since its isolation in the 1930s, digoxin has played a pivotal role in the treatment of cardiac conditions including heart failure and supraventricular tachyarrhythmias.... (Review)
Review
Since its isolation in the 1930s, digoxin has played a pivotal role in the treatment of cardiac conditions including heart failure and supraventricular tachyarrhythmias. The parasympathomimetic activity makes digoxin a reasonable option for controlling ventricular rate in atrial fibrillation (AF). However, the unique pharmacokinetic properties, electrolyte-dependent effects, and P-glycoprotein drug interactions influence the clinical use of digoxin. In addition, the delayed onset and narrow therapeutic index can make digoxin utilization cumbersome and often necessitates serum drug monitoring. Despite digoxin's extensive history, recent literature has cast doubt on the efficacy and safety of this medication in the population with AF. Large amounts of data suggest digoxin offers no benefit on mortality and may increase the risk of mortality though this was not consistent in all evaluations. While robust, the majority of the available studies are not randomized which limits the ability to draw firm conclusions. The potential risk of mortality must be weighed against the expected benefits of digoxin use to make individualized patient care decisions. Clinicians should refrain from utilizing digoxin monotherapy for rate control in AF when other options are viable.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans
PubMed: 27067743
DOI: 10.1177/0897190016642361 -
Frontiers in Immunology 2023Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and...
BACKGROUND
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects.
OBJECTIVE
This study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein.
METHODS
We exploited a rat needle model to investigate digoxin's role in intervertebral disc degeneration . Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects . Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin.
RESULTS
Digoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells.
CONCLUSION
These findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases.
Topics: Humans; Rats; Mice; Animals; Intervertebral Disc Degeneration; NF-kappa B; Digoxin; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Inflammation; LDL-Receptor Related Proteins
PubMed: 37790932
DOI: 10.3389/fimmu.2023.1251517 -
Ageing Research Reviews Apr 2023The geroscience hypothesis proposes biological hallmarks of ageing are modifiable. Increasing evidence supports targeting these hallmarks with therapeutics could prevent... (Review)
Review
The geroscience hypothesis proposes biological hallmarks of ageing are modifiable. Increasing evidence supports targeting these hallmarks with therapeutics could prevent and ameliorate age-related conditions - collectively termed "geroprotector drugs". Cellular senescence is a hallmark with considerable potential to be modified with geroprotector drugs. Senotherapeutics are drugs that target cellular senescence for therapeutic benefit. Repurposing commonly used medications with secondary geroprotector properties is a strategy of interest to promote incorporation of geroprotector drugs into clinical practice. One candidate is the cardiac glycoside digoxin. Evidence in mouse models of pulmonary fibrosis, Alzheimer's disease, arthritis and atherosclerosis support digoxin as a senotherapeutic agent. Proposed senolytic mechanisms are upregulation of intrinsic apoptotic pathways and promoting intracellular acidification. Digoxin also appears to have a senomorphic mechanism - altering the T cell pool to ameliorate pro-inflammatory SASP. Despite being widely prescribed to treat atrial fibrillation and heart failure, often in multimorbid older adults, it is not known whether digoxin exerts senotherapeutic effects in humans. Further cellular and animal studies, and ultimately clinical trials with participation of pre-frail older adults, are required to identify whether digoxin has senotherapeutic effect at low dose. This paper reviews the biological mechanisms identified in preliminary cellular and animal studies that support repurposing digoxin as a geroprotector in patients with frailty and multimorbidity.
Topics: Animals; Mice; Humans; Aged; Digoxin; Frailty; Multimorbidity; Drug Repositioning; Senotherapeutics; Cellular Senescence
PubMed: 36682465
DOI: 10.1016/j.arr.2023.101860 -
MMW Fortschritte Der Medizin May 2018
Review
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans
PubMed: 29754346
DOI: 10.1007/s15006-018-0527-8 -
Postgraduate Medical Journal Sep 2015Digoxin has been a key therapeutic for heart failure and atrial tachyarrhythmias for over 200 years following Withering's groundbreaking work depicting the therapeutic... (Review)
Review
Digoxin has been a key therapeutic for heart failure and atrial tachyarrhythmias for over 200 years following Withering's groundbreaking work depicting the therapeutic benefit of the common botanical foxglove in his 1785 monograph. The use of digoxin preceded any randomised evidence or even basic understanding of its mechanism of action. Over the past two decades, there has been mounting evidence further challenging the safety and efficacy of digoxin, while multiple other therapies for both heart failure and atrial tachyarrhythmias have proven to be more effective and safe. Altogether, digoxin still has an important role in contemporary pharmacotherapeutics, though its role remains controversial and should be reserved for selective patients and clinical situations, with careful attention to serum concentrations.
Topics: Cardiotonic Agents; Digoxin; Drug Interactions; Evidence-Based Medicine; Heart Failure; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; Retrospective Studies; Tachycardia; Treatment Outcome
PubMed: 26265790
DOI: 10.1136/postgradmedj-2014-132937