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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 -
Vascular Health and Risk Management 2022Bidirectional ventricular tachycardia (BiVT) is a rare form of ventricular tachycardia that manifests on surface electrocardiogram by dual QRS morphologies alternating... (Review)
Review
Bidirectional ventricular tachycardia (BiVT) is a rare form of ventricular tachycardia that manifests on surface electrocardiogram by dual QRS morphologies alternating on a beat-to-beat basis. It was first reported in the 1920s as a complication of digoxin, and since then, it has been reported in other conditions including fulminant myocarditis, sarcoidosis, catecholaminergic polymorphic ventricular tachycardia, and Andersen-Tawil syndrome. The mechanism for BiVT is not as well known as other forms of ventricular tachycardia but appears to include typical mechanisms including triggered activity from afterdepolarizations, abnormal automaticity, or reentry. This review will go beyond the definition, surface electrocardiogram, mechanisms, causes, and treatment of BiVT as per our current understanding.
Topics: Andersen Syndrome; Electrocardiography; Humans; Tachycardia; Tachycardia, Ventricular
PubMed: 35698640
DOI: 10.2147/VHRM.S274857 -
Toxins May 2021Cardiac glycosides (CGs), toxins well-known for numerous human and cattle poisoning, are natural compounds, the biosynthesis of which occurs in various plants and... (Review)
Review
Cardiac glycosides (CGs), toxins well-known for numerous human and cattle poisoning, are natural compounds, the biosynthesis of which occurs in various plants and animals as a self-protective mechanism to prevent grazing and predation. Interestingly, some insect species can take advantage of the CG's toxicity and by absorbing them, they are also protected from predation. The mechanism of action of CG's toxicity is inhibition of Na/K-ATPase (the sodium-potassium pump, NKA), which disrupts the ionic homeostasis leading to elevated Ca concentration resulting in cell death. Thus, NKA serves as a molecular target for CGs (although it is not the only one) and even though CGs are toxic for humans and some animals, they can also be used as remedies for various diseases, such as cardiovascular ones, and possibly cancer. Although the anticancer mechanism of CGs has not been fully elucidated, yet, it is thought to be connected with the second role of NKA being a receptor that can induce several cell signaling cascades and even serve as a growth factor and, thus, inhibit cancer cell proliferation at low nontoxic concentrations. These growth inhibitory effects are often observed only in cancer cells, thereby, offering a possibility for CGs to be repositioned for cancer treatment serving not only as chemotherapeutic agents but also as immunogenic cell death triggers. Therefore, here, we report on CG's chemical structures, production optimization, and biological activity with possible use in cancer therapy, as well as, discuss their antiviral potential which was discovered quite recently. Special attention has been devoted to digitoxin, digoxin, and ouabain.
Topics: Animals; Antineoplastic Agents; Cardiac Glycosides; Cattle; Digitoxin; Digoxin; Humans; Molecular Targeted Therapy; Neoplasms; Ouabain; Sodium-Potassium-Exchanging ATPase
PubMed: 34064873
DOI: 10.3390/toxins13050344 -
International Journal of Molecular... Aug 2022In addition to classical steroids, which have cholesterol as a precursor, there are steroids with 7-dehydrocholesterol as a precursor. This review describes the... (Review)
Review
In addition to classical steroids, which have cholesterol as a precursor, there are steroids with 7-dehydrocholesterol as a precursor. This review describes the identification of these steroids, their biosynthesis, and some aspects of their function. There are three classes of these compounds, distinguished by the number of their carbon atoms, 23, 24, and 25. Each class has a spiral steroid and is a phosphodiester. Up until these investigations, no spiral steroids or steroid phosphodiesters were known. There are at least 13 compounds, of which six have been purified to near homogeneity; each one has been characterized by its mass and proposed composition, and they function by regulating the NaK-ATPase. Based on the tissues in which they have been detected, each class of compound seems to regulate a different isoform of the NaK-ATPase. This is an important site of endocrine regulation.
Topics: Sodium-Potassium-Exchanging ATPase; Steroids
PubMed: 36076935
DOI: 10.3390/ijms23179523 -
Emergencias : Revista de La Sociedad... Oct 2023
Topics: Humans; Digoxin
PubMed: 37801413
DOI: 10.55633/s3me/E022.2023 -
Frontiers in Pharmacology 2023Digoxin is one of the most widely and commonly used cardiac drug, which plays an irreplaceable role in treating heart failure and arrhythmia. stipulates that the... (Review)
Review
Digoxin is one of the most widely and commonly used cardiac drug, which plays an irreplaceable role in treating heart failure and arrhythmia. stipulates that the effective range of digoxin plasma concentration is 0.5-2.0 ng/mL and it is toxic at plasma concentration >2 ng/mL. Its effective plasma drug concentration is close to the toxic concentration, and large individual differences in the effects of the drug have been observed. It is often used in combination with other drugs, but drug interactions have a great impact on the plasma concentration of digoxin and lead to adverse reactions (ADRs), such as poisoning. Most of the reported drug interactions are with Western drugs. However, there are many combinations of traditional Chinese medicine (TCM) and Western drugs, TCM interacting with digoxin comprises monomer components, single medicines, and Chinese patent medicines. We aimed i) to provide an overview of the TCM formulations affecting the pharmacology of digoxin and their mechanisms of action and ii) to provide a theoretical reference for the safe and rational use of digoxin in combination with TCM in clinical practice and to avoid ADRs. A literature search of electronic databases, including PubMed, MEDLINE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WANFANG Data, was performed to search for articles published between 1 January 1960, and 1 August 2022. Search terms used included "digoxin," "traditional Chinese medicine," "Chinese patent medicine," and "adverse reactions" and their combinations. A total of 49 articles were obtained, including clinical reports, pharmacological experiments and experiments. The mechanisms of action affecting the pharmacology of digoxin are complex. TCM formulations may affect the pharmacology of digoxin by influencing gastrointestinal motility or gastric juice pH, regulating P-glycoprotein levels, exerting cumulative pharmacological effects, and enhancing the sensitivity of the heart to digoxin. Although studies have shown that some TCM formulations interact with digoxin, they may be influenced by the complexity of the composition and the pharmacological effects of the TCM, the sensitivity of digoxin concentration determination methods, etc. The results of existing studies are controversial and further in-depth studies are required. Combinations of digoxin and TCM formulations are commonly used. This article serves as a reference to understand the interactions between TCM formulations and digoxin to avoid the occurrence of ADRs and improve the efficacy and safety of digoxin.
PubMed: 36825153
DOI: 10.3389/fphar.2023.1040778 -
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