-
Tidsskrift For Den Norske Laegeforening... Oct 2018
Topics: Anti-Arrhythmia Agents; Digitoxin; Digoxin; Drug Substitution; Humans; Norway
PubMed: 30277041
DOI: 10.4045/tidsskr.18.0700 -
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 -
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 -
Journal of the American College of... May 1985Clinical manifestations of digitalis toxicity were clearly described by Withering in 1785. One hundred years later, certain digitalis-induced arrhythmias were inscribed... (Review)
Review
Clinical manifestations of digitalis toxicity were clearly described by Withering in 1785. One hundred years later, certain digitalis-induced arrhythmias were inscribed on the smoked drum, and shortly thereafter with the introduction of the electrocardiograph, manifestations of digitalis toxicity as recognized today were recorded in animals and human beings. With popularization of the direct-writing electrocardiograph in the late 1940s and the introduction of digitoxin in recommended doses (that in retrospect appear inappropriately high), the documented prevalence of digitalis toxicity increased rapidly. With increased understanding of the interaction of electrolytes and digitalis and perhaps, and more importantly, the widespread use of digoxin in doses derived largely from its inotropic action and, thus, inappropriately low for the management of many of the arrhythmias, the prevalence of digitalis toxicity began to decline again. In addition, the advent of serum level determinations and the widespread acceptance of the concept of "therapeutic" levels which, although frequently falling short of the desired clinical end point, served to preclude digitalis toxicity. With the decline in the incidence of digitalis toxicity consequent to these factors, some of the digitalis-related arrhythmias that were common are now rarely observed. This report focuses on arrhythmias that are highly specific for digitalis toxicity and on those that now are less commonly encountered. The discussion and classification of the arrhythmias are based on their most probable electrophysiologic mechanism.
Topics: Animals; Arrhythmias, Cardiac; Digitalis Glycosides; Electrocardiography; Electrophysiology; Heart Block; Heart Conduction System; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Pacemaker, Artificial
PubMed: 3886755
DOI: 10.1016/s0735-1097(85)80467-8 -
Journal of Experimental Pharmacology 2020Over the past 15 years, investigators have reported on the utility and safety of cardiac glycosides for numerous health benefits including those as treatments for... (Review)
Review
Over the past 15 years, investigators have reported on the utility and safety of cardiac glycosides for numerous health benefits including those as treatments for malignant disease, stroke-mediated ischemic injury and certain neurodegenerative diseases. In addition to those, there is a growing body of evidence for novel antiviral effects of selected cardiac glycoside molecules. One unique cardiac glycoside, oleandrin derived from , has been reported to have antiviral activity specifically against 'enveloped' viruses including HIV and HTLV-1. Importantly, a recent publication has presented in vitro evidence for oleandrin's ability to inhibit production of infectious virus particles when used for treatment prior to, as well as after infection by SARS-CoV-2/COVID-19. This review will highlight the known in vitro antiviral effects of oleandrin as well as present previously unpublished effects of this novel cardiac glycoside against Ebola virus, , and Herpes simplex viruses.
PubMed: 33262663
DOI: 10.2147/JEP.S273120 -
Global Cardiology Science & Practice Apr 2021We present the case of a 34-year-old woman with recurrent depressive disorder who ingested purple foxglove with suicidal intent. She bought a foxglove plant over the... (Review)
Review
We present the case of a 34-year-old woman with recurrent depressive disorder who ingested purple foxglove with suicidal intent. She bought a foxglove plant over the internet and used all of its leaves to make a tea that she then drank over a period of a few hours. Seventeen hours later, she developed abdominal pain, emesis and bradycardia and was admitted via the emergency department to the intensive care unit for further treatment and monitoring. The plasma digoxin concentration measured 3.53 nmol/l (therapeutic reference range 0.77-1.50 nmol/l) 21 hours after ingestion of the tea. She remained heamodynamically and neurologically stable, was treated with antiemetics and simple analgesia and did not require digoxin-specific antibodies. Despite normal renal function, her plasma digoxin half-life was prolonged (estimated 76 h), reflecting the long half-life of the parent compound digitoxin which is the main cardiac glycoside in . She was transferred to psychiatric care 48 h after admission. In this report, we compare this case to other similar cases, which to date have only been rarely reported in the literature.
PubMed: 34036088
DOI: 10.21542/gcsp.2021.2 -
International Journal of Molecular... Jul 2022Digitoxin has repeatedly shown to have negative effects on cancer cell viability; however, the actual mechanism is still unknown. In this study, we investigated the...
Digitoxin has repeatedly shown to have negative effects on cancer cell viability; however, the actual mechanism is still unknown. In this study, we investigated the effects of digitoxin (1-100 nM) in four pancreatic cancer cell lines, BxPC-3, CFPAC-1, Panc-1, and AsPC-1. The cell lines differ in their KRAS/BRAF mutational status and primary tumor or metastasis origin. We could detect differences in the basal rates of cell proliferation, glycolysis, and ROS production, giving the cell lines different phenotypes. Digitoxin treatment induced apoptosis in all four cell lines, but to different degrees. Cells derived from primary tumors (Panc-1 and BxPC-3) were highly proliferating with a high proportion of cells in the S/G2 phase, and were more sensitive to digitoxin treatment than the cell lines derived from metastases (CFPAC-1 and AsPC-1), with a high proportion of cells in G0/G1. In addition, the effects of digitoxin on the rate of glycolysis, ROS production, and proliferation were dependent on the basal metabolism and origin of the cells. The KRAS downstream signaling pathways were not altered by digitoxin treatment, thus the effects exerted by digitoxin were probably disconnected from these signaling pathways. We conclude that digitoxin is a promising treatment in highly proliferating pancreatic tumors.
Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Digitoxin; Humans; Pancreatic Neoplasms; Phenotype; Proto-Oncogene Proteins p21(ras); Reactive Oxygen Species
PubMed: 35897809
DOI: 10.3390/ijms23158237