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Therapeutic Drug Monitoring Feb 2015A routine audit revealed that the analytical method used to measure digoxin concentrations by our statewide pathology provider in 2009 was underestimating digoxin...
BACKGROUND
A routine audit revealed that the analytical method used to measure digoxin concentrations by our statewide pathology provider in 2009 was underestimating digoxin concentrations by 10%. The assay was recalibrated by the manufacturer in 2010, but clinical outcomes of the underestimation were never measured. This is a pilot study to describe the prescribing behavior around out-of-range digoxin concentrations and to assess whether miscalibrated digoxin immunoassays contribute to clinically relevant effects, as measured by inappropriate alterations in digoxin doses.
METHODS
About 30,000 digoxin concentrations across the State Hospital system were obtained in 2 periods before and after recalibration of the digoxin assay. Digoxin concentration means were calculated and compared and were statistically significantly different. Subsequently, a single-centered retrospective review of 50 randomly chosen charts was undertaken to study the clinical implications of the underestimated concentrations.
RESULTS
Mean digoxin concentrations for 2009 and 2011 were significantly different by 8.8% (confidence interval, 7.0%-10.6%). After recalculating the 2009 concentrations to their "corrected" values, there was a 16% increase in the number of concentrations within the range when compared with the 2011 concentrations (41.48% versus 48.04%). However, overall, this did not cause unnecessary dose changes in patients who were "borderline" or outside the therapeutic range when compared with controls (P = 0.10). The majority of decisions were based on the clinical impression rather than concentration alone (85.1% versus 14.9%), even when the concentration was outside the "therapeutic range."
CONCLUSIONS
Although recalculating digoxin concentrations measured during 2009 to their corrected values produced a significant change in concentration and values inside and outside the range, this does not seem to have had an influence on patient treatment. Rather, clinicians tended to use the clinical impression to dose digoxin.
Topics: Calibration; Digoxin; Drug Prescriptions; Humans; Immunoassay; Medical Errors; Pilot Projects; Reproducibility of Results; Retrospective Studies
PubMed: 25072948
DOI: 10.1097/FTD.0000000000000118 -
Journal of Accident & Emergency Medicine May 1998A case of digoxin poisoning following the co-administration of digoxin and clarithromycin in a 28 year old male is described. Since the aetiology of chronic digoxin...
A case of digoxin poisoning following the co-administration of digoxin and clarithromycin in a 28 year old male is described. Since the aetiology of chronic digoxin poisoning is often unclear, clinicians should be aware of the potential drug-drug interaction between digoxin and clarithromycin.
Topics: Adult; Anorexia; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Clarithromycin; Digoxin; Drug Interactions; Drug Therapy, Combination; Emergency Service, Hospital; Humans; Male; Vomiting
PubMed: 9639187
DOI: 10.1136/emj.15.3.194 -
Journal of the American College of... Oct 1993Although supported by 2 centuries of anecdotal clinical evidence, the safety and efficacy of the cardiac glycosides for the treatment of congestive heart failure due to... (Comparative Study)
Comparative Study Review
Although supported by 2 centuries of anecdotal clinical evidence, the safety and efficacy of the cardiac glycosides for the treatment of congestive heart failure due to systolic ventricular dysfunction had never been rigorously examined by prospective clinical trials until the past decade. A reevaluation of the appropriate role of these drugs in modern cardiovascular pharmacology was prompted by the introduction in the 1970s of new classes of drugs for the treatment of congestive heart failure and supraventricular arrhythmias. Concurrently, several reports appeared, questioning the routine prescription of digoxin for the treatment of heart failure, particularly in patients in sinus rhythm. The majority of clinical trials published since 1980, most of which examined patients with New York Heart Association class II and III congestive heart failure, indicate that digoxin with or without concomitant administration of a vasodilator lessens symptoms and reduces the morbidity associated with congestive heart failure, particularly in patients with more advanced symptoms and ventricular dysfunction. The data on efficacy are less clear in support of the routine prescription of digoxin in the treatment of mild (class I and II) congestive heart failure. Although most recent trials attest to the relative safety and efficacy of digoxin in patients with congestive heart failure whose serum levels are maintained between 1 and 2 ng/ml, there is no conclusive evidence as yet that cardiac glycosides improve survival, as has been documented for vasodilators and, in particular, angiotensin-converting enzyme inhibitors. The National Institutes of Health-sponsored Digitalis Investigators Group (DIG) trial now underway should provide an answer to this question within the next few years.
Topics: Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 8376681
DOI: 10.1016/0735-1097(93)90472-d -
Biomolecules Mar 2021Cellular senescence is a cellular condition that involves significant changes in gene expression and the arrest of cell proliferation. Recently, it has been suggested in...
Cellular senescence is a cellular condition that involves significant changes in gene expression and the arrest of cell proliferation. Recently, it has been suggested in experimental models that the elimination of senescent cells with pharmacological methods delays, prevents, and improves multiple adverse outcomes related to age. In this sense, the so-called senoylitic compounds are a class of drugs that selectively eliminates senescent cells (SCs) and that could be used in order to delay such adverse outcomes. Interestingly, the first senolytic drug (navitoclax) was discovered by using chemoinformatic and network analyses. Thus, in the present study, we searched for novel senolytic compounds through the use of chemoinformatic tools (fingerprinting and network pharmacology) over different chemical databases (InflamNat and BIOFACQUIM) coming from natural products (NPs) that have proven to be quite remarkable for drug development. As a result of screening, we obtained three molecules (hinokitiol, preussomerin C, and tanshinone I) that could be considered senolytic compound candidates since they share similarities in structure with senolytic leads (tunicamycin, ginsenoside Rb1, ABT 737, rapamycin, navitoclax, timosaponin A-III, digoxin, roxithromycin, and azithromycin) and targets involved in senescence pathways with potential use in the treatment of age-related diseases.
Topics: Aging; Animals; Azithromycin; Biological Products; Cheminformatics; Digoxin; Humans; Roxithromycin
PubMed: 33809876
DOI: 10.3390/biom11030467 -
Systematic Reviews Apr 2017Atrial fibrillation is the most common arrhythmia of the heart with a prevalence of approximately 2% in the western world. Atrial flutter, another arrhythmia, occurs... (Meta-Analysis)
Meta-Analysis
Digoxin versus placebo, no intervention, or other medical interventions for atrial fibrillation and atrial flutter: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis.
BACKGROUND
Atrial fibrillation is the most common arrhythmia of the heart with a prevalence of approximately 2% in the western world. Atrial flutter, another arrhythmia, occurs less often with an incidence of approximately 200,000 new patients per year in the USA. Patients with atrial fibrillation and atrial flutter have an increased risk of death and morbidities. In the management of atrial fibrillation and atrial flutter, it is often necessary to use medical interventions to lower the heart rate. Lowering the heart rate may theoretically prevent the development of heart failure and tachycardia-mediated cardiomyopathy. The evidence on the benefits and harms of digoxin compared with placebo or with other medical interventions is unclear. This protocol for a systematic review aims at identifying the beneficial and harmful effects of digoxin compared with placebo, no intervention, or with other medical interventions for atrial fibrillation and atrial flutter.
METHODS
This protocol for a systematic review was conducted following the recommendations of Cochrane and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials comparing digoxin with placebo, no intervention, or with other medical interventions. We plan to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded on Web of Science, and BIOSIS to identify relevant trials. Any eligible trial will be assessed and classified as either at high risk of bias or low risk of bias, and our primary conclusions will be based on trials with low risk of bias. We will perform our meta-analyses of the extracted data using Review Manager 5.3 and Trial Sequential Analysis ver. 0.9.5.5 beta. For both our primary and secondary outcomes, we will create a 'Summary of Findings' table based on GRADE assessments of the quality of the evidence.
DISCUSSION
The results of this systematic review have the potential to benefit millions of patients worldwide as well as healthcare economy.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42016052935.
Topics: Atrial Fibrillation; Atrial Flutter; Digoxin; Heart Failure; Humans; Placebos; Systematic Reviews as Topic
PubMed: 28381269
DOI: 10.1186/s13643-017-0470-2 -
BMJ (Clinical Research Ed.) Nov 1992
Review
Topics: Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Humans; Time Factors
PubMed: 1463955
DOI: 10.1136/bmj.305.6862.1149 -
Journal of the American College of... Jun 2015
Topics: Atrial Fibrillation; Digoxin; Female; Humans; Male
PubMed: 26112192
DOI: 10.1016/j.jacc.2015.04.044 -
PloS One 2016Some chemicals are ligands to efflux transporters which may result in high concentrations in milk. Limited knowledge is available on the influence of maternal exposure...
Some chemicals are ligands to efflux transporters which may result in high concentrations in milk. Limited knowledge is available on the influence of maternal exposure to chemicals on the expression and function of transporters in the lactating mammary gland. We determined gene expression of ABC and SLC transporters in murine mammary tissue of different gestation and lactation stages, in murine mammary cells (HC11) featuring resting and secreting phenotypes and in bovine mammary tissue and cells (BME-UV). Effects on transporter expression and function of the imidazole fungicide prochloraz, previously reported to influence BCRP in mammary cells, was investigated on transporter expression and function in the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2, OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured in mammary glands of mice were detected in bovine mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME-UV cells. Prochloraz treatment induced MDR1 gene and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin. In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters. An altered expression, induced by a drug or toxic chemical, on any of the transporters expressed in the mammary epithelial cells during lactation may modulate the well-balanced composition of nutrients and/or secretion of contaminants in milk with potential adverse effects on breast-fed infants and dairy consumers.
Topics: ATP-Binding Cassette Transporters; Animals; Biological Transport, Active; Cattle; Cell Line; Digoxin; Female; Gene Expression Regulation; Imidazoles; Mammary Glands, Animal; Mice; Organic Anion Transporters
PubMed: 27028005
DOI: 10.1371/journal.pone.0151904 -
Canadian Journal of Veterinary Research... Apr 1991The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six...
The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six healthy adult Beagle dogs following a multiple-dose regimen of 0.0625 mg every 12 h for 23 days. From days 14 to 23 enrofloxacin was administered orally at a dosage of 2.5 mg/kg every 12 h, with subjects receiving enrofloxacin 2 h prior to digoxin. Trough serum concentrations of digoxin were measured using an immunoassay technique. On days 13 and 22, dogs were catheterized for multiple blood sample collection during the 12 h digoxin dosing interval and serum samples were analyzed for digoxin concentrations. In general, steady-state digoxin concentrations in trough serum were not significantly different during enrofloxacin treatment than before enrofloxacin administration. Similarly, digoxin oral clearance was not significantly different between pre-enrofloxacin and digoxin + enrofloxacin periods. We conclude that enrofloxacin is unlikely to have a significant impact on digoxin disposition in dogs.
Topics: 4-Quinolones; Administration, Oral; Animals; Anti-Infective Agents; Digoxin; Dogs; Drug Interactions; Drug Therapy, Combination; Enrofloxacin; Female; Fluoroquinolones; Male; Quinolones
PubMed: 1884291
DOI: No ID Found -
Postgraduate Medical Journal May 1993
Review
Topics: Charcoal; Digoxin; Humans; Immunoglobulin Fab Fragments; Poisoning
PubMed: 8346128
DOI: 10.1136/pgmj.69.811.337