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International Journal of Molecular... Jan 2023Fetal arrhythmia develops in 0.1-5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely...
Fetal arrhythmia develops in 0.1-5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely initiation of transplacental antiarrhythmic therapy (ART) promotes the conversion of fetal tachycardia to sinus rhythm and the regression of the concomitant non-immune fetal hydrops. The optimal treatment regimen search for the fetus with tachyarrhythmia is still of high value. Polymorphisms of these genes determines the individual features of the drug pharmacokinetics. The aim of this study was to study the pharmacokinetics of transplacental anti-arrhythmic drugs in the fetal therapy of arrhythmias using HPLC-MS/MS, as well as to assess the effect of the multidrug-resistance gene 3435C > T polymorphism on the efficacy and maternal/fetal complications of digoxin treatment. The predisposition to a decrease in the bioavailability of the digoxin in patients with a homozygous variant of the CC polymorphism showed a probable association with the development of ART side effects. A pronounced decrease in heart rate in women with the 3435TT allele of the gene was found. The homozygous TT variant in the fetus showed a probable association with an earlier response to ART and rhythm disruptions on the digoxin dosage reduction. high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) methods for digoxin and sotalol therapeutic drug monitoring in blood plasma, amniotic fluid, and urine were developed. The digoxin and sotalol concentrations were determined in the plasma blood, urine, and amniotic fluid of 30 pregnant women at four time points (from the beginning of the transplacental antiarrhythmic therapy to delivery) and the plasma cord blood of 30 newborns. A high degree of correlation between the level of digoxin and sotalol in maternal and cord blood was found. The ratio of digoxin and sotalol in cord blood to maternal blood was 0.35 (0.27 and 0.46) and 1.0 (0.97 and 1.07), accordingly. The digoxin concentration in the blood of the fetus at the moment of the first rhythm recovery episode, 0.58 (0.46, 0.8) ng/mL, was below the therapeutic interval. This confirms the almost complete transplacental transfer of sotalol and the significant limitation in the case of digoxin. Previously, ABCB1/P-glycoprotein had been shown to limit fetal exposure to drugs. Further studies (including multicenter ones) to clarify the genetic features of the transplacental pharmacokinetics of antiarrhythmic drugs are needed.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chromatography, High Pressure Liquid; Digoxin; Drug Monitoring; Hydrops Fetalis; Pregnant Women; Sotalol; Tachycardia; Tachycardia, Supraventricular; Tandem Mass Spectrometry
PubMed: 36768172
DOI: 10.3390/ijms24031848 -
Dermatologic Therapy Dec 2022Although being a benign lesion, Warts can affect the quality of life by causing discomfort, disfigurement, and social embarrassment besides the tendency to spread.... (Randomized Controlled Trial)
Randomized Controlled Trial
Although being a benign lesion, Warts can affect the quality of life by causing discomfort, disfigurement, and social embarrassment besides the tendency to spread. Cutaneous wart treatment faces many challenges as the development of an antiviral drug that can eradicate the human papilloma virus (HPV) is difficult. This clinical study aimed to assess the efficacy and safety of intralesional combined furosemide and digoxin in the treatment of multiple cutaneous warts. This double blinded randomized clinical trial included 80 adult patients with multiple cutaneous warts (≥2 warts) who were randomized into two groups, Group I (40 patients) treated with intralesional combined furosemide and digoxin and Group II (40 patients) who were treated with intralesional normal saline solution as a control group, weekly till improvement or for maximum five sessions. Clinical and dermoscopic evaluation at baseline, every session, and monthly for 6 months after the last session to detect any recurrence was performed. Complete wart clearance was observed in 92.5% of patients in the intralesional combined furosemide and digoxin group (Group I) compared with 10.0% in saline group (Group II), with highly statistically significant difference (P-value = 0.000). Pain during injection in 95.0% and 45.0% of patients in Group I and Group II respectively, treatment group was superior compared to control group. Intralesional injection of combined furosemide and digoxin can be a safe and effective treatment option in multiple cutaneous warts with minimal side effects in this study.
Topics: Adult; Humans; Furosemide; Digoxin; Quality of Life; Warts; Injections, Intralesional; Treatment Outcome; Papillomaviridae
PubMed: 36226802
DOI: 10.1111/dth.15935 -
World Journal of Gastroenterology Mar 2023Repurposing of the widely available and relatively cheap generic cardiac gly-coside digoxin for non-cardiac indications could have a wide-ranging impact on the global... (Review)
Review
Repurposing of the widely available and relatively cheap generic cardiac gly-coside digoxin for non-cardiac indications could have a wide-ranging impact on the global burden of several diseases. Over the past several years, there have been significant advances in the study of digoxin pharmacology and its potential non-cardiac clinical applications, including anti-inflammatory, antineoplastic, metabolic, and antimicrobial use. Digoxin holds promise in the treatment of gastrointestinal disease, including nonalcoholic steatohepatitis and alcohol-associated steatohepatitis as well as in obesity, cancer, and treatment of viral infections, among other conditions. In this review, we provide a summary of the clinical uses of digoxin to date and discuss recent research on its emerging applications.
Topics: Humans; Digoxin; Non-alcoholic Fatty Liver Disease; Fatty Liver, Alcoholic; Obesity; Anti-Inflammatory Agents
PubMed: 37032732
DOI: 10.3748/wjg.v29.i12.1824 -
Cancers Dec 2020Estrogen receptor α expressing breast cancers (BC) are classically treated with endocrine therapy. Prolonged endocrine therapy often results in a metastatic disease...
Estrogen receptor α expressing breast cancers (BC) are classically treated with endocrine therapy. Prolonged endocrine therapy often results in a metastatic disease (MBC), for which a standardized effective therapy is still lacking. Thus, new drugs are required for primary and metastatic BC treatment. Here, we report that the Food and Drug Administration (FDA)-approved drugs, ouabain and digoxin, induce ERα degradation and prevent proliferation in cells modeling primary and metastatic BC. Ouabain and digoxin activate the cellular proteasome, instigating ERα degradation, which causes the inhibition of 17β-estradiol signaling, induces the cell cycle blockade in the G2 phase, and triggers apoptosis. Remarkably, these effects are independent of the inhibition of the Na/K pump. The antiproliferative effects of ouabain and digoxin occur also in diverse cancer models (i.e., tumor spheroids and xenografts). Additionally, gene profiling analysis reveals that these drugs downregulate the expression of genes related to endocrine therapy resistance. Therefore, ouabain and digoxin behave as 'anti-estrogen'-like drugs, and are appealing candidates for the treatment of primary and metastatic BCs.
PubMed: 33352737
DOI: 10.3390/cancers12123840 -
The American Journal of Medicine Oct 2019Over the past 2 decades, guidelines for digoxin use have changed significantly. However, little is known about the national-level trends of digoxin use, hospitalizations...
BACKGROUND
Over the past 2 decades, guidelines for digoxin use have changed significantly. However, little is known about the national-level trends of digoxin use, hospitalizations for toxicity, and subsequent outcomes over this time period.
METHODS
To describe digoxin prescription trends, we conducted a population-level, cohort study using data from IQVIA, Inc.'s National Prescription Audit (2007-2014) for patients aged ≥65 years. Further, in a national cohort of Medicare fee-for-service beneficiaries aged ≥65 years in the United States, we assessed temporal trends of hospitalizations associated with digoxin toxicity and the outcomes of these hospitalizations between 1999 and 2013.
RESULTS
From 2007 through 2014, the number of digoxin prescriptions dispensed decreased by 46.4%; from 8,099,856 to 4,343,735. From 1999 through 2013, the rate of hospitalizations with a principal or secondary diagnosis of digoxin toxicity decreased from 15 to 2 per 100,000 person-years among Medicare fee-for-service beneficiaries. In-hospital and 30-day mortality rates associated with hospitalization for digoxin toxicity decreased significantly among Medicare fee-for-service beneficiaries; from 6.0% (95% confidence interval [CI], 5.2-6.8) to 3.7% (95% CI, 2.2-5.7) and from 14.0% (95% CI, 13.0-15.2) to 10.1% (95% CI, 7.6-13.0), respectively. Rates of 30-day readmission for digoxin toxicity decreased from 23.5% (95% CI, 22.1-24.9) in 1999 to 21.7% (95% CI, 18.0-25.4) in 2013 (P < .05).
CONCLUSION
While digoxin prescriptions have decreased, it is still widely prescribed. However, the rate of hospitalizations for digoxin toxicity and adverse outcomes associated with these hospitalizations have decreased. These findings reflect the changing clinical practice of digoxin use, aligned with the changes in clinical guidelines.
Topics: Aged; Aged, 80 and over; Cohort Studies; Digoxin; Female; Heart Failure; Humans; Male; Practice Patterns, Physicians'; Retrospective Studies; United States
PubMed: 31077654
DOI: 10.1016/j.amjmed.2019.04.022 -
American Journal of Medicine Open Dec 2023Studies show that digoxin use is declining but is still prevalent. Recent data on digoxin prescription and characteristics of digoxin prescribers are unknown, which can...
BACKGROUND
Studies show that digoxin use is declining but is still prevalent. Recent data on digoxin prescription and characteristics of digoxin prescribers are unknown, which can help understand its contemporary use.
METHODS
Using Medicare Part D data from 2013 to 2019, we studied the change in number and proportion of digoxin prescriptions and digoxin prescribers, overall and by specialty. Using logistic regression, we identified prescriber characteristics associated with digoxin prescription.
RESULTS
From 2013 to 2019, total digoxin prescriptions (4.6 to 1.8 million) and proportion of digoxin prescribers decreased (9.1% to 4.3% overall; 26.6% to 11.8% among General Medicine prescribers and 65.4% to 48.9% among Cardiology). Of digoxin prescribers from 2013 practicing in 2019 (91.2% remained active), 59.1% did not prescribe digoxin at all, 31.7% reduced, and 9.2% maintained or increased prescriptions. The proportion of all digoxin prescriptions that were prescribed by General Medicine prescribers declined from 59.7% to 48.2% and increased for Cardiology (29% to 38.5%). Among new prescribers in 2019 ( = 85,508), only 1.9% prescribed digoxin. Digoxin prescribers when compared to non-digoxin prescribers were more likely male, graduated from medical school earlier, were located in the Midwest or South, and belonged to Cardiology (all < .001).
CONCLUSIONS
Digoxin prescriptions continue to decline with over half of 2013 prescribers no longer prescribing digoxin in 2019. This may be a result of the increasing availability of newer heart failure therapies. The decline in digoxin prescription was greater among general medicine physicians than cardiologists, suggesting a change in digoxin use to a medication prescribed increasingly by specialists.
PubMed: 38213879
DOI: 10.1016/j.ajmo.2023.100048 -
Pediatrics International : Official... 2023Atrial flutter is an uncommon arrhythmia that can cause severe morbidity, including heart failure and even death in refractory cases. This study investigated the...
BACKGROUND
Atrial flutter is an uncommon arrhythmia that can cause severe morbidity, including heart failure and even death in refractory cases. This study investigated the clinical characteristics, treatment, and long-term outcomes of patients with neonatal atrial flutter and its association with heart failure.
METHODS
We retrospectively reviewed atrial flutter cases observed in our center between 1999 and 2021 and analyzed the clinical characteristics, treatment, and recurrence according to the presence of heart failure.
RESULTS
The study comprised 15 patients with atrial flutter, with median bodyweight and gestational age of 2.7 kg, 37 weeks, respectively. Twelve patients were diagnosed with atrial flutter on the first day of life. The median atrial and ventricular rates were 440/min, 220/min, respectively. Four patients exhibited congestive heart failure. Episodic recurrence was noted in five patients and occurred at a higher rate in patients with congestive heart failure (p = 0.004). Antiarrhythmic drugs for maintenance treatment were administered more often in patients with heart failure (p = 0.011). Initial treatment included direct current cardioversion (n = 9), digoxin (n = 4), and observation (n = 2). Four patients treated with cardioversion experienced recurrence during the neonatal period, and none of those treated with digoxin experienced recurrence. The median follow-up duration was 7 years, during which no atrial flutter recurrence was evident.
CONCLUSION
Neonates with congestive heart failure had a higher recurrence of atrial flutter. Direct current cardioversion is the most reliable treatment for neonatal atrial flutter, whereas digoxin may be a viable treatment option in refractory and recurrent cases.
Topics: Infant, Newborn; Humans; Atrial Flutter; Retrospective Studies; Digoxin; Anti-Arrhythmia Agents; Heart Failure
PubMed: 38108210
DOI: 10.1111/ped.15714 -
Expert Review of Cardiovascular Therapy Aug 2022Infants with single ventricle congenital heart disease are vulnerable to complications between stage 1 and stage 2 of palliation. Pharmaceutical treatment during this... (Review)
Review
INTRODUCTION
Infants with single ventricle congenital heart disease are vulnerable to complications between stage 1 and stage 2 of palliation. Pharmaceutical treatment during this period is varied and often dependent on institutional practices as there is little evidence supporting a particular treatment path.
AREAS COVERED
This review focuses on medical management of patients following stage I palliation. We performed a scoping review of the current literature regarding angiotensin converting enzyme inhibitors and digoxin treatment in the interstage period. In addition, we discuss other medication classes frequently used in these patients.
EXPERT OPINION
Due to significant heterogeneity of anatomy, rarity of disease, and other confounding factors, there is limited evidence to support most commonly used medications within the interstage period. Digoxin is associated with improved mortality within the interstage period and should be considered; however, no large randomized controlled trial exists supporting its use. Prevention of thrombotic complication with aspirin is also associated with improved outcomes and should be considered unless a contraindication exists. The addition of other prescriptions in this patient population should be considered only after an evaluation of the risks and benefits of each medication, recognizing the burden and risk of polypharmacy in this fragile patient population.
Topics: Digoxin; Heart Defects, Congenital; Heart Ventricles; Humans; Hypoplastic Left Heart Syndrome; Infant; Norwood Procedures; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 35848073
DOI: 10.1080/14779072.2022.2103542 -
Molecular Neurobiology Jan 2023Astrocyte reaction is a complex cellular process involving astrocytes in response to various types of CNS injury and a marker of neurotoxicity. It has been abundantly...
Astrocyte reaction is a complex cellular process involving astrocytes in response to various types of CNS injury and a marker of neurotoxicity. It has been abundantly studied in rodents but relatively poorly in human cells due to limited access to the brain. Astrocytes play important roles in cerebral energy metabolism and are also key players in neuroinflammation. Astroglial metabolic and inflammatory changes have been reported with age, leading to the hypothesis that mitochondrial metabolism and inflammatory responses are interconnected. However, the relationship between energy metabolism and astrocyte reactivity in the context of neurotoxicity is not known. We hypothesized that changes in energy metabolism of astrocytes will be coupled to their activation by xenobiotics. Astrocyte reaction and associated energy metabolic changes were assessed by immunostaining, gene expression, proteomics, metabolomics, and extracellular flux analyses after 24 h of exposure of human ReN-derived astrocytes to digoxin (1-10 µM) or TNFα (30 ng/ml) used as a positive control. Strong astrocytic reaction was observed, accompanied by increased glycolysis at low concentrations of digoxin (0.1 and 0.5 µM) and after TNFα exposure, suggesting that increased glycolysis may be a common feature of reactive astrocytes, independent of the triggering molecule. In conclusion, whether astrocyte activation is triggered by cytokines or a xenobiotic, it is strongly tied to energy metabolism in human ReN-derived astrocytes. Increased glycolysis might be considered as an endpoint to detect astrocyte activation by potentially neurotoxic compounds in vitro. Finally, ReN-derived astrocytes may help to decipher mechanisms of neurotoxicity in ascertaining the ability of chemicals to directly target astrocytes.
Topics: Humans; Astrocytes; Central Nervous System; Digoxin; Energy Metabolism; Tumor Necrosis Factor-alpha; Cells, Cultured
PubMed: 36223047
DOI: 10.1007/s12035-022-03057-1 -
American Journal of Therapeutics 2020Many patients receiving dabigatran treatment might also require bisoprolol therapy. However, there is a possibility that bisoprolol as significant P-glycoprotein...
BACKGROUND
Many patients receiving dabigatran treatment might also require bisoprolol therapy. However, there is a possibility that bisoprolol as significant P-glycoprotein inhibitor might interact with dabigatran.
STUDY QUESTION
To investigate the impact of concomitant bisoprolol therapy on dabigatran plasma level in patients with nonvalvular atrial fibrillation.
STUDY DESIGN
A pilot drug interaction study in 29 patients with nonvalvular atrial fibrillation on dabigatran therapy. Bisoprolol was administrated in 18 patients. Blood samples were collected at baseline (in the morning, before any medication was administered) and at hour 2 (2 hours after administration of dabigatran and bisoprolol).
RESULTS
The dabigatran plasma level was significantly higher at baseline and at hour 2 in patients treated with bisoprolol compared with patients without bisoprolol therapy. In addition, we have shown that this increase is affected by dabigatran dosage and concomitant treatment with proton-pump inhibitor and digoxin. The impact of bisoprolol on dabigatran concentration was still significant despite these confounders.
CONCLUSIONS
This study demonstrated the interaction between dabigatran and bisoprolol, which is modulated with dabigatran dosage and concomitant treatment with proton-pump inhibitor and digoxin.
Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Cardiotonic Agents; Dabigatran; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Pilot Projects; Proton Pump Inhibitors
PubMed: 30074534
DOI: 10.1097/MJT.0000000000000786