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Basic & Clinical Pharmacology &... Jun 2022Digoxin is used for rate control in atrial fibrillation (AF), but evidence for its efficacy and safety after myocardial infarction (MI) is scarce and mixed. We studied...
Digoxin is used for rate control in atrial fibrillation (AF), but evidence for its efficacy and safety after myocardial infarction (MI) is scarce and mixed. We studied post-MI digoxin use effects on AF patient outcomes in a nationwide registry follow-up study in Finland. Digoxin was used by 18.6% of AF patients after MI, with a decreasing usage trend during 2004-2014. Baseline differences in digoxin users (n = 881) and controls (n = 3898) were balanced with inverse probability of treatment weight adjustment. The median follow-up was 7.4 years. Patients using digoxin after MI had a higher cumulative all-cause mortality (77.4% vs. 72.3%; hazard ratio [HR]: 1.19; confidence interval [CI]: 1.07-1.32; p = 0.001) during a 10-year follow-up. Mortality differences were detected in a subgroup analysis of patients without baseline heart failure (HF) (HR: 1.23; p = 0.019) but not in patients with baseline HF (HR: 1.05; p = 0.413). Cumulative incidences of HF hospitalizations, stroke and new MI were similar between digoxin group and controls. In conclusion, digoxin use after MI is associated with increased mortality but not with HF hospitalizations, new MI or stroke in AF patients. Increased mortality was detected in patients without baseline HF. Results suggest caution with digoxin after MI in AF patients, especially in the absence of HF.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Follow-Up Studies; Heart Failure; Humans; Myocardial Infarction; Risk Factors; Stroke
PubMed: 35420260
DOI: 10.1111/bcpt.13733 -
Chronic Digoxin Toxicity: An Evaluation of Digoxin-Specific Antibodies and Other Management Options.Cureus May 2023Chronic digoxin toxicity comprises the bulk of digoxin poisonings and can be more difficult to manage than acute intoxications. A 60-year-old lady presented with severe...
Chronic digoxin toxicity comprises the bulk of digoxin poisonings and can be more difficult to manage than acute intoxications. A 60-year-old lady presented with severe chronic digoxin toxicity after ingesting digoxin 250mcg twice a day (BD) for two weeks. Due to hemodynamic instability on presentation, she was treated with digoxin-specific antibodies and admitted to the coronary care unit. This case of chronic digoxin toxicity did not respond to digoxin-specific antibodies and required intensive cardiac therapy with isoprenaline and intravenous electrolyte replacement, highlighting the complexities in the management of toxicity. Our patient has since recovered and remains stable. There are newer, novel therapies being trialed for the treatment of digoxin toxicity, including dextrose-insulin infusions, therapeutic plasma exchange, and rifampicin, but these require more research and investigation in this cohort of patients.
PubMed: 37292530
DOI: 10.7759/cureus.38692 -
The Journal of Maternal-fetal &... Sep 2022To present the crucial role of echocardiographic examination in perinatal care and analyze influence of prenatal treatment for neonatal outcome. Furthermore, the attempt...
OBJECTIVES
To present the crucial role of echocardiographic examination in perinatal care and analyze influence of prenatal treatment for neonatal outcome. Furthermore, the attempt to answer the question if there was any relationship between the occurrence of fetal Ebstein's anomaly and environmental risk factors in polish population.
METHODS
Forty-five prenatal diagnoses of Ebstein's anomaly were compiled over the 21-year period (1998‒2018) form our single unit. The analysis included the assessment of maternal parameters (age, past obstetric history, and place of residence) and fetal parameters (sex, gestational age, anatomy, the fetal cardiovascular condition assessed by the CVPS, associated extracardiac anomalies or malformations, prenatal treatment, delivery and follow-up).
RESULTS
The average age of gravida was 29.5 years (± 5.2 years) and gravidae <35 years of age accounted for 80% . There were 43 singleton pregnancies and 2 cases of multiple pregnancy. Ebstein's anomaly was mostly (averagely) diagnosed at 28th week of gestation. Forty-three fetuses had normal karyotypes and two had trisomy 21. Cardiomegaly was present in 91% (41) of fetuses. The average heart area to chest area ratio was 0.56 (± 0.12). In 21 cases, there was only fetal monitoring - echocardiographic examinations and postnatal mortality was 44.4%. In 5 cases, transplacental digoxin treatment was administered and mortality was: 40%. In another 5 cases, only steroid therapy was applied and postnatal mortality was 100%. Steroids and transplacental digoxin treatment were administered in 11 cases and mortality was 63.6%. In 3 last cases transplacental digoxin treatment, steroids and maternal hyperoxygenation therapy were given and mortality was 0%. Cesarean section rate was 49%. Moreover, due to Ebstein's anomaly regional peak of occurrence benzopyrene was deliberated as environmental risk factor.
CONCLUSIONS
Fetal Ebstein's anomaly occurred in our population in healthy young women, expecting their first child and malformation was not related to fetus gender, nor to maternal health condition. Our data can be a new signal for the development of novel treatment strategies in therapy in fetuses with Ebstein's anomaly.
Topics: Adult; Cesarean Section; Digoxin; Ebstein Anomaly; Female; Fetal Diseases; Humans; Infant, Newborn; Pregnancy; Retrospective Studies
PubMed: 32933366
DOI: 10.1080/14767058.2020.1818207 -
Journal of Clinical and Translational... Aug 2022The safety and efficacy of the antiarrhythmic agents, amiodarone, and digoxin, in patients with pulmonary hypertension (PH), is not described well in the literature,...
BACKGROUND AND AIM
The safety and efficacy of the antiarrhythmic agents, amiodarone, and digoxin, in patients with pulmonary hypertension (PH), is not described well in the literature, although their use is common practice. Our study aims to investigate the effect of these drugs on pulmonary arteries (PA) which may have implications for their use in patients with PH.
METHODS
Human PAs were obtained from consenting patients undergoing lobectomies. Arterials rings (n=40 from ten patients) were dissected form the tissue and mounted onto a multiwire myograph. The rings were preconstricted using prostaglandin F2α before the addition of additive dilutions of amiodarone and digoxin. Finally, the reagents were washed out and the arterial rings' viability was confirmed using acetylcholine and potassium chloride.
RESULTS
Amiodarone had a slightly vasodilatory effect on the arterial rings, whereas digoxin had a relatively neutral effect. Amiodarone caused the greatest vasodilatory response at 100 µM with an active tension of -0.494 gram force with an EC50 of 9.42 µM. Digoxin produced no significant vasodilatory or vasoconstrictive response.
CONCLUSIONS
This study demonstrated the ex vivo effects of amiodarone and digoxin on human pulmonary arterial tension. The results of the study showed that neither amiodarone nor digoxin had any vasoconstrictive effects. Amiodarone also exhibited vasodilatory properties and, therefore, may be used preferentially as it could help reduce the impact of PH. However, more studies need to be conducted before we can confirm the safety of these drugs.
RELEVANCE FOR PATIENTS
The ambivalence surrounding treatment of postoperative arrhythmias in patients with PH results is a significant disparity between individual cases. Our study takes the first step in elucidating, in which drugs may be a safer treatment for patients with the aim to resolve the doubts clinicians may have about using these treatments. The principal goal of our work is to ensure that we are providing patients with the most effective and, more importantly, safest treatment.
PubMed: 35991084
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Oct 2023Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug...
Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1-15), followed by RIF40 (days 16-30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%-115%); tolbutamide, 80% (74%-86%); omeprazole, 55% (47%-65%); dextromethorphan, 77% (68%-86%); midazolam, 62% (49%-78%), and 117% (105%-130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number NCT04525235.
Topics: Adult; Humans; Cytochrome P-450 CYP1A2; Midazolam; Cytochrome P-450 CYP2D6; Caffeine; Rifampin; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Dextromethorphan; Tolbutamide; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Omeprazole; Drug Interactions; Tuberculosis, Pulmonary; Digoxin
PubMed: 37768317
DOI: 10.1128/aac.00683-23 -
American Journal of Cardiovascular... Sep 2022Digoxin is indicated for the management of heart failure with reduced ejection fraction and atrial fibrillation. Despite stronger guideline recommendations for other...
BACKGROUND
Digoxin is indicated for the management of heart failure with reduced ejection fraction and atrial fibrillation. Despite stronger guideline recommendations for other pharmacologic and device therapies, digoxin retains a role in select patients unable to tolerate or refractory to standard therapies. Contemporary utilization of and costs related to digoxin in the United States of America (USA) remain uncharacterized. The objective of this study was to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017.
METHODS
We utilized the Medical Expenditure Panel Survey to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. The Medical Expenditure Panel Survey is an overlapping panel survey that interviews households in the USA to ascertain their healthcare utilization and expenditures. Complex sampling procedures allow for nationally representative estimates of utilization and expenditures. We report the number of digoxin users and expenditures across key subgroups in 2-year increments from 2010 to 2017.
RESULTS
The number of digoxin users in the USA declined by 47% from 766 users per 100,000 adults in 2010-11 to 402 users per 100,000 adults in 2016-17. While digoxin use declined among women and self-identified White adults, adults living at or below the federal poverty level and those who self-identified as Asian or Hispanic represent an increasing proportion of overall digoxin users. While nationwide digoxin expenditures declined by 26% from 2010-11 to 2012-13, they peaked at $260.3 million in 2014-15 and remained elevated at $188.7 million in 2016-17.
CONCLUSIONS
Despite a nationwide trend towards declining use, digoxin remains prevalent amongst people of Asian and Hispanic descent in the USA. After a spike in cost in 2013, digoxin prices have yet to return to pre-spike levels. The role of digoxin in contemporary heart failure and arrhythmia management will continue to evolve as additional randomized and observational analyses become available.
Topics: Adult; Digoxin; Female; Health Expenditures; Heart Failure; Humans; Patient Acceptance of Health Care; Surveys and Questionnaires; United States
PubMed: 35739347
DOI: 10.1007/s40256-022-00540-x -
Current Drug Targets 2023One of the major indications for digoxin use is the treatment of heart failure (HF). Although the clinical application of digoxin in long-term outcomes in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
One of the major indications for digoxin use is the treatment of heart failure (HF). Although the clinical application of digoxin in long-term outcomes in patients with HF and reduced ejection fraction (HFrEF) patients is well explained, the association between digoxin therapy and outcomes in patients with HF and preserved ejection fraction (HFpEF) is not very clear.
OBJECTIVES
The aim of this study was to show the clinical efficacy of digoxin on long-term outcomes in subjects with HFpEF.
METHODS
PubMed, Embase, Scopus and Web of Science (ISI) electronic databases were searched until May 2021 to obtain relevant studies. The primary outcome was all-cause mortality attributed to treatment with digoxin. The secondary outcomes were "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF".
RESULTS
Seven studies with more than 23000 patients with HFpEF, of which more than 4900 were treated with digoxin, fulfilled the eligibility criteria and were included in this meta-analysis. Treatment with digoxin was associated with a neutral effect on all-cause mortality (HR 1.04, 95 % CI 0.91-1.20, I2 = 57.9 %), all-cause hospitalization (HR 0.97, 95 % CI 0.88-1.07, I2 = 0.0 %), HFhospitalization (HR 0.96, 95 % CI 0.90-1.02, I2 = 41.4 %), and all-cause mortality or HFhospitalization (HR 1.07, 95 % CI 0.91-1.26, I2 = 81.2 %). In subgroup meta-analyses based on ejection fraction (EF), treatment with digoxin did not significantly alter these outcomes in each subset of patients.
CONCLUSION
The results of this meta-analysis suggest that digoxin does not have any significant effect on long-term outcomes of HFpEF patients, including "all-cause mortality", "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF".
Topics: Humans; Digoxin; Heart Failure; Hospitalization; Prognosis; Stroke Volume; Treatment Outcome; Cardiotonic Agents
PubMed: 36065922
DOI: 10.2174/1389450123666220906093058 -
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 -
Cardiovascular Toxicology Jan 2022In the present study, we investigated the cardioactive glycosides oleandrin and ouabain, and compared them to digoxin in a model of cardiotoxicity induced by... (Comparative Study)
Comparative Study
In the present study, we investigated the cardioactive glycosides oleandrin and ouabain, and compared them to digoxin in a model of cardiotoxicity induced by doxorubicin. Adult rats were distributed into four experimental groups. Each group was challenged with a single intraperitoneal application of doxorubicin at a dose of 12 mg/kg. Then, they were treated with saline solution and the glycosides oleandrin, ouabain, and digoxin at a dose of 50 µg/kg, for 7 days. They underwent echocardiography, electrocardiography, hematologic, biochemical tests, and microscopic evaluation of the heart. All animals presented congestive heart failure, which was verified by a reduction in the ejection fraction. Oleandrin and digoxin were able to significantly reduce (p < 0.05) the eccentric remodeling caused by doxorubicin. Oleandrin and digoxin were significantly lower (p < 0.05) than the control group in maintaining systolic volume and left ventricular volume in diastole. Other parameters evaluated did not show significant statistical differences. All animals showed an increase in erythrocyte count, and an increase in the duration of the QRS complex on the ECG and myocardial necrosis at the histopathological analysis. It is concluded that the glycosides oleandrin, ouabain, and digoxin in the used dosage do not present therapeutic potential for the treatment of congestive heart failure caused by doxorubicin.
Topics: Animals; Cardenolides; Cardiac Glycosides; Cardiotonic Agents; Cardiotoxicity; Digoxin; Disease Models, Animal; Doxorubicin; Heart Failure; Ouabain; Rats, Wistar; Recovery of Function; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling; Rats
PubMed: 34655414
DOI: 10.1007/s12012-021-09702-w -
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