digitoxin and Inflammation

In the 19th century, cardio-active steroid glycosides, shortly cardiac glycosides, were scientifically established as drugs against heart failure. Their

Topics: Anti-Inflammatory Agents; Cardiac Glycosides; Cell Proliferation; Digitalis; Heart; Humans; Inflammation; Myocardium; Signal Transduction; Sodium-Potassium-Exchanging ATPase

Cystic fibrosis (CF) lung disease progresses by a combination of airway inflammation, bacterial colonization, and infection. Airway inflammation is predominantly neutrophilic and complicates airway clearance therapies through cellular debris; excessive DNA; excessive and viscous mucus; and high concentrations of neutrophils, IL-8, and related cytokines liberated along the nuclear factor-κB signaling pathway.. We conducted a preliminary, single-site, randomized, double-blind, placebo-controlled study to evaluate the effects over 28 days of two dose levels (0.05 mg and 0.1 mg daily) of an older cardiac glycoside, digitoxin, as compared with placebo, on safety, pharmacokinetics, and inflammatory markers in induced sputum obtained from 24 subjects with mild to moderate CF lung disease.. Patients with CF 18-45 years old with any genotype combination were eligible. The primary objective was to measure the effects of digitoxin on IL-8 and neutrophil counts in induced sputum. Secondary objectives were to measure (1) the pharmacokinetics of digitoxin in sera of patients with stable CF; (2) safety indices, including ECG changes and sputum microbiology; (3) the effect of digitoxin on gene expression in nasal epithelial cells of patients with stable CF; and (4) quality-of-life scores using the Cystic Fibrosis Questionnaire-Revised.. It took several weeks to achieve a therapeutic serum level of digitoxin in subjects with CF. No safety concerns emerged during the study. Digitoxin treatment showed a trend toward reduction in sputum free neutrophil elastase and neutrophil counts, but not a reduction in sputum IL-8. Digitoxin treatment did not reach statistical significance for the primary or secondary outcome measures over the 28-day study period. However, the nasal mRNA from the group receiving 0.1 mg of digitoxin daily had a distinct distribution of global gene expression levels as compared with either the 0.05-mg dose or placebo treatment. The mRNAs encoding chemokine/cytokine or cell surface receptors in immune cells were decreased in nasal epithelial cells at the higher dose, leading to pathway-mediated reductions in IL-8, IL-6, lung epithelial inflammation, neutrophil recruitment, and mucus hypersecretion.. At a dose of 0.1 mg daily for 28 days, digitoxin was safe for adults with CF lung disease, but it did not achieve a significant decrease in sputum inflammatory markers. Clinical trial registered with www.clinicaltrials.gov (NCT00782288).

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Biomarkers; Cystic Fibrosis; Digitoxin; Double-Blind Method; Female; Humans; Inflammation; Interleukin-8; Leukocyte Count; Lung; Male; Maryland; Neutrophils; Sputum; Young Adult

New-onset of atrial fibrillation (NOAF) in critically ill patients is the most common acute cardiac dysrhythmia, but evidence-based data regarding treatment strategies are scarce. In this retrospective monocentric study, we compared effectiveness of amiodarone versus digitalis for heart rate control in critically ill patients with new-onset of atrial fibrillation. We identified a total of 209 patients for the main analysis. Amiodarone as compared to digitalis was associated with a clinically relevant faster time to heart rate control < 110 bpm (2 h (IQR: 1 h to 6 h) versus 4 h (2 h to 12 h); p = 0.003) and longer durations of sinus rhythm during the first 24 h of treatment (6 h (IQR: 6 h to 22 h) versus 0 h (IQR: 0 h to 16 h); p < 0.001). However, more bradycardic episodes occurred in association with amiodarone than with digitalis (7.7% versus 3.4%; p = 0.019). Use of amiodarone was associated with an increase of noradrenalin infusion rate compared to digitalis (23.9% versus 12.0%; p = 0.019). Within the tertile of patients with the highest CRP measurements, amiodarone treated patients presented with a higher decrease in heart rate than digoxin treated patients. Clinical trials comparing different NOAF treatment strategies are much needed and should report on concomitant sympathetic activity and inflammatory status.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Critical Illness; Digitalis; Digoxin; Female; Heart Rate; Humans; Inflammation; Male; Middle Aged; Propensity Score; Retrospective Studies; Sepsis; Treatment Outcome

Inter-individual variation in drug serum protein binding was studied in healthy dogs and in dogs with inflammatory diseases for lidocaine, oxprenolol and propranolol, which bind mainly to alpha 1-acid glycoprotein (alpha 1-AGP), and for diazepam, digitoxin and phenytoin, which bind mainly to albumin. For the drugs mostly bound to alpha 1-AGP, in both groups of dogs binding varied considerably, and it was markedly higher in dogs with inflammatory disease. For the other drugs, the variation in binding was smaller and did not differ between the two groups of dogs. In both groups of dogs, the alpha 1-AGP concentration varied widely; it was higher in the serum of the dogs with inflammation, while the concentration of albumin was lower in these animals. There was a significant negative correlation between percentage free lidocaine, oxprenolol or propranolol and alpha 1-AGP concentration, suggesting that the inter-individual variation in binding of these drugs is due to the variation in alpha 1-AGP concentration. There was a marked intra-individual variation in lidocaine binding and in serum alpha 1-AGP concentration, studied over a period of 3 weeks in healthy dogs; a significant negative correlation between percentage free lidocaine and alpha 1-AGP concentration was obtained.

Topics: Animals; Blood Sedimentation; Diazepam; Digitoxin; Dog Diseases; Dogs; Female; Inflammation; Lidocaine; Male; Orosomucoid; Oxprenolol; Phenytoin; Propranolol; Protein Binding; Reference Values; Serum Albumin

Topics: Conjunctivitis; Dermatitis; Digitalis; Digitalis Glycosides; Dogs; Inflammation; Pharmacology; Plants, Medicinal; Rabbits; Research

Topics: Anti-Inflammatory Agents; Digitalis; Digitalis Glycosides; Hydrocortisone; Inflammation