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Adverse drug reactions (ADR) may cause morbidity and mortality, potential drug-drug interactions (DDI) increase the probability of ADR. Research on ADR and DDI in infants is of particular urgency and importance but the related profiles in these individuals are not well known.
Heart failure (HF) is a syndrome characterized by upregulation of the sympathetic nervous system and abnormal responsiveness of the parasympathetic nervous system. Studies in the 1980s and 1990s demonstrated that inhibition of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors improved symptoms and mortality in HF resulting from systolic dysfunction, thus providing a framework to consider the use of β-blockers for HF therapy, contrary to the prevailing wisdom of the time. Against this backdrop, this article reviews the contemporary understanding of the sympathetic nervous system and the failing heart.
Thirty-six digoxin samples were assayed; in 39% of these, digoxin concentrations were discordant and different dosage adjustments would have followed. The presence of digoxin-like immunoreactive substances may explain some of this discordance. The mean of the equation-based result was similar to the immunoassay results, but marked variability was evident. The DGNA assay produced higher results on 24 samples; 9 higher values occurred with the DRI method.
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If outpatients are allowed to rest in the supine position before their blood is sampled, serum digoxin increases. In a recent study, the serum digoxin concentration after 2-h standardized supine rest correlated better with the clinical status of patients than the value before rest. In the present study, 21 outpatients were studied on 2 consecutive days, approximately 24 h after the latest dose of digoxin. Blood samples for the assay of serum digoxin were taken on arrival at the department and after 1.5- and 2-h rest either supine or sitting (random order). The increases after 1.5-h rest were 12% (0-25%; p less than 0.001) and 12% (-3-47%; p less than 0.001), supine and sitting, respectively. The respective increases after 2-h rest were 14% (-11-32%; p less than 0.001) and 16% (0-74%; p less than 0.001). There were no statistically significant differences between the increases in serum digoxin concentration after supine and sitting rest. These results make it possible to recommend standardized rest in the sitting position (1.5-2 h) for outpatients before blood samples are collected when reliable serum digoxin analyses are of importance.
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The ELISA, in the presence of IgY, provided a sensitivity of the average intraassay coefficient of variation(CV) was 2.03%, and the inter-assay CV was 2.34% respectively. In contrast, IgG were 2.83% and 3.29%. No significant interferences were observed with hydrocortisone and dexamethasone. There was 3.45% vs. 5.95%, 3.20% vs. 5.20% of crossreaction with cedilanid and digoxin.
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To evaluate digoxin pharmacokinetic parameters using Bayesian estimation in 60 patients, and to identify factors that appeared to affect the risk of digoxin toxicity.
In a randomized placebo-controlled double-blind trial of 230 congestive heart failure patients, four treatments were evaluated for efficacy, with exercise tolerance time (ETT) as the primary outcome. Various two-sample tests were applied to the analysis of ETT data. It is shown in this paper that the conventional two-sample tests (t and rank-sum) are insensitive to situations where the effect of the experimental therapy is not consistent across a patient population. Tests recommended by O'Brien are more appropriate for these data. It is also shown that the application of the O'Brien tests led to the identification of sub-groups where the observed effect of the experimental therapy was most pronounced.
Twelve randomly selected general practices (GP) were screened for patients receiving ACE-inhibitor, digoxin, or loop diuretic treatment. The first 500 volunteers of 959 potential subjects were invited to a cardiac examination after exclusion of 235 frail, physically or mentally disabled patients. A diagnosis of heart failure during hospital admission (Hospital-HF, n = 102) was more related (p < 0.05) to male sex (45% vs. 21%), advanced age (73 vs. 70 years), breathlessness (75% vs. 62%), LV systolic dysfunction (47% vs. 20%), objective cardiac abnormality (92% vs. 65%) and higher 4-year mortality (33% vs. 15%) than patients taking loop diuretics due to signs and symptoms of heart failure in GP (GP-HF). Patients without clinical heart failure (n = 301) had the same survival but less symptoms and cardiac abnormalities than GP-HF patients.
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In this study the prescription of drugs in an outpatients geriatric population was evaluated in terms of age and body weight.
Medical history, physical examination, laboratory evaluation (including 72 h stool collection), upper endoscopy, colonoscopy and histologic analysis of biopsy samples.
The mechanism of a renal tubular digoxin-cyclosporin A interaction was elucidated using a kidney epithelial cell line and the isolated perfused rat kidney. The cells expressed an excess amount of human P-glycoprotein on the apical membranes by transfection with MDR1 cDNA. Cyclosporin A inhibited the transepithelial transport of digoxin mediated by human P-glycoprotein; net basal-to-apical transport across the cell monolayer was 22.8, 21.2, 6.61 and 0.91 pmol/mg of protein/3 hr in the presence of 0, 1, 5 and 10 microM cyclosporin A, respectively. Cyclosporin A also reduced the renal tubular secretion of digoxin by the kidney. The ratio of fractional excretion/filtration fraction for digoxin was 2.88 +/- 0.71 (mean +/- S.D.) in the control, and this was decreased to 1.21 +/- 0.09 and 1.05 +/- 0.13 in the presence of 1 and 5 microM cyclosporin A, respectively. Because no signs of acute nephrotoxicity were observed, a direct effect of cyclosporin A accounted for the reduced secretion. On the other hand, digoxin did not affect cyclosporin A transport by P-glycoprotein. These findings indicate that serum concentrations of digoxin in patients should be carefully monitored when administered concurrently with cyclosporin A. The present transepithelial transport system using the transfectant cells is a simple and useful screening system for predicting drug interactions that can occur in a clinical situation.