Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Digoxin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources
PubMed1993

Effect of autonomic blockade on digoxin-induced ECG changes at rest and during exercise in healthy subjects.

The effect of pharmacological autonomic blockade on digoxin-induced electrocardiographic changes at rest and during exercise was studied in nine healthy men. The subjects performed bicycle exercise tests on four occasions after: (1) intravenous injection of sodium chloride, (2) intravenous injection of propranolol and atropine, (3) oral ingestion of digoxin 0.5 mg daily for 2 weeks and intravenous injection of sodium chloride, and (4) oral ingestion of digoxin 0.5 mg daily for 2 weeks and intravenous injection of propranolol and atropine. The ST-T segment was significantly depressed after digoxin plus sodium chloride and digoxin plus propranolol and atropine in comparison with sodium chloride only and propranolol and atropine only. The digoxin-induced ST-T changes after sodium chloride and propranolol-atropine injections were not significantly different. Thus, judging from the results of this study, an effect mediated via the autonomic nervous system is an unlikely explanation of digitalis-induced ST-T changes.

Adult↗
PubMed1993

P-glycoprotein-mediated renal tubular secretion of digoxin: the toxicological significance of the urine-blood barrier model.

We provide direct evidence that verapamil inhibits active digoxin secretion in renal tubular cells (LLC-PK1), and that verapamil increases cellular accumulation of digoxin. These findings suggest that verapamil inhibits the digoxin active secretory transport at the apical membranes, supporting the theory that P-glycoprotein mediates digoxin secretion in the renal tubular cells. Based on existing data on digoxin transport, we present a hypothetical model for the renal handling of digoxin, implying that P-glycoprotein functions as a driving mechanism of a unidirectional "urine-blood" barrier.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Ibopamine as a substitute for digitalis in patients with congestive heart failure on chronic digoxin therapy. Smith Kline and French Ibopamine Group.

The substitution of digoxin with ibopamine, a new inotropic and vasodilating agent, was evaluated in a multicenter study in 58 patients with mild-to-moderate congestive heart failure, stabilized on diuretics, and digoxin therapy. The study was a parallel, double-blind, randomized trial of four weeks duration in which half of the group continued the pre-study medication (diuretics and digoxin) and half of the group was treated with diuretics and ibopamine (100 mg, three times a day). At baseline evaluation, the two groups were similar for age, sex, underlying cardiac disease, duration of congestive heart failure, symptom score, cardiothoracic ratio, echocardiographic parameters of left ventricular function and exercise tolerance as measured by bicycle ergometry. After four weeks, no clinical deterioration was found in the patients treated with ibopamine in any measured parameter. There were two deaths during the study: a sudden death and one following an acute myocardial infarction. Both patients were on digoxin. This study suggests that in patients with mild-to-moderate congestive heart failure, ibopamine therapy may effectively and safely substitute digoxin therapy for up to four weeks, representing an option for patients requiring inotropic support but are at risk for potential digoxin toxicity.

Adult↗
PubMed1990

Intra-cellular electrolyte changes and levels of endogenous digoxin-like substance within the plasma in patients with congestive heart failure.

In this study, the lymphocytes and erythrocytes from peripheral venous blood were used as the study model from which were measured the cellular contents of potassium, sodium, calcium and magnesium in 50 patients with chronic congestive heart failure and 39 control patients. Levels of endogenous digoxin-like substance in the plasma and activities of Na/K ATPase in red cell membrane wer monitored simultaneously. In the patients with heart failure, the intracellular contents of potassium and magnesium were decreased while those of sodium and calcium were increased significantly. The levels of endogenous digoxin-like substance were much higher in the plasma than those either in healthy controls or in patients with heart disease but without congestive failure (273.7 +/- 35.5 vs 23.3 +/- 2.2 and vs 32.9 +/- 3.6 pg/ml, respectively, P less than 0.001 for both). The activities of Na/K-ATPase were much lower in the patients with heart failure than in the controls. Values for intracellular electrolytes were significantly correlated with the rising levels of digoxin-like substance in the plasma. Non-digitalis inotropic therapy was associated with the recovery of these alterations of heart function, with the levels of the digoxin-like substance decreasing and activity of Na/K-ATPase going up. We conclude that endogenous digoxin-like substance might play a role in the imbalance of intra-cellular electrolytes seen in patients with congestive heart failure. Digoxin may exacerbate the loss of intracellular potassium.

Adult↗
PubMed1994

A controlled study on oral propafenone versus digoxin plus quinidine in converting recent onset atrial fibrillation to sinus rhythm.

UNLABELLED: Eighty-seven patients with recent onset atrial fibrillation (< or = 8 days) without clinical signs of heart failure were randomly allocated to one of the following treatments: (i) oral propafenone (600 mg as a loading dose followed after 8 h by 300 mg t.i.d.); (ii) intravenous digoxin as acute scheme (up to 1.125 mg/24 h) followed after 6 h by hydroquinidine chlorhydrate (total dose, 1350 mg); or (iii) placebo. The patients were submitted to Holter monitoring for 48 h. RESULTS: propafenone achieved higher successful conversion rates at 6, 12 and 24 h compared either with placebo (62% vs. 17%, 83% vs. 34%; 86% vs. 55%; P < 0.01, respectively) or with digoxin at 6 h (62% vs. 38%; P < 0.05) and digoxin plus quinidine at 12 h (83% vs. 48%; P < 0.05). At 48 h, a placebo conversion rate of 76% was observed with consequent lack of any significant difference with the active treatments. Mean conversion times within 48 h were 267 +/- 238 min for propafenone, 648 +/- 631 min for digoxin plus quinidine (P < 0.01 vs. propafenone) and 893 +/- 622 min for placebo (P < 0.001 vs. propafenone). Propafenone and digoxin plasma levels were within the therapeutic range. Asymptomatic phases of atrial flutter with > or = 2:1 atrio-ventricular conduction ratio were observed during Holter monitoring, before conversion to sinus rhythm, in four patients treated with propafenone, in one patient taking digoxin plus quinidine and in four patients with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Digoxin-stimulated calcium transport across rat diaphragm interactions with aminophylline and verapamil.

1. The effect of digoxin on calcium transport across muscle strips isolated from rat diaphragms was investigated. 2. Digoxin at concentrations ranging between 0.2-5.0 ng/ml in the incubation solution increased significantly (P less than 0.5) intracellular calcium in the diaphragm muscle strips in a dose-dependent pattern. 3. The inclusion of digoxin (2 ng/ml) and aminophylline (18.75 micrograms/ml) in the incubation medium showed a significant increase (P less than 0.001) in calcium uptake suggesting a synergistic effect on intracellular calcium accumulation. 4. The presence of digoxin with verapamil in the incubation medium showed a partial alleviation of the inhibitory effect of verapamil on calcium transport. 5. The effect of increasing calcium concentration in the presence of digoxin and digoxin plus aminophylline in the incubation medium, showed a nonsaturable linear relationship between calcium concentration and intracellular calcium accumulation.

Aminophylline↗
PubMed1990

Life span differences in digoxin uptake and excretion.

Little is known about the underlying mechanisms for the altered susceptibility to digitalis with age. To this end, we investigated the digoxin uptake and excretion in mice and rats of different ages through the life span, including the periods of growth, maturity, and aging. Digoxin uptake by cardiac slices was linear from 0 to 15 min, with steady state occurring at 45 min. The rate in the mature 12-month mouse was significantly less than that of the senescent 30-month mouse. The kinetic parameters revealed a significant decrease in Km with a concomitant increase in Vmax during senescence. On the other hand, digoxin uptake by renal cortical slices was highest during growth, decreased to a maturation plateau and then declined further during senescence. Renal clearance and the secretory capacity for digoxin increased 30 and 62%, respectively, during growth and progressively decreased from maturity through senescence and were 59 and 77%, respectively, during aging. In summary, there was an increase in digoxin clearance and tubular activity during growth, and an increase in myocardial uptake of digoxin and a decrease in renal excretion during aging. Thus, these results may explain the clinical observations of altered susceptibility to digitalis with age.

Aging↗
PubMed1995

Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure.

OBJECTIVES: This study was conducted to determine the effect of long-term digoxin therapy on autonomic function in patients with mild to moderate chronic heart failure. BACKGROUND: Chronic heart failure is characterized by increased sympathetic activity and decreased parasympathetic activity. Intravenous digitalis has been found to reduce sympathetic activity immediately in these patients, but whether short-term neurohormonal effects are sustained during long-term oral therapy has not been assessed. METHODS: We determined sympathetic activity in 26 patients with heart failure by measuring plasma norepinephrine levels and parasympathetic activity from variables of heart period variability derived from 24-h ambulatory electrocardiographic Holter recordings obtained before and after 4 to 8 weeks of digoxin therapy. RESULTS: After digoxin therapy, plasma norepinephrine decreased significantly from a mean +/- SEM of 552 +/- 80 to 390 +/- 37 ng/ml. In addition, the RR interval increased significantly from 719 +/- 19 to 771 +/- 20 ms. High frequency power increased from 84 +/- 24 to 212 +/- 72 ms2, and the root mean square of successive differences in RR interval increased from 20.3 +/- 1.8 to 27.0 +/- 3.4 ms, indicating a substantial increase in parasympathetic activity. Low frequency power, an index of baroreflex activity, was also significantly increased (239 +/- 80 to 483 +/- 144 ms2) by digoxin therapy. CONCLUSIONS: These results indicate 1) that long-term therapy with digoxin acts to ameliorate the autonomic dysfunction of patients with heart failure, and 2) that the short-term neurohormonal effects of digoxin are sustained during prolonged treatment with the drug.

Autonomic Nervous System↗
PubMed1995

Digoxin or flecainide for prophylaxis of supraventricular tachycardia in infants?

OBJECTIVES: This study compared the safety and efficacy of digoxin and flecainide in the prophylaxis of supraventricular tachycardia in infants. BACKGROUND: Recurrence of supraventricular tachycardia in infants is common. Digoxin is the conventional drug of first choice for prophylaxis, but its efficacy has not been tested in a controlled clinical trial, and there is no consensus on the drug of choice when digoxin is ineffective. METHODS: We reviewed retrospectively the records of all infants with supraventricular tachycardia due to atrioventricular (AV) reentry admitted to our hospital between January 1986 and December 1993. RESULTS: Thirty-nine infants presented with sustained AV reentrant tachycardia at age 1 to 330 days (median 12). Intravenous flecainide was required to maintain immediate control in six patients who were then treated with oral flecainide. The other 33 patients were treated with oral digoxin. There was no recurrence of tachycardia in 14 (42%) of the 33 patients (95% confidence interval [CI] 25% to 61%). In the other 19 patients (58%) (95% CI 39% to 75%), digoxin was replaced by oral flecainide because of multiple recurrence of tachycardia. Full control was achieved in all 19 of these patients (100%) (95% CI 82% to 100%) and in 5 of the 6 patients treated with both intravenous and oral flecainide. Thus, overall, flecainide was effective in 24 (96%) of 25 patients (95% CI 80% to 100%). CONCLUSIONS: Comparison with previous natural history studies suggests that digoxin is ineffective in the prophylaxis of supraventricular tachycardia. Oral flecainide was effective in a small number of infants, with no adverse effects (95% CI 0% to 12%), and may now be preferred as the primary prophylactic agent.

Anti-Arrhythmia Agents↗
PubMed1986

Acute massive digoxin overdose: survival without use of digitalis-specific antibodies.

Acute massive digoxin overdose may result in life-threatening arrhythmias, with reported mortality of up to 20% prior to the introduction of digitalis-specific antibodies. Digitalis-specific Fab antibody fragments remain under experimental protocol and are not widely available. Interpretation of serum digoxin levels and indications for the use of Fab are not clearly established. The authors report a case of massive digoxin overdose in an 18-month-old child with the highest reported digoxin level (48 ng/ml) with which a victim survived without the need for Fab administration. She developed only mild manifestations of digitalis intoxication, and her serum potassium never exceeded 5.2 mEq/l. Her course may be explained by the distribution kinetics of digoxin, which follows a two-compartment model, and the relative resistance of children to digitalis intoxication. This case emphasizes the need for better criteria than the digoxin level for the administration of Fab. The serum potassium concentration, which is usually elevated in acute type digitalis intoxication, may be a better predictor of the need for Fab in acute massive digitalis ingestion.

Digoxin↗
PubMed1995

Expression in Escherichia coli of soluble and M13 phage-displayed forms of a single-chain antibody fragment specific for digoxin: assessment in a novel drug immunoassay.

A high affinity anti-digoxin single-chain Fv antibody fragment (scFv) was cloned from the mouse 2C2 hybridoma cell line and was functionally expressed both in the Escherichia coli periplasm as a soluble molecule and at the surface of the filamentous M13 bacteriophage as a fusion protein with the gene III minor coat protein. The 2C2 scFv sequence significantly differs from that of all the other anti-digoxin antibodies previously described. The 2C2 scFv shares with its parental monoclonal antibody a high specificity for digoxin, a cross-reactivity with active digoxin metabolites, but none with inactive metabolites. M13 phages displaying the 2C2 scFv at their surface have a high apparent affinity constant for digoxin (6.6 x 10(8) M-1) and were directly used to set up a novel type of immunoenzymatic assay for monitoring digoxin in sera of patients treated for either congestive heart failure or cardiac arrythmias. We thus report for the first time that phages displaying scFv may constitute a large source of important new reagents in the field of immunodiagnosis.

Animals↗
PubMed2005

Comparison of P-glycoprotein-mediated drug-digoxin interactions in Caco-2 with human and rodent intestine: relevance to in vivo prediction.

Inhibition of P-glycoprotein (PGP) resulting from the co-administration of substrate drugs represents a potential source of drug-drug interactions. Although in vitro screens can readily identify such interactions, the accuracy with which they mimic interactions in tissues or their value in predicting interactions in vivo is unresolved. This was addressed for the model PGP substrate digoxin by comparing the modulation of its permeability across Caco-2 cells and ex vivo human and rodent intestine by drugs for which pharmacokinetic data on interactions with digoxin in man is available. All five compounds (talinolol, omeprazole, verapamil, quinidine, cyclosporin) dose-dependently increased absorptive (A-B) digoxin permeability with maximal increases of 2.2-4.5-fold across Caco-2. Quantitatively similar increases were observed in ex vivo human and mouse intestine and studies in mdr1a(-/-) intestine confirmed that these interactions are mediated solely by PGP. In vitro changes in digoxin permeability were qualitative indicators of the increase in digoxin C(max) for these compounds in man, although accounting for the luminal drug concentrations expected for a given oral dose was a critical consideration. Based on a limited dataset these data suggest that Caco-2 accurately mimics intestinal digoxin interactions and may be useful in predicting the threshold dose at which interactions become clinically significant. Further studies across a wider range of drugs are needed to determine the broader applicability of in vitro data for quantitative prediction of clinical drug interactions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Digoxin use is associated with increased platelet and endothelial cell activation in patients with nonvalvular atrial fibrillation.

OBJECTIVES: The purpose of this study was to determine whether digoxin use is associated with increased flow cytometric markers of endothelial cell and platelet activation in patients with nonvalvular atrial fibrillation (AF). BACKGROUND: Increased intracellular calcium is a key event in platelet activation, and several studies have demonstrated that digitalis activates platelets in vitro. Intracellular calcium also is a key regulator of endothelial cell function, and endogenous digitalis-like substances have been shown to affect biologic processes in endothelial cells. METHODS: We studied 30 patients with nonvalvular AF. We measured the levels of (1) platelet expression of P-selectin (CD62P), (2) platelet microparticles (PMP); and (3) endothelial microparticles (EMP) identified by anti-CD31 (EMP31) and by anti-E-selectin antibodies (EMP62E). RESULTS: Patients who were taking digoxin (n = 16; mean digoxin level = 0.93 ng/dL) did not demonstrate any significant differences in clinical or echocardiographic characteristics compared with patients not taking digoxin (n = 14). Patients taking digoxin had significantly increased levels of CD62P expression in platelets and platelet-leukocyte conjugates and markedly increased markers of endothelial activation: EMP62E and EMP31. After adjusting for potential confounders (including age, congestive heart failure, coronary artery disease, ejection fraction, antiplatelet, beta-blocker, and calcium channel blocker use), the differences persisted. CONCLUSIONS: Digoxin use in patients with AF is associated with increased levels of endothelial and platelet activation. If digitalis activates endothelial cells and platelets at pharmacologic doses, use of digitalis in conditions such as AF could predispose to thrombosis and vascular events.

Aged↗
PubMed2005

Digoxin may reduce the mortality rates in patients with congestive heart failure.

Digoxin has been used to treat congestive heart failure (CHF) for more than two centuries. It's clinical efficacy, however, has been under question in recent years because recent clinical trials showed that digoxin therapy in CHF patients was associated with no beneficial effects in mortality, but only a modest reduction in clinical symptoms and the frequency of heart failure related hospitalisation. Digoxin's effect on mortality seems closely related to its serum concentrations; high serum concentrations (e.g. >or=1.2 ng/ml) have been found to increase the risk of all-cause mortality in heart failure patients. Digoxin-associated risk in mortality may be due to an increases in myocardial oxygen consumption and arrhythmogenesis at higher serum concentrations. We hypothesized that the serum concentration of digoxin is a major determinant factor of its efficacy on mortality rates in patients with congestive heart failure. The maintenance of digoxin's serum concentration at the lower end of the reference range, i.e., between 0.5 and 0.8 ng/ml, may reduce mortality rates as well as improve clinical symptoms.

Cardiotonic Agents↗
PubMed1976

The effect of intravenous digoxin on the occurrence of ventricular tachyarrhythmias in acute myocardial infarction in man.

Patients with acute myocardial infarction were allocated to two groups according to a double blind-system of radomization. The patients (n = 18) in one of the groups received digoxin intravenously as an injection of 0.01 mg. per kilogram of body weight during 10 minutes. The patients in the other group (n = 15) received saline and served as controls. A continuous ECG record was obtained from each patient during 1 hour preceding the administration of digoxin or saline and was continued for 3 hours following the injection. No antiarrhythmic treatment was given during the time of the study. Based on the continuous ECG, calculations were made of the relative incidence of patients with different types of ventricular tachyarrhythmias during the period of observation as well as the percentage of arrhythmia-containing 1 minute intervals observed during this period. There was no statistical difference between the incidence of ventricular tachyarrhythmias in the two groups in the 1 hour period preceding drug injection. The administration of digoxin and saline did not change the incidence of ventricular tachyarrhythmias and there was also no statistically significant difference between the two groups as regards the incidence of patients showing different types of ventricular tachyarrhythmias during the 3 hour period following drug administration, Considering the 1-minute intervals, those without any ventricular premature contractions were less in the digoxin group (92 per cent) than in the saline group (88 per cent; p less than 0.001). Serum levels of digoxin at the end of the observation period were well above what is considered the minimum therapeutic level and in three patients the level approached or reached the toxic range. In these three patients there was still no increased incidence of ventricular tachyarrhythmias. It is concluded that patients with acute myocardial infarction complicated by incipient left ventricular failure do not show an increased sensitivity to an ordinary dose of digoxin as measured by the occurrence of ventricular tachyarrhythmia.

Acute Disease↗
PubMed1977

Effect of cholestyramine on digoxin absorption and excretion in man.

Six subjects receiving digoxin therapy for heart disease were studied on two occasions with a single oral dose of 0.5 mg of tritiated digoxin. In every study, all stools and urine were saved for 1 week. Before the second study, treatment with cholestyramine, 4 g every 6 hours, was begun and continued throughout. In three patients, a third study was performed after cholestyramine treatment had been continued for 1 month. Results showed that after cholestyramine administration serum levels, stool output and urinary output of tritiated digoxin varied over a wider range, but cholestyramine had no net short-term effect of any of these variables. After 1 month of cholestyramine administration, there was a small statistically significant increase in stool output of tritiated digoxin and metabolites. In vitro studies suggested that cholestyramine is likely to be a weak digoxin binder in the gut and that changes induced by this resin in digoxin metabolism are not likely to be due to drug binding.

Administration, Oral↗
PubMed1983

Effects of oral digoxin on ventricular ectopy and its relation to left ventricular function.

The ventricular antiarrhythmic properties of oral digoxin were examined in 13 patients with chronic ventricular ectopy using serial 24-hour electrocardiographic monitoring. Mean premature ventricular complex frequency (per 1,000 normal beats) decreased from 56 +/- 47 during the placebo period to 40 +/- 27 (p = not significant [NS]) and 25 +/- 17 (p less than 0.05) during daily administration of digoxin, 0.25 and 0.375 mg. Digoxin had no significant effect on the qualitative occurrence of complex ventricular arrhythmia patterns (multiformity, bigeminy, couplets, ventricular tachycardia). Radionuclide left ventricular (LV) ejection fraction was measured during the placebo period. Seven patients had normal (ejection fraction greater than 50%) and 6 abnormal global LV performance. In the normal group, the mean premature ventricular complex frequency decreased from 69 +/- 58 to 20 +/- 18 (p less than 0.05) and the mean couplet frequency decreased from 0.59 +/- 0.85 to 0.07 +/- 0.06 (p less than 0.04) during the placebo and 0.375 mg digoxin dosing periods, respectively. In contrast, no significant changes in either variable occurred after digoxin in subjects with depressed LV function. This study indicates that oral digoxin is moderately effective in suppressing premature ventricular complexes, and that its effects are greatest in patients with normal overall LV performance.

Administration, Oral↗
PubMed1979

Evaluation of serum digoxin and serum cortisol by radioimmunoassay with the Concept-4.

The solid-phase radioimmunoassay procedures for serum digoxin and cortisol with the Concept-4 were evaluated for specificity, correlation with other radioimmunoassay procedures, parallelism, recovery, carryover, and precision. 1. The detection limits of the digoxin and cortisol assays were 10 pg/tube and 40 pg/tube, respectively. These detections correspond to serum concentrations of 0.25 micrograms/liter and 20 micrograms/liter, respectively, for digoxin and cortisol. 2. Specificity of the digoxin assay was characterized by a 18.3% cross reaction with digitoxin. The anti-cortisol with 11-deoxycortisol, cross reaction with 11-deoxycortisol. 3. The values obtained with the Concept-4 for both procedures demonstrated acceptable correlations with other existing RIA procedures. 4. Dilution studies conducted to determine the parallelism of the 2 assays indicated that both assays demonstrated excellent proportionality between the volume of specimen and the quantity of analyte measured. 5. Analytical recoveries of digoxin and cortisol added to the individual assays average 95% and 101%, respectively. 6. Carryover studies indicated a routine sample-to-sample interaction of less than 0.05% for both assays. 7. The digoxin assay routinely demonstrated intra- and inter-assay variations of less than 7.4% and less than 10.0%, respectively. The precision data for cortisol indicated intra- and inter-assay variations of less than 6.7% and less than 9.1%, respectively.

Chemistry, Clinical↗