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 1,531 records · Page 85Linked to original sources
PubMed1985

Digoxin disrupts the inflammatory response in experimental pneumococcal pneumonia.

Digoxin was administered to normal CD-1 mice (4 micrograms/kg per 24 hr), and the mice were inoculated intratracheally with Streptococcus pneumoniae in order to assess the effects of the cardiac glycoside on pulmonary antibacterial mechanisms. Digoxin-treated animals experienced a worse survival rate than did controls (19 of 50 versus 33 of 50; P less than .01). When challenged with a high inoculum (1 X 10(6) cfu), animals given the glycoside demonstrated a significant impairment in their capacity to clear viable pneumococci from the lungs; the depression in pulmonary clearance was associated with a marked attenuation in the ability of digoxin-treated mice to recruit granulocytes and macrophages into the bronchoalveolar spaces. Following low inoculum challenge (1 X 10(5) cfu), animals treated with the cardiac glycoside exhibited an inefficient pulmonary clearance and a blunted macrophage influx. At clinically relevant concentrations, digoxin demonstrated no effect on the in vitro pneumococcidal activity of resident murine alveolar macrophages. We conclude that digoxin can disrupt host defense against pneumococcus by impeding the normal inflammatory response to organisms deposited into the lower respiratory tract.

Animals↗
PubMed1987

A comparison of verapamil and digoxin in the treatment of atrial fibrillation.

Twelve patients (including 2 females) with chronic atrial fibrillation were entered into a randomized, double blind crossover study to compare the effects of digoxin and verapamil upon heart rate, exercise tolerance and symptom control. The dose of digoxin was adjusted so as to give serum concentrations within the range 1.3 to 2.6 nmol l-1 between four and six hours after dosing, and was continued for six weeks. The dose of verapamil was increased from 40 mg tds to 80 mg tds to 120 mg tds at fortnightly intervals. Three patients did not complete the study; two because of adverse effects attributable to verapamil. In the remaining nine patients, mean post exercise heart rates were significantly lower during treatment with verapamil 80 mgs tds (126.7 bpm) than with verapamil 40 mg tds (148.6 bpm) or digoxin (146.7 bpm). However, exercise tolerance was similar with both verapamil and digoxin and the superior control of exercise induced tachycardia achieved with higher doses of verapamil was not associated with improved exercise endurance. Visual analogue scale scores for constipation were significantly higher during treatment with verapamil; scores for other possible side effects and for overall wellbeing were similar. The results do not confirm the findings of others who have reported that verapamil is superior to digoxin in the treatment of atrial fibrillation.

Aged↗
PubMedDate not supplied

Differential uptake of tritiated digoxin in benign and malignant central nervous system neoplasms.

The purpose of this study was to measure uptake of tritiated digoxin by neoplastic tissues known to have differential contents of sodium-potassium adenosine triphosphatase (Na + K + ATPase), the presumed receptor for digoxin. Tumor samples were removed at the time of craniotomy in seven patients with meningiomas (Group 1) and seven patients with more malignant central nervous system tumors (Group 2) (three astrocytomas, three glioblastomas, one meduloblastoma). Patients with meningiomas were found to have a significantly higher digoxin uptake (21.8 +/- 7.3 ng/gm tumor versus 5.7 +/- 5.2 ng/gm tumor; (p less than 0.01) and a significantly greater tissue/serum ratio (13.9 +/- 11.7 versus 3.26 +/- 3.7, p less than 0.0). This study provides the first demonstration of increased uptake of digoxin by noncardiac pathologic tissues. The results are most likely due to differences in the number of digoxin receptor sites.

Adenosine Triphosphatases↗
PubMed1985

Amiodarone-associated hypothyroidism--a possible cause of digoxin intoxication.

The problem of a possible interaction between amiodarone and digoxin is still unsettled. We have recently treated two patients with digoxin intoxication who had received amiodarone for eight and 36 months respectively. Both developed extreme bradycardia requiring temporary pacemakers. The presence of hypothyroidism was confirmed in both cases by laboratory data. Judging by present knowledge concerning the interaction between amiodarone, thyroid function, and digoxin, it is suggested that digoxin intoxication was not the result of its direct interaction with amiodarone. The possibility that amiodarone-induced hypothyroidism precipitated digoxin intoxication seems to be more plausible. Prevention of digitalis toxicity in amiodarone-treated patients would therefore require monitoring of thyroid function every three to six months. Frequent monitoring of digitalis blood levels is also indicated in patients with amiodarone associated hypothyroidism. Early detection of hypothyroidism and digitalis intoxication is necessary in view of the severity of the course of the disease.

Aged↗
PubMed1987

Haemodynamic effects of intact digoxin antibody and its Fab fragments in experimental hypertension.

The effects of i.v. injection of intact digoxin antibody (0.3 mg/rat) and of its Fab fragment (40 mg/rat) on blood pressure, cardiac output and total peripheral resistance were measured in conscious spontaneously hypertensive and deoxycorticosterone hypertensive rats. In vitro findings showed that Fab fragment bound radio-labelled digoxin, digitoxin and ouabain more efficiently than did intact antibody. In vivo, Fab fragment prevented the increase of total peripheral resistance induced by i.v. injection digoxin. However, Fab fragment of digoxin antibody did not alter blood pressure, cardiac output or total peripheral resistance in normal and salt-loaded spontaneously hypertensive rats (SHR) in uraemic SHR and in deoxycorticosterone hypertensive rats. We confirmed that intact digoxin antibody--bearing Fc domains with complement activating properties--lowered blood pressure in SHR and in deoxycorticosterone hypertension. This was due to a decrease in total peripheral resistance. Our data suggest that a circulating endogenous digitalis-like factor is unlikely to be important in blood pressure regulation in salt-loaded hypertension in the rat.

Animals↗
PubMedDate not supplied

Tissue distribution and elimination of digoxin and methyldigoxin after single and multiple doses in dogs.

Glycoside concentrations in plasma and various tissues of dogs were determined after a single and repeated intravenous administration of tritium-labeled digoxin and beta-methyldigoxin. Twenty-four hours after single dosing, the highest concentrations were measured in the kidney. This was followed by the heart, adrenal gland, liver, pancreas, lung, spleen, diaphragm, and skeletal muscle. The glycoside concentration in the brain was low after a single administration of dogoxin. A higher concentration was found after a single dose of the more lipophilic methyldigoxin. After repeated daily administration, the glycoside concentration in plasma and tissues increased continuously and, except for the brain, reached a plateau level after 6 to 8 days. The accumulation factor for both digoxin and methyldigoxin was 2.6. During daily administration for 10 days, the glycoside cconcentration in the brain increased continuously. The mean accumulation factor in all brain areas amounted to 12.4 for methyldigoxin. The concentration of digoxin and methyldigoxin in the tissues decreased, with mean half-lives of 33 and 28 hr, respectively. Glycoside elimination from the brain was clearly slower. A mean half-life of 73 hr was measured for digoxin and of 154 hr for methyldigoxin. The elimination of digoxin was largely renal, while that of methyldigoxin was largely fecal.

Animals↗
PubMedDate not supplied

Digoxin withdrawal after cardiac failure in patients with sinus rhythm.

A double-blind placebo-controlled crossover trial of digoxin withdrawal was undertaken in 22 patients with sinus rhythm who had a previous history of frank heart failure and were taking therapeutic doses of the drug. During the course of the study, 14 patients showed no clinical change whether taking digoxin or placebo, five patients deteriorated on placebo (four with heart failure and one with supraventricular tachycardia), and three on digoxin (two with heart failure and one with digoxin toxicity). These differences were not statistically significant. Compared to placebo, patients, while taking digoxin, had lower resting heart rates and significant shortening of all the systolic time intervals. The drug appears to exert a sustained positive inotropic effect during maintenance therapy, but this is not of clinical benefit to the majority of patients.

Aged↗
PubMedDate not supplied

Half-life of digoxin in myocardium after stopping maintenance treatment.

The rate of decline of digoxin level in myocardium was estimated from operative samples of atrial and ventricular tissue from 40 patients undergoing cardiac surgery 1-20 days after maintenance digoxin treatment was stopped. Linear regression of myocardial log concentration-time curves for the group as a whole gave half-lives of 2.9 and 3.1 days in ventricular and atrial myocardium, respectively. Serum concentrations of digoxin were measured twice in each patient in this study: once while receiving treatment and once at the time of operation. Analysis of the 22 pairs of serum samples in which the second sample contained measurable levels of digoxin gave an estimated half-life of 2.3 days. The serum half-life was shorter than either the ventricular or the atrial myocardial half-life when data were analysed by unpaired statistics. Considering data only from those patients in whom the serum half-life was measured, to allow comparison by paired statistics, estimated ventricular and atrial half-lives were 1.5 and 1.3 days, respectively, which are significantly less than the respective serum half-lives of 2.3 and 2.1 days. Relatively slow clearance of digoxin from myocardium received further, anecdotal support from its demonstration in one patient 20 days after treatment was stopped.

Adult↗
PubMed1989

Quinidine enhancement of digoxin toxicity in rats and minipigs.

The combined use of digoxin and quinidine has been associated with potentially fatal toxic reactions. The mechanisms involved in this drug interaction were investigated in Wistar rats and Hormel miniature pigs (minipigs). Infusions of digoxin alone (0.013 mg/min) and in combination with quinidine (0.051 mg/min) demonstrated that quinidine pretreatment significantly decreases the time of onset of arrhythmias and death in these animals as compared with digoxin alone. Similarly, when administered as a slow, bolus intravenous (i.v.) injection to either anesthetized or unanesthetized minipigs, quinidine pretreatment (10 mg/kg, i.v.) led to the rapid development of arrhythmias and death. Quinidine administration in both species also causes a dramatic reduction in blood pressure, and it appears that this hypotension may trigger the irregular rhythms of the heart once digoxin is administered. Electrocardiographic (ECG) evidence showed that the toxicity associated with digoxin administration alone was characterized by bradyarrhythmias and death was attributed to cardiac arrest. In contrast, quinidine pretreatment led to severe tachyarrhythmias and earlier death by ventricular fibrillation. These studies demonstrate the usefulness of these two species, particularly the minipigs, in assessing the magnitude of this drug interaction and also confirm the risks involved when these two drugs are combined.

Anesthesia↗
PubMed1990

Amiodarone, verapamil, and quinidine do not affect equilibrium binding of digoxin.

The binding of [3H]digoxin to purified canine cardiac sarcolemmal vesicles was characterized. Scatchard analysis of saturation isotherms yielded linear plots with a maximal binding capacity of 174 +/- 31.9 pmol/mg, a dissociation constant of 31.7 +/- 4.59 nM, and a Hill coefficient of 0.947 +/- 0.02 (mean +/- SEM), suggesting that [3H]digoxin bound to a single class of sites. In contrast to their marked effect on steady-state serum digoxin levels when administered in combination, quinidine, verapamil, and amiodarone were without effect on equilibrium binding of [3H]digoxin. Thus, increased steady-state serum concentrations of digoxin resulting from combination therapy with these particular drugs probably will have cardiac effects that may increase the risk of digitoxicity to the patient.

Amiodarone↗
PubMed1992

Effects of sinoaortic denervation on the reflex actions of digoxin and a polar aminocardenolide.

To determine the role of carotid sinus and aortic arch baroreceptors in the reflex cardiac sympathetic nerve activity (SNA) responses to administration of ASI-222, a polar aminocardenolide, and to digoxin, a neutral cardenolide, we used anesthetized dogs from which these reflex receptor areas had been removed. The SNA was measured in postganglionic fibers from the stellate ganglion. After we made baseline measurements, we infused either ASI-222 or digoxin intravenously (i.v.) at dose rates that produce cardiac arrhythmias in approximately 100 min (0.7 and 1.2 micrograms/kg/min), respectively. Our data indicate that with sinoaortic baroreceptors removed, progressive infusion of digoxin increases cardiac SNA. In contrast, cardiac SNA decreases progressively during continuous infusion of ASI-222. In saline-treated dogs, SNA was not significantly altered. In another series of experiments, we examined the effects of these drugs and saline on cardiac vagal afferent nerve activity (VANA). ASI-222 (50 micrograms/kg i.v. in 10 min) caused a progressive increase in cardiac VANA in a 60-min observation period. Neither digoxin, at less than or equal to 120 micrograms/kg i.v. in 100 min, nor saline altered VANA. Digoxin appears to reduce SNA by interacting with the carotid sinus and aortic arch baroreceptors, which are myelinated. It does not affect VANA acutely. In contrast, ASI-222 appears to decrease cardiac SNA by interacting with other reflex receptor areas--the unmyelinated cardiopulmonary afferent nerve endings, particularly cardiac mechanoreceptors.

Animals↗
PubMed1987

Fab fragments in the treatment of digoxin overdose: pediatric considerations.

Serious digoxin toxicity due to accidental or deliberate overdose is uncommon, but more than half of the cases reported in 1985 involved children. Toxicity can occur acutely, as with accidental overdose, or with long-term maintenance dosing. In children it is almost always acute. Conventional treatment includes gastric lavage or ipecac-induced emesis, and activated charcoal or nonabsorbable resins and cathartics to reduce absorption. Although children appear to tolerate massive ingestions without specific therapy, serum digoxin levels must be reduced quickly and safely when conventional measures have failed. Fab fragments of digoxin-specific antibodies have been successfully used to treat refractory digoxin toxicity. Indications for use should be limited to life-threatening digoxin toxicity when conventional therapy has failed.

Antibody Specificity↗
PubMed1985

Interaction between digoxin and nifedipine at steady state in patients with atrial fibrillation.

The possible kinetic and hemodynamic interactions between digoxin and nifedipine were evaluated in nine patients with atrial fibrillation who were receiving chronic digoxin. After 2 control weeks, nifedipine (20 mg b.i.d.), in a new formulation with sustained release characteristics, was added to the therapeutic regimen for 2 weeks. Trough serum digoxin concentrations and peak nifedipine concentrations were determined repeatedly. On the same days, resting blood pressure and heart rate were measured. During nifedipine administration, serum digoxin levels increased by 15% from 0.87 +/- 0.38 to 1.04 +/- 0.37 ng/ml (mean +/- SD, p less than 0.05). This was accompanied by a reduction in systolic and diastolic blood pressure of 16 +/- 6 (p less than 0.01) and 12 +/- 5 mm Hg (p less than 0.001), respectively. In two patients, noncardiac side effects were reported. In two other patients, nifedipine was discontinued because of skin rash and severe headache, respectively. In conclusion, plasma digoxin levels were elevated slightly in the presence of nifedipine, but this probably has little clinical relevance.

Adult↗
PubMed1989

Interaction between digoxin and propafenone.

The pharmacokinetic and pharmacodynamic interactions between digoxin and propafenone were investigated in 10 hospitalized patients with heart disease and cardiac arrhythmias. During steady state (0.25 mg/day) the glycoside was combined with 600 mg of propafenone daily for 1 week. The mean +/- SD serum digoxin concentration (SDC) was 0.97 +/- 0.29 ng/ml before and 1.54 +/- 0.65 ng/ml (p less than 0.003) during propafenone administration. Propafenone induced a mean decrease in 31.1 and 31.7% in total and renal digoxin clearances, respectively. The increase in SDCs was accompanied by a decrease in heart rate (HR) and shortening of QTC (QT interval corrected for HR). In patients receiving digoxin and propafenone simultaneously, the SDCs should be monitored and the digoxin dose reduced if there is evidence of toxicity.

Adult↗
PubMed1989

Reassessment of cross-reactivity of spironolactone metabolites with four digoxin immunoassays.

Spironolactone and one of its metabolites, canrenone, cross-react with some digoxin immunoassays to result in erroneous serum digoxin concentrations. Recently, additional compounds, 7-alpha-thiomethylspirolactone (7-a-TMS) and 6-beta-hydroxy-7-alpha-thiomethylspirolactone (6-B-OH-7-a-TMS), have been reported to be quantitatively important metabolites of spironolactone. This study was initiated to evaluate the cross-reactivity of these metabolites, canrenone, and spironolactone with four different digoxin immunoassays. Blank serum was spiked with each compound to yield concentrations reported to occur in vivo. Samples were analyzed in duplicate by each of the following immunoassays: fluorescence polarization immunoassay (FPIA); affinity-column-mediated immunoassay (ACMIA); radioimmunoassay (RIA); and enzyme immunoassay (EIA). The 7-a-TMS metabolite cross-reacted with both the RIA and ACMIA methods. Apparent digoxin concentrations were as great as 0.39 ng/ml for this metabolite at the highest concentration evaluated, 600 ng/ml. At the lowest concentrations evaluated with the 7-a-TMS metabolite, 50 ng/ml, apparent digoxin concentrations as high as 0.28 ng/ml were reported. The 6-B-OH-7-a-TMS metabolite did not cross-react to a significant extent with any of immunoassays studied. Canrenone cross-reacted with the ACMIA method at a concentration of 100 ng/ml. The EIA method exhibited no apparent cross-reactivity with any of the compounds, whereas the FPIA method exhibited minimal cross-reactivity. The results of this study indicate that the 7-a-TMS metabolite cross-reacts to a significant extent with some immunoassays; however, this is not true for the 6-B-OH-7-a-TMS metabolite.

Adult↗
PubMed1998

A model for the prediction of digoxin-drug interactions at the renal tubular cell level.

Digoxin-drug interactions are relatively common causes of digitalis toxicity. Recently, the clinical importance of the renal tubular secretion of digoxin has been proven by documenting drug interactions at this level. The authors describe a model using cultured renal tubular cell monolayers that can be used to predict drug interactions with the cardiac glycoside. This model accurately documents known clinical digoxin interactions such as those with verapamil and propafenone. The common feature of these interactions is that they involve P-glycoprotein substrates (e.g., digoxin, vincristine, vinblastine) or inhibitors (e.g., quinidine, cyclosporine). In the case of the newly described interaction of digoxin with itraconazole, the model preceded the emergence of clinical cases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Population pharmacokinetics of digoxin in pediatric patients.

Digoxin pharmacokinetics were studied in a pediatric population with an age range of 6 days to 1 year using the population pharmacokinetic approach. Digoxin data were analyzed by mixed-effects modeling according to a one-compartment steady-state pharmacokinetic model using NONMEM software. The final model selected for the population prediction of digoxin clearance in pediatric patients was as follows: [equation: see text] Individual empirical Bayesian estimates were generated on the basis of the population estimates and were used to correlate the optimum dose of digoxin and patient age according to the following equation: [equation: see text] This equation and its derived nomogram may be used for the initial dosing of digoxin in children aged between 0 and 1 year. The use of this nomogram in routine monitoring requires further pharmacokinetic and clinical validation.

Algorithms↗
PubMed2003

Activated charcoal is effective but equilibrium dialysis is ineffective in removing oleander leaf extract and oleandrin from human serum: monitoring the effect by measuring apparent digoxin concentration.

Accidental poisoning from oleander leaf or oleander tea can be life threatening. The authors studied the effectiveness of activated charcoal and equilibrium dialysis in removing oleander leaf extract and commercially available oleandrin as well as oleandrigenin, the active components of oleander plant, from human serum. Oleander leaf extract was prepared in distilled water and drug-free serum was supplemented with the extract. Then serum was treated with activated charcoal at room temperature and an aliquot was removed at 0 minutes, 10 minutes, 20 minutes, and finally 30 minutes to study the presence of oleander extract by measuring the apparent digoxin concentration using the FPIA for digoxin. The authors observed effective removal of oleander extract by activated charcoal. When the authors supplemented other drug-free serum pools with pure oleandrin or oleandrigenin and then subsequently treated them with activated charcoal, the authors observed complete removal of digoxin-like immunoreactivity at the end of 30 minutes' treatment. When drug-free serum pool supplemented with either oleander leaf extract, oleandrin, or oleandrigenin was passed through a small column packed with activated charcoal, the authors observed almost no apparent digoxin concentration following the passage through the column indicating that activated charcoal is very effective in removing oleander from human serum in vitro. In contrast, when serum pools containing either oleander leaf extract or oleandrin were subjected to equilibrium dialysis against phosphate buffer at pH 7.4, the authors observed no significant reduction in apparent digoxin concentration even after 24 hours. The authors conclude that activated charcoal is effective but equilibrium dialysis is ineffective in removing oleander leaf extract from human serum.

Cardenolides↗