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PubMedDate not supplied

The effect of age and everyday exercise on steady-state plasma digoxin concentrations.

Age-related physiologic changes may significantly alter the disposition and pharmacologic characteristics of many drugs. The elderly are the most frequent users of digoxin because of increased prevalence of atrial fibrillation and congestive heart failure. This study was conducted to confirm the decrease in digoxin concentrations during exercise, to determine if age is a factor in this decrease, and to explore the difference between chronologic age and physiologic age. Eighteen men age 50-85 years were treated with digoxin for more than 1 month before enrolling and had serum digoxin concentrations of 0.4-2.0 micrograms/L. They were evaluated during a 3-hour period in the morning (A.M. dose withheld). Blood samples were obtained every 10 minutes during sequential 60-minute periods of rest (phase I), walking (phase II), and rest (phase III). There were no significant differences in mean concentration between phases II and I (p < 0.76), phases III and phase I (p < 0.70), or phases II and III (p < 0.37). The effect of age was positively correlated with the mean concentration of phase II but was not statistically significant (p < 0.62). Statistically significant correlations were seen only between the exercise phase and serum albumin and Mini-Mental Status Examination scores. We conclude that exercise has minimal, if any, clinically relevant effects on plasma digoxin concentrations. Increasing chronologic age has no influence on a decrease in the concentrations with exercise; a younger physiologic age may play a role.

Age Factors↗
PubMed1978

The clinical value of digoxin in patients with heart failure and sinus rhythm.

Six patients in sinus rhythm with congestive heart failure due to either myocardial infarction or cardiomyopathy, were given oral frusemide to eliminate oedema. Symptomatic relief occurred as body weight was reduced, and after a 'dry' basal weight had been achieved, progressive-load exercise testing was done to examine any benefit that derived from adding oral digoxin to the diuretic. Three pairs of sub-maximal exercise tests were done at intervals over three months, and the responses of each patient when using digoxin and diuretics were compared with those when using diuretics alone. One patient did not complete this study, because more frequent premature beats and increased angina followed the withdrawal of digoxin. For the five patients who completed three pairs of tests, there was no significant change in symptoms, in workload achieved, or in heart rate, respiratory rate, ventilation and respiratory quotient, whether digoxin was added or removed. It is concluded that in these patients where salt and water retention was controlled with diuretics, digoxin did not improve the capacity for exercise, and it is suggested that for such patients with myocardial disease in sinus rhythm, treatment should begin with diuretics.

Adult↗
PubMedDate not supplied

[The effect of hemodilution and autotransfusion on diagnostic levels of digoxin in serum of patients operated on with extracorporeal circulation].

In many patients operated on for valvular heart diseases indications are present to digitalis administration in the preoperative period. During extracorporeal circulation fluctuations occur of blood potassium concentration which increase the risk for toxic effect of digitalis. In the work, digoxin concentration was studied in the serum of patients operated on in extracorporeal circulation in whom administration of this drug was discontinued 48 hours before the operation. The first digoxin dose (0.5 mg) was given directly after withdrawal of extracorporeal circulation, and another 0.5 mg was given after 4 hours. Digoxin concentrations were determined by fluorescence-polarization-immunological method using TD* Abbott device. The digoxin concentration increased rapidly and reached its peak after 6 hours (1.9 ng/ml), decreasing after 12 hours to 0.9 ng/ml and persisted at this therapeutic level in further samples. The present studies demonstrated that digoxin administration directly after withdrawal of extracorporeal circulation and within 24 hours after the operation in commonly accepted doses provided therapeutic concentration of the drug and caused no increase of the risk for toxic reaction development.

Adult↗
PubMed1994

[Biochemical evaluation of digoxin dosage in patients with heart failure].

The investigations were carried out in 56 patients aged 54 to 84 years, treated with a supporting dosage 0.25 mg of digoxin because of chronical insufficiency of the heart, according to the NYHA classification II and III degree, in whom the functions of liver and kidneys have not been ascertained. A fourfold determination of digoxin concentrations in the blood was established in the time of distribution balance. From among the examined patients three groups were separated: receiving the drug chronically at 8.00 a.m. (group A), receiving it at 8.00 p.m. (group B) and group C, for which the sacral method was used. Depending on medical indications the patients received during the examination other drugs. In group C the therapy was limited to diuretic drugs. In no clinical symptoms of digitalism could be observed. Subtherapeutic levels of digoxin (< 0.8 ng/ml) were found in the three groups on an average in 50% of the patients. The high percentage of patients with nontherapeutic concentration in blood serum confirms once more, that treatment with digoxin without checking their concentration in the serum does not give the certainty of suitable dosage. The results of the studies show that the optimalization of digoxin therapy from the point of pharmacological view should be based on a penetrating estimation of the whole of the clinical image, the checking of the image with the help of the concentration determinations of the drug.

Aged↗
PubMed1995

Interaction between nifedipine and digoxin in rats.

Possible nifedipine-digoxin interaction was investigated in rats by comparing lethal doses of intravenously infused digoxin in control and experimental rats. In the experimental rats, nifedipine was administered intraperitoneally, 30 minutes prior to infusing digoxin at a constant rate of 40mcg per minute. Results indicate that nifedipine administered within the dosage range 0.5-2.0mg per kg rat body weight, lowered the lethal dose of intravenously infused digoxin by 26-38% compared with control rats, thus indicating a synergistic effect between the two drugs. There was very little dose dependence of this effect. It is concluded that concomitant administration of nifedipine and digoxin in humans may lead to drug interactions.

Animals↗
PubMed1994

Endogenous digoxin-like substance in liver failure.

Digoxin-like immunoreactive substance (DLIS) has been detected in several patient populations that were not receiving digoxin. We therefore studied the sensitivity of EMIT Convenience Pack Digoxin immunoassay to interference by DLIS in patients with liver failure. Serum digoxin was measured in cirrhotic patients with moderate to severe liver failure (Child-Pugh B or C grade), patients with mild liver disease (chronic hepatitis) and matched control patients without liver disease. Excluded were patients taking or who had ever received any cardiac glycoside in the past. Blood samples were obtained by venipuncture and assayed in duplicate. Twenty-two out of 30 cirrhotic patients (73%) showed false-positive results, vs. one of 6 patients (16.7%) with mild liver disease, and 1 of 10 (10%) controls. The serum DLIS level was negatively correlated with prothrombin activity (r = -0.55, p < 0.00011). Digoxin levels must be interpreted carefully in patients with moderate to severe liver failure.

Chronic Disease↗
PubMed1994

Digoxin amplifies the effects of deoxycorticosterone acetate (DOCA) in intact water-drinking rats: implications for the mechanism of DOCA hypertension?

INTRODUCTION: An increase in digitalis-like substances has been reported in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We hypothesized that the role of saline and unilateral nephrectomy in DOCA hypertension may be due to stimulation of endogenous digitalis-like substances. METHODS: We investigated the effects of digoxin and DOCA alone and in combination in intact rats drinking water. Forty male Sprague-Dawley rats were used (body weight 223-298 g). RESULTS: Neither digoxin (40 micrograms/kg per day, by gavage, for 35 days, n = 10) nor DOCA (30 mg/kg twice a week, subcutaneously, for 5 weeks, n = 10) caused a consistent increase in blood pressure in intact rats drinking water. In contrast, combined digoxin and DOCA administration (n = 10) increased systolic blood pressure from day 18 of treatment onwards, to a maximum at day 34 compared with sham-treated rats (n = 10). There were no consistent changes in water intake, urine volume, urinary sodium or potassium excretion, or plasma sodium or potassium concentration with digoxin treatment. DOCA increased water intake and urine volume, and caused an initial decrease in urinary sodium excretion, but no change in urinary potassium excretion or plasma sodium concentration. Plasma potassium excretion was lower in DOCA- than sham-treated rats. CONCLUSION: Combined digoxin and DOCA administration in intact rats drinking water increased blood pressure significantly compared with either drug alone, raising the possibility that the mechanism by which nephrectomy and salt loading contribute to DOCA hypertension in the rat might be through stimulation of endogenous digitalis-like substances.

Animals↗
PubMed1994

High-performance assays of small molecules: enhanced sensitivity, rapidity, and convenience demonstrated with a noncompetitive immunometric anti-immune complex assay system for digoxin.

We report the first clinical application of a noncompetitive immunometric assay system that provides advantages for the rapid and robust assay of small molecules similar to those realized for larger molecules with two-site immunometric assays. This anti-immune complex assay is based on the interaction of a receptor such as a primary antibody with its ligand, such that new binding sites, recognizable by a secondary antibody, are formed. In this report the system is applied to the measurement of digoxin in serum. Utilizing an anti-complex antibody that recognizes a digoxin-bound primary antibody with affinity > 2000-fold over its binding to the primary antibody alone, we show that this anti-complex assay system provides a high-performance assay for serum samples, being conveniently simple (immobilized primary antibody binds digoxin and then labeled secondary antibody so that when excess unbound label is washed away the immunometric readout reflects the digoxin concentration), rapid (incubation time 1-10 min), sensitive (detection limit 30 ng/L), precise (3-4% within-run CV, 1-8% total CV), and free from interference from digoxin-like immunoreactive factors.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

[Intrauterine therapy of fetal supraventricular tachycardia with digoxin and verapamil].

Fetal supraventricular tachycardia may cause intrauterine heart failure and thus require transplacental treatment. During a period of nine years, we treated nine of eleven fetuses (gestational age ranging from the 26th to the 36th week) suffering from paroxysmal supraventricular tachycardia (10) or atrial flutter (1). The remaining two fetuses did not receive antiarrhythmic therapy because of only short lasting supraventricular tachycardia. Two fetuses were hydropic at the onset of therapy. Diagnosis of the rhythm disorder was established by m-mode echocardiography. All nine fetuses treated received digoxin after diagnosis of supraventricular tachycardia. Three of these reverted to sinus rhythm, one remained in supraventricular tachycardia which, however, was well tolerated. Five fetuses (three because of failure of digoxin alone and two because of a severely symptomatic supraventricular tachycardia) were treated with a combination of digoxin and verapamil. All five fetuses responded to the combined treatment, two of them, however, were delivered prematurely because of recurrence of supraventricular tachycardia in one and amnion-infection syndrome in the other. All patients survived and no severe fetal or maternal side effects were observed. Our experience confirms that digoxin and verapamil are usually effective in treating fetal supraventricular tachycardia. Some fetuses with short lasting and self limiting supraventricular tachycardia may not need any treatment, and a few not responding to digoxin and verapamil may require other antiarrhythmic drugs.

Cardiotocography↗
PubMed1993

[Digoxin intoxication due to unadjusted loading dose in renal failure].

We describe a case of digoxin intoxication due to an unadjusted loading dose in a patient with renal failure. The importance of individual calculation of the digoxin dosing regimen in patients with renal failure is reemphasized. The volume of distribution of digoxin decreases significantly in chronic renal failure, due to decreased tissue binding in the uremic state. Accordingly, not only the digoxin maintenance dose, but the digoxin loading dose as well must be adjusted in this condition.

Aged↗
PubMed1977

Renal clearance of digoxin in young infants.

The renal clearance of digoxin and creatinine were measured in eleven infants, aged one to five months, with congenital heart disease and heart failure. The renal clearances of digoxin were low at one month of age (50 ml/min/1.73 m2) but increased progressively until the adult range was attained at about five months of age (130-150 ml/min/1.73 m2). At any given age, however, the renal clearance of digoxin was almost twice as great as the simultaneously determined creatinine clearance (mean ratio 1.73). This stands in marked contract to older subjects where creatinine and digoxin clearances are usually similar. These data explain (in part) the larger digoxin dosage requirement of infants.

Aging↗
PubMed1993

[Simultaneous prescription of digoxin and an anti-arrhythmia agent, is it dangerous?].

Many anti-arrhythmic drugs modify the pharmacokinetics of digoxin and increase serum levels. This possibility is considered for the majority of main anti-arrhythmics on the basis of a review of the literature. Quinidine, propafenone, flecainide, amiodarone and verapamil increase blood digoxin levels, sometimes to twice their baseline values. Suggested mechanisms involve above all a decrease in clearance of digoxin and changes in its volume of distribution. Reported accidents considered to be a direct consequence of these interactions are nevertheless rare in the literature, and the need for modifying dose and increased cardiological surveillance in the case of such a combination is essentially a question of precaution. Disopyramide, procainamide and mexiletine do not appear to have any reported effects on the pharmacokinetics of digoxin, their combined prescription never having had any effect on blood digoxin levels.

Anti-Arrhythmia Agents↗
PubMed1996

Evidence for presence of a reduced form of digoxin-like immunoreactive factor (dihydro-DLIF) in mammalian tissues.

Digoxin-like immunoreactive factor (DLIF) from adrenal glands is an endogenous ligand structurally related to the plant-derived cardiac glycoside digoxin. Cardiac glycosides regulate the activity of the sodium pump and thus play key roles in disease processes involving regulation of ion transport. We now report the discovery of an endogenous dihydro-DLIF analogous to dihydrodigoxin. We used HPLC, ultraviolet spectrophotometry, and cross-reactivity with two antibodies, one specific for digoxin and one for dihydrodigoxin, to support the hypothesis that dihydro-DLIF contains a chemically reduced lactone ring. The spectral absorbance maximum for dihydro-DLIF is at 196 nm, identical to dihydrodigoxin. DLIF and dihydro-DLIF are 975- and 2588-fold less immunoreactive than digoxin and dihydrodigoxin for their respective antibodies. The molar ratio of dihydro-DLIF to DLIF is approximately 5.3 in bovine adrenocortical tissue and approximately 0.38 in human serum. Dihydrodigoxin (reduced lactone ring) added to microsomes isolated from bovine adrenal cortex produced a 4.5-fold increase in digoxin-like immunoreactivity (oxidized lactone ring) after 3 h of incubation. The biotransformation is likely mediated by a cytochrome P-450 NADPH-dependent process. Our findings demonstrate the presence of a dihydro-DLIF in mammals and suggest a metabolic route for synthesis of endogenous DLIF in mammalian tissue.

Adrenal Cortex↗
PubMed1996

Investigation into the possible mechanisms involved in altered digoxin levels in diabetic patients.

The present study was undertaken to investigate the possible factors which may contribute to the altered digoxin levels in diabetic patients. The digoxin levels were found to be significantly higher in diabetics (1.74 +/- 0.09 ng/ml) as compared to non-diabetics (0.76 +/- 0.07 ng /ml). There was a positive correlation between digoxin levels and glycosylated haemoglobin levels. All diabetic patients had serum creatinine, urea and potassium levels within normal limits. However, serum TSH levels were found to be significantly higher in diabetics as compared to controls. Serum tri-iodo-1-thyronine (T3) levels were found to be lower in diabetics as compared to non-diabetics. Our data suggests that diabetes-mellitus causes alteration of digoxin levels. One of the causes of this increase in digoxin levels may be a tendency towards mild hypothyroidism associated with diabetes mellitus.

Aged↗
PubMed1977

Development of a highly sensitive radioimmunoassay for digoxin and its application in pediatric practice.

The sensitivity of two established routine digoxin radioimmunoassay methods has been increased to enable the provision of a rapid and relatively atraumatic inpatient and outpatient service for neonates and small children, using capillary blood samples obtained by heel-prick. The methods employ 125I- or 3H-labelled digoxin, a rabbit antiserum raised against a digoxin: bovine serum albumin conjugate and only 10 or 25 microliter of plasma as the sample. The results obtained using these highly sensitive assays correlate closely with those found using conventional assays, requiring larger sample volumes. An apparent difference in sensitivity to digoxin has been demonstrated between infants and children more than 1 yr old. Thus infants appear to tolerate plateau phase plasma levels (mean value for non toxic infants 2.6 +/- 1.8 ng/ml) that in older children or adults would be associated with digoxin toxicity.

Binding Sites, Antibody↗
PubMedDate not supplied

Effects of terbinafine on the pharmacokinetics of digoxin in healthy volunteers.

STUDY OBJECTIVE: To assess the potential effects of terbinafine, a new synthetic allylamine antifungal agent, on the pharmacokinetics of a single 0.75-mg oral dose of digoxin. DESIGN: Randomized, double-blind, placebo-controlled, crossover study consisting of two treatment periods. SUBJECTS: Sixteen healthy men and women volunteers. INTERVENTIONS: During treatment A, placebo was administered once/day for 12 days; during treatment B, terbinafine 250 mg was administered orally once/day for 12 days. The washout period between treatments was at least 2 weeks. A single 0.75-mg oral dose of digoxin was administered on day 8 of each period. Blood samples were collected after administration of digoxin to determine pharmacokinetics. MEASUREMENTS AND MAIN RESULTS: Compared with placebo, terbinafine did not alter the time course of the digoxin serum levels. Although the time to maximum peak concentration with terbinafine was slightly reduced, the maximum concentration and area under the serum drug concentration-time curve from time zero to 120 hours were not significantly different with terbinafine than with placebo. No drug-related side effects were reported with either active treatment, and no clinically significant changes in vital signs, physical examination results, electrocardiograms, or clinical laboratory results were observed. CONCLUSIONS: No special dosage adjustments for digoxin appear to be necessary during concomitant therapy with terbinafine.

Adult↗
PubMed1998

Toxic digoxin-drug interactions: the major role of renal P-glycoprotein.

The clinical use of digoxin is complicated by a large number of drug interactions leading to severe toxicity of the cardiac glycoside. The discovery that digoxin is actively secreted by the renal tubular cell via the p-glycoprotein drug efflux pump has led us to examine whether commonly interacting drugs do so by inhibiting renal tubular secretion of digoxin. We review digoxin-drug interactions which have been studied kinetically in humans, where there are sufficient data on renal clearance of digoxin and GFR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1976

Calcium-dependent toxic effects of digoxin in isolated myocardial preparations.

On isolated guinea-pig papillary muscles as well as on electrically driven atria digoxin was infused into the bath fluid until cardiac arrest occurred. The concentration of digoxin which caused standstill is defined as the toxic one. The toxicity was determined under various Ca2+-concentrations. On the papillary muscle the increase of extracellular Ca2+ from 0.9 to 7.2 mM increased the toxicity of digoxin, i.e. significantly diminished its toxic concentrations. Likewise, on electrically driven atria an increase of Ca2+ from 0.45 to 7.2 mM increased the toxicity of digoxin. These results demonstrate that with regard to the toxicity Ca2+ and digoxin act synergistically.

Animals↗