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PubMed1979

Enhanced cardiac effect of digoxin during quinidine treatment.

Quinidine causes an increase in the serum digoxin concentration. Three patients were studied to determine if the increase in serum concentration is paralleled by an increase in the cardiac effect of digoxin. Each patient's clinical condition and serum digoxin concentration were stable when quinidine administration was begun. In all three patients, serum digoxin concentrations increased significantly after beginning quinidine, and decreased when quinidine was discontinued. While taking quinidine, all three patients had ECG findings that suggested enhanced digitalis effect and one patient had clinical evidence of an increased hemodynamic effect. These effects paralleled the increases in serum digoxin concentration. Our findings suggest that the increase in serum digoxin concentration, which occurs after beginning quinidine, is associated with an increase in the effect of digoxin on the heart.

Aged↗
PubMed1979

[Digoxin concentrations in plasma and tissue. A postmortal investigation (author's transl)].

Postmortal tissue digoxin concentration and prefinal and postmortal plasma digoxin concentrations from 9 patients were determined using the 125J-digoxin radioimmunoassay. The concentration of digoxin in the myocardium of the left ventricle was 61.44 +/- 45.17 ng/g. In the right ventricle the concentration was 36.78 +/- 33.11 ng/g. Higher digoxin concentrations were found in the right atrium (34.93 +/- 21.86 ng/g) than in the left atrium (25.43 +/- 14.57 ng/g). In plasma samples taken after death approximately 62% higher digoxin concentrations were found than in samples of patients in prefinal state. Histological examination revealed positive correlation between in the high varying digoxin concentrations and the pathological conditions of the tissue structure.

Aged↗
PubMed1979

[Is hemoperfusion effective in the treatment of digoxin intoxication? (author's transl)].

Digitalis therapy is frequently accompanied by adverse drug reactions. Severe digitalis intoxications are still a problem. Therapeutical methods, which could be used in the case of a life threatening digoxin intoxication, are known, but not yet generally available. Hemodialysis has only a minor effect on digoxin excretion. This study was planned to test the hypothesis that hemoperfusion across dextran-cocoated charcoal or the resin Amberlite XAD 4 could be more effective in the therapy of digoxin intoxications. The ability of hemoperfusion to eliminate digoxin was tested in a patient who had to undergo treatment beacuse of a severe bromcarbamide intoxication. Additionally we compared the effect of several modifications on this method in 12 dogs, which had received 0.05 mg/kg body weight per day for three days prior to the experiment. Although hemoperfusion across Amberlite XAD 4 may eliminate as much digoxin as normal human kidneys during the few hours of treatment, the amount of digoxin removed after all is only a small percentage of the total body pool. Thus compared to the risks of hemoperfusion as an invasive treatment its effect is small. According to our results, hemoperfusion cannot be recommended as a standard therapy of severe digoxin intoxications.

Adult↗
PubMed1979

Decreased calcium content in patients with digoxin intoxication.

The platelet calcium content, the plasma calcium level and the serum digoxin were examined in 90 individuals divided into the following four groups : I -- patients with digoxin intoxication; II -- treated with digoxin; III -- treated with digoxin and furosemide, and IV -- control subjects. The patients with digoxin intoxication showed a lower platelet calcium content as compared to subjects of the other groups (p less than 0.001), whereas the serum digoxin level was significantly higher than in the patients of groups II and III (p less than 0.001). Since the examination of the platelet calcium level is a relatively simple and rapid procedure, with reliable results, its use as a routine method in the determination of digoxin intoxication is suggested.

Adult↗
PubMed1979

[Biological availability of digoxin from a combination drug].

In a randomized cross-over study with 14 voluntary test persons the absolute biological availability of digoxin in Card-Dusodril 1/8 and 1/4 respectively was investigated. 6 test persons received 4 drag. Card-Dusodril 1/8 (= 0.5 mg digoxin), 8 test persons 4 drag. Card-Dusodril 1/4 (= 1 mg digoxin) orally, in comparison to the corresponding group with intravenously applied digoxin as standard. Based on the cumulative digoxin excretion in the urine an absolute biological availability of Card-Dusodril 1/8 of 79%, of Card-Dusodril 1/4 of 76% could be demonstrated. With regard to an average resorption of oral digoxin preparations of approx. 70%, the present values, which correspond in direct comparison to those of acetyl digoxin, can be considered good. Maximum serum levels were achieved after 86 +/- 6.8 minutes which also indicates a quick resorption.

Administration, Oral↗
PubMed1979

[Comparative study of the absolute bioavailability of four oral digoxin preparations (author's transl)].

In a randomized cross over study on 19 normal subjects the absolute bioavailability of four oral digoxin preparations (Digacin containing a silica gel matrix as preparation A and three other commercial digoxin tablet preparations, B, C and D) were investigated applying digoxin in a daily dose of 0.25 mg for 10 consecutive days. On day 8, 9 and 10, the serum digoxin concentration and the amount of digoxin excreted with 24-h urine were measured radioimmunologically. After i.v. administration the mean serum digoxin concentration amounted to 0.58 ng/ml. With oral administration preparation A achieved the highest concentration (0.51 ng/ml) and preparation C the lowest (0.42 ng/ml). Accordingly, after i.v. administration 118 microgram digoxin were excreted with the 24-h urine and 95 microgram after the oral preparation A and 73 microgram after preparation C, respectively. From the serum concentrations and the amount excreted with the urine the absolute bioavailability was calculated: 88.0 and 80.4%, respectively, for preparation A, 82.5 and 67.2% for preparation B, 72.7 and 61.8% for preparation C, 76.2 and 67.3% for preparation D.

Administration, Oral↗
PubMed1977

Monitoring the dose of digoxin.

All patients being prescribed digoxin in a general practice were examined and the serum urea, creatinine, electrolytes, and digoxin concentrations were determined.Sixty-six patients were identified (0.73 per cent of the practice population). After excluding six, whose tablet-taking was unreliable, it was found that two patients had serum digoxin levels above the usually accepted upper limit and a total of 23 patients (38 per cent of the digoxin takers) had some alteration made to their dose, including eight whose digoxin was stopped. We believe that serum digoxin estimations are useful in determining the optimum dose of digoxin in general practice.

Adult↗
PubMed1978

Variability among commercially available digoxin radioimmunoassay kits in cross reactivity to dihydrodigoxin.

We evaluated four commercially available 125I-digoxin radioimmunoassay kits with regard to their ability to cross react with the digoxin metabolite dehydrodigoxin. We prepared dihydrodigoxin serum samples in digoxin-free serum over the concentration range 0.4 to 5.0 microgram/liter and assayed them with each kit according to the manufacturer's instructions. The metabolite was able to displace the 125I-labeled digoxin derivative from the antibody supplied with all four kits. However, the extent of the cross reactivity depended on the kit, ranging from essentially zero to a high degree of interference. Dihydrodigoxin is the only metabolite of digoxin to have been quantitiated in human serum, and may comprise up to 30% of total glycosides. Over the clinical and therapeutic range of serum digoxin concentrations, enough dihydrodigoxin can be produced to interfere in the determination of serum digoxin concentrations by this method. We suggest that laboratories evaluate their specific kit with regard to cross reactivity to this metabolite.

Antibodies↗
PubMed1984

Effect of protein concentration on the determination of digoxin in serum by fluorescence polarization immunoassay.

Determination of digoxin by fluorescence polarization immunoassay (FPIA) with the Abbott "TDx" is significantly influenced by the concentration of total serum protein. Each 10 g/L increase in serum protein results in an 8% decrease in measured digoxin. Studies with [3H]digoxin confirmed that digoxin binds to the protein pellet during the trichloroacetic acid precipitation step before the immunoassay. Serum protein, or equal concentrations of albumin or gamma-globulin, exert an equivalent effect on the apparent digoxin value. Because the total protein concentration of the assay calibrators is low (50 g/L) compared with its reference interval in serum (60-80 g/L), results by FPIA may be expected to be low by an average of 16% (range, 8-24%). Digoxin results by FPIA will be most nearly accurate when the calibrators include a total protein concentration of about 70 g/L. Patients' specimens with abnormally high or low protein content will give falsely high or low results for digoxin.

Blood Proteins↗
PubMed1983

Central alpha receptors and their role in digoxin cardiotoxicity.

The purpose of this study was to determine the role of alpha receptors in the inotropic and cardiotoxic actions of digoxin. Pentobarbital-anesthetized dogs were pretreated centrally with either prazosin, a selective alpha-1 antagonist, or yohimbine, a selective alpha-2 antagonist. Cardiac rhythm, blood pressure and contractile force were monitored during a 60-min period after pretreatment and during a continuous i.v. infusion of digoxin (2.5 micrograms/kg/min). Both agents, when administered into the lateral ventricle, produced depressant effects on hemodynamic parameters. Yohimbine (100 and 200 micrograms/kg i.c.v.) significantly increased the arrhythmogenic and lethal doses of digoxin in a dose-dependent manner. The protective effects of yohimbine (200 micrograms/kg) were not evident when the drug was given peripherally. Central alpha-1 blockade with prazosin increased the lethal dose of digoxin only at the largest dose (100 micrograms/kg i.c.v.) and its effects may be attributed to nonspecific central activity. BHT-933 (5 micrograms/kg i.c.v.), a selective alpha-2 agonist, enhanced the toxic effects of digoxin by decreasing both the arrhythmogenic and lethal dose of digoxin. These results suggest a central alpha-2 receptor mediation of the cardiotoxic actions of digoxin.

Animals↗
PubMed1978

Plasma digoxin levels and the interbeat interval signal in atrial fibrillation.

Fifty-eight patients with atrial fibrillation treated with digoxin were studied to determine the correlation between serum digoxin levels and the ventricular rate. The study was a computer-based exercise, processing a signal consisting of R-R intervals, derived by point-digitising electrocardiograms. The means, variances and centers of gravity of power-spectra from the signal were correlated with serum digoxin levels, the peripheral pulse and with each other. A poor negative correlation of -0.31 was calculated between the means of interbeat-intervals and serum digoxin levels. Other Ecg-derived rate parameters did not correlate any better with serum digoxin. The mean interbeat-interval in a group of patients with higher serum digoxin levels (2 ng/ml) was significantly (p is less than or equal to 0.05) shorter than in a group with a low level (1 ng/ml). The negative correlation and this significant difference are best explained by the gradual increase in the dose administered to non-responders by the attending physicians who did not fear over-dosage because of frequent serum level determinations. It is concluded that the serum digoxin level is a poor predictor of the ventricular rate in patients with atrial fibrillation because of marked individual differences. These are due to the poor representation by serum levels of drug concentration at the point of interest (A-V node) and the non-linearity of the chronotropic effect of digitalis.

Adult↗
PubMed1983

[Action of digoxin on systolic and diastolic time intervals. An echocardiographic study in infants].

The effects of digoxin on systolic and diastolic time intervals were studied in 25 children and infants the majority of whom had congenital heart disease by M mode echocardiography. The recordings were performed before and after the administration of digoxin. Serum digoxin levels were measured to confirm therapeutic dosage. After digoxin, the right and left ventricular pre-ejection periods, the duration of the corrected electromechanical systole and the Weissler indices decreased, and the isovolumic relaxation periods increased. The ventricular ejection times were unchanged except for the corrected right ventricular ejection time which was only slightly decreased. Our results concerning left ventricular systolic time intervals are in agreement with other studies in children. As no other studies of the effects of digoxin on the right ventricular systolic time intervals, or of the right and left isovolumic relaxation time are available, confirmatory studies are required. The decrease in the right and left pre-ejection periods, electromechanical systole and the Weissler indices, is interpreted as being related to the positive inotropic effect of digoxin whilst the increase in isovolumic relaxation reflects only a decrease in preload. This study allows a better understanding of the effects of digoxin on the different phases of the cardiac cycle and a better appreciation of its action potential.

Diastole↗
PubMed1978

Digoxin disposition kinetics in dogs before and during azotemia.

The purpose of this study was to evaluate the disposition kinetics of digoxin after the administration of a single intravenous dose to the same dogs before and during azotemia. The digoxin plasma concentration-time data were fitted to a multicompartment model using nonlinear regression analysis. During azotemia, the biological half-life of digoxin was prolonged in six of seven dogs, while digoxin renal clearance, body clearance and apparent volume of distribution were significantly decreased. There was a corresponding increase in the apparent volume of the "central" compartment of digoxin. Approximately 45% of a digoxin dose was excreted by the kidney in these animals indicating a substantial nonrenal component to digoxin elimination in the dog. This nonrenal elimination did not change during azotemia, despite a decrease in renal clearance by 61%.

Animals↗
PubMed1984

Effect of repeated plasma exchange on steady state kinetics of digoxin and digitoxin.

The effect of repeated plasma exchanges on the steady state kinetics of digoxin (3 patients) and digitoxin (4 patients) was investigated in 7 patients. Plasma exchange was performed 3 times a week for 4 weeks up to 12 exchanges using a hollow fiber membrane. In each exchange, 4000 ml plasma were filtered within 1 to 2 h and replaced by an albumin containing (20 g/l) physiological electrolyte solution. Digoxin and digitoxin concentrations in blood and filtered plasma were measured by radioimmunoassay. The effects due to the amount eliminated by plasma exchange were distinguished from the effects due to hypoalbuminemia. The eliminative effect was confined to the plasma compartment. It resulted in a marginal decrease in the elimination half-life from 1.6 to 1.59 days for digoxin and 4.3 to 4.2 days for digitoxin. Theoretically, it can be calculated that the hypoalbuminemia caused an increase in the volume of distribution from 451 to 497 l (digoxin) and 35 to 50 l (digitoxin) and a further decrease in the elimination half-life from 4.2 to 4.1 days in the case of digitoxin (not digoxin). If given within 2 h prior to plasma exchange, 13 to 50% of the digitoxin dose (not digoxin) was eliminated. Alteration of digoxin and digitoxin dosage during repeated plasma exchanges is not recommended, but drugs should be given after, not before plasma exchange.

Adult↗
PubMed1978

[Dihydrogenated metabolites of digoxin: clinical importance and identification (author's transl)].

Several methods for the determination of dihydrometabolites of digoxin are described. Dihydrometabolites of digoxin are essentially inactive. They are the most important group of metabolites of digoxin. Seven (7) percent of a group of in-patients excreted more than 35% of these metabolites. The average was 13%, with respect to total extractable digoxin and metabolites in urine. In blood up to 40%, and in urine up to 52% dihydrogenated metabolites were found. The main metabolite was dihydrodigoxin, but the hydrolytic metabolites of digoxin exist also in reduced form. Neither the dose of digoxin, impaired renal function, nor an increased body content of digoxin seems to affect the rate of formation of these dihydrometabolites.

Chromatography, Gas↗
PubMed1982

Inhibition of digoxin absorption but not of digitoxin during cytostatic drug therapy.

Digoxin absorption is found to be decreased in patients with malabsorption syndromes on the basis of mucosal defects. Since intestinal mucosa can be damaged by cytostatic drugs, it was the purpose of these studies to investigate the influence of various cytostatic drugs on digoxin and digitoxin plasma levels and urinary excretion. In 9 patients with malignant lymphoma, who received 0.8 mg beta-acetyldigoxin (n = 6) or 0.5 mg digitoxin (n = 3) before and 24 h after combined therapy with cyclophosphamide, vincristine, procarbazine, and prednisone (CVPP) or cyclophosphamide, vincristine and prednisone (CVP), plasma glycoside concentrations were measured 0 to 8 h after digoxin and 0--168 h after digitoxin application and the areas under the plasma concentration-time curves were calculated. In 12 patients on 0.3 mg beta-acetyldigoxin and in 10 patients on 0.1 mg digitoxin, daily plasma glycoside concentrations and daily renal excretion were measured before and after CVPP, CVP or cyclophosphamide, vincristine, cytarabine and prednisone (CVAP) treatment schemes. The diminished steady-state plasma digoxin concentrations and daily renal glycoside excretion during the 24-168 h period after the cytostatic dose demonstrate a reversible impairment of digoxin absorption. In contrast cytostatic drug therapy does not lead to reduction in steady-state digitoxin plasma levels and daily renal glycoside excretion. The delayed time to peak after a single dose of digoxin or digitoxin during cytostatic drug therapy shows that rate of absorption of both glycosides is reduced. Our results indicate the need for very exact monitoring of digoxin dosage during cytostatic therapy. The use of digitoxin for these patients is an alternative in maintaining adequate digitalization.

Antineoplastic Agents↗
PubMed1980

Spironolactone interference with digoxin radioimmunoassay in cirrhotic patients.

The effects of spironolactone and cirrhosis on the measurement of serum digoxin levels by radioimmunoassay were studied in patients not receiving cardiac glycosides. Three groups of 10 patients each were studied. Groups 1 and 2 included patients with alcoholic cirrhosis, with Group 1 patients receiving spironolactone and Group 2 receiving no spironolactone. Group 3, the control group, included patients who were not receiving spironolactone and did not have cirrhosis. Apparent digoxin serum levels were measured by radioimmunoassay, and the mean levels of each group were compared. Group 1 had significantly higher apparent digoxin levels (1.3 +/- 0.62 ng/ml, p 0.05) than Groups 2 or 3. The apparent digoxin level of Group 2 (0.74 +/- 0.44 ng/ml) did not differ significantly from that of Group 3 (0.40 +/- 0.35 ng/ml). Significant correlations were found between apparent serum digoxin levels and daily spironolactone dose (Group 1), SGOT levels (Group 1), and prothrombin time/control ratios (Group 2 and all groups combined). Spironolactone appears to increase digoxin levels measured by radioimmunoassay. The effect of cirrhosis on digoxin radioimmunoassay has not been confirmed.

Digoxin↗
PubMed1981

[Digoxin and sinus node function in the sick-sinus syndrome (author's transl)].

In 12 patients with sinus node syndrome, the influence of Digoxin on the sinus-node function was examined. After having determined the sinus-node recovery time (SNRT), the calculated sinuatrial conduction time (SACT), and the mean cycle length, 1.2 mg Digoxin were applied intravenously; 45 minutes later the above mentioned determinations were repeated. Before applying Digoxin, the mean value of the SNRT was 1665.8 +/- 1381.5 ms, after Digoxin it was 1372.1 +/- 546.1 ms; there was no statistical significance. In regard of the SACT the values were 95.9 +/- 38.6 ms before and 125.0 +/- 31.9 ms after Digoxin (p less than 0.05). The mean cycle length remained almost unchanged (841 +/- 113.2 ms before and 847 +/- 138.4 ms after Digoxin, no significance). Thus it is to be regarded as the clinical therapeutic consequence that in these patients the glycoside application in absence of syncopes or equivalents can be administered in most of the cases without previous pacemaker-implantation. In special cases, however, mainly if there are signs of greater disturbances of the sinus node function and of the SACT, electrophysical functional-analytic examination previous to the Digoxin long-term therapy should be performed.

Adult↗