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At least 253 records · Page 14Linked to original sources
PubMed1984

Effect of intravenous digitoxin on inotropy, haemodynamics and P-Q interval in ischaemic heart disease.

The haemodynamic and electrophysiologic responses to rapid intravenous injection of digitoxin (0.6 mg over 5 min) were measured in 6 patients with chronic coronary heart disease without clinical heart failure. Two minutes after end of injection peripheral resistance increased and stroke volume fell, while peak dP/dt in the right ventricle showed minimal increase. AV nodal conduction velocity decreased markedly. Thereafter, the peripheral resistance remained unchanged, stroke volume and peak dP/dt in the right ventricle increased slightly, while AV conduction remained stable. In 2 control patients stable values were found during 60 min. We conclude that digitoxin given intravenously as a single bolus injection induces an abrupt slight increase in peripheral resistance. Thereafter, a gradual increase in inotropy is found. The effect on the AV node appears rapidly and remains stable.

Aged↗
PubMed1977

Collagen metabolism in experimental cardiac hypertrophy in the rat and the effect of digitoxin treatment.

It is generally agreed that cardiac hypertrophy is accompanied by the hyperplasia of connective tissue cells. In the present work, collagen metabolism was studied in the heart of nondigitalised and digitalised rats after the constriction of the aorta. The activity of prolyl hydroxylase was maximally increased 2 days after the operation. The incorporation of proline into collagen hydroxyproline increased without any increase in the specific radioactivity of free intracellular proline, the peak labelling of collagen occurring at 4 days. Although the treatment of the rats with digitoxin prevented the development of cardiac hypertrophy and an increase in collagen labelling, an increase in the activity of prolyl hydroxylase was observed. The intracellular free proline pool and its specific radioactivity were significantly lower in digitalised rats as compared with non-digitalised rats. The results indicate that constriction of the aorta is accompanied by an activation of connective tissue cells leading to increased synthesis of collagen. However, digitoxin treatment can prevent the increase in collagen labelling, possibly by inhibiting the amino acid transport, but it is unable to remove the stimulus for hypertrophy.

Aminoisobutyric Acids↗
PubMed2001

Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells.

The saponin digitonin, the aglycone digitoxigenin and five cardiac glycosides were evaluated for cytotoxicity using primary cultures of tumor cells from patients and a human cell line panel (representing different cytotoxic drug-resistance patterns). Of these seven compounds, proscillaridin A was the most potent (IC(50): 6.4--76 nM), followed by digitoxin, and then ouabain, digoxin, lanatoside C, digitoxigenin and digitonin. Correlation analysis of the log IC(50) values for the cell lines in the panel showed that compound cytotoxicity was only slightly influenced by resistance mechanisms that involved P-glycoprotein, topoisomerase II, multidrug resistance-associated protein and glutathione-mediated drug resistance. Digitoxin and digoxin expressed selective toxicity against solid tumor cells from patients, while proscillaridin A expressed no selective toxicity against either solid or hematological tumor cells. The results revealed marked differences in cytotoxicity between the cardiac glycosides, both in potency and selectivity, and modes of action for cytotoxicity that differ from that of commonly used anticancer drugs.

Antineoplastic Agents↗
PubMed1986

Practical value of a new serum digitoxin assay.

The purpose of this study was to evaluate a new fluorescence polarization immunoassay, TDx, for digitoxin by comparing the results of this assay with those of a radioimmunoassay (RIA). Thirty-three serum samples were obtained from 15 patients during, and for 4 weeks after, a 4-week course of digitoxin therapy. Each sample was separated by centrifugation, coded, and frozen until analysis. At the time of analysis, each sample was divided and analyzed simultaneously by TDx and RIA. Nine samples yielded results less than 2 ng/ml (limit of assay sensitivity) by one or both methods and were excluded from further data analysis. Linear regression analysis of the results of the remaining 24 paired samples (x = TDx, y = RIA) revealed a strong correlation coefficient of r2 = 0.95, slope = 0.95, and a y intercept of -0.99 (y = -0.99 + 0.95x). Additionally, the TDx results were lower than the RIA values in only five of 33 paired samples; and these occurred in four patients who had a significantly lower mean estimated creatinine clearance than that of the other 11 patients (39.0 +/- 9.1 ml/min/1.73 m2 vs. 63.3 +/- 11.8 ml/min/1.73 m2, p less than 0.01). The TDx system is a comparable alternative to the RIA method, but differences in specificity and sensitivity may exist and should be evaluated more thoroughly.

Aged↗
PubMed1982

Effect of administration of activated charcoal and fibre on absorption, excretion and steady state blood levels of digoxin and digitoxin. Evidence for intestinal secretion of the glycosides.

The effects of activated charcoal and fibre on absorption and stationary plasma levels of digoxin and digitoxin have been studied. The effect of fibre alone is small but an interactive effect on absorption may occur if fibre and digoxin are ingested simultaneously. Charcoal effectively decreases glycoside absorption even when administered after the glycosides. During maintenance therapy with digoxin or digitoxin, charcoal administration decreased the glycoside plasma levels by 31.2% and 18.3% respectively. It is suggested that even digoxin may have a significant biliary excretion and enterohepatic circulation or that this glycoside has a significant intestinal secretion. The therapeutic implication of this study is that charcoal may be of value, not only in the management of acute glycoside poisoning, but also in some cases of more chronic intoxication.

Adult↗
PubMed1992

The effect of ageing on plasma albumin and plasma protein binding of diazepam, salicylic acid and digitoxin in healthy subjects and patients with renal impairment.

1. Plasma albumin concentration was measured in 118 healthy subjects (aged between 18 and 87 years), in 95 renal patients with creatinine clearances between 15 and 50 ml min-1 (aged between 14 and 79 years) and in 101 uraemic patients maintained on chronic haemodialysis (aged between 27 and 83 years). 2. There was a significant (P less than 0.001) negative correlation between albumin concentration and age in healthy subjects, but no correlation in patients with low creatinine clearance or in uraemic patients. 3. The ex vivo plasma binding of diazepam (1 microM), salicylic acid (2 mM) and digitoxin (37 nM) was studied in groups of age-selected young and aged healthy subjects in patients with low creatinine clearance and in patients with uraemia. The unbound fractions of diazepam and salicylic acid were about double in old compared with young healthy subjects whereas they were similar in young and old patients with lowered creatinine clearance. In uraemic patients, ageing did not affect the binding of salicylic acid whereas the unbound fraction of diazepam was slightly but significantly greater in elderly subjects. The unbound fraction of digitoxin was independent of age in both healthy subjects and in those with renal disease. 4. Decreased plasma binding of diazepam and salicylic acid was partially corrected by extensive dialysis of plasma. The lower plasma binding of diazepam and salicylic acid associated with ageing may be ascribed to the effects of endogenous displacers and to hypoalbuminaemia. The influence of these two factors appears to be drug-dependent.

Adolescent↗
PubMed1985

Effect of digitoxin on vaginal epithelial differentiation in the Balb/c mouse.

Vaginal epithelial differentiation (VED) in the mouse and the human is the replacement of columnar by squamous epithelium in the vagina. This occurs in humans in late first and second trimesters of pregnancy and in mice after birth. In both diethylstilbestrol (DES) exposure during the process is associated with persistence of columnar epithelium and later reproductive tract tumor. Cardiac glycosides are estrogenic in both species. The concern: could cardiac glycosides produce similar effects to those seen after DES? Digitoxin was administered to Balb/c neonates at increasing doses. VED occurred by 10 days in three low-dose groups. Cardiotoxic mortality precluded study at higher doses. Therefore digitoxin did not affect VED.

Animals↗
PubMed1994

Prospective, randomized, placebo-controlled, double-blind testing of colour vision and electroretinogram at therapeutic and subtherapeutic digitoxin serum levels.

In a prospective, randomized, double-blind study with 10 healthy probands, changes in colour discrimination and in the pattern electroretinogram (P-ERG) and visually evoked cortical potentials (P-VECP) were monitored at therapeutic and subtherapeutic digitoxin serum levels. There was a slight increase in the total error score in the Farnsworth-Munsell 100-hue test at 0.1 mg digitoxin per day in comparison with the placebo. P-ERG and P-VECP did not show any significant changes.

Adult↗
PubMed1976

Collagen metabolism of the rat heart during experimental cardiac hypertrophy and the effect of digitoxin treatment.

In cardiac hypertrophy the total content of collagen is increased in the myocardium. The first indicator of the increased activity of connective tissue cells is an increase in the activity of prolyl hydroxylase of the myocardium. This is later followed by an increase in the rate of collagen synthesis and subsequently collagen is accumulated in the myocardium. Digitoxin treatment prevents the hypertrophy and the accumulation of proteins to the myocardium. This effect of digitoxin is, at least partly, explained by a decreased transport of amino acids into the cells, The results emphasize the importance of amino acid supply to the process of hypertrophy.

Animals↗
PubMed1986

Digoxin- and digitoxin-like immunoreactive substances in amniotic fluid, cord blood, and serum of neonates.

Using four different digoxin kits, it was disclosed that the majority of various samples including amniotic fluid, cord blood, and serum from neonates contained substantial levels of digoxin-like immunoreactive substance. The differences in data seemed to be due to the range of epitopes which are recognized by antidigoxin antiserum. The day-to-day studies on sera serially obtained from infants at birth to 48 days old revealed that the level of the substance (0.31 +/- 0.12 ng/ml) in sera of the 1-day-old neonates rapidly declined to the level of 0.1 ng/ml by the 2nd postnatal wk and thereafter gradually declined. The immunological specificity and accuracy of the detection of digoxin-like immunoreactive substance was confirmed by a sample dilution test, a recovery test for standard digoxin, and an absorption test with antidigoxin antiserum. The amniotic fluid and cord blood also contained four to eight times more of a digitoxin-like immunoreactive substance than they did digoxin-like immunoreactive substance. A significant correlation was observed between the levels of digoxin-like immunoreactive substance and of digitoxin-like immunoreactive substance (p less than 0.01).

Amniotic Fluid↗
PubMed1980

Effects of phenobarbital on digitoxin metabolism in guinea-pig liver slices.

1. [3H]Digitoxin was incubated for 2-5 h with liver slices from control and phenobarbital-pretreated guinea-pigs. Metabolites were the same in both groups. 2. After 5 h incubation, a 6-fold increase in unmetabolized digitoxin was found in the phenobarbital-pretreated group compared with controls. 3. The major metabolite extracted by chloroform is formed by hydroxylation at an unknown position of the cardenolide nucleus, which is not the 12 beta-hydroxy position. Only half the amount of this metabolite was formed in livers of pretreated animals, compared to controls, in 2 h, after 5 h incubation similar amounts occurred in both groups. 4. Water-soluble metabolites decreased 2-fold in phenobarbital-pretreated animals at 2 and 5 h of incubation.

Animals↗
PubMed1977

Acute digitoxin intoxication treated by intracardiac pacemaker: experience in sixty-eight patients.

Out of 124 patients who had taken massive doses of digitoxin in attempted suicide, emergency endocardial pacing was performed in the 68 with the worst prognosis. The mortality (13%) in the 124 patients compared favorably with the mortality (20%) in a previous series of 70 similar patients none of whom were paced. Sixteen (23%) of the 68 paced patients died. The causes of death were: asystole (two); cardiogenic shock (two); septicemia (one); and ventricular fibrillation (eleven). Ventricular fibrillation occurred during introduction of the pacing catheter in two patients, as a result of electrode displacement in these patients, because of premature withdrawal of the catheter in one patient, and for no detectable reason, during normally proceeding pacing, in five patients. Endocardial pacing has a place in the emergency treatment of massive digitoxin poisoning. Its chief hazards are mechanical, and one of the commonest is electrode displacement.

Adolescent↗
PubMed1975

Effects of phenobarbital on digitoxin and digoxin elimination in the dog.

When normal dogs were orally pretreated with a known microsomal enzyme inducer, phenobarbital, the serum biological half-life of digitoxin was not significantly affected, whereas the serum biological half-life of digoxin was significantly shortened by nearly 30%. These results are variant with that previously reported for human beings, wherein microsomal enzyme induction resulted in shortening of plasma biological half-life of digitoxin by more than 40% and insignificant effects on plasma biological half-life of digoxin. Because of the effect on plasma biological half-life, concomitant digoxin and phenobarbital administration to the canine cardiac patient may necessitate careful evaluation of the digitalization.

Administration, Oral↗
PubMed1975

Effect of cyanoketone on digitoxin-induced mortality and hepatic mixed function oxidases in rats.

Cyanoketone pretreatment protected female rats against digitoxin-induced mortality. Cyanoketone also acts as an inducer of hepatic mixed function oxidases, increasing cytochrome P-450 content and enhancing aniline hydroxylase and aminopyrine demethylase activities. The protective effect of cyanoketone against digitoxin toxicity may be due to the enhanced conversion of the glycoside to more polar metabolites which are more readily excretable.

Androstenols↗
PubMed1975

[Proceedings: Clinical value of serum digoxin and digitoxin determination in renal insufficiency].

Plasma digoxin and digitoxin determination has proven to have an important bearing, particularly in patients with renal failure. It permits early detection of digitalis intoxication in the absence of marked clinical and ECG evidence, and adjustment of dosage accordingly. Also, in patent intoxication it makes it possible to select the right moment for resumption of therapy. To illustrate the importance of the method some cases are cited involving plasma digoxin and digitoxin determination.

Acute Kidney Injury↗
PubMed1992

Cross-reactivity of anti-digoxin antibodies with digitoxin depends on tracer structure.

The most common methods for measuring digoxin concentrations in serum are immunoassays. The prerequisite for exact determination of the digoxin value is an antibody that specifically binds digoxin. Because digitoxin differs from digoxin only in the C-12 hydroxy group, it is difficult to obtain anti-digoxin antibodies that do not cross-react with this compound. During the development of a fluorescence polarization immunoassay (FPIA) for digoxin, we investigated digoxin tracers with different structures. We found that in FPIA the digitoxin cross-reactivity of an antibody could be reduced by varying the structure of the tracer molecule.

Animals↗
PubMedDate not supplied

[Fluoroimmunometric method of determining digitoxin].

Digitoxin at concentrations up to 5 x 10(-10) M (therapeutic concentrations are 2 x 10(-8) M) can be reliable measured by a fluoroimmunometric method with coproporphyrin as a tracer. The use of nylon filters with immobilized digitoxin to remove an excess of labelled antibodies increases reliability and reduces the time of measurements, and thus simplifies the assay.

Chromatography, Ion Exchange↗
PubMed1990

[Production and characterization of a high affinity monoclonal antibody with digoxin and digitoxin specificity].

A monoclonal antibody with a high affinity for digoxin (KA = 5.5 x 10(10) M-1) and digitoxin KA = 5.0 x 10(10) M-1) was produced by somatic cell fusion. This antibody, designated 2A3, displayed little cross reactivity with other glucosides and no cross reactivity with endogenous steroids. It was shown that 2A3 is a suitable tool in an enzyme immunoassay for digoxin and digitoxin.

Antibodies, Monoclonal↗