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At least 235 records · Page 13Linked to original sources
PubMed1993

[Thrombocytopenia caused by digitoxin overdose].

The authors report a new case of digitoxin-related thrombocytopenia. It involved a patient hospitalised for torsades de pointe in whom blood digitoxin was 85 micromols/l on admission. This rare complication progressed to a satisfactory conclusion in seven days. The mechanism is immuno-allergic and/or toxic since thrombocytopenia occurs only following therapeutic overdose. The prognosis is determined by the cardiac arrhythmia rather than the hemostasis abnormality. Treatment is symptomatic and should include the withdrawal of digitoxin which can be replaced by digoxin. Oral activated charcoal decreases the plasma half-life by blocking the enterohepatic cycle and is hence recommended in this situation.

Aged↗
PubMed1976

Interaction of pentobarbital, diphenylhydantoin and digitoxin with ethanol in the isolated perfused guinea-pig liver.

In the isolated guinea-pig liver the interactions of ethanol with the metabolism of three drugs (14C-pentobarbital, 14C-diphenylhydantoin, and 2H-digitoxin) has been investigated. The disappearance of ethanol could be described by zero-order kinetics and was not influenced by the three drugs. In the case of 14C-pentobarbital and 14C-diphenylhydantoin after a short period of distribution disappearance of radioactivity was faster under the influence of ethanol, whereas radioactivity in liver tissue was increased. The radioactivity accumulated in the liver tissue predominantly represented the unchanged drugs suggesting that the inhibition of drug metabolism by ethanol was the cause of the altered distribution. In the case of 3H-digitoxin ethanol did neither significantly influence the distribution of radioactivity nor the pronounced biliary excretion. However there exists some evidence for a minor inhibition of 3H-digitoxin's metabolism by ethanol.

Animals↗
PubMed1988

Reconstitution of cytochrome P-450-dependent digitoxin 12 beta-hydroxylase from cell cultures of foxglove (Digitalis lanata EHRH.).

Cytochrome P-450-dependent digitoxin 12 beta-hydroxylase from cell cultures of foxglove (Digitalis lanata) was solubilized from microsomal membranes with CHAPS (3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulphonic acid). Cytochrome P-450 was separated from NADPH: cytochrome c (P-450) reductase by ion-exchange chromatography on DEAE-Sephacel. NADPH:cytochrome c (P-450) reductase was further purified by affinity chromatography on 2',5'-ADP-Sepharose 4B. This procedure resulted in a 248-fold purification of the enzyme; on SDS/polyacrylamide-gel electrophoresis after silver staining, only one band, corresponding to a molecular mass of 80 kDa, was present. The digitoxin 12 beta-hydroxylase activity could be reconstituted by incubating partially purified cytochrome P-450 and NADPH:cytochrome c (P-450) reductase together with naturally occurring microsomal lipids and flavin nucleotides. This procedure yielded about 10% of the original amount of digitoxin 12 beta-hydroxylase.

Cells, Cultured↗
PubMed1993

Protein binding of digitoxin, valproate and phenytoin in sera from diabetics.

Chronic hyperglycaemia results in glycation of serum albumin and might affect the binding of drugs. The aim of the present study was to compare, using an equilibrium dialysis method, the protein binding of therapeutic concentrations digitoxin, valproate and phenytoin in sera from 70 insulin-dependent diabetics and 25 controls. Drug concentrations were measured by fluorescence immunopolarisation. Glycated albumin was measured by laser nephelometry after affinity chromatography. In sera from diabetics, protein binding of digitoxin (88.8 versus 89.9%) was unchanged; the protein binding of valproate (75.2 versus 80.7%) and phenytoin (67.9 versus 75.3%) was significantly decreased, but with no correlation with the concentration of glycated albumin. We conclude that the difference in protein binding between diabetic and control sera is due to glucose-independent modification of albumin in diabetics.

Adult↗
PubMed1975

The effect of ouabain and digitoxin on hexobarbitone sleeping time in the mouse.

The effect of ouabain and digitoxin upon the duration of loss of righting reflex produced by hexobarbitone in mice pretreated with the liver microsomal enzyme inhibitor SKF 525 A was studied. Both ouabain and, to a greater extent digitoxin, produced a dose dependent potentiation of the activity of hexobarbitone. These results confirm and extend previous observations and may be explained by a direct interaction at the level of the CNS and by a modified distribution of the barbiturate. Furthermore, they re-emphasize the possibility of such an interaction in the clinic.

Animals↗
PubMed1975

Concentration of digoxin, methyldigoxin, digitoxin and ouabain in the myocardium of the dog following coronary occulsion.

26 mongrel dogs were given a single dose of 0.03mg/kg tritium-labelled digoxin, beta-methyldigoxin, digitoxin or ouabain 2 hrs or 95 hrs following experimental coronary occlusion. Examination of the epicardial ECG was performed by moving from intact to ischemic or necrotic zones. 60 min after glycoside administration the animals were sacrificed and tissue samples from the marked heart muscles areas and from the skeletal muscle were analysed for glycoside content. The early glycoside uptake in acute ischemic or necrotic myocardium was diminished independently of the physicochemical properties of the glycoside. Significantly higher glycoside concentrations (ng/g wet weight) were measured in the injured myocardium 3 hrs after coronary occlusion than 96 hrs afterward (p less than 0.005). The values in acute ischemic myocardium varied considerably. This nonhomogeneity of glycoside uptake in the acute ischemic heart muscle may partly explain the increased sensitivity to glycosides in myocardial infarction. The decline of glycoside concentration correlates with the alterations in the epicardial ECG. The cardiac effects of cardenolides 60 min after intravenous administration was caused by the unchanged glycoside. In contrast to the myocardium, glycoside accumulation could not be found in the skeletal muscle. The concentrations of digoxin, beta-methyldigoxin and digitoxin in the skeletal muscle were significantly higher than the concentration of ouabain, which was rapidly eliminated via the urine.

Animals↗
PubMed1984

A comparative study between animals and monoclonal anti-digitoxin antibodies.

Anti-digitoxin antibodies have been produced by immunizing rabbits and by monoclonal techniques using the same digitoxin-protein conjugate. Titres, inhibition curves, affinities, dissociation and association rate-constants have been investigated for the two antibodies. It appears that the animal immune serum gives better criteria (except specificity) than the monoclonal ones. However, both can be used for quantitative assays, with less sensitivity for the monoclonal antibody. The main advantage of monoclonal production is to conduct large amounts of specific immunoglobulins which are very useful for human administration after a digitalis overdose.

Animals↗
PubMed1992

12 beta-Hydroxylation of digitoxin by suspension-cultured Digitalis lanata cells: production of digoxin in 20-litre and 300-litre air-lift bioreactors.

A biotransformation process for the production of digoxin was developed using Digitalis lanata cell suspension cultures. Digitoxin was used as the substrate for biotransformation. Digoxin production was carried out in a variety of vessels, including 1-l exsiccators, 20-l glass reactors and a 300-l air-lift bioreactor. A culture volume of 200 l was established after 28 d and the cells were then cultured semi-continuously in a 300-l bioreactor employing the draw-fill cultivation method. Maximal digoxin production was achieved in an 8% glucose medium with a production optimum after 40-60 h of incubation in the presence of 0.65-0.8 mmol digitoxin per l. Levels of 0.52, 0.53 and 0.60 mmol digoxin per l suspension were achieved in 1-l, 20-l and 300-l vessels, respectively. About 80% of the digoxin produced was found in the bathing medium.

Air↗
PubMed1986

Endogenous digitalis-like immunoreactive substances in cord serum characterized by anti-digitoxin and anti-digoxin antibodies. Effect of modulated incubation conditions.

Digoxin-like immunoreactive substances (DLIS) have been extensively described in biological fluids of pregnant women, neonates and renal impaired patients, by the use of several digoxin immunoassays. In this paper a similar interference with anti-digitoxin antibodies is reported by investigating 20 cord sera. By increasing both the time and the temperature of the incubation, the levels of digitalis-like immunoreactive substances may be modulated and decreased to zero. Digitoxin- and digoxin-like immunoreactive substances have been successfully extracted with methanol and concentrated from cord serum. Our data suggest the competitive nature of DTLIS and DLIS interactions with digitalis antibodies. They also show a means of minimizing these interferences in routine digitalis immunoassays.

Antibodies↗
PubMed1976

Studies on digitalis. IV. A method for thin-layer chromatographic separation and determination of digitoxin and cardioactive metabolites in human blood and urine.

A thin-layer chromatographic method for the separation of digitoxin and its cardioactive metabolites in one system is described. Pre-coated silica gel plates impregnated with 15% formamide solution in acetone were developed twice in the same direction (running distance 18cm) with ethyl methyl ketone-xylene (50:50) as solvent. The system showed no border-zone effects, and the reproducibility was good. Samples (5 ml) of serum or urine were extracted with dichloromethane, the extracts were evaporated, the residues were dissolved in 70% ethanol, the ethanol solutions were washed twice with light petroleum and then evaporated, and the residues were dissolved in chloroform-methanol for application to the thin-layer plates. After development, the metabolites were scraped from the plates and analyzed by means of a modified rubidium-86 method. The recovery for the whole procedure was 59%, and the sensitivity of the method permitted the determination of down to 0.5 ng per spot. The method will facilitate the study of digitoxin metabolism in patients undergoing treatment with the drug.

Chromatography, Thin Layer↗
PubMed1982

Separation of digoxin, digitoxin and their potential metabolites, impurities or degradation products by high-performance liquid chromatography.

A rapid and versatile series of high-performance liquid chromatographic systems are described for the resolution of digoxin, digitoxin and their potential metabolites or degradation products and impurities. These systems consist of isocratic, single-step gradient and linear gradient modes that provide resolution of the glycosides in 25, 17 and 14 min respectively. Digoxin, its mono- and bisdigitoxosides, digoxigenin and gitoxin, a potential impurity, may be isocratically separated in 11 min. The two semi-synthetic glycosides alpha- and beta-acetyldigoxin are resolved and separated from digoxin and its metabolites in a chromatographic time of 23 min. Digitoxin and its metabolites or degradation products may be separated in as little as 9 min using an isocratic system. The solvent systems employ varying proportions of methanol, water, isopropanol and dichloromethane and a conventional 5 micrometers bonded, octadecyl phase. Detection was accompanied using a variable wavelength detector set at 220 nm.

Chemical Phenomena↗
PubMed1975

Isolation and quantitation of picomole quantities of digoxin, digitoxin and their metabolites by high-pressure liquid chromatography.

The following high-pressure liquid chromatographic (HPLC) separations are described: (1) isocratic separation of digoxin and its metabolites, (2) isocratic separation of digitoxin and its metabolites, (3) gradient elution separation of digoxin, digitoxin and their metabolites, and (4) gradient elution separation of gitoxin from digoxin and its metabolites. These methods utilize a multi-wavelength UV detector set at 220 nm and a reversed-phase column with various mixtures of acetonitrile and water as the mobile phase. The feasibility of using these HPLC methods as qualitative and quantitative techniques for digitalis glycosides is discussed.

Chromatography, High Pressure Liquid↗
PubMed1982

Effects of atropine on the cardiac arrest induced by propranolol and digitoxin in dogs.

The present study examines the hypothesis that vagal activity can accelerate the onset of cardiac arrest produced by administering a beta-adrenergic blocking dose of propranolol to digitoxin-intoxicated dogs. In 11 experiments, intravenous injection of 0.75 mg/kg propranolol into digitoxin intoxicated dogs induced a sustained ventricular asystole (early-phase cardiac arrest). In six of these eleven experiments, intermittent pacing of the ventricles for as long as 150 min to maintain blood pressure after the onset of asystole, led to the resumption of spontaneous heart beats in only one dog. In five other experiments, injection of atropine (1 mg/kg) three min after the onset of early-phase cardiac arrest elicited sustained spontaneous junctional rhythms. In another four experiments the injection of atropine prior to or simultaneously with propranolol prevented the occurrence of asystole and caused the emergence of a junctional pacemaker. In eight experiments in which the cardiac arrest was reversed or prevented, injection of maintenance doses of atropine and propranolol caused eventual failure of the junctional pacemaker (late-phase cardiac arrest). This failure could not be prevented or reversed by atropine. The results suggest that early-phase cardiac arrest is due to vagal suppression of cardiac pacemakers and therefore supports the above hypothesis.

Animals↗
PubMed1983

Quantitation of digitoxin and the bis- and monodigitoxosides of digitoxigenin in serum.

A specific assay is described for measuring the concentration of digitoxin and the bis- and monoglycosides of digitoxigenin in serum. The procedure includes: (1) addition of a tracer amount of tritium labeled parent compound to the serum in order to measure percentage recovery; (2) solvent extraction to separate polar and non-polar metabolites; (3) reversed-phase thin-layer chromatography of the non-polar fraction to separate digoxigenins from digitoxigenins; (4) thin-layer chromatography to isolate digitoxin, and the bis- and monoglycosides of digitoxigenin; and (5) use of an 125I-radioimmunoassay to determine the concentration of the glycosides. Each of these three glycosides was administered intravenously to a normal subject, and the concentration of parent compound was measured in the serum at various times.

Adult↗
PubMed2006

A stereoselective synthesis of digitoxin and digitoxigen mono- and bisdigitoxoside from digitoxigenin via a palladium-catalyzed glycosylation.

A convergent and stereocontrolled route to trisaccharide natural product digitoxin has been developed. The route is amenable to the preparation of both the digitoxigen mono- and bisdigitoxoside. This route featured the iterative application of the palladium-catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation, and regioselective protection. The natural product digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8a or 18 steps from achiral acylfuran.

Carbohydrate Sequence↗
PubMed1984

Kinetics of digitoxin and the bis- and monodigitoxosides of digitoxigenin in renal insufficiency.

The kinetics of digitoxin and two of its major metabolites, the bis- and monodigitoxosides of digitoxigenin, were determined in six subjects with renal insufficiency and compared to those in six age- and sex-matched normal control subjects. No significant differences between the two groups were found in elimination t 1/2, total body clearance, or volume of distribution. Average renal clearances of all three drugs were reduced in subjects with renal failure, but the differences were significant only in the case of digitoxin. The bis-digitoxoside of digitoxigenin has kinetic properties that offer clinical advantages.

Acute Kidney Injury↗
PubMed1984

Drug-binding properties of rat alpha 1-foetoprotein. Binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid.

As part of an investigation into whether alpha 1-foetoprotein (alpha 1-FP) plays the same transport role in foetal serum as albumin does in the adult, the binding properties of both proteins were compared with respect to the binding of a series of compounds known to be bound by albumin's specific drug-binding sites. The binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid by rat alpha 1-FP and serum albumin was studied by equilibrium dialysis at 4 degrees C. Rat alpha 1-FP was shown to have neither albumin's high-affinity site II (diazepam as marker) nor its site III (digitoxin and cholic acid as markers). High-affinity binding by alpha 1-FP was found for the specific markers (warfarin, phenylbutazone, azapropazone) of albumin's drug-binding site I. However, instead of albumin's one high-affinity site/molecule, a mean value of 0.5 site/molecule was obtained with rat alpha 1-FP. Charcoal treatment at neutral pH of rat serum albumin did not affect its measured binding properties, but treatment of the alpha 1-FP led to an increased affinity for warfarin, phenylbutazone and azapropazone without a change in the measured number of sites, indicating competition for binding at this site by (an) endogenous ligand(s). These results are discussed in terms of the structures of the two proteins and with respect to the physiological implications of the differences found.

Animals↗