Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Digitoxin”

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 73 records · Page 4Linked to original sources
PubMed2001

Measurement of serum digitoxin in patients by radioimmunoassay using specific antiserum.

INTRODUCTION: Digitoxin is used to treat patients with heart failure. METHODS: A radioimmunoassay procedure for the specific determination for digitoxin in serum was developed using the antiserum (antiserum (A)) raised against digitoxin 3'-hemisuccinate-BSA conjugate. RESULTS: The intra- and interassay variability were <10% in the range of 5-100 ng/ml. The specificities of antiserum (A) and the commercial anti-digitoxin antiserum (antiserum (B)) were assessed by cross-reactivity studies with various related compounds. Antiserum (A) was highly specific for digitoxin. Mean digitoxin concentrations in serum samples (n=34) from digitalized patients by RIA using these antisera were 10.0 and 12.4 ng/ml, respectively. CONCLUSION: This RIA using antiserum (A) measure unmetabolized digitoxin and may be applicable for pharmacokinetic studies.

Animals↗
PubMedDate not supplied

Effects of autonomic blockade on the inotropic and electrophysiologic response to digitoxin in the intact dog.

Inotropic and electrophysiologic effects in dogs of a single dose of digitoxin with and without autonomic blockade with propranolol plus atropine were observed for 8 hr. Left heart catheterization and His bundle registration were performed in 14 Labrador dogs anesthetized with pentobarbital. Pacing and programmed electrical stimulation were used to determine heart rate-independent changes in dP/dt, intra-atrial, AV nodal, His-Purkinje, and intraventricular conduction velocity. The effective and the functional refractory periods of the atrium, and the functional nodal refractory period (AV-FRP) were measured. Six dogs were given propranolol 0.5 mg/kg plus atropine 0.05 mg/kg every hour. After determination of inotropic and electrophysiologic parameters, digitoxin (2.0 mg) was given to 5 of the dogs, while 1 dog served as control. The other 8 dogs were given only digitoxin (2.0 mg). The dP/dt increased after digitoxin in both groups with maximum values after 2 hr. The autonomic nervous system had only minor influence on changes in contractility caused by digitoxin. The marked fall in heart rate and increase in A-H time (i.e., AV nodal conduction time) and AV-FRP after digitoxin were almost completely blocked by atropine and propranolol. Minor increases in A-H time and AV-FRP indicated a slight direct effect of digitoxin on the AV node.

Animals↗
PubMedDate not supplied

Relationship of cardiac muscle tension to Na+,K+-adenosine triphosphatase activity after chronic digitoxin administration in cats.

To obtain a better understanding of the mechanism of action of the cardiac glycosides, we examined inotropic and biochemical effects of digitoxin in myocardium from cats chronically exposed to the drug. The mechanical function of papillary muscles was tested isometrically and left ventricular tissue was analyzed for Na+,K+-dependent adenosine triphosphatase ATPase activity. Muscles from control cat hearts developed tension at 2.5 +/- 0.7 g/mm2; muscles from cats that received subcutaneous digitoxin--100 micrograms/kg on day 1, followed by 40 micrograms/kg/day for 4 days (group A), and 75 micrograms/kg on day 1, followed by 25 micrograms/kg/day for 9 days (group B)--developed significantly greater (p less than 0.05) tension of 4.8 +/- 0.3 and 3.6 +/- 0.6 g/mm2, respectively. Further, in vitro maximal responsiveness to digitoxin was greater in the muscles from digitalized groups than in controls (p less than 0.05): Muscles from control cats had a maximal response to in vitro addition of digitoxin of 3.5 +/- 0.1 g/mm2; muscles from cats in group A reached 4.9 +/- 0.3 g/mm2, and those from group B, 4.5 +/- 0.7 g/mm2. Specific activity of microsomal Na+,K+-ATPase from hearts of digitalized groups A and B was inhibited by 50-70% (p less than 0.01). Developed tension, specific Na+,K+-ATPase activity, and in vitro maximal responsiveness to digitoxin in a third group (C) of cats receiving the least daily digitoxin (75 micrograms/kg on day 1, followed by 15 micrograms/kg/day for 29 days) were not different from controls. Mean plasma digitoxin concentrations were 33, 16, and 3 ng/ml in groups A, B, and C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Digitoxin accumulation.

1 Nine healthy volunteers received single 1 mg intravenous doses of digitoxin, following which serum digitoxin concentrations were measured at multiple points in time over the next 14 days. 2 Mean kinetic variables for digitoxin were: volume of distribution, 0.76 l/kg; elimination half-life, 8 days; total clearance, 0.049 ml min-1 kg-1. 3 After a drug-free interval of at least 4 months, subjects took 0.07 mg of oral digitoxin daily for 28 consecutive days. Serum digitoxin concentrations were measured during the period of dosage and in the 21 day post-dosage washout. 4 Digitoxin accumulation was slow, proceeding with a mean half-life (7.9 days) that was nearly identical to the single-dose half-life. However, the two were not significantly correlated. 5 Mean observed steady-state serum concentrations (15.4 ng/ml) also were nearly identical to those predicted from the single-dose study (15.3 ng/ml), but again the two were not significantly correlated. 6 Steady state is very slowly attained after initiation of maintenance therapy with digitoxin. The kinetic data suggest that a loading dose on the average should be 12 times the maintenance dose.

Adult↗
PubMed1980

The modifying effect of autonomic blockade on digitoxin-induced changes in monophasic action potential and refractoriness of the right ventricle of the dog heart.

The aim of the present investigation was to study the modifying effect of autonomic blockade with atropine plus propranolol and atropine alone on the electrophysiologic response to digitoxin during an observation period of 8 hours. Twenty-five pentobarbital-anaesthetised Labrador dogs were used. Pacing and programmed electrical stimulation were used to determine heart rate independent changes in repolarisation times and the effective (V-ERP) and the functional (V-FRP) refractory periods. The dogs were divided into three groups and all dogs got digitoxin (2.0 mg) intravenously during 5 min. Fourteen dogs were given digitoxin without blockade, while 5 dogs were pretreated with propranolol 0.5 mg/kg plus atropine 0.05 mg/kg every hour for 8 hours and 6 dogs with atropine in the same dose and with the same interval. Digitoxin alone increased 50 and 90% repolarisation times 2-4 hours after injection of the drug. During autonomic blockade digitoxin induced a shortening of action potential duration, and thus digitoxin interacts with autonomic transmitters resulting in prolongation of action potential duration. The "direct" effects of digitoxin, the action potential shortening effect, the decrease in membrane responsiveness (i.e. V-ERP/50% repolarisation time) reached a maximum 2-3 hours after injection of the drug.

Action Potentials↗
PubMed1968

The measurement of digitoxin in human serum by radioimmunoassay.

A sensitive, specific, and relatively simple immunoassay permitting measurement of pharmacological levels of digitoxin in human serum has been developed. The assay involves binding of (125)I-labeled tyrosine-digitoxigenin (specific activity > 400 mc/mg) by rabbit antibody to digitoxin. Antibody-bound radioactivity is precipitated by addition of a second antibody (goat anti-rabbit gamma globulin), and precipitate radioactivity is measured. Unlabeled digitoxin can be determined by the extent to which it competes with (125)I-labeled digitoxigenin and thus reduces precipitation of radioactivity. Before the assay, unlabeled digitoxin is extracted from serum with chloroform, and the chloroform solution is evaporated to dryness. Quantitation is accomplished by reference to a standard curve in which known amounts of digitoxin are added to normal serum. As little as 1 mmug of digitoxin per ml of serum produces significant reduction in precipitate radioactivity. The sera of 5 patients were analyzed before and after digitalization. A highly significant reduction in precipitate counts in the postdigitalization sera was observed (P < 0.001). Serum digitalis levels were measured in 19 patients receiving no digitalis and in 19 patients taking digitoxin or digitalis leaf. Little of no digitalis-like activity was detected in control sera, whereas serum levels averaged 27 mmug/ml in those on digitalis (range 4-60 mmug/ml, P < 0.001). Patients judged clinically to show digitals toxicity in general had higher levels than those without signs of toxicity. Patients receiving digoxin had little or no detectable digitalis in their serum with this method. In addition to the assay itself, other potential uses of the antidigitalis antibody include treatment of digitalis toxicity and studies on the tissue localization of digitalis.

Antibodies↗
PubMed2001

Adverse drug reaction monitoring--digitoxin overdosage in the elderly.

Drug-related illness is an everlasting universal problem and also an important cause of admissions to hospitals. Adverse reactions are still grossly underreported by medical professions. Little information is available regarding the frequency or type of ADRs managed in hospitals. Since January 1997, we have taken part in a study, supported by the German Federal Institute for Drugs and Medical Device to improve the spontaneous drug information reporting system in Germany. Three German regionalized Departments of Clinical Pharmacology--Jena, Dresden, Rostock--serve as Pharmacovigilance Centers in collaboration with the Pharmacoepidemiology Research Group of the University of Munich. Since January 1997, the regional group in Jena has been monitoring the University Clinic of Internal Medicine for admissions caused by adverse drug reactions. All emergency cases and patients on intensive care units were checked for adverse drug reactions. We present our results, including clinical and demographic data, concerning intoxications and especially those involving digitoxin in 210 patients with ADR. Forty patients with digitoxin toxicity had an average age of 81 years (81.1+/-6.3), a low body weight (59.7+/-12.7 kg) and 3 out of 4 were women. 75% of all patients with digitoxin side effects had elevated serum digitoxin levels with concentrations higher than 25 microg/ml. The relatively high frequency of digitoxin intoxications in our hospital may reflect the advanced age and low body weight of patients. Patients received digitoxin regardless of age, weight and, sometimes, clinical indication. Physicians should be aware of drugs having a high risk when used in elderly patients. The use of digitoxin assays and keeping serum levels within or near the therapeutic range will diminish the incidence of overdoses.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

[Prolonged half-life of digitoxin in the elderly].

Digitoxin is frequently used in Norway in the treatment of cardiac failure. Digitalis glycosides may give rise to a number of side effects difficult to separate from disease in the elderly. Six patients aged 77-93 years, treated with digitoxin 0.05 mg/day, were hospitalized due to digitalis intoxication. Mean digitoxin half-life was 25.2 days. This is significantly more than reported in other studies on younger patients. The symptoms of digitoxin intoxication disappeared on discontinuation of medication. The slow elimination of digitoxin may be related to reduced serum albumin concentration. When digitoxin is used in the treatment of heart failure in the very elderly patients, one should be aware of the possibility of digitoxin intoxication, even at a low dose.

Aged↗
PubMed1990

Influence of induced cholestasis on pharmacokinetics of digoxin and digitoxin in dogs.

Dogs with ligated common bile ducts were used to determine effects of cholestasis on pharmacokinetics of digoxin and digitoxin. Forty-three dogs were assigned to: group 1--sham-operated controls (n = 13); group 2--dogs with ligated common bile duct (n = 17); group 3--dogs given phenobarbital for 2 weeks before common bile duct was ligated (n = 11); or group 4--dogs with an induced biliary fistula (n = 2). Digoxin (group A) or digitoxin (group B) was given as single IV injections, and digitalis concentration in plasma was measured by radioimmunoassay. In 18 dogs given digoxin, differences in plasma digoxin concentrations among groups 1A to 3A were not significant (P greater than 0.1). Plasma elimination rate of digoxin was delayed in group 2A. Group-3A dogs had a shortened beta phase half-life (t1/2 (beta] and a decreased distribution volume. In 25 dogs given digitoxin, group-2B dogs maintained a significantly higher plasma digitoxin concentration (P less than 0.01) and had a significantly longer t1/2 (beta] than did dogs in groups 1B and 3B (P less than 0.05). In group-3B dogs, plasma digitoxin concentration was decreased and t1/2 (beta] of digitoxin was shortened. In 10 group-B dogs given 3H-digitoxin (groups 1B, 2B, and 4B), the excretion of total radioactivity in urine and bile was 15 to 20 and 7% of the dose, respectively in the first 24 hours. Most radioactivity in urine and bile was a dichloromethane-unextractable fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Haemodynamic and endocrine effects of digitoxin in healthy volunteers.

A study was conducted to evaluate the effects of a single oral dose of digitoxin on the circulatory function and the renin-angiotensin-aldosterone system. Seven doses of digitoxin and 6 of a placebo were given at random to 13 healthy volunteers, all of whom remained at rest, without smoking, throughout the study. Blood samples were taken initially after 1 h at rest, and at 1, 2 and 24 h after receiving the dose. Concentrations of serum digitoxin, aldosterone, angiotensin II (A II) as well as plasma renin activity (PRA) were determined by radioimmunoassay (RIA). In all subjects the blood pressure did not change throughout the study. Digitoxin decreased the heart rate significantly during the first and second hours, while in the placebo group the heart rate remained unchanged during the same period. The placebo had no detectable effect on PRA, A II and aldosterone. Digitoxin decreased PRA and A II levels, reaching its maximum effect 2 h after the administration. There was no correlation between the serum digitoxin concentration and PRA, A II or the aldosterone values. Digitoxin reached its maximum effect upon these parameters faster than what is generally accepted.

Adult↗
PubMed1978

Quantitative studies on acid hydrolysis of digitoxin.

Hydrolysis of 3H(G)-digitoxin by hydrochloric acid and human gastric juice is described. Incubation temperatures of 37 degrees C and 22 degrees C were chosen for electrolyte solutions, and 37 degrees C for the experiments with gastric juice. After dichloromethane extraction, the radioactive metabolites were separated by thin-layer chromatography, localized and quantified by a radiochromatogram scanner. The degradation products separated by TLC were digitoxigeninbis-digitoxoside, digitoxigenin-mono-digitoxoside, and digitoxigenin. After 10 min of incubation at pH 1, digitoxin amounted to 38.6% of the total radioactivity in electrolyte solution and 37.6% in gastric juice. After 60 min, the percentage of digitoxin decreased to 5.9% and 0%, respectively. After 120 min at 22 degrees C, amounts of unhydrolyzed digitoxin were: at pH 1 55%; and at pH 2 84%. After 10 min at pH 1, and 60 min at pH 2, digitoxin was hydrolyzed to such an extent that bioavailability should have been significantly reduced. Absorption of digitoxin (liquid) from the stomach was studied during gastroscopy in five patients. Among them, significant differences in absorption kinetics and bioavailability existed, as revealed by radioimmunological measurements of the digitoxin blood levels.

Chemical Phenomena↗
PubMed1984

[Serum digitoxin levels in pacemaker patients].

In most cases pacemaker patients represent a diverse geriatric group in which ECG and clinical signs are of minor usefulness in diagnosing digitalis toxicity. We therefore determined serum glycoside concentrations in 200 consecutive patients attending our pacemaker clinic (with a mean maintenance dose of 0.093 mg digitoxin per day) and tried to correlate these to clinical, ECG and chemical findings. Multivariate analyses were also carried out to assess whether serum digitoxin concentrations lay in a subtherapeutic (0 to 8.99 ng/ml), therapeutic (9 to 27 ng/ml) or toxic (above 27 ng/ml) range on the basis of a combination of variables. The mean digitoxin concentration was 24.0 +/- 10.3 ng/ml (0 to 45 ng/ml) and correlated poorly with patient compliance (r = 0.36), serum potassium (r = 0.24), weight (r = 0.17) and digitoxin dose (r = 0.13), but not with ECG and subjective or clinical findings. A prediction of the three ranges of the serum digitoxin concentration was possible by means of variable compliance, body weight and digitoxin dose with a probability of up to 79%. In view of the above-mentioned problems indications for digitalis therapy in pacemaker patients must be constantly reviewed and control determination of serum digitoxin concentration should be frequently undertaken.

Adult↗
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↗
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↗
PubMed1979

Use of cholestyramine resin in the treatment of digitoxin toxicity.

Two case reports describing the treatment of digitoxin toxicity with cholestyramine resin are presented. Both female patients were receiving 100 microgram/day of digitoxin when toxicity occurred. In both patients, digitoxin was discontinued and hypokalemia was corrected. In patient 1, lidocaine hydrochloride and phenytoin sodium also were administered. Serum digitoxin levels were decreased from 43 ng/ml to 21.8 ng/ml and from 42 ng/ml to 29 ng/ml in patients 1 and 2, respectively, following administration of three 4-g doses of cholestyramine resin over a one-day period. Previous studies on the treatment of digitoxin intoxication with potassium chloride, phenytoin sodium, lidocaine hydrochloride, digitoxin-specific antibodies, colestipol hydrochloride and cholestyramine resin are discussed. Ion-exchange resins may be valuable adjuncts in the treatment of digitoxin intoxication but further studies of their utility are needed.

Aged↗
PubMed1977

[The biological availability of digitoxin].

The bioavailability of digitoxin after a single dose of 0.5 mg was studied in 6 healthy volunteers by estimation of tmax, cmax, AUC und urinary excretion rate. After tablets, absorption was rapid, after dragées delayed. The mean t1/2 of digitoxin for i.v. administration was 9.5 +/- 0.9 days, for oral administration of tablets 7.4 +/- 0.5 days and for dragées 9.7 +/- 2.0 days. The cumulative recovery of glycosides in urine during the first 48 hours was higher after tablets than after i.v. administration. The shorter t1/2 of digitoxin after tablets compared with the longer t1/2 after gastric juice resistent dragées demonstrated the presence of a substantial extrahepatic "first pass"-effect by degradation of digitoxin before absorption. Such mechanism would partly explain the shorter t1/2 after digitoxin-tablets due to an increased elimination of splitting products. By extrapolation to t-infinite AUC and urinary excretion rates were not significantly different between various formulations. The mean absolute bioavailability of digitoxin-dragées amounted to 82-88 percent and the relative bioavailability of digitoxin-tablets to 84-93 percent.

Administration, Oral↗
PubMed1997

[Serum digitoxin in concomitant use of antiepileptics in routine therapy].

Concomitant use of digitoxin and enzyme-inducing antiepileptics may lower serum levels, and accordingly the effect of digitoxin, unless the higher metabolic clearance is compensated for by higher dosage. Use of digitoxin is almost always guided by serum concentration measurements. Information on a possible enzyme-inducing effect of phenobarbital, phenytoin and carbamazepine is easily accessible. Compilation of serum level measurements for digitoxin showed that serum levels shifted towards lower values during concomitant use of phenytoin or carbamazepine than when digitoxin was used alone. As a consequence, the fraction of patients with serum levels below the therapeutic range was doubled. Concomitant use of phenobarbital did not cause a shift in the levels of digitoxin. In fact, in this group, a larger fraction of the serum level measurements were within the therapeutic range. Thus, the dosage of digitoxin appears to be fully compensated during concomitant use of phenobarbital, but obviously deserves attention during concomitant use of phenytoin or carbamazepine.

Anticonvulsants↗
PubMed1976

Disposition of digitoxin in renal failure.

The disposition of digitoxin was studied for a period of 8 days in 6 uremic patients given a single oral dose of 1 mg 3H-digitoxin. In plasma, the time-course of radioactivity indicated a diminished absorption velocity of tritium compared to that of control subjects already reported and, after reaching of a pseudostate-equilibrium at 24 hr, an exponential decline with a mean half-life of 8.0 days. In urine, smaller amounts of tritiated compounds were eliminated in uremic patients (8.7% of the dose) than in controls (22.5%). The average fecal excretion of digitoxin and its metabolites was not significantly increased. Chloroform extraction and thin-layer chromatography in plasma, urine and feces suggested no qualitative alteration in the metabolism of digitoxin. Calculations of the total body tritium content (body stores) after each 24-hr interval and its pharmacokinetic behavior showed that the elimination of digitoxin is determined by the transfer constant from tissue to plasma. The differences in elimination kinetics of digitoxin and its metabolites of uremic patients and healthy subjects were not significant.

Chromatography, Thin Layer↗