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At least 1,711 records · Page 95Linked to original sources
PubMed2003

Digoxin antibody decreases natriuresis and diuresis in cerebral hemorrhage.

OBJECTIVE: Brain-damaged patients may develop hyponatremia and natriuresis. Clinical evidence of digoxin antibody effect on natriuresis we found in an 11-year-old boy who developed excessive natriuresis and hyponatremia after brain tumor excision. To better understand the mechanisms involved in these clinical disturbances we used an experimental model of rats subjected to intracerebroventricular (ICV) hemorrhage. The participation of serum ouabainlike activity, possibly a natriuretic compound, and the effects of a specific blocker, digoxin antibody, were studied. METHODS: The experimental study was performed in four groups of ICV infused Wistar rats: venous autologous blood infused, blood preceded by digoxin antibody, CSF-like solution, and a control group with no cannulation and no infusions. The following parameters were analyzed before and after ICV infusions: weight, urinary volume, and natriuresis. Ouabainlike activity was measured by proportional serum inhibitory activity on normal rat renal medullary Na-K-ATPase activity. RESULTS: ICV blood but not CSF-like infusion increased urinary volume, natriuresis, and serum ouabainlike activity without weight gain. Natriuresis was positively correlated with serum ouabain activity in ICV blood and blood plus antibody rats. Digoxin antibody restored urinary volume, natriuresis, and ouabainlike activity. CONCLUSIONS: These data provide evidence of ouabainlike activity involvement in natriuresis and urinary volume changes that occur in cerebral hemorrhage. A possible therapeutic action of digoxin antibody is proposed.

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↗
PubMed1991

Experience with digoxin immune Fab (ovine) in patients with renal impairment.

Digibind is a purified antigen binding fragment (Fab) of immunoglobulin G antibodies raised to bind digoxin. Studies in animals suggest renal excretion accounts for a substantial portion of Fab's elimination. Thus it is expected that elimination of antidigoxin Fab fragments would be prolonged in patients with renal impairment; it remains unclear whether digoxin might be released with possible recurrence of toxicity. To shed light on this potential for recrudescent digitalis toxicity following release of bound digoxin, the author scrutinized the records of patients with impaired renal function who were treated with Digibind. Data are available from three sources: the original multicenter investigation of Digibind in 150 patients with life-threatening digoxin or digitoxin toxicity, a postmarketing surveillance study of 745 patients treated with Digibind, and all other reports in the literature or to Burroughs Wellcome Co of physician experience with any antidigoxin Fab. Sixty percent of patients in the multicenter trial and 80% of patients in the postmarketing surveillance trial had some degree of renal impairment. Patients with poor renal function had no evidence of decreased effectiveness or safety either in terms of percent of patients responding, onset of effect or evidence of recrudescence. From all sources the authors identified 28 patients treated with Fab who were functionally anephric. Twenty-seven of these patients had no evidence of recrudescent toxicity. One patient was reported to have complete resolution of digoxin-induced third-degree atrioventricular (AV) block, but AV block recurred 10 days after Fab treatment and persisted for 10 days thereafter. Although this case offers the only clinical evidence suggesting recrudescence can occur, there were no likely alternative explanations for the clinical findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine↗
PubMed2000

Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial.

BACKGROUND: Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing. We did a randomised controlled trial to investigate whether anti-digoxin Fab could reverse serious oleander-induced arrhythmias. METHODS: After a preliminary dose-finding study, 66 patients who presented to hospital with a serious cardiac arrhythmia were randomised to receive either 1200 mg of anti-digoxin Fab or a saline placebo. A 12-lead electrocardiogram, 3 min rhythm strip, and blood sample for measurement of electrolytes and cardiac glycosides were taken before treatment and at 12 timepoints thereafter. FINDINGS: 34 patients received anti-digoxin Fab and 32 received placebo. The presenting arrhythmia had resolved completely after 2 h in 15 antibody-treated patients and two controls (p<0.001); 24 and five patients, respectively, were in sinus rhythm at 8 h (p<0.001). Kaplan-Meier analysis of time to first reversal showed a significant response to anti-digoxin Fab. The heart rate increased in cases, from 49.1 per min at baseline to 66.8 at 2 h, but not in controls (50.6 per min at baseline to 51.5; p<0.001). Mean serum potassium concentrations decreased from 4.9 mmol/L to 4.1 mmol/L at 2 h in cases; no such decrease occurred in controls. INTERPRETATION: Anti-digoxin Fab fragments are a safe and effective treatment for serious cardiac arrhythmias induced by yellow oleander. Their use in small rural hospitals in Sri Lanka should minimise costly transfer of patients and reduce the numbers of deaths; however, further study will be required to confirm this reduction.

Adult↗
PubMed1990

The use of enzyme-linked immunosorbent assays to study the plasma disposition of sheep polyclonal and rat monoclonal digoxin-specific Fab fragments in the rabbit.

The plasma disposition of sheep polyclonal digoxin-specific Fab (fragment antigen-binding) fragments has been studied in rabbits after their intravenous injection (1 mg kg-1) using enzyme-linked immunosorbent assays exploiting both the species-specificity (ELISA1) and the digoxin-specificity (ELISA2) of digoxin-specific Fab fragments. The log concentration versus time profiles were best described by a biexponential plasma disposition when either assay was used. Although the plasma concentrations determined by ELISA1 and ELISA2 at each sampling time were not significantly different, there was a tendency for certain ELISA2 values to be higher. This resulted in the ELISA2-derived data giving a significantly longer distribution half-life (t1/2 alpha), but similar values for elimination half-life (t1/2 beta), apparent volume of distribution at steady state (Vdss), and clearance. Using ELISA2, which was generally the more sensitive assay, to compare the plasma disposition of the sheep polyclonal digoxin-specific Fab fragments with rat monoclonal digoxin-specific Fab fragments, it was shown that the rat product had a shorter t1/2 alpha (11 vs 22 min), a t1/2 beta which was not significantly different (253 vs 168 min), but a faster clearance (1.2 vs 0.7 mL kg-1 min-1), associated with a much larger Vdss (321 vs 108 mL kg-1). The extracellular fluid volume, using thiocyanate as a marker, was about 216 mL kg-1 for the nine rabbits used. This suggests that the rat preparation penetrates more extensively into the extracellular space and may indicate that some degree of extracellular binding or cell penetration is occurring.

Animals↗
PubMed1990

Treatment of digitalis intoxication with emphasis on the clinical use of digoxin immune Fab.

Many studies and cases of digitalis intoxication have been reported since the time of William Withering's first publication in 1785. Recognition and management of digitalis toxicity is challenging. Before digoxin immune Fab was commercially available, treatment consisted of managing the signs and symptoms of toxicity until the digitalis was eliminated. Digoxin immune Fab offers a safe, effective, and specific method of quickly reversing digitalis toxicity. Factors that must be considered with the clinical use of this agent include the dosage calculation, administration technique, postdose monitoring, pharmacokinetics, mechanism of action, interference with commercially available digoxin assays, partial neutralizing dosing, rebound of free digoxin, and indications for use. For severe, life-threatening toxicity, digoxin immune Fab is the treatment of choice.

Animals↗
PubMed2006

Serum cystatin C levels to predict serum concentration of digoxin in Japanese patients.

Cystatin C (Cys-C) has been recently paid great attention as a better endogenous marker of the glomerular filtration rate than creatinine (Cr). In this study, the usefulness of Cys-C was compared with Cr in terms of the estimation of the steady-state serum trough concentrations of digoxin in Japanese patients. Forty patients treated with digoxin and 56 healthy elderly subjects were participated in this study. The serum levels of Cys-C and Cr in the patients were higher than those in the healthy elderly subjects, but the increase of Cys-C was more predominant in the patients. Their levels were well-correlated for both of the healthy elderly subjects (r=0.691) and patients (r=0.774), but the serum concentrations of digoxin were better correlated with those of the reciprocal values of Cr (r=0.667) than those of Cys-C (r=0.383), presumably due to the fact that digoxin and Cr were excreted via both glomerular filtration and tubular secretion. Cys-C is useful for the substratification of the patients diagnosed to have normal renal function with Cr of < 1.3 mg/dL into those with normal and pseudo-normal renal function, resulting in the corresponding serum concentrations of digoxin.

Journal Article↗
PubMed1981

Digoxin retinal toxicity. Clinical and electrophysiological evaluation of a cone dysfunction syndrome.

A 70-year-old man was studied both during and after resolution of clinical digoxin toxicity using color vision tests, ganzfeld electroretinography and electro-oculography. Concomitant administration of quinidine sulfate probably contributed to digoxin toxicity. Abnormalities in color vision and subnormal amplitude and prolonged implicit time for cone-mediated electroretinogram (ERG) responses suggested a cone dysfunction syndrome. The electro-oculographic light-to-dark ratio during clinical toxicity was high for our laboratory, but this is probably normal. Notable improvement was seen in color vision and the ERG after cessation of digoxin therapy. Inhibition of sodium-potassium adenosine triphosphatase by digoxin probably influences normal uptake of extracellular potassium by Müller's cells and other retinal neurons. This mechanism may contribute to subnormal, prolonged cone-mediated ERG responses in retinal toxic reactions from cardiac glycosides.

Adaptation, Ocular↗
PubMed1986

Echocardiographic diagnosis and intravenous digoxin management of fetal tachyarrhythmias and congestive heart failure.

Fetal echocardiography now affords an accurate clinical diagnosis of nonimmune fetal hydrops secondary to fetal tachyarrhythmias and/or certain types of congenital heart disease. Individual case reports of the treatment of tachyarrhythmias have been reported that use various drugs, including digoxin, propranolol hydrochloride, procainamide hydrochloride, and digoxin plus verapamil hydrochloride. We found no report of intrauterine treatment of congestive heart failure due to congenital heart disease with sinus rhythm. The seven cases presented herein include five cases of isolated supraventricular tachycardia, one with supraventricular tachycardia and myocardial tumors, and one of congenital heart disease with congestive heart failure. Maternal treatment with digoxin converted tachyarrhythmia to sinus rhythm in all six fetuses, and resolved the hydrops in the fetus with congenital heart disease. Premature delivery was avoided in five of the seven cases with favorable outcome in six of the cases. In five mothers who were given oral digitalization, the fetuses had delayed (three to 35 days) response to therapy. Two mothers were treated intravenously and the fetus responded to therapy in less than 24 hours. Because of problems possibly related to poor absorption and/or rapid clearance of digoxin, the intravenous route of administration should be used as the best way to achieve adequate therapeutic levels in the fetus.

Atrioventricular Node↗
PubMed1994

Long-term use of K-strophanthin in advanced congestive heart failure due to dilated cardiomyopathy: a double-blind crossover evaluation versus digoxin.

K-strophanthin or digoxin were added to diuretics (all cases) and vasodilators (most cases) for treating advanced congestive heart failure in 22 patients with dilated cardiomyopathy and sinus rhythm. K-strophanthin (0.125 mg intravenously) or digoxin (0.25 mg orally) were administered daily in two 3-month periods, during which vasodilators and diuretics were kept constant and patients received one of the two digitalis preparations in a double-blind fashion, crossing over to the alternative preparation in the next period. Blindness was assured throughout the trial with a daily intravenous injection of 10 ml normal saline solution either containing K-strophanthin or not, and with daily oral administration of either placebo or active digoxin. At the end of the run-in period, 15 days after starting active preparations, and thereafter every month for the next 6 months, we evaluated left ventricular pump function at rest and patients' functional performance by a cardiopulmonary exercise test. At Day 15, cardiac index and ejection fraction at rest, compared with run-in, were significantly raised with both glycosides; during exercise while on K-strophanthin, peak oxygen consumption was augmented by 1.4 ml/min/kg (p < 0.01) and oxygen consumption at anaerobic threshold by 2.2 ml/min/kg (p < 0.01); corresponding variations on digoxin (-0.1 and +0.3, respectively) were not significant versus run-in. These patterns were duplicated at repeated tests during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1975

Bioavailability of different lots of digoxin tablets from the same manufacturer.

The bioavailability of single doses from 4 randomly selected lots of digoxin from a single manufacturer that were recently marketed in the United States was compared. In a crossover study in 6 normal volunteers, serum digoxin concentrations for 0 to 6 hr and urinary glycoside excretion for 24 hr after 0.5-mg doses were measured by radioimmunoassay. The variation in bioavailability between the 4 lots was no greater than that seen when one of them was taken twice. Intersubject variation in areas under the serum concentration-time curves and in the 24-hr urinary digoxin measurements was more than twice that of intrasubject variation. The variability of the urinary digoxin determinations was somewhat less than that of the areas under the serum concentration-time curves.

Adult↗
PubMed1976

Human serum and myocardium digoxin.

Linear correlation was demonstrated between serum digoxin and papillary muscle digoxin concentrations in patients undergoing mitral valve surgery. The mean ratio of myocardial tissue to serum digoxin concentrations was 6711. This result supports the use of serum digoxin as a guide for assessing the degree of digitalization under steady-state conditions.

Adult↗
PubMed1976

Biliary excretion of digoxin in man.

We have measured the biliary excretion of 3H-digoxin in normal subjects by intestinal perfusion methods which impose minimal interruption of the enterohepatic circulation. In contrast to data obtained in patients with liver disease and postoperative patients with biliary fistulas, our data show that about 30% of an intravenous dose of 3H-digoxin reaches the digestive tract in 24 hr. Most of the excreted radioactivity is chloroform-soluble and presumably reabsorbably and most of this fraction is probably biologically active drug. The results suggest that (1) consideration of hepatobiliary function may be relevant in observations regarding digoxin pharmacokinetics and that this route may be exploited in trials of therapy designed to shorten the duration of digoxin intoxication.

Adult↗
PubMed1976

Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin.

The aim of the present investigation is to study digitoxin and digoxin protein binding in patients with normal renal and hepatic function, in patients with uremia, and in patients under treatment with hemodialysis for renal failure. The binding of digitoxin and cardioactive metabolites to serum proteins was studied using equilibrium dialysis (an in vitro chemical assay) alone and in combination with a modified 86Rb method. The following values for protein binding were found: DT-3 (digitoxin), 95.7%; DT-2 (digitoxigenin-bis-digitoxoside), 96.5%; DT-1 (digitoxigenin-mono-digitoxoside), 98.7%; DT-0 (digitoxigenin), 92.7%; DG-3 (digoxin), 21.2%; DG-2 (digoxigenin-bis-digitoxoside), 16.3%; DG-1 (digoxigenin-mono-digitoxoside), 18.5%; and DG-0 (digoxigenin), 13.3%. In vitro addition of procainamide, phenytoin, heparin, and rifampicillin did not influence the in vitro binding of digitoxin. Protein binding of digitoxin showed small individual variations in patients with normal renal and hepatic function. Uremia per se did not influence the in vitro binding of digitoxin. There were marked changes in digitoxin and digoxin protein binding during an 8-hr hemodialysis, digitoxin binding decreasing from 97.1% to 93.7% (p less than 0.0025) and digoxin binding from 23.5% to 15.4% (p less than 0.05). In the uremic patient the metabolic pattern of digitoxin tended toward a decrease in protein-bound metabolites.

Blood Proteins↗
PubMed1977

Greater bioavailability of digoxin solution in capsules. Studies in the postprandial state.

A liquid concentrate of digoxin administered as a capsule has recently been found to be better absorbed by normal subjects in the fasting state than a standard tablet or even a solution as such. It was not known whether the enchanced bioavailability of the encapsulated digoxin solution could also be demonstrated when given postprandially. In a crossover study single 0.4 mg doses of digoxin solution in a capsule, a solution in 10% ethanol as such, and a standard tablet were given to 12 normal volunteers immediately following a high-fat breakfast. The mean area under the serum concentration-time curve (AUC) and 6-day cumulative urinary glycoside excretion (CUE) were greater after the capsule than that of either the solution or the tablet. The latter two preparations appeared to be bioequivalent. Intersubject variability in the CUE was less than with the AUC, but did not differ when the three drug formulations were compared. The bioavailability of an encapsulated liquid digoxin concentrate was thus also found to be enhanced when administered postprandially.

Adult↗
PubMed1977

Digoxin kinetics during furosemide administration.

The urinary excretion of a 0.75-mg oral dose of digoxin was assessed in 8 healthy men during a control 5-day period and then, after a washout period of at least 2 wk, during a 5-day period when the subjects also took oral furosemide, 40 mg daily. Analysis of the raw data by a paired Student's test and analysis of variance of log-transformed urinary digoxin excretion data revealed no significant difference attributable to the addition of furosemide (F = 1.16; df = 1,21). The treatment by day interaction showed the slopes to be consistent between the two treatments. It seems that in the presence of normal renal function there is no need to alter loading or maintenance doses of digoxin when furosemide is also given. Analysis of variance with log transformation of data is suggested as a practical approach to handling digoxin urinary excretion results when the transformation linearizes the data through examination by the method of orthogonal polynomials.

Adult↗
PubMed1980

The role of furosemide alone and in combination with digoxin in the relief of symptoms of congestive heart failure.

Clinical and cardiovascular responses to drug therapy with furosemide were compared with those to furosemide plus digoxin in 15 heart patients with sinus rhythm admitted to the hospital for the management of congestive heart failure. Except for two patients in the group treated with furosemide alone, who required the addition of intravenous furosemide for more complete relief of symptoms, the responses to the two therapeutic regimens were not significantly different. One patient in the digoxin-treated group developed atrial fibrillation with frequent ventricular premature beats and transient runs of bigeminal rhythm typical of digitalis toxicity, which disappeared as the dose of digoxin was lowered. Side effects were otherwise considered to be minor and similar in the two groups. The results support the view that the indications for digoxin as a positive inotropic agent in patients with congestive heart failure need to be reevaluated.

Adult↗
PubMed1987

Diltiazem increases steady state digoxin serum levels in patients with cardiac disease.

Diltiazem has been reported to decrease or not to affect digoxin elimination. The effects of diltiazem on steady state concentrations of digoxin was evaluated in eleven patients with congestive heart failure receiving this drug for at least two weeks. The mean trough digoxin was 1.11 +/- 0.18 ng/ml before the coadministration of diltiazem (180 mg/day). This concentration increased to 1.54 +/- 0.22 ng/ml after three days and to 1.54 +/- 0.23 ng/ml after seven days of coadministration (P less than 0.01). Clinically, no patient showed signs of digitalis toxicity. Creatinine clearance was unchanged. The present results show that when diltiazem is added to a regimen that includes digoxin, steady state concentrations of this glycoside may increase.

Adult↗