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At least 217 records · Page 12Linked to original sources
PubMed1998

Serum digoxin in the presence of digibind: determination of digoxin by the Abbott AxSYM and Baxter Stratus II immunoassays by direct analysis without pretreatment of serum samples.

We have reevaluated the feasibility of using direct immunochemical methods to track free digoxin in patients receiving Digibind. We report here that results obtained by the Stratus II and AxSYM immunoassays on patients receiving digoxin (without Digibind), digoxin-fortified serum samples supplemented with Digibind, and a digitoxic patient treated with Digibind, show no clinically significant biases. We conclude that useful free digoxin concentrations may be obtained for Digibind-treated patients using either the AxSYM or Stratus immunoassays without subjecting samples to ultrafiltration before analysis.

Digoxin↗
PubMed1996

The affinity of binding of digoxin to ovine anti-digoxin Fab (DIGIBIND) preparations.

A fundamental study was performed to assess the binding characteristics of an ovine anti-digoxin-Fab preparations, DIGIBIND, for digoxin, using equilibrium dialysis. The average mass of the antibody fragment was determined by matrix-assisted laser-desorption mass spectrometry to be 46,200 Da. The main conclusions are that the binding affinity and capacity are similar for several batches, produced over a period of several years. The average median affinity for digoxin of five batches determined by Sips analysis was 3.4 x 10(11) M-1 (range 1.95-6.15 x 10(11) M-1) (corresponding to dissociation constants, Kd, in the range 1.63-5.13 pM), and the index of heterogeneity was 0.78 +/- 0.03.

Animals↗
PubMed1990

Heavy and light chain contributions to antigen binding in an anti-digoxin chain recombinant antibody produced by transfection of cloned anti-digoxin antibody genes.

We used immunoglobulin gene transfection to study the effect that substituting an homologous light (L) chain for a parental L chain has on antigen fine specificity and affinity. High-affinity monoclonal anti-digoxin antibodies 26-10 and 40-100 were selected for study because their L chains are 92% homologous (although the H chains differ), and their binding with digoxin and digoxin analogs show very different properties. In order to generate a recombinant transfectoma, the genes encoding the 26-10 H and L chains were cloned. After the sequenced clones had been shown to contain the V gene and the transcriptional control elements, the H and L chain V region genes were subcloned into different expression vectors. Both constructs were transfected into myeloma J558L, a lambda 1 chain producer, to verify that the genetic constructs expressed correctly. The recombined 26-10 antibody was identical to parental 26-10 antibody in fine specificity and affinity. The 26-10 L chain construct was then transfected into a cell line, CR-101, that expresses the 40-100 H chain and a lambda 1 chain. The transfectoma 1E6, secreting 40-100 H chain and 26-10 L chain, was selected. Appropriate gene expression in 1E6 was proven by polymerase chain reaction cloning and sequencing. The fine specificity properties of the 1E6 recombinant derive from both the 40-100 and 26-10 antibodies; however, the affinity of 1E6 is 130 times less than that of the parental antibodies. We conclude that, in 1E6, the H and L chains are codominant in their influence on antigen specificity and that homologous pairing of H and L chains is required for optimal affinity.

Amino Acid Sequence↗
PubMed1987

Fatal digoxin poisoning: an unsuccessful resuscitation with use of digoxin-immune Fab.

A 1-month-old infant suffered cardiac arrest shortly after presentation to the emergency department. The child had a history of heart disease treated with digoxin. The infant died despite intensive resuscitative efforts, including the use of digoxin-specific Fab antibodies. A brief discussion of this case and the use of digoxin-specific antibodies is presented.

Antibodies↗
PubMed1988

Acute digoxin overdose: use of digoxin-specific antibody fragments.

An acute ingestion of 6 to 7 mg digoxin as a suicidal gesture in a 76-year-old man with chronic heart disease is presented. The patient arrived in the emergency department approximately 5 hours after ingestion with a normal serum potassium and increasing numbers of multifocal premature ventricular contractions. Digoxin-specific antibody fragments were administered. The patient developed ventricular tachycardia and ventricular fibrillation and was eventually stabilized 35 minutes after the Fab fragments were infused. A review of the pharmacology and indications for use of digoxin-immune Fab fragments is also presented.

Aged↗
PubMed1984

Reduction of digoxin effect during the digoxin-quinidine interaction.

The effects of the digoxin-quinidine interaction on cardiac function was examined in healthy subjects. Our results indicate that while serum digoxin levels were elevated, the improved cardiac function due to digoxin declined during combined therapy. Our data also provide an alternate explanation for the changes previously interpreted as "enhanced digitalis effects" during the interaction.

Adult↗
PubMed2003

Immediate control of life-threatening digoxin intoxication in a child by use of digoxin-specific antibody fragments (Fab).

Digoxin-immune antibody fragments (Fab) for treatment of digitalis intoxication was introduced in 1976. Many reports have been published concerning this therapy for children, but few have focused on its immediate reversal of cardiac as well as extracardiac life-threatening manifestations of digoxin toxicity. We present a case of life-threatening digitalis intoxication in a child with postoperative renal insufficiency, after a Sennings procedure for transposition of the great arteries. Digoxin administration according to the nationally recommended dosage and intervals unexpectedly resulted in serum levels in the toxic range. Severe cardiac arrhythmias, haemodynamic instability and a rapid-increasing serum potassium level resulted. This report demonstrates how administration of Fab according to the manufacturer's dosage recommendation reversed the tachyarrhythmia immediately and re-established a normal level of serum potassium within minutes.

Antibodies, Blocking↗
PubMed1988

[Disorders of color perception in subtoxic and toxic digoxin and serum digoxin concentrations].

Using the Farnsworth-Munsell 100-hue test, investigations were carried out in 14 patients with subtoxic to toxic serum concentrations of digoxin (greater than 2.0 ng/ml) and 13 patients with subtoxic to toxic serum concentrations of digitoxin (greater than 30 ng/ml), in order to detect color vision deficiencies related to serum levels of digitalis. As compared to the control group (n = 24) the total error scores were significantly increased for both glycosides and all serum level ranges. No evidence was found indicating that digoxin and digitoxin influence color vision differently. The FM 100-hue test indicated definite improvements in the digoxin group within one day of discontinuing the glycosides, while the digitoxin group only started to normalize a week later. The results are discussed, taking the different pharmacokinetics of the two digitalis glycosides into account.

Aged↗
PubMed1983

[Treatment of life-threatening digoxin poisoning with heterologous digoxin-specific antibody fragments].

A 72-year-old woman was admitted to hospital four hours after taking, with suicidal intent, 20 mg digoxin (100 tablets Novodigal) and 50 mg nitrazepam (10 tablets Mogadan). No digoxin tablet residues were found on gastroscopic gastric lavage. A pacemaker was placed transvenously into the apex of the right ventricle. Multifocal ventricular premature systoles and recurrent ventricular fibrillation, which was difficult to terminate, alternating with extreme bradycardia quickly responded to the administration of heterologous digoxin-specific antibodies. Five hours after treatment had been started (total dose 800 mg antibody fragments) the patient again had a stable sinus rhythm of normal rate.

Aged↗
PubMedDate not supplied

Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin.

The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase.

Animals↗
PubMed2004

Renal function, digoxin therapy, and heart failure outcomes: evidence from the digoxin intervention group trial.

Renal dysfunction is a common complication for patients with heart failure, but its association with clinical outcomes has not been fully characterized. We evaluated the association of glomerular filtration rate (GFR) with heart failure survival and the effect of digoxin on heart failure outcomes across GFR strata. A secondary analysis from the Digitalis Intervention Group trial was conducted of 6800 outpatients with systolic heart failure. Renal function was categorized as estimated GFR (expressed in ml/min per 1.73 m(2)). All-cause mortality (mean, 3 yr) was inversely proportional to GFR (GFR >60, 31% mortality; GFR 30 to 60, 46% mortality; GFR <30, 62% mortality; P < 0.001). Among patients with a GFR <50, lower GFR were associated with greater adjusted mortality risk (GFR <30: hazard ratio [HR], 2.06, 95% confidence interval [CI], 1.69 to 2.51; GFR 30 to 40: HR, 1.42, 95% CI, 1.22 to 1.67; GFR 40 to 50: HR, 1.22, 95% CI, 1.07 to 1.39; GFR 50 to 60: HR, 1.00, referent). In contrast, participants with GFR 60 to 70 had similar risk (HR, 1.00; 95% CI, 0.88 to 1.14) compared with GFR 50 to 60, and those with GFR >70 had a slightly lower mortality hazard (0.89; 95% CI, 0.78 to 1.00). Linear spline analyses confirmed that GFR = 50 was the appropriate risk threshold; above 50, GFR had no association with mortality, whereas below 50, mortality risk increased sharply with declining GFR (spline coefficient, P < 0.0001). Digoxin efficacy did not differ by level of GFR (P = 0.19 for interaction). Renal dysfunction is strongly associated with mortality in stable outpatients with heart failure, notably in patients with estimated GFR <50 ml/min per 1.73 m(2). The effect of digoxin did not differ by level of renal function.

Aged↗
PubMed1983

Digoxin and the geriatric in-patient. A randomized trial of digoxin versus placebo.

The effects of oral digoxin and placebo in 41 geriatric in-patients were compared using a randomized, double-blind, cross-over method. The patients were in sinus rhythm or had atrial fibrillation. The observation period was two months on digoxin or placebo. Patients with symptoms of cardiac failure at rest or during light physical activity, X-ray signs of pulmonary congestion, proven need of digoxin therapy following earlier withdrawal, atrial fibrillation with a ventricular rate greater than 95 beats/min and patients in whom digitalis intoxication was suspected were excluded from the study. Five (14%) of 37 patients deteriorated during the placebo phase. Four of these developed rapid atrial fibrillation and one patient developed sinus tachycardia and symptoms of heart failure.

Aged↗
PubMed1979

The acute changes seen in cardiac glycoside receptor sites, 86rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients during the early phases of digoxin therapy are not found during chronic therapy: pharmacological and therapeutic implications for chronic digoxin therapy.

1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocyte 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of various groups of patients--those who have not received digoxin, those during the early phases of treatment, those during chronic (greater than 2 months) treatment, and those toxic. 2 The values of those measurements in the patients in the early phases of therapy and in the toxic patients differed significantly from those of the untreated patients. 3 However, the values in the chronically treated patients were not different from those of the untreated patients. 4 The results suggest that the biochemical pharmacological effects of digoxin which occur during the early phases of therapy do not persist in the long-term. 5 The possible clinical significance of these observations is discussed.

Aged↗
PubMed1993

Digoxin pharmacokinetics in patients with high serum digoxin concentrations.

Digitalis intoxication is a frequent iatrogenic effect in patients on treatment with digoxin. In the present study we evaluated the pharmacokinetic behaviour of digoxin and the factors responsible for intoxication by this drug in monitored patients exhibiting clinical signs of overdosing with serum levels > 2 ng/ml. A control group of patients was used as a reference whose population pharmacokinetic parameters obtained by a maximum likelihood method were: Vd = 542.92 +/- 274.53 (litre); Cl = 8.73 +/- 1.55 (litre/h) (mean +/- SD). Statistically significant differences (P < 0.001) were found between the mean Cl values in both groups of patients. The difference between the dose-level ratios established in both populations studied also proved to be significant (P < 0.001). Calculation of the optimum dose for each patient showed that the doses recommended in intoxicated patients should be three times lower than those used in the control population. A good correlation was found between the concentrations observed 24 h after administration and the mean concentrations observed at steady state predicted for both population groups. Multiple regression analysis showed that the variables with the greatest predictive value for clearance in intoxicated patients were age and renal function. The modifications observed in the pharmacokinetic behaviour and in the response to digoxin in this type of patient suggest systematic monitoring using pharmacokinetic and clinical criteria jointly.

Adult↗
PubMed1988

Progesterone, some progesterone derivatives and urinary digoxin-like substances from pregnant women in radioimmuno- and 86Rb-uptake assays of digoxin.

Progesterone and some derivatives were tested in a radioimmunoassay (RIA) of digoxin and in a bioassay measuring the 86Rb-uptake into red blood cells as an index of Na+, K+-ATPase activity. The digitalis-like activity of the hormones was compared with that found in chromatographic fractions of material extracted from the urines of pregnant women at term. Progesterone at concentrations greater than 10(-6) M cross-reacted in the RIA, and at 10(-3) M it decreased 86Rb-uptake by 18%. The anaesthetic progesterone derivates 5 alpha-pregnane-3 alpha-ol-20-one and 5 alpha-pregnane-3,20-dione crossreacted to a lesser degree in the RIA and lacked effect in the bioassay. Similar results were obtained with pregnandiol-glucuronide, the major urinary metabolite of progesterone. In contrast, several fractions of the urinary material had significant effects in both assays. It is concluded that the digitalis-like activity of progesterone is not coupled to properties associated with its anaesthetic effects. Furthermore, although progesterone may account for a part of the endogenous digoxin-like substances in serum of neonates and pregnant women, neither progesterone proper nor pregnandiol-glucuronide explains the great amount of digoxin-like substances found in the urines.

Anesthetics↗
PubMed1975

Treatment with digoxin and measurement of serum digoxin levels after myocardial infarction.

Forty-nine patients admitted to a Coronary Care Unit with myocardial infarction complicated by left ventricular failure, were treated with 1.75 mg Lanoxin over 36 hours. Serum digoxin levels were measured by radioimmunoassay at 8, 24, and 48 hours. No difference in serum levels was observed between those patients who received 'old' (reduced bioavailability) and those who received 'new' Lanoxin. Serum levels were significantly higher at 8 and 24 hours in those patients who received their first dose intramuscularly compared with those who received their first dose orally, irrespective of the bioavailability of the oral preparation used. No correlation was observed between serum digoxin levels and serum urea or creatinine during the 48-hour period of study. The incidence of arrhythmias is reported, but no conclusion can be drawn as to whether or not the glycoside contributed to this in any way. The use of digoxin in patients with acute myocardial infarction complicated by left ventricular failure is justifiable in the light of available evidence. However, in view of the possible predisposition of such patients to toxicity, lower serum levels than were achieved in many of our patients seem desirable and a modified dosage schedule is suggested.

Administration, Oral↗
PubMed1990

Treatment of digoxin intoxication in a renal failure patient with digoxin-specific antibody fragments and plasmapheresis.

A patient with renal failure due to myeloma kidney and coincident digitalis intoxication due to prescribed daily digoxin administration was treated with digoxin-specific antibody fragments and plasmapheresis. Rapid response to therapy was noted, removal of digoxin-antidigoxin antibody complexes was confirmed, and prevention of delayed rebound toxicity was documented. We suggest that this is the therapy of choice in similar individuals.

Acute Kidney Injury↗