Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Digoxin”

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 1,189 records · Page 66Linked to original sources
PubMed1981

Precision of digoxin radioimmunoassays and matrix effects: four kits compared.

We studied the interference of the sample matrix on digoxin radioimmunoassays using four commercial kits. Plasma samples from non-digitalized patients of the following categories were assayed: uncomplicated essential hypertension treated with spironolactone, uremia, and acute myocardial infarction (AMI). Digoxin 2.50 nmol/L was added to all samples. Digoxin in plasma from patients on spironolactone was overestimated by two of the kits (means 2.77 and 2.68 nmol/L, respectively; p less than 0.01) and underestimated in samples from uremic patients by one kit (2.32 nmol/L; p less than 0.01). The digoxin content of AMI plasma was overestimated by one kit (2.62 nmol/L; p less than 0.05). Significant differences were found between radioimmunoassays when estimating digoxin concentration in the same category of patient and within individual methods used for different categories. Precision expressed as 95% confidence intervals ranged from 0.43 to 0.80 nmol/L for the kits. Thus, deviations in recorded digoxin concentrations from the true values found, but were of secondary importance because of the relatively low precision of the assays.

Digoxin↗
PubMed1996

A possible interaction of potential clinical interest between digoxin and acarbose.

This case report describes a 69-year-old woman with diabetes mellitus and heart failure who repeatedly had unusual subtherapeutic levels of plasma digoxin. When the drug therapeutic regimen was checked it was found that a new drug, acarbose, had been added to the therapeutic regimen before the unexpected laboratory reported results. Because other drugs included in her therapeutic menu were rejected as being responsible for decreased levels of digoxin, it was recommended to discontinue acarbose to evaluate its role. In the absence of acarbose, the plasma concentration of digoxin increased to the therapeutic range. We concluded that acarbose may be responsible for a pharmacokinetic interaction with digoxin by a still unknown mechanism. Although discontinuation of acarbose was recommended, the attending physician discontinued administration of digoxin because the clinical condition of the patient did not get worse during subtherapeutic levels of digoxin.

Acarbose↗
PubMed1997

Quantitation of interference in digoxin immunoassay in renal, hepatic, and diabetic disease.

A comparison of the results of a newly developed fluorescence-derivatization/HPLC method and a commercial immunoassay method (ACA, Dupont) for the measurement of serum digoxin concentrations in patients indicates that (1) the results from the ACA method agree well with those from the HPLC method in patients with cardiovascular disease but without renal, diabetic, and liver disease, (2) serum digoxin concentrations determined by the ACA method are overestimated in patients with renal, diabetic, or liver disease, and (3) the steady-state serum concentrations of hydrolyzed and reduced metabolites are relatively insignificant in patients receiving digoxin therapy, including patients with renal failure. The excellent reproducibility of the HPLC and immunoassay methods (coefficient of variation < 9.0%), together with the demonstrated specificity of the HPLC method with respect to potential interference from digoxin metabolites, endogenous digoxin-like immunoactive substances, and coadministered drugs and their metabolites, allows quantitation of the degree of interference in digoxin immunoassays under actual therapeutic drug monitoring conditions. Clinically significant interferences (0.3 to 1.1 ng/ml) with immunoassay determination were found in the majority of patients in all three diseases studied.

Adult↗
PubMed1998

Furosemide and digoxin inhibit thiamine uptake in cardiac cells.

Heart cells in culture were used to clarify whether furosemide or digoxin cause thiamine deficiency and if so, by what mechanism. The intracellular level of thiamine pyrophosphate gradually decreased, with a half-life of 16-19 days, after treatment of cardiac cells with furosemide or digoxin. When thiamine was excluded from the growth medium, thiamine pyrophosphate levels gradually decreased, with a half-life of 5-6 days. No additive effect was observed in the presence of the above drugs when thiamine was excluded from the medium. Thiamine uptake by cardiac cells grown in a thiamine-free medium for 7 days decreased significantly in the presence of furosemide or digoxin. The effect of furosemide or digoxin on thiamine uptake was found to be dose dependent. Co-administration of furosemide and digoxin to the cardiac cell cultures resulted in an additive effect on thiamine uptake. Our results demonstrate that furosemide and digoxin inhibit thiamine uptake by cardiac cells in culture and may therefore cause thiamine deficiency in patients undergoing chronic treatment with these drugs.

Animals↗
PubMed1995

Structure and specificity of the anti-digoxin antibody 40-50.

We determined the sequence, specificity for structurally related cardenolides, and three-dimensional structure of the anti-digoxin antibody 40-50 Fab in complex with ouabain. The 40-50 antibody does not share close sequence homology with other high-affinity anti-digoxin antibodies. Measurement of the binding constants of structurally distinct digoxin analogs indicated a well-defined specificity pattern also distinct from other anti-digoxin antibodies. The 40-50-ouabain Fab complex crystallizes in space group C2 with cell dimensions of a = 93.7 A, b = 84.8 A, c = 70.1 A, beta = 128.0 degrees. The structure of the complex was determined by X-ray crystallography and refined at a resolution of 2.7 A. The hapten is bound in a pocket extending as a groove from the center of the combining site across the light chain variable domain, with five of the six complementarity-determining regions involved in interactions with the hapten. Approximately three-quarters of the hapten surface area is buried in the complex; two hydrogen bonds are formed between the antibody and hapten. The surface area of the antibody combining site buried by ouabain is contributed equally by the light and heavy chain variable domains. Over half of the surface area buried on the Fab consists of the aromatic side-chains. The surface complementarity between hapten and antibody is sufficient to make the complex specific for only one lactone ring conformation in the hapten. The crystal structure of the 40-50-ouabain complex allows qualitative explanation of the observed fine specificities of 40-50, including that for the binding of haptens substituted at the 16 and 12 positions. Comparison of the crystal structures of 40-50 complexed with ouabain and the previously determined 26-10 anti-digoxin Fab complexed with digoxin, demonstrates that the antibodies bind these structurally related haptens in different orientations, consistent with their different fine specificities. These results demonstrate that the immune system can generate antibodies that provide diverse structural solutions to the binding of even small molecules.

Amino Acid Sequence↗
PubMed1978

Digoxin therapy in low-birth-weight infants with patent ductus arteriosus.

Digoxin therapy was evaluated retrospectively in a group of 30, and prospectively in a group of 16 low-birth-weight, premature infants with cardiorespiratory symptoms due to persistent patency of the ductus arteriosus. The response to decongestive therapy was equivocal. Digoxin levels in serum varied between 1.5 and 13 ng/ml. Digoxin half-life in serum exceeded three days in four patients. Fourteen of the combined group of 46 infants had signs of toxicity of digoxin. High dosage, inadvertent overadministration, and variable clearance of digoxin, as well as special characteristics of the patients studied, are postulated as explanations for the high incidence of toxicity. This study suggests that digoxin therapy in low-birth-weight, premature infants with patent ductus arteriosus is not without risk.

Digoxin↗
PubMed1979

Dosage of digoxin in premature infants.

The pharmacokinetics and pharmacodynamics of digoxin in premature infants was studied. During maintenance therapy, after a total digitalizing dose of 30 microgram/kg, the measured digoxin level was related inversely to body weight at birth and to estimated gestational age. The serum digoxin levels found in the immature and smaller infants were two to three times the values usually reported to be toxic in older children. Based on these findings, a second group of premature infants was digitalized with 20 microgram/kg; in this group, the serum digoxin levels were below the toxic range, irrespective of gestational age or birth weight. The cardiac effects of digoxin, i.e., shortened left ventricular pre-ejection period and ejection time as determined by echocardiography, were similar in the two groups. For both groups, the half-life of digoxin in the serum was twice that reported for term infants and children. Since digitalis effect is obtained with lower dose and serum concentration, we recommend that this dose be used in premature infants.

Birth Weight↗
PubMed1999

Efficacy of digoxin specific Fab fragments (Digibind) in the treatment of toad venom poisoning.

Chan Su, a traditional Chinese medication, and Love Stone, a topical aphrodisiac, are both made from dried venom of the toad bufo bufo gargarizans and contain bufalin, cinobufotalin, cinobufagin, and other cardioactive steroids of the bufadienolide class. Deaths have occurred following ingestion of these products and the clinical course resembles digoxin toxicity. The purpose of this study was to determine the efficacy of digoxin specific Fab fragments in treating Chan Su poisoning. An ethanolic extract was prepared from Chan Su. Digoxin specific Fab fragments were reconstituted in normal saline to a concentration of 80 mg/ml. An approximate LD90 dose was determined in preliminary experiments. Mice were then randomly divided into a treatment group of 15 mice and a control group of 30 mice. The treatment group was pretreated with 20 ml/kg of digoxin specific Fab fragment solution by intraperitoneal injection at t = 0, followed by 10 ml/kg of digoxin specific Fab fragments intraperitoneal at t = 30 min. The control group was pretreated with equal volumes of intraperitoneal normal saline at the same times. Immediately following the 30 min injection, both groups were given the estimated LD90 dose of Chan Su extract by subcutaneous injection. An endpoint of survival at 6 h was chosen after preliminary results showed that all deaths occurred in the first 4 h. All 30 of the control mice had seizures followed by death compared to 11 seizures and 7deaths in the 15 treatment mice. These results were statistically significant by Fisher's exact test (p = 0.00003 for mortality and p = 0.009 for seizures). Digoxin specific Fab fragments are effective in the treatment of Chan Su poisoning in mice and may be effective for poisoning by other cardioactive steroids of the bufadienolide class.

Amphibian Venoms↗
PubMed2003

Hypothalamic digoxin--central role in conscious perception, neuroimmunoendocrine integration and coordination of cellular function--relation to hemispheric dominance.

A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome-X, rheumatoid arthritis and epilepsy has been described. The psychological behavioural patterns of the family were as follows--creativity and high IQ, hypersexual behaviour, reduced appetite and eating behaviour, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less of bonding and affectionate behaviour and left handedness. Digoxin, an endogenous Na(+)-K(+) ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na(+)-K(+) ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarising tryptophan catabolites - serotonin, quinolinic acid, strychnine and nicotine and decreased levels of hyperpolarising tyrosine catabolites dopamine, noradrenaline and morphine contributing to membrane Na(+)-K(+) ATPase inhibition in all the above disorders and the indexed family. Digoxin induced membrane Na(+)-K(+) ATPase inhibition can result in increased intracellular Ca(2+) and reduced Mg(++) levels leading to glutamate excitotoxicity, oncogene activation and immune activation. Digoxin induced altered Ca(++)/Mg(++) ratios, reduced ubiquinone and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure and mitochondrial function leading to the diverse disorders described above including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/left hemispheric dominant and left-handed/right hemispheric dominant individuals. The biochemical patterns in the indexed family and the diverse disorders studied correlated with those obtained in right hemispheric dominance. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and co-ordinate the functions of various cellular organelles.

Digoxin↗
PubMed1986

Development of a high-performance liquid chromatographic assay for digoxin using post-column fluorogenic derivatization.

An efficient high-performance liquid chromatographic (HPLC) separation for digoxin and its metabolites has been developed. Quantitation of digoxin at plasma levels was possible after the column effluent was passed through a fluorogenic post-column reactor. A study of the optimum post-column conditions was undertaken using a combination of ascorbic acid, hydrogen peroxide and hydrochloric acid, which was known to induce fluorescence in the digoxin molecule. Digoxin and its metabolites were separated on a 15 cm X 4.6 mm I.D., 3-microns reversed-phase (C18) HPLC column using methanol--ethanol--isopropanol--water (52:3:1:45) as the mobile phase at a flow-rate of 0.3 ml/min. A solution of 1.1 X 10(-3) M hydrogen peroxide in a 0.1% ascorbic acid solution and concentrated hydrochloric acid were added into the post-column reactor through a peristaltic pump at a combined flow with a flow-rate of 0.23 ml/min. The mixture was passed into the 20-m reaction coil maintained at 79 +/- 1 degrees C. The resulting digoxin fluorophore was monitored with a fluorescence detector. Detector responses were linear from 1.5 to 10 ng injected on-column. The overall performance demonstrated that this system has the sensitivity, linearity and stability desired in a digoxin plasma level determination. The total chromatographic time including the postcolumn derivatization step was about 40 min.

Chromatography, High Pressure Liquid↗
PubMed1991

Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study.

An observational surveillance study was conducted to monitor the safety and effectiveness of treatment with Digoxin Immune Fab (Ovine) (Digibind) in patients with digitalis intoxication. Before April 1986, a relatively limited number of patients received treatment with digoxin-specific Fab fragments through a multicenter clinical trial. Beginning with commercial availability in July 1986, this study sought additional, voluntarily reported clinical data pertaining to treatment through a 3 week follow-up. The study included 717 adults who received Digoxin Immune Fab (Ovine). Most patients were greater than or equal to 70 years old and developed toxicity during maintenance dosing with digoxin. Fifty percent of patients were reported to have a complete response to treatment, 24% a partial response and 12% no response. The response for 14% of patients was not reported or reported as uncertain. Six patients (0.8%, 95% confidence interval 0.3% to 1.8%) had an allergic reaction to digoxin-specific antibody fragments. Three of the six had a history of allergy to antibiotic drugs. Twenty patients (2.8%, 95% confidence interval 1.7% to 4.3%) developed recrudescent toxicity. Risk of recrudescent toxicity increased sixfold when less than 50% of the estimated dose of antibody was administered. A total of 215 patients experienced posttreatment adverse events. The events for 163 patients (76%) were judged to result from manifestations of underlying disease and thus considered unrelated to Fab treatment. Digoxin-specific antibody fragments were generally well tolerated and clinically effective in patients judged by treating physicians to have potentially life-threatening digitalis intoxication.

Adolescent↗
PubMed1990

The cardiovascular response to digoxin in conscious dogs with left atrial obstruction.

In addition to positive inotropic and atrioventricular conduction-blocking properties, digoxin is capable of producing systemic and pulmonary vasoconstriction. However, whether chronic digoxin treatment exacerbates the pulmonary hypertension that results from left atrial (LA) outflow obstruction has not been specifically examined. This study assessed the vascular and inotropic responses to 5 days of digoxin treatment in six conscious dogs before and after filling a permanently implanted LA balloon. Dogs were also instrumented to measure left ventricular (LV) pressure, LV dP/dt, mean systemic arterial (MAP), right atrial (RAP), pulmonary arterial, and pulmonary capillary wedge pressures, as well as cardiac output (CO). Under normal conditions with the balloon empty, digoxin treatment (40 micrograms/kg loading dose and 12 micrograms/kg/d for 5 days) reduced CO (-17%) and increased systemic (SVR) and pulmonary (PVR) vascular resistances 27% and 37%, respectively; heart rate (HR) and LV dP/dt were not changed. Filling the balloon with enough saline to double PVR also increased SVR (52%), HR (42%), and RAP (92%), and reduced CO (-24%). During LA outflow obstruction, 5 days of digoxin reduced HR (-17%), SVR (-29%), and RAP (-23%), but did not alter PVR, CO, or LV dP/dt. This study demonstrates that although systemic and pulmonary vasoconstriction result from chronic digoxin treatment under normal conditions, the drug produces systemic vasodilation and no change in PVR during LA outflow obstruction.

Animals↗
PubMed2000

Noncompetitive immunoassay of small analytes at the femtomolar level by affinity probe capillary electrophoresis: direct analysis of digoxin using a uniform-labeled scFv immunoreagent.

A general method for noncompetitive immunoassay of small analytes using affinity probe capillary electrophoresis (APCE) is demonstrated using digoxin as a model analyte. A uniform immunoreagent was prepared from a single-chain antibody (scFv) gene specific for digoxin. Site-directed mutagenesis introduced a unique cysteine residue for uniform labeling with a thiol-reactive fluorochrome. After expression in E. coli, the scFv was purified by immobilized metal affinity chromatography (IMAC) using an added C-terminal 6-histidine sequence. The protein was renatured and labeled while immobilized on the IMAC resin. After 0.02-microm filtration to remove microaggregates, the resulting reagent was highly uniform and stable at -12 degrees C for at least 1 year. Three formats of APCE using the scFv reagent were explored. A "mix-and-inject" assay optimized for low detection limits demonstrated analysis of 10 pM digoxin in aqueous standard solutions in 10 min. A rapid mix-and-inject format in a short capillary allowed detection of 1 nM digoxin in 1 min. Digoxin samples in serum and urine were injected directly after 10-fold dilution. In combination with solid-phase extraction, 400 fM digoxin was detected in 1 mL of serum. Including solid-phase extraction, reproducibility was within 2.5%, and the linear range was 3 orders of magnitude. The strategy adopted in this paper should be of general use in the low-level analysis of small analytes.

Affinity Labels↗
PubMed2001

Endocardial stimulation of efferent parasympathetic nerves to the atrioventricular node in humans: optimal stimulation sites and the effects of digoxin.

UNLABELLED: The purposes of this study were to identify optimal sites of stimulation of efferent parasympathetic nerve fibers to the human atrioventricular node via an endocardial catheter and to investigate the interaction between digoxin and vagal activation at the end organ. METHODS: The ventricular rate was measured during atrial fibrillation, prior to and during parasympathetic nerve stimulation, in 8 patients taking digoxin and in 10 controls. High frequency electrical stimuli were delivered via an hexapolar or quadripolar electrode catheter, placed at the posteroseptal right atrium near the atrioventricular node (n=18 patients) or in the coronary sinus (n=12 of 18 patients). In 4 patients, stimulation was repeated after intravenous administration of 1 to 2 mg of atropine. RESULTS: Nerve stimulation prolonged the R-R interval in all patients. Stimulation close to the posteroseptal right atrium led to maximal atrioventricular nodal slowing. The mean R-R intervals at baseline and during parasympathetic nerve stimulation (60 mA) from the posteroseptal right atrium and the proximal coronary sinus were 581+/-79 ms, 2440+/-466, and 900+/-228 ms respectively (p=0.0001). The response to nerve stimulation was greater in patients taking digoxin than in patients not taking the drug (p=0.02). Junctional rhythm occurred during nerve stimulation in 8/8 patients taking digoxin and 0/10 not taking the drug (p=0.0001). The response to stimulation was eliminated after atropine (p=0.01). CONCLUSIONS: Parasympathetic nerves to the atrioventricular node were stimulated from the proximal coronary sinus as well as the posteroseptal right atrium. Stimulation at the posteroseptal right atrium resulted in the greatest response, and digoxin enhanced this response. The augmented response suggests that an interaction may exist between parasympathetic stimulation and digoxin at the end organ.

Aged↗
PubMed1981

Maturation and renal digoxin clearance.

To evaluate the effect of maturation on the renal disposition of digoxin, the ratio of digoxin clearance to creatinine clearance was determined in 35 patients who were 3 days to 79 yr old. All were at steady-state levels for digoxin treatment. A mean ratio of 1.49 +/- 0.67 (SD) was obtained in the group of prepubertal children and infants greater than or equal to 2 mo of age. The mean ratio decreased to 0.82 +/- 0.25 (SD) in the adult group; adults were defined as sexually mature adolescents or older (P less than 0.005). The decrease in net renal tubular secretion of digoxin appears to occur at puberty. This observation can provide one explanation for the apparently larger doses of digoxin required by infants and children than by adults. It may also represent a developmental change in renal tubular physiology with broader significance than for digoxin disposition alone.

Adolescent↗
PubMed1982

Kinetics of the digoxin-aspirin combination.

Digoxin interacts kinetically with many drugs in man. These interactions may result in digoxin toxicity. Aspirin has been shown to raise serum digoxin levels in the dog. We evaluated the effect of aspirin on digoxin single-dose kinetics in eight healthy adults. Aspirin induced no change in digoxin total body clearance, volume of distribution, elimination half-life, or renal or creatinine clearance. Trough serum salicylate levels ranged from 93 to 163 microgram/ml. We conclude that no alteration is required in digoxin dosing when aspirin is used.

Adult↗
PubMed1983

Verapamil-induced changes in digoxin kinetics and intraerythrocytic sodium concentration.

Verapamil increases plasma digoxin concentration by about 60% to 80%. To explore the clinical consequences of this interaction, we evaluated single-dose digoxin kinetics along with repeated measurements of intraerythrocytic sodium concentration in eight healthy subjects before and during verapamil coadministration. Verapamil reduced mean total body clearance of digoxin from 4.68 +/- 0.41 to 3.29 +/- 0.26 ml/min/kg and prolonged digoxin biologic t1/2 from 33.5 +/- 2.4 to 41.4 +/- 2.3 hr. These kinetic changes were associated with a greater elevation of intraerythrocytic sodium concentration than controls. Verapamil had no effect on intraerythrocytic sodium content. In vitro experiments revealed no influence of verapamil on the number of glycoside receptors on human lymphocytes. Since intracellular sodium concentration has proved to correlate closely with clinical signs of digoxin toxicity, our indicate that verapamil is likely to increase the risk of digoxin-induced arrhythmias.

Adult↗
PubMed1983

Decreased digoxin cardioinactive-reduced metabolites after administration as an encapsulated liquid concentrate.

The generation by intestinal bacteria of large amounts of cardioinactive metabolites of digoxin with a reduced lactone ring (digoxin reduction products, or DRP) may be associated with increased dosage requirements. Since DRP excretion varies inversely with bioavailability, we compared the 6-day urinary excretion (CUE) of digoxin and DRP after 0.4-mg doses of an encapsulated liquid concentrate and a standard tablet in 22 normal subjects known to form substantial amounts of DRP. Mean (+/- SE) CUE of digoxin was greater with the capsules than the tablets (195.9 +/- 8.6 and 137.5 +/- 6.3 micrograms). CUE of DRP was less after the capsules (60.8 +/- 5.5 and 102.7 +/- 9.5 micrograms). Percent DRP was greater after the tablets in every subject (mean for tablets, 41.2 +/- 2.7%; capsules, 23.5 +/- 1.8%). Patterns of DRP excretion differed with the two preparations, probably reflecting differences in the routes whereby digoxin reached the colon. The use of highly bioavailable capsules in subjects with heavy DRP production should minimize metabolic inactivation during digoxin therapy.

Adult↗