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At least 1,621 records · Page 90Linked to original sources
PubMed1992

Pharmacokinetics of the digoxin-quinidine interaction via mixed-effect modelling.

It was the purpose of this study to evaluate the effect of quinidine administration on the population estimates of the volume of distribution (Vdpop) and clearance (CLpop) of digoxin. The data collected on 94 patients included 230 measured serum digoxin concentrations, height, age, sex, weight (wt), serum creatinine, history of digoxin and quinidine administration and the presence or absence of congestive heart failure (CHF). Using the NONMEM software program, estimates were obtained for CLpop and Vdpop. Variables tested for inclusion in the CLpop model were creatinine clearance (CLCR), CHF, wt, ideal bodyweight, quinidine (QUIN) [both as a discrete variable and in a dose-dependent manner], and body surface area. Variables tested for inclusion in the Vdpop model were CLCR, wt, ideal bodyweight, body surface area and quinidine. During model building a p-value of 0.05 was chosen for variable inclusion. The final model was as follows: CLpop (L/h) = (3.1 + 0.0516 x CLCR) x QUIN Vdpop (L) = (4.03 + 0.0832 x CLCR) x wt F = 0.82 where F is bioavailability. In the above, QUIN is 0.567 if quinidine is being concurrently administered and 1.0 if it is not. The coefficient of variation (CV) of CLpop was 44% while that of Vdpop was 48%. The residual intrasubject CV was 26%. These results compare favourably with previously derived methods of estimating digoxin CLpop and Vdpop but may improve on those methods due to the inclusion of quinidine in the model. These better estimates should result in improved initial dosage of digoxin.

Adult↗
PubMed1981

Effect of digoxin upon intracellular potassium in man.

The effect of digoxin upon intramuscular potassium was studied by use of whole body counting and biopsy technique. Twelve healthy subjects and twelve outpatients with mild cardiac insufficiency or atrial arrhythmia were digitalised. Before and after digitalization total body potassium (TBK) was measured. Potassium concentration in muscle specimens (MK) was analysed by the neutron activation technique. Digoxin was measured in serum and in skeletal muscle tissue by radioimmunoassay, and QS2-index as a measure of the electromechanical systole. In both groups a significant decrease in TBK (P less than 0.05) and MK (P less than 0.01) was demonstrated in connection to digitalization. There was no correlation between the decrease in TBK and MK, or between the concentrations of digoxin in serum or muscle and the decrease in potassium concentration. The digoxin in serum in healthy subjects was 0.9 +/- 0.33 nmol/l and in patients 1.2 +/- 0.41 nmol/l. The digoxin in muscle was 39 +/- 10.9 nmol/kg dry weight in seven of the healthy individuals and 37 +/- 9.5 nmol/kg dry weight in nine patients. After digitalization a decrease of QS2-index was found in both groups (P less than 0.01).

Adult↗
PubMed1993

The effect of digoxin on the serum potassium concentration.

In recent studies on the influence of muscular and symphatoadrenergic activity on digoxin pharmacokinetics, the serum potassium concentration was found to increase during 2 h of supine rest in digitalized healthy subjects and out-patients. The present study was made in order to find out whether this change in serum potassium concentration is dependent on inhibition of the Na-K-ATPase activity by digitalis treatment. Ten healthy subjects were investigated on two separate occasions: before and after digitalization with digoxin 0.37-0.50 mg daily for 10 days. Serum potassium and digoxin concentrations were analysed before and after 2 h of rest in the sitting position. Without digoxin treatment, no change in serum potassium concentration was seen. During digoxin treatment, the serum potassium concentration increased by 0.19 +/- 0.23 mmol(l)-1 (p < 0.05) during the period of rest. Thus, a digitalis-induced depression of Na-K-ATPase activity seems to be a prerequisite for the described change in serum potassium concentration.

Adult↗
PubMed1977

Microencapsulated charcoal hemoperfusion: a possible therapeutic adjunct in digoxin toxicity.

Attempts to remove substantial quantities of digoxin by either peritoneal or hemodialysis, have been unsuccessful due to their low clearance rate. The present study determined the in-vivo clearance rate for digoxin of a single microcapsule of 300 gm of activated charcoal. The clearance rate was 55 +/- 5 ml/min (mean +/- SEM) in the first hour and 48.4 +/- 4 ml/min in the second; these values are approximately five-fold higher than with other dialysis techniques. No evidence of a post-dialysis rebound increase in serum digoxin levels was found, implying that peripheral tissues can rapidly release digoxin to the diminishing serum pool. Preliminary data obtained suggest a beneficial effect on arrhythmias and lowering of the myocardial to serum rate of digoxin after hemoperfusion.

Animals↗
PubMed1985

Digoxin specific antibody (Fab) fragments in 34 cases of severe digitalis intoxication.

34 patients aged between 2 and 80 years were treated with digoxin specific antibody (Fab) fragments for severe digitalis poisoning. In 27 cases, the glycoside was taken with suicidal intent; in 3 cases accidentally and 4 were iatrogenic. The following criteria were considered to be indications for use of Fab fragments: the appearance of life-threatening arrhythmias such as high-grade atrioventricular conduction disorders (grade 2 and 3 A-V block), multifocal ectopic beats, ventricular tachycardia, and relapsing ventricular fibrillation. Serum digoxin concentrations were between 3.4 and 29ng/ml before the start of treatment. Between 240 and 800mg of Fab were administered; the majority of patients received 480mg. Regression of arrhythmias was seen between 0.5 and 8 hours after Fab infusion. There was a rapid fall in the free digoxin in the serum to concentrations that were no longer measurable and a marked rise in bound digoxin with a simultaneous increase of excretion of bound digoxin in the urine. Fab therapy is considered to be a major advance in the treatment of severe, previously fatal, glycoside poisoning. No notable side effects or allergic reactions were observed.

Adolescent↗
PubMed1975

Combined propranolol and digoxin therapy in angina pectoris.

The effects of oral propranolol and digoxin and digoxin alone and in combination on angina frequency, heart size, systolic time intervals and treadmill exercise tolerance, were assessed in 20 patients with coronary heart disease. Oral propranolol alone reduced the average frequency of angina pectoris from 16 to 7 attacks per week (P less than 0.02). However, the mean duration of exercise was not significantly improved because 8 patients with abnormal left ventricular function exhibited a decrease in exercise tolerance. Combined propranolol and digoxin improved exercise tolerance in these patients, and, consequently, mean exercise duration in all patients increased significantly from the control value of 390 +/- 42 to 458 +/- 46 s (P less than 0.01). Propranolol alone also resulted in a significant increase in left heart size from 46.5 +/- 1.3 to 47.7 +/- 1.5 mm/m2 (P less than 0.001), which was reversed by the addition of digoxin. Therefore, oral propranolol combined with digoxin is advantageous in patients with angina pectoris who have abnormal ventricular function or large hearts.

Administration, Oral↗
PubMed1976

[Radioimmune method of determining the concentration of digoxin in the blood during treatment of patients with cardiac insufficiency].

Digoxin concentrations were studied in the blood serum of 128 patients with cardiac insufficiency of different etiology (acute myocardial infarction, postinfarction cardiosclerosis, mitral valve disease). Radioimmunoassay with standard kits was employed, the kits containing 125 I-labelled Digoxin. Mean concentrations of Digoxin were determined in the blood serum corresponding to different maintenance doses of the drug. It was found that signs of overdosage usually appear with concentrations exceeding 2.5 ng/ml. Disorders in the renal excretory function in patients with severe edematous syndrome help a prompt cumulation of Digoxin and the development of glucoside intoxication. Some patients demonstrated a reduced Digoxin tolerance in the acute period of their myocardial infarction. The advantages of the radioimmunoassay, especially in severely ill patients with cardiac pathology are emphasized.

Digoxin↗
PubMed1984

A utilization review of digoxin assays: sampling patterns and use.

A review of digoxin assay utilization concurrent with patient hospitalization was conducted at the University of Texas Medical Branch. An interdepartmental committee of clinicians adapted audit criteria for the collection and use of digoxin assays. This included rational indications, correct performance (i.e., collection and processing of serum sample) and appropriate dose adjustment. The charts of all patients receiving digoxin were examined daily, whether or not the physician had ordered a drug assay. Contributory data were collected and analyzed, including serum electrolyte concentrations, arterial blood gases, renal function tests, vital signs, physician assessments, and other information relating to pertinent and concomitant diseases or drug therapy. The 2-month review included 104 hospital inpatients who received 245 evaluations. Only 38.4% of the evaluations were determined to be compliant with all criteria. When the audit categories of rational indication, correct performance, and appropriate dosage adjustment were evaluated independently, compliance rates were 66%, 73% and 86%, respectively. In 108 cases (52%), the physicians provided inadequate instructions in their request for the digoxin assay to insure proper collection time by the phlebotomist. Approximately 94% of all assay results were verbally communicated to the physician or returned to the patients' charts for use in patient management within a minimum of 24 hours. Hospital laboratory charges for unnecessary, incorrectly performed, or inappropriately used digoxin assays were estimated to exceed $100,900 annually. The audit was used to demonstrate the need for changes in hospital procedures and house staff training. A collaborative pharmacokinetics service was organized with reimbursement accomplished through the physician billing charge.

Digoxin↗
PubMed1999

Monoclonal antibodies that distinguish between two related digitalis glycosides, ouabain and digoxin.

The exogenous digitalis glycosides, ouabain and digoxin, have been widely used in humans to treat congestive heart failure and cardiac arrhythmias. Several reports have also pointed to the existence of endogenous ouabain- and digoxin-like compounds, but their precise roles in mammalian physiology and various disorders of the circulation are not clear. In an attempt to produce specific Abs for the purification and identification of endogenous ouabain-like compounds, somatic cell fusion was used to produce mAbs specific for ouabain. Our attempts to produce ouabain-specific mAbs were unsuccessful when ouabain was coupled to exogenous proteins such as bovine gamma-globulins, BSA, and human serum albumin. However, when ouabain was coupled to an Ab of A/J mice origin and the same strain of mouse was used for immunization with ouabain-Ab conjugate, three Abs (1-10, 5A12, and 7-1) specific for ouabain were obtained. In assays of fluorescence quenching and saturation equilibrium with tritiated ouabain, Ab 1-10 exhibited 200 nM affinity for ouabain. These three mAbs are distinguished from existing Abs to ouabain and digoxin by their specificity for ouabain and lack of cross-reactivity with digoxin. Specificity studies showed that the loss of cross-reactivity was correlated with the presence of a hydroxyl group at either position 12beta (digoxin) or 16beta (gitoxin) of the steroid ring. These Abs can be used to develop assays for detection and characterization of ouabain-like molecules in vivo.

Animals↗
PubMedDate not supplied

Digoxin and membrane sodium potassium ATPase inhibition in cardiovascular disease.

Kerala has a high incidence of mucoid angiopathy, metabolic syndrome X and endomyocardial fibrosis. Magnesium deficiency has been reported in these disorders even though the Keralite diet has adequate magnesium. A possible cause of magnesium deficiency is the increased digoxin, a potent inhibitor membrane Na(+)-K+ ATPase which can lead to magnesium depletion. Digoxin is known to be synthesised by the hypothalamus and other tissues and can also be obtained from plant sources in the diet. Inhibition of Na(+)-K+ ATPase can cause intracellular magnesium depletion and increase in intracellular calcium. In view of these, a study has been carried out on the activity of membrane Na(+)-K+ ATPase, using RBC membrane, serum digoxin, magnesium and glycosaminoglycan levels in patients of mucoid angiopathy, endomyocardial fibrosis and syndrome X. Significant decrease in the membrane Na(+)-K+ ATPase was observed in patients while serum digoxin levels showed an increase. Serum magnesium was significantly lower while glycosaminoglycan levels were increased. The inhibition of Na(+)-K+ ATPase activity may be due to increase in endogenous and/or exogenous digoxin. This inhibition leads to depletion of intracellular magnesium and an increase in intracellular calcium load. The role of underlying magnesium-related insulin resistance and the consequence of this intracellular magnesium and calcium alteration in the pathogenesis of these disorders is discussed.

Adult↗
PubMed2001

Effects of digoxin on chemoreflex in patients with chronic heart failure.

The effects of digitalis on the baroreflexes in human chronic heart failure have been well studied. Similarly, since it has been recently shown that chemoregulation remains generally effective during cardiac failure, the goal of this study was to evaluate the effects of a chronic administration of digoxin on the chemoreflexes. Hemodynamic and blood gas parameters were assessed in 7 patients with chronic congestive heart failure before and after chronic administration for 10 days of digoxin therapy (0.25 mg daily). In both situations measurements were performed 1/ in baseline conditions at room air and, 2/ after inhalation of pure O2 for 30 min, in order to inhibit the activation of the chemoreflexes. At room air, acute O2 inhalation resulted in a significant decrease in heart rate and cardiac output. After digoxin therapy, comparatively to pre-treatment values, cardiac output, stroke volume and PaO2 were significantly higher while heart rate, systemic resistance and pulmonary wedge pressure were lower. Furthermore, acute O2 inhalation did not modify heart rate or any hemodynamic variables. These results suggest that after digoxin therapy chemoreflex was no more activated in these patients. This effect may be related to the sympatho-inhibitory and to the positive inotropic effects of digoxin: improving hemodynamic and blood gas parameters may result in the inactivation of the reflex.

Aged↗
PubMed1975

Increased salivary calcium levels as an indicator of digoxin intoxication.

One hundred ten individuals were divided into patients with digoxin intoxication; patients treated with digoxin; patients treated with digoxin and diuretics; patients treated with diuretics; and control subjects. Measurement of salivary potassium and calcium levels showed that 81% of the patients with digoxin intoxication had noticeable elevation of the salivary calcium level. In 22%, elevation of the salivary calcium level preceded clinical manifestations of intoxication. The high calcium level in the saliva was not accompanied by changes in serum or urinary calcium levels. The elevation of salivary calcium levels can be used not only as an additional indicator of digoxin intoxication but also for detecting impending intoxication in patients treated with this drug.

Adult↗
PubMedDate not supplied

Hypothalamic digoxin and irritable bowel syndrome.

BACKGROUND: The hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor digoxin that can modulate neurotransmitter transport and may play a role in hemispheric dominance. It can also modulate glycoconjugate synthesis and thus affect synaptic connectivity in the bowel wall. Digoxin could play a role in the genesis of irritable bowel syndrome (IBS). AIM: To study digoxin status in IBS and to correlate it with hemispheric dominance. METHODS: The isoprenoid pathway, tryptophan/tyrosine catabolic patterns and glycoconjugate metabolism were assessed in patients with IBS and in right hemispheric dominant/left hemispheric dominant/bihemispheric dominant individuals. RESULTS: The isoprenoid pathway was upregulated in IBS, with increased HMG CoA reductase activity (0.8 [0.07] vs 0.4 [0.06] in controls; p<0.01), serum digoxin (14.8 [1.0] vs 29.0 [1.2] ng/dL; p<0.01) and dolichol levels (63.8 [3.0] vs 120.3 [3.6] mg/dL; p<0.01). RBC membrane Na+-K+ ATPase activity (3.0 [0.2] vs 1.0 [0.1] microg/p/mg protein; p<0.01), serum magnesium (1.7 [0.1] vs 1.0 [0.1] mg/dL; p<0.01) and ubiquinone (86.4 [5.9] vs 39.8 [1.2] microg/dL; p<0.01) were reduced. There was increase in tryptophan catabolites and reduction in tyrosine catabolites. Serum total glycosaminoglycan and carbohydrate component of glycoproteins were increased in IBS. The activity of glycosaminoglycan degrading enzymes and glycohydrolases were increased. This pattern correlated with those obtained in right hemispheric chemical dominance. CONCLUSION: Hypothalamic digoxin and right hemispheric dominance could play a role in the genesis of irritable bowel syndrome.

Biomarkers↗
PubMedDate not supplied

Serum and tissue glycoconjugates, digoxin and magnesium levels in chronic calcific pancreatitis.

BACKGROUND: Endogenous or exogenous digoxin can lead to membrane Na+,K+-ATPase inhibition and hypomagnesemia. Low magnesium levels can lead to increased glycosaminoglycans (GAG) concentration in many organs. AIM: To measure the serum levels of pancreatic GAG and glycoproteins, two major components of the extracellular matrix, in patients with chronic calcific pancreatitis (CCP). Serum levels of magnesium and digoxin were also assessed. METHODS: Patients with CCP and age- and sex-matched healthy control subjects (15 each) were studied. Serum GAG, Mg and digoxin levels were measured. RBC membrane Na+,K+-ATPase activity was also assessed. Pancreatic tissue obtained at autopsy from seven patients with CCP and sex- and age-matched healthy subjects who had died in accidents were also tested for GAG and glycoproteins. RESULTS: Total GAG levels were significantly increased in the serum and pancreas of patients with CCP. This was associated with lower serum Mg levels, increased serum digoxin levels and decreased RBC membrane Na+,K+-ATPase activity. CONCLUSION: Exogenous or endogenous digoxin-induced hypomagnesemia and the consequent altered glycoconjugate metabolism may be important in the pathogenesis of CCP.

Adult↗
PubMed1992

High myocardial accumulation of radioiodinated digoxin derivative: a possible Na,K-ATPase imaging agent.

In view of the high binding ability of cardiac glycosides to the myocardial Na,K-ATPase, radioiodinated digoxin derivatives were surveyed as candidates for myocardial imaging, with particular emphasis on the noninvasive monitoring of cardiac glycoside therapy. Among the radioiodinated digoxin derivatives surveyed, 125I-digoxin-iodohistamine(bis(O-carboxymethyloxime)) showed the highest accumulation in the myocardium and similar binding ability to Na,K-ATPase as digoxin itself against ouabain displacement, as indicated by in vivo and in vitro studies. Based on these results, 123I labeling of digoxin-histamine(bis(O-carboxymethyloxime)) and imaging in a dog demonstrated uptake in the myocardium.

Animals↗
PubMed2003

Digoxin therapeutic drug monitoring: an audit and review.

AIM: The measurement and assessment of digoxin concentrations are often performed poorly. We have conducted an audit to assess the appropriateness of digoxin therapeutic drug monitoring in Christchurch Hospital. METHODS: One hundred consecutive requests for digoxin concentrations in Christchurch Hospital inpatients were assessed. The case notes and hospital medication records were reviewed to determine the indication for testing, the appropriateness of the sampling time and of the subsequent alteration to dosing. RESULTS: In 53% of requests no clear indication for digoxin therapeutic drug monitoring (TDM) could be determined. In the remainder, 'suspected toxicity' accounted for 31% and 'therapeutic failure' for 16%. Samples were inappropriately taken within eight hours post-dose in 32% of requests. In 19% of cases, the samples did not reflect steady-state conditions. In 5% of occasions, the subsequent decision regarding dose adjustment was felt to be clearly inappropriate, and there was uncertainty regarding appropriateness in some other cases. Overall, in only 29% of requests was TDM performed appropriately with regard to indication, sampling and subsequent dose alteration. CONCLUSIONS: At Christchurch Hospital, the practice of TDM for digoxin is often inappropriate. It would seem that medical staff education is required to improve this practice.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

Current perspectives on intravenous administration of digoxin.

Cardiac glycosides were used as early as the first century A.D. The most commonly prescribed compound of this family is digoxin, because of its relatively short half-life. Intravenous digoxin has high utility 1) for instances in which digitalization must be rapidly accomplished; 2) when oral digitalization is not feasible; and/or 3) as augmentation therapy to other medication protocols. Myocardial uptake of I.V. digoxin is rapid and extensive; yet, serum half-life is approximately 34 hours, the same as in oral administration. Intravenous digoxin can be administered in divided doses every 4 to 8 hours, the 24-hour dose not to exceed 1.0 mg for a 155-pound, or 70.0-kg patient. Awareness of risk factors along with state-of-the-art technology can improve ongoing monitoring of the patient receiving I.V. digoxin.

Digoxin↗
PubMed1992

Results of the multicenter evaluation of a novel homogeneous immunoassay for digoxin based on the cloned enzyme donor immunoassay technology.

A new CEDIA assay for the measurement of digoxin in serum on random access analyzers was evaluated by twelve laboratories in Europe and the United States. Studies on the analytical range, reproducibility, calibration stability, recovery in controls, interlaboratory comparability, comparability with routine methods, and the effect of various interfering factors have been performed and the results are presented in this paper. The analytical performance was comparable to that of routine methods provided the manual pipetting step for pre-incubation was performed with accurate pipettes. A major advantage of the CEDIA Digoxin assay in terms of convenience is the simple two-point calibration procedure. Moreover, digoxin can be determined within 15 minutes after receiving the samples on random access analyzers like Boehringer Mannheim/Hitachi analysis systems. Thus, the CEDIA Digoxin assay represents an attractive alternative to the measurement of digoxin on dedicated immunochemical assay systems.

Calibration↗