digoxin and Heart-Diseases

Heart failure (HF) is a leading cause of morbidity and mortality. Appropriate medical therapy using angiotensin converting enzyme inhibitors and beta-blockers improves outcomes in HF, whereas the role of digoxin is still not clearly defined. Digoxin is currently recommended for patients with HF who are symptomatic despite standard therapy and for controlling the ventricular rate in atrial fibrillation. Digoxin is a time-tested drug that accounts for 20 million drug prescriptions annually in the United States. It has favorable hemodynamic effects for patients with HF and atrial tachyarrhythmias. We conducted a systematic literature search for the current indications for digoxin. Despite extensive research and safety data, the literature suggests that digoxin is underused in clinical settings. Citing the literature where available, our review highlights the various clinical settings where digoxin is indicated. Despite difficulties with designing prospective studies in acute HF settings and lack of outcomes data, we believe that digoxin will continue to serve an important role in optimizing care in certain acute and chronic cardiac conditions.

Topics: Cardiotonic Agents; Digoxin; Heart; Heart Diseases; Humans; Hypertension, Pulmonary; Vascular Diseases

Because of the common use of digoxin and because of its narrow therapeutic index, digoxin toxicity has been prevalent historically and, therefore, most clinicians are well aware of the classical dose/concentration-related signs and symptoms of toxicity. Yet, in the modern era the incidence of digoxin toxicity has been declining for a variety of reasons, including a new (lower) therapeutic range, the development of more effective drug therapies for heart failure, and more accurate dosing methods. In addition, digoxin toxicity, once commonly fatal, can now be quickly and effectively treated by the emergency administration of antidigoxin Fab fragments. Indeed, it may be possible to expand the use of Fab fragments to select patients with non-life-threatening digoxin toxicity, in order to save costs and improve patient comfort. Most cases of digoxin toxicity are caused by inappropriately high dosages, which are usually prescribed in the setting of renal dysfunction, while other cases can be attributed to system errors such as multiple prescriptions, poor patient counseling, or errors in transcribing. With modern computerized prescribing systems, such as direct physician order entry and prompts that alert the clinician to the potential for error, it is possible to decrease the incidence of digoxin toxicity even further. A realistic goal is to nearly eradicate once commonplace digoxin toxicity or at least make its occurrence a rare event.

Topics: Adverse Drug Reaction Reporting Systems; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Heart Diseases; Humans

Endoxin is a factor with a digitalis-like biological activity. It is a Na+ pump inhibitor and may be an endogenous medium of digitalis receptor. There are abnormal plasma levels of endoxin in some pathophysiologic states such as hypertension, acute myocardial infarction, arrhythmia, heart failure, etc. Some studies have demonstrated that the abnormal endoxin levels may be implicated in pathogenesis of these diseases or pathophysiologic process involved. Therefore, to clarify the effects of endoxin has much significance in understanding pathogenesis, prevention and treatment of hypertension and other cardiovascular diseases.

Topics: Animals; Cardenolides; Cardiomegaly; Cardiovascular System; Diabetes Mellitus; Digoxin; Enzyme Inhibitors; Heart Diseases; Heart Failure; Humans; Hypertension; Myocardial Infarction; Pulmonary Heart Disease; Saponins; Sodium-Potassium-Exchanging ATPase

Topics: Animals; Anti-Arrhythmia Agents; Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Dog Diseases; Dogs; Heart Diseases; Humans

Treatment of chronic heart failure (CHF) remains a major medical problem. Although in the last decades the benefits of several therapies in different patient populations with left ventricular dysfunction have been established, morbidity and mortality of CHF patients are high. Consequently, in the last decade improvement of survival has become the primary therapeutic endpoint in CHF studies, and the evaluation of the influence of (new) drugs on mortality has become crucial. In the present article an overview of the large mortality trials is given, and the shifts and alterations in the drug treatment strategy of CHF are discussed.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Chronic Disease; Digoxin; Diuretics; Heart Diseases; Humans; Phosphodiesterase Inhibitors; Prognosis; Quality of Life; Stroke Volume; Survival Analysis

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Digoxin; Drug Interactions; Heart Diseases; Humans

Monoclonal antibody technology has resulted in an entirely new class of agents, which have been applied to a variety of problems in cardiology and which hold great promise for future diagnostic, as well as therapeutic, applications. The four antibodies, which have been most widely used in clinical cardiology, are Digibind, OKT3, Myoscint, and 7E3. Each demonstrates the unique potential for the use of antibodies in clinical cardiology.

Topics: Antibodies; Antibodies, Monoclonal; Blood Platelets; Digoxin; Graft Rejection; Heart Diseases; Heart Transplantation; Humans; Muromonab-CD3; Myocardial Infarction; Myocarditis; Myosins; Radionuclide Imaging; Receptors, Antigen, T-Cell

Topics: Digoxin; Drug Interactions; Heart Diseases; Humans

In this article literature concerning the major drugs used in the treatment of heart failure is reviewed. Because of major discrepancies in results from short term and uncontrolled studies versus long term randomised control trials, only the latter group of studies are addressed in detail. Of 3 randomised control trials of digoxin, 1 has been positive, and 2 negative. Digoxin is probably of benefit to a minority of heart failure patients. Four randomised control trials of oral nitrates have shown a reduction in left ventricular filling pressure, and trends favouring active treatment for the indices of exercise capacity and functional status. Of 2 randomised control trials of hydralazine one is totally negative, the other difficult to interpret because of major loss of patients to followup. Of 5 trials of quinazolone derivatives (prazosin and trimazosin), 2 have been positive, 2 showed non-statistically significant trends favouring active treatment, and 1 was completely negative. These results are consistent with a modest benefit of prazosin and trimazosin in some heart failure patients. Five trials of angiotensin-converting enzyme inhibitors (captopril and enalapril) have shown dramatic and consistent benefit in exercise capacity and functional status. These results support a clinical policy of initial treatment with diuretics and addition of either captopril or enalapril for patients who remain symptomatic on optimal diuretic therapy. A trial of digoxin is warranted in patients whose functional capacity remains reduced on this regimen.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Diuretics; Heart Diseases; Humans; Hydralazine; Nitrates; Piperazines; Prazosin; Pyridines; Research Design

Antibodies, long used as discriminating tools in immunoassay, are now being used in vivo, both in diagnosis and therapy. In cardiovascular medicine, applications that have reached the stage of clinical trial include the reversal of digitalis intoxication by digoxin-specific antibodies and the imaging of cardiac necrosis with monoclonal myosin-specific antibodies. An exciting future prospect, still in an early experimental stage, is the application of fibrin-specific monoclonal antibodies to both the visualization of thrombi and emboli and the targeting of fibrinolytic agents.

Topics: Adolescent; Adult; Animals; Antibodies, Monoclonal; Cells, Cultured; Child; Child, Preschool; Clinical Trials as Topic; Digoxin; Dogs; Fibrinolytic Agents; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Infant; Male; Myocardial Infarction; Myocardium; Myosins; Necrosis; Rabbits; Thrombosis

Topics: Angina Pectoris; Arrhythmias, Cardiac; Calcium Channel Blockers; Coronary Vasospasm; Digoxin; Diltiazem; Heart Block; Heart Diseases; Heart Rate; Humans; Hypertension; Nifedipine; Verapamil

Fluid movement from the pulmonary capillaries into the interstitial space occurs continuously and is drained by the lymphatics. With increased leakage or decreased clearance, excessive extravascular lung water accumulates, initially as interstitial edema and subsequently as alveolar edema. The most common cause of pulmonary edema is an increase in microvascular hydrostatic pressure. An increased permeability of the capillaries is the other mechanism of production of pulmonary edema. An acute, critical reduction in colloid osmotic pressure may play a contributory role in pulmonary edema even at normal hydrostatic pressures. Dyspnea, diaphoresis, and anxiety characterize the clinical picture. A history of heart disease and congestive heart failure may be present in CPE, whereas evidence of an inciting event or disease process suggests NCPE. Hypoxia, decreased lung compliance, and increased shunt fraction are seen in both types of pulmonary edema, but the duration of pulmonary edema tends to be more severe and prolonged in NCPE. Evidence of increased permeability in NCPE distinguishes it from CPE. Clinically, this is assumed when pulmonary edema is demonstrated at normal PCWP and when edema fluid protein concentration and COP are close to those of plasma. The management of pulmonary edema consists of the improvement of gas exchange by methods that range from supplemental oxygen administration to mechanical ventilatory support with PEEP, depending on the severity of the disturbance in lung function. Improvement in myocardial function and a decrease in pulmonary congestion are accomplished with diuretics and morphine; in those patients who do not respond to this therapy, manipulation of preload, afterload, and myocardial contractility by vasodilators and inotropic agents may be required. In acute pulmonary edema, intravenously administered agents with a short half-life and rapid onset of action are preferred. The role of colloids in the treatment of pulmonary edema is controversial. The indications for the use of corticosteroids in ARDS are controversial, and an optimum dose has not been determined. Many clinicians tend to choose steroids to treat these patients, but the value of these agents in this setting awaits the results of controlled trials now under way.

Topics: Adrenal Cortex Hormones; Bloodletting; Capillary Permeability; Digoxin; Diuretics; Dobutamine; Dopamine; Emergencies; Heart Diseases; Humans; Hydrostatic Pressure; Lung; Morphine; Nitroglycerin; Nitroprusside; Osmotic Pressure; Plasmapheresis; Posture; Pulmonary Edema; Respiration, Artificial; Tourniquets; Vasodilator Agents

Topics: Arrhythmias, Cardiac; Digoxin; Drug Synergism; Heart Diseases; Humans; Poisoning; Potassium; Vision Tests

Topics: Adolescent; Captopril; Cardiomyopathies; Child; Digoxin; Dobutamine; Dopamine; Echocardiography; Electrocardiography; Endocarditis, Bacterial; Furosemide; Heart; Heart Defects, Congenital; Heart Diseases; Heart Failure; Humans; Hydralazine; Isoproterenol; Nitroprusside; Physical Examination; Radionuclide Imaging; Rheumatic Heart Disease

Topics: Adult; Amino Acids; Cardiac Output; Cardiovascular System; Cells; Digoxin; Energy Intake; Energy Metabolism; Female; Heart Diseases; Humans; Infections; Intubation; Metabolic Diseases; Multiple Organ Failure; Myocardium; Positive-Pressure Respiration; Probability; Respiratory Insufficiency; Vascular Resistance

The clinical and laboratory findings in and the treatment of congestive heart failure, supraventricular tachycardia, pericardial disease, and hypoxemic spells are discussed.

Topics: Child; Child, Preschool; Digoxin; Emergencies; Heart Diseases; Heart Failure; Humans; Hypoxia; Infant; Infant, Newborn; Pericarditis; Tachycardia, Paroxysmal

Topics: Digoxin; Drug Interactions; Half-Life; Heart Diseases; Humans; Intestinal Absorption; Kinetics

0.3 mg/day betamethyldigoxin was given per os in three daily administrations to 8 healthy subjects, and 8 compensated and 8 decompensated heart patients. Prior to the treatment, and 6 hr after the last administration, blood digoxin values were determined radio-immunologically, together with cardiac output, systolic stroke volume, cardiac index (dilution of indocyanine green), and systolic time intervals, by simultaneous recording of the ECG, carotid pulse, and the phonocardiogram. No significant change in output, stroke volume and cardiac index was noted in the healthy subjects, whereas these parameters were distinctly improved in the decompensated patients. Changes in the systolic intervals after treatment were significant in all cases though there was no significant correlation with the blood digoxin levels reached. In particular, the healthy and compensated subjects displayed a reduction in the corrected electromechanical systole (delta Q-S2), the corrected pre-ejection period (delta PEP), the corrected left ventricular ejection time (delta LVET), and their ratio (PEP/LVET), whereas in the decompensated patients the picture differed to the extent that the LVET increased owing to an augment-systolic stroke volume, the other parameters being reduced. In the healthy subjects, the polygraphic data were normal prior to the treatment, while in the compensated patients delta PEP and the PEP/LVET ratio were enhanced, and the delta LVET was less than in the normal subjects. It is felt that recording of the systolic intervals may be regarded as a sound method, owing to its simplicity and its ability to demonstrate latent cardiac failure before haemodynamic changes appear. Simultaneous determination of serum digoxin and the polygraphic data, therefore, opens the way to the commencement of appropriate, safe and timely management of as yet non-decompensated heart patients.

Topics: Adult; Aged; Cardiac Output; Cardiovascular System; Carotid Arteries; Digoxin; Electrocardiography; Heart Diseases; Hemodynamics; Humans; Male; Medigoxin; Middle Aged; Myocardial Contraction; Phonocardiography; Pulse; Stroke Volume; Systole

The authors refer to the technique of the serum digoxin enzyme immunoassay, and they report the results of 297 dosages concerning 111 hospitalized patients. The normal plasmatic rates are of 1,4 +/- 0,6 microgram/l in patients who present no sign of digitalic overdosage. The rates are of 5,2 +/- 1,6 microgram/l in cases of intoxication. The difference between these rates is greatly significant (p less than 0.001). The limit between therapeutic and toxic rates is situated around 3 microgram/l with an overlapping from 2 to 3 microgram/l. Authors then examine the individual factors that intervene in digoxin metabolism and especially study the influence of age, myocardic factors and renal insufficiency. On the basis of these results and review of the literature, they emphasize the interest of serum digoxin determination in the diagnosis of digitalis toxicity, as well as in the management of high risk patients, and of cardiopathies difficult to stabilize.

Topics: Aged; Aging; Digoxin; Electrolytes; Enzyme-Linked Immunosorbent Assay; Heart Diseases; Humans; Kidney Failure, Chronic; Middle Aged; Myocardium

Topics: Biological Availability; Cardiovascular Agents; Digoxin; Half-Life; Heart Diseases; Humans; Kinetics; Lidocaine; Models, Biological; Procainamide; Propranolol; Quinidine

Topics: Biological Availability; Digoxin; Heart Diseases; Humans; Intestinal Absorption

Topics: Age Factors; Aged; Blood Pressure; Blood Proteins; Body Weight; Coronary Disease; Digoxin; Electrolytes; Female; Heart Diseases; Heart Rate; Humans; Kidney Function Tests; Male; Middle Aged

Topics: Animals; Biological Availability; Cats; Digoxin; Drug Evaluation; Half-Life; Heart Diseases; Humans; Myocardial Contraction

Topics: Animals; Cardiomyopathies; Cat Diseases; Cats; Diet, Sodium-Restricted; Digoxin; Electrocardiography; Furosemide; Heart Diseases; Heart Failure; Lidocaine; Propranolol; Thromboembolism

Topics: Blood Specimen Collection; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Drug Resistance; Heart Diseases; Humans; Kidney Diseases; Radioimmunoassay

Digoxin rapidly crosses the placenta and reaches equilibrium, with maternal and fetal sera having equal concentrations. Virtually nothing is known about the effects of transplacentally administered digoxin on the fetus. Toxicity has been reported in the fetus of a woman ingesting a huge overdose of digitoxin; the same result would be anticipated with digoxin poisoning. Serum levels in pregnant women receiving the standard dose of 0.25 mg tend to be subnormal and certain patients may require a small increase in dose during the last trimester. While the full-term neonate appears to tolerate relatively high doses and the resultant high serum levels, there is no compelling evidence that such doses are necessary or even useful. Since toxicity can and does occur in neonates, especially during administration of loading (digitalizing) doses, it is recommended that maintenance doses of 0.01 mg per kg per day be used routinely. If the full inotropic effect is needed immediately, a loading dose of 0.03 mg per kg may be employed. Maintenance therapy is then begun on the following day. Without a loading dose cumulation occurs for about 3 days; after 5 or so days, serum levels will equal those found after use of a loading dose followed by maintenance therapy. Results of a single study suggest that the daily dose should be divided and given every 12 hours. After about 1 week of therapy, the serum level should be determined and the dose modified to maintain a serum level of 1 to 2 ng per ml. If the therapeutic effect is less than desired, a cautions increase in dose to as high as 0.02 mg per kg per day or to that dose which produces serum levels up to 3 ng per ml can be tried. Certain infants appear to tolerate serum levels of 3.5 to 4 ng per ml but such infants must be closely monitored. There are no data which indicate that a greater inotropic response will occur at these high serum levels, though this point has not been definitively investigated, and is the highest priority question for research. The intramuscular route should be researved for the unusual situation. Vomiting should be considered an early sign of toxicity and may act as a "safety valve." When adminstered in solution (as in the elixir or solution for intravenous use), oral digoxin is rapidly absorbed an an inotropic response is found within minutes, reaching a peak within hours, so that little is gained by parenteral administration. If an inotropic effect is urgently needed, intravenous administration o

Topics: Animals; Digitalis Glycosides; Digoxin; Female; Fetus; Heart; Heart Diseases; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy

Topics: Acute Disease; Aminophylline; Assisted Circulation; Cardiac Glycosides; Digoxin; Diuretics; Electric Countershock; Heart; Heart Diseases; Heart Failure; Humans; Morphine; Ouabain; Oxygen Inhalation Therapy; Phentolamine; Pulmonary Edema; Tachycardia; Vasodilator Agents

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiac Catheterization; Cardiac Surgical Procedures; Coronary Disease; Depression, Chemical; Digitalis; Digoxin; Heart; Heart Diseases; Humans; Injections, Intravenous; Ouabain; Phenytoin; Plants, Medicinal; Plants, Toxic; Ventricular Fibrillation

Topics: Administration, Oral; Animals; Biopharmaceutics; Cats; Digoxin; Guinea Pigs; Half-Life; Heart Diseases; Humans; Kidney; Kidney Diseases; Kinetics; Models, Theoretical; Protein Binding; Radioimmunoassay; Serum Albumin; Solutions; Tablets; Tritium; United Kingdom; United States

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Atrioventricular Node; Diagnosis, Differential; Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Heart Rate; Heart Ventricles; Humans; Myocardium; Poisoning; Radioimmunoassay

Topics: Creatinine; Digitalis Glycosides; Digitoxin; Digoxin; Glomerular Filtration Rate; Heart Diseases; Humans; Kinetics; Lanatosides

Topics: Animals; Antibody Formation; Antibody Specificity; Binding Sites, Antibody; Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Humans; Immune Sera; Rabbits; Radioimmunoassay

Topics: Age Factors; Arrhythmias, Cardiac; Calcium; Child; Coronary Care Units; Digitalis Glycosides; Digoxin; Electric Countershock; Electrocardiography; Endocrine System Diseases; Heart Diseases; Heart Failure; Heart Rate; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Liver Diseases; Lung Diseases; Magnesium; Obesity; Ouabain; Poisoning; Potassium; Psychophysiologic Disorders; Pulmonary Heart Disease; Thyroid Diseases; Time Factors

Topics: Aspartic Acid; Bufanolides; Cardanolides; Cardiac Glycosides; Digitoxin; Digoxin; Heart; Heart Diseases; Humans; Khellin; Lanatosides; Nitrites; Plants, Medicinal; Procainamide; Quinidine; Strophanthins; Sympatholytics; Sympathomimetics; Vasodilator Agents

We determined in vitro the potency of macrolides as P-glycoprotein inhibitors and tested in hospitalised patients whether coadministration of P-glycoprotein inhibitors leads to increased serum concentrations of the P-glycoprotein substrates digoxin and digitoxin.. In vitro, the effect of macrolides on polarised P-glycoprotein-mediated digoxin transport was investigated in Caco-2 cells. In a pharmacoepidemiological study, we analysed the serum digoxin and digitoxin concentrations with and without coadministration of P-glycoprotein inhibitors in hospitalised patients.. All macrolides inhibited P-glycoprotein-mediated digoxin transport, with concentrations producing 50% inhibition (IC(50)) values of 1.8, 4.1, 15.4, 21.8 and 22.7 micromol/L for telithromycin, clarithromycin, roxithromycin, azithromycin and erythromycin, respectively. Coadministration of P-glycoprotein inhibitors was associated with increased serum concentrations of digoxin (1.3 +/- 0.6 vs 0.9 +/- 0.5 ng/mL, p < 0.01). Moreover, patients receiving macrolides had higher serum concentrations of cardiac glycosides (p < 0.05).. Macrolides are potent inhibitors of P-glycoprotein. Drug interactions between P-glycoprotein inhibitors and substrates are likely to occur during hospitalisation.

Topics: Aged; Aged, 80 and over; Alanine Transaminase; Aspartate Aminotransferases; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bilirubin; Biological Transport; Caco-2 Cells; Creatinine; Digitoxin; Digoxin; Drug Interactions; Erythromycin; Female; Heart Diseases; Humans; Inpatients; Inulin; Ketolides; Macrolides; Male; Pharmacoepidemiology

We evaluated the effects of long-term digoxin therapy on exercise capacity and on physiological parameters reflecting autonomic tone in 23 patients with mild to moderate heart failure. Before and after maintenance digoxin treatment, all patients underwent cardiopulmonary exercise testing and indexes of heart rate variability (HRV) and baroreceptor sensitivity (BRS) were measured. Long-term digoxin therapy significantly (P < 0.05) increased time domain indexes (rMSSD, pNN50) which reflect parasympathetic activity (from 30 +/- 16 to 37 +/- 14 and from 8 +/- 9 to 12 +/- 7, respectively). High-frequency (HF) and low-frequency (LF) power spectral components also showed a significant increase (from 4.5 +/- 1 to 5.1 +/- 1 and from 5.4 +/- 1 to 5.8 +/- 1, respectively), but the ratio LF/HF decreased, indicating a predominance of vagal activity. The magnitude of these changes exhibited a strong negative Pearson correlation coefficient when compared with initial values before treatment. BRS increased from 2.95 +/- 1.2 to 5.32 +/- 3 ms/mmHg (P < 0.05). Oxygen consumption at peak exercise and at the anerobic threshold increased significantly (from 17 +/- 3 to 19 +/- 3 mL/kg/min and from 14.7 +/- 3 to 16.5 +/- 3 mL/kg/min, respectively). A persistent negative correlation was found between initial values of HRV and the magnitude of changes in exercise capacity. These findings show that long-term digoxin therapy increases vagal activity and improves exercise capacity in patients with mild to moderate heart failure and seems to exert a more marked therapeutic effect on patients with poorer initial autonomic function.

Topics: Aged; Cardiotonic Agents; Digoxin; Exercise Test; Exercise Tolerance; Female; Heart Diseases; Heart Rate; Humans; Male; Middle Aged; Pressoreceptors

Digoxin continues to be an important cause of drug toxicity. On the basis of a healthy volunteer study, activated charcoal has been proposed as a treatment for digoxin chronic intoxication. In order to evaluate the effect of activated charcoal on digoxin elimination in intoxicated patients during routine practice, we reviewed all Serum Digoxin Level Requests for adult in-patients from 1991 to 1993, with digoxin levels > 2.5 ng/ml. Of a total of 39 cases, 23 had been treated with activated charcoal while 16 had not. Digoxin elimination half-life during activated charcoal therapy was 36 h (S.D. 14 h; 95% C.I. 30-42 h) while in the non-treated group it was 68 h (S.D. 19 h, 95% C.I. 57-78). Calculated total body clearance of digoxin was 55 ml/min (S.D. 17 ml/min; 95% C.I. 45-64 ml/min) for the non-treated group versus 98 ml/min (S.D. 34 ml/min; 95% C.I. 83-113 ml/min) for the group receiving charcoal, representing an 78% increase in digoxin elimination.

Topics: Aged; Aged, 80 and over; Charcoal; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Inactivation, Metabolic; Male; Retrospective Studies

Because life-threatening digitalis intoxication is unusual in children, treatment with digoxin-specific-antibody Fab fragments (Fab) has rarely been reported. We describe the efficacy of Fab in the treatment of children with severe digitalis intoxication.. Twenty-nine children with intoxication due to digoxin (28) or digitoxin (1) received Fab at 21 participating hospitals between 1974 and 1986. Data were gathered about the patients' medical illnesses, doses and serum concentrations of digitalis, responses to Fab therapy, and outcomes.. In the infants and young children with acute digoxin intoxication, the digoxin doses ranged from 0.30 to 0.96 mg per kilogram of body weight; two adolescents had severe intoxication after doses of only 0.20 and 0.26 mg per kilogram. The serum digoxin concentrations ranged from 3.0 to greater than 100 ng per milliliter (mean, 13.8). Atrioventricular block (present in 22 patients [76 percent]) was the most common sign of toxicity. All the patients in this series had severe disturbances of cardiac rhythm, hyperkalemia (mean serum potassium concentration, 5.4 mmol per liter), or both. In 27 patients (93 percent), digitalis toxicity resolved after the administration of Fab. Of the 19 patients for whom data were available on the timing of the response to Fab, 15 responded within 180 minutes. Three patients required retreatment with Fab. Seven died of complications unrelated to the administration of Fab.. We recommend that Fab be used in the treatment of digitalis poisoning in infants and young children who have ingested greater than or equal to 0.3 mg of digoxin per kilogram, who have underlying heart disease, or who have a serum digoxin concentration of greater than or equal to 6.4 nmol per liter (greater than or equal to 5.0 ng per milliliter) in the elimination phase; and who also have a life-threatening arrhythmia, hemodynamic instability, hyperkalemia, or rapidly progressive toxicity. Adolescents, who are more sensitive to the toxic effects of digoxin than younger children, may require treatment with Fab after ingesting lower doses.

Topics: Acute Disease; Adolescent; Arrhythmias, Cardiac; Child, Preschool; Digitoxin; Digoxin; Female; Heart Block; Heart Diseases; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Infant; Infant, Newborn; Male; Poisoning

Intravenous digoxin, 1 mg, was administered over 8 hours to 10 cardiac patients with left ventricular (LV) dysfunction after coronary artery bypass grafting. The cardiovascular effects of digoxin were monitored over 20 hours by indwelling pulmonary artery and radial artery lines and were compared with those of a control group of 10 patients who had normal postoperative LV function. Digoxin administration produced an increased cardiac index and mean arterial blood pressure within 2 hours. Within 4 hours after digoxin administration pulmonary artery wedge pressure in patients receiving digoxin was significantly lower than in control patients. At 16 hours there was a significant increase in both the LV stroke work and LV stroke work index in patients receiving digoxin vs control patients. Two patients receiving digoxin and 3 control patients had changes in cardiac rhythm during the study. Thus, digoxin can be safely administered to postoperative patients with LV dysfunction and is an acceptable inotropic agent.

Topics: Arrhythmias, Cardiac; Cardiovascular System; Clinical Trials as Topic; Coronary Artery Bypass; Digoxin; Heart; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Pulmonary Wedge Pressure; Time Factors

In this article literature concerning the major drugs used in the treatment of heart failure is reviewed. Because of major discrepancies in results from short term and uncontrolled studies versus long term randomised control trials, only the latter group of studies are addressed in detail. Of 3 randomised control trials of digoxin, 1 has been positive, and 2 negative. Digoxin is probably of benefit to a minority of heart failure patients. Four randomised control trials of oral nitrates have shown a reduction in left ventricular filling pressure, and trends favouring active treatment for the indices of exercise capacity and functional status. Of 2 randomised control trials of hydralazine one is totally negative, the other difficult to interpret because of major loss of patients to followup. Of 5 trials of quinazolone derivatives (prazosin and trimazosin), 2 have been positive, 2 showed non-statistically significant trends favouring active treatment, and 1 was completely negative. These results are consistent with a modest benefit of prazosin and trimazosin in some heart failure patients. Five trials of angiotensin-converting enzyme inhibitors (captopril and enalapril) have shown dramatic and consistent benefit in exercise capacity and functional status. These results support a clinical policy of initial treatment with diuretics and addition of either captopril or enalapril for patients who remain symptomatic on optimal diuretic therapy. A trial of digoxin is warranted in patients whose functional capacity remains reduced on this regimen.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Diuretics; Heart Diseases; Humans; Hydralazine; Nitrates; Piperazines; Prazosin; Pyridines; Research Design

Antibodies, long used as discriminating tools in immunoassay, are now being used in vivo, both in diagnosis and therapy. In cardiovascular medicine, applications that have reached the stage of clinical trial include the reversal of digitalis intoxication by digoxin-specific antibodies and the imaging of cardiac necrosis with monoclonal myosin-specific antibodies. An exciting future prospect, still in an early experimental stage, is the application of fibrin-specific monoclonal antibodies to both the visualization of thrombi and emboli and the targeting of fibrinolytic agents.

Topics: Adolescent; Adult; Animals; Antibodies, Monoclonal; Cells, Cultured; Child; Child, Preschool; Clinical Trials as Topic; Digoxin; Dogs; Fibrinolytic Agents; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Infant; Male; Myocardial Infarction; Myocardium; Myosins; Necrosis; Rabbits; Thrombosis

Topics: Acetyldigoxins; Adult; Aged; Calcium; Clinical Trials as Topic; Digoxin; Female; Heart Diseases; Humans; Male; Medigoxin; Middle Aged; Potassium

Topics: Digoxin; Doxorubicin; Heart Diseases; Humans; Leukemia, Myeloid, Acute; Systole; Vitamin E

1 The influence of daily dosage frequency on drug compliance has been studied in 80 outpatients for whom maintenance digoxin 0.25 mg daily had been prescribed. 2 Each patient took one tablet (0.25 mg) daily, two tablets (0.125 mg) daily and four tablets (0.0625 mg) daily in randomised order for 2 month periods. 3 Compliance was assessed by tablet counting and by serial measurement of the plasma digoxin concentration. 4 Of the 67 patients (100%) who could have completed the study, 19 (28.4%) were withdrawal for a variety of reasons; in the majority these were consistent with gross non-compliance. 5 The remaining 48 patients (71.6%) took significantly more tablets when prescribed once daily (98.5 +/- 1.0% of the total) or twice daily (96.4 +/- 1.6%) than when given four times daily (92.2 +/- 1.9%). However, there were no significant differences between the plasma digoxin levels obtained at the three dosage frequencies. 6 We conclude that the small improvement in compliance with once or twice daily dosage was clinically unimportant. Dosage frequency did not appear to have a major influence on the grossly non-compliant patients.

Topics: Digoxin; Drug Administration Schedule; Female; Heart Diseases; Humans; Male; Middle Aged; Patient Compliance

A loading dose of digoxin (750 microgram) in two commercial formulations was administered to 14 patients with heart disease according to a crossover design. One formulation consisted of soft gelatin capsules containing a solution of digoxin; the other formulation was compressed tablets. All parameters investigated, i.e., serum peak height, time of the peak, area under the serum level--time curve (AUC), and area above the Q--S2I (electromechanical systole) decrease (obtained from polycardiographic evaluation), showed better bioavailability of digoxin capsules than tablets, averaging 36.3%. The better bioavailability of digoxin capsules than tablets seems to be more evident in heart disease patients than that encountered previously in healthy subjects. The AUC and the area above the Q-S2I decrease were linearly correlated only with digoxin capsules.

Topics: Adult; Biological Availability; Capsules; Clinical Trials as Topic; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Myocardial Contraction; Solubility; Systole; Tablets

Topics: Clinical Trials as Topic; Digitalis Glycosides; Digoxin; Heart Diseases; Humans

Topics: Adolescent; Adult; Blood Pressure; Cardiac Glycosides; Coronary Disease; Digoxin; Female; Heart Diseases; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Placebos; Pulmonary Artery; Time Factors

Topics: Adult; Aged; Clinical Trials as Topic; Digoxin; Drug Synergism; Female; Fructose; Fructosephosphates; Heart Diseases; Humans; Male; Middle Aged

Topics: Biological Availability; Clinical Trials as Topic; Digoxin; Dosage Forms; Heart Diseases; Humans

Topics: Clinical Trials as Topic; Digoxin; Heart Diseases; Rubidium

The results are reported from the observations on the activity of the semi-synthetic preparation beta-Methyl-Digoxin in 60 patients with chronic cardiac insufficiency. The conclusions are based on the data, obtained by a series of clinical and instrumental examinations, electro- and balistocardiography included, measurements of venous pressure, etc. The high efficiency and good tolerance of the preparation is stressed upon. It is stressed to be especially suitable for the treatment of patients with bradycardic form of chronic heart decompensation as well as in the treatment of cardiac cirrhosis.

Topics: Adult; Aged; Arrhythmias, Cardiac; Ballistocardiography; Bulgaria; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Evaluation; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged

Topics: Adult; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Coronary Disease; Digoxin; Evaluation Studies as Topic; Heart Diseases; Heart Failure; Humans; Middle Aged; Time Factors

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Digoxin; Drug Evaluation; Heart Diseases; Humans; Middle Aged

Topics: Administration, Oral; Age Factors; Aged; Body Weight; Creatinine; Digoxin; Electrocardiography; Female; Heart Block; Heart Diseases; Humans; Kidney; Male; Middle Aged; Radioimmunoassay; Sex Factors

Topics: Administration, Oral; Adult; Aged; Clinical Trials as Topic; Digoxin; Edema; Female; Heart Diseases; Heart Rate; Humans; Injections, Intravenous; Intestinal Absorption; Male; Middle Aged

Topics: Cardiac Glycosides; Clinical Trials as Topic; Digoxin; Female; Heart Diseases; Humans; Male

Topics: Administration, Oral; Adult; Aged; Digoxin; Heart Diseases; Humans; Middle Aged; Time Factors

Topics: Aged; Bradycardia; Clinical Trials as Topic; Digoxin; Female; Heart Diseases; Heart Valve Diseases; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Pulmonary Edema; Pulmonary Heart Disease; Sclerosis

Topics: Clinical Trials as Topic; Coronary Disease; Digitoxin; Digoxin; Electrocardiography; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Strophanthins

Topics: Aged; Clinical Trials as Topic; Coronary Disease; Digoxin; Female; Heart Diseases; Humans; Hypertension; Male; Pulmonary Heart Disease; Rheumatic Heart Disease; Tachycardia, Paroxysmal

Topics: Cardiac Glycosides; Digoxin; Heart Diseases; Humans

Heart diseases are known as the most primary causes of mortality worldwide. Although many therapeutic approaches and medications are proposed for these diseases, the identification of novel therapeutics in fatal heart conditions is promptly demanded. Besides, the interplay between gene expression data and molecular docking provides several novel insights to discover more effective and specific drugs for the treatment of the diseases. This study aimed to discover potent therapeutic drugs in the heart diseases based on the expression profile of heart-specific genes exclusively. Initially, the heart-specific and highly expressed genes were identified by comparing the gene expression profile of different body tissues. Subsequently, the druggable-genes were identified using in silico techniques. The interaction between these druggable genes with more than 1600 FDA approved drugs was then investigated using the molecular docking simulation. By comprehensively analyzing RNA-sequencing data obtained from 949 normal tissue samples, 48 heart-specific genes were identified in both the heart development and function. Notably, of these, 24 heart-specific genes were capable to be considered as druggable genes, among which only MYBPC3, MYLK3, and SCN5A genes entered the molecular docking process due to their functions. Afterward, the pharmacokinetics properties of top 10 ligands with the highest binding affinity for these proteins were studied. Accordingly, methylergonovine, fosaprepitant, pralatrexate, daunorubicin, glecaprevir, digoxin, and venetoclax drugs were competent, in order to interact with the target proteins perfectly. It was shown that these medications can be used as specific drugs for the treatment of heart diseases after fulfilling further experiments in this regard.

Topics: Aminoisobutyric Acids; Aminopterin; Bridged Bicyclo Compounds, Heterocyclic; Cyclopropanes; Daunorubicin; Digoxin; Drug Repositioning; Gene Expression; Heart Diseases; Humans; Lactams, Macrocyclic; Leucine; Ligands; Methylergonovine; Molecular Docking Simulation; Morpholines; Proline; Quinoxalines; Sulfonamides

Topics: Animals; Antioxidants; Cardenolides; Cardiotoxicity; Digoxin; Dose-Response Relationship, Drug; Heart; Heart Diseases; Heart Rate; Male; Myocytes, Cardiac; Necrosis; Ouabain; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species; Ventricular Remodeling

Topics: Aged, 80 and over; Antineoplastic Agents; Benzamides; Cardiovascular Agents; Digoxin; Drug Monitoring; Heart Diseases; Humans; Immunoassay; Luminescent Measurements; Male; Middle Aged; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms

Regulator of G protein signaling (RGS) proteins have emerged as novel drug targets since their discovery almost two decades ago. RGS2 has received particular interest in cardiovascular research due to its role in regulating Gqsignaling in the heart and vascular smooth muscle. RGS2(-/-)mice are hypertensive, prone to heart failure, and display accelerated kidney fibrosis. RGS2 is rapidly degraded through the proteasome, and human mutations leading to accelerated RGS2 protein degradation correlate with hypertension. Hence, stabilizing RGS2 protein expression could be a novel route in treating cardiovascular disease. We previously identified cardiotonic steroids, including digoxin, as selective stabilizers of RGS2 protein in vitro. In the current study we investigated the functional effects of digoxin-mediated RGS2 protein stabilization in vivo. Using freshly isolated myocytes from wild-type and RGS2(-/-)mice treated with vehicle or low-dose digoxin (2µg/kg/day for 7 days) we demonstrated that agonist-induced cAMP levels and cardiomyocyte contractility was inhibited by digoxin in wild-type but not in RGS2(-/-)mice. This inhibition was accompanied by an increase in RGS2 protein levels in cardiomyocytes as well as in whole heart tissue. Furthermore, digoxin had protective effects in a model of cardiac injury in wild-type mice and this protection was lost in RGS2(-/-)mice. Digoxin is the oldest known therapy for heart failure; however, beyond its activity at the Na(+)/K(+)-ATPase, the exact mechanism of action is not known. The current study adds a novel mechanism, whereby through stabilizing RGS2 protein levels digoxin could exert its protective effects in the failing heart.

Topics: Animals; Cardiotonic Agents; Cyclic AMP; Digoxin; Heart Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Contraction; Myocytes, Cardiac; Receptors, G-Protein-Coupled; RGS Proteins; Sodium-Potassium-Exchanging ATPase; Up-Regulation

Digoxin use is associated with increased incidence of breast and uterus cancers. We postulated that digoxin use might affect tumor characteristics and increase relapse risk in women with breast cancer.. Incident breast cancer cases in Danish women (n = 49,312; 1995 to 2008) were identified. Analyses were conducted in women 20 to 74 years old. Relapse hazard ratios (HR) were compared in women using and not using digoxin, adjusting for age, calendar period, protocol, tumor size, nodal involvement, histology grade, estrogen-receptor (ER) status, and anti-estrogen therapy in Cox regression models.. At diagnosis, tumors in digoxin users were more likely ER+ (85.4% vs. 78.6%: P = 0.002) and have grade 1 ductal histology (37.2% vs. 25.7%; P = 0.004), compared to non-users. 45 relapses occurred in women already using digoxin at breast cancer diagnosis (1,487 person-years); 24 relapses occurred in women later starting digoxin (384 person-years). Overall relapse risk HR in digoxin users was 1.13 (95% confidence interval: 0.88, 1.46) compared to non-users. Relapse risk in digoxin users was significantly increased in the first year (2.19; 1.26, 3.78) but not thereafter (0.99; 0.74, 1.32) (P = 0.02 for difference in HRs). First-year relapse hazard was high in digoxin-using women with ER+ tumors (2.51; 1.39, 4.55) but not ER- tumors (0.72; 0.10, 5.27). Recurrence hazard was not significantly changed among digoxin-using women also using tamoxifen.. Breast cancers arising in digoxin-using women had better prognostic features. After adjustment for markers, overall breast cancer relapse risk in digoxin users was not increased significantly, although recurrence hazards for ER+ tumors were higher in the first year following diagnosis.

Topics: Adult; Aged; Aromatase Inhibitors; Breast Neoplasms; Denmark; Digoxin; Female; Heart Diseases; Humans; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Receptors, Estrogen; Risk Factors; Tamoxifen

Topics: Adrenergic beta-Agonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzazepines; Digoxin; Diltiazem; Heart Diseases; Heart Rate; Humans; Hypertension; Ivabradine; Verapamil

Topics: Aged; Digoxin; Female; Heart Diseases; Humans; Male; Retrospective Studies; Time Factors

A retrospective study of 147 consecutive cases of suicidal digoxin poisoning was undertaken in order to determine the severity and outcome of toxicity without use of digoxin-specific Fab fragments. This study showed that suicidal digoxin poisoning in young patients is usually mild to moderate; even underlying cardiac disease and chronic use of digoxin has no effect on the severity of toxicity and incidence of lethal dysrhythmia in these cases. This type of toxicity responds appropriately to conventional treatment.

Topics: Adolescent; Adult; Digoxin; Electrocardiography; Female; Fluid Therapy; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Immunologic Factors; Iran; Male; Potassium; Retrospective Studies; Severity of Illness Index; Young Adult

Atrial thrombosis is a relatively rare event in children. We report a case of a newborn with AFI who after restoration of sinus rhythm, developed atrial thrombus on a prominent Chiari network floating between the right and left atrium through the patent foramen ovale. The thrombus was resolved following treatment with heparin without events.. Atrial stunning was proposed as a key mechanistic phenomenon because the thrombus occurred after the cardioversion of AFI to sinus rhythm. Heparin may be effective in the resolution of atrial thrombus within a few days.

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Flutter; Digoxin; Electrocardiography; Fibrinolytic Agents; Heart Atria; Heart Diseases; Heparin; Humans; Infant, Newborn; Male; Secondary Prevention; Thrombosis; Ultrasonography

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Creatinine; Cystatin C; Cystatins; Digoxin; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Heart Diseases; Humans; Male; Middle Aged; Monitoring, Physiologic

A chronically depressed 44-year-old man was rescued by the French medicalised ambulance service four hours after the ingestion of Nerium oleander leaves in a suicide attempt. Cardiotoxicity was evidenced by the presence of bradycardia with mental confusion and vomiting. The patient was empirically treated in the prehospital phase with a single dose of digoxin-specific Fab antibody fragments (Digidot). In spite of this treatment, the patient presented a new episode of important bradycardia (25 b/minute). Thereafter, the patient's rhythm stabilized and neurological signs and vomiting resolved. The patient recovered uneventfully and was discharged from the intensive care unit two days later.

Topics: Adult; Antibodies, Blocking; Bradycardia; Digoxin; Emergency Medical Services; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Male; Nerium; Suicide, Attempted; Vomiting

To better define the reported increased digitalis-like immunoreactive substances (DLIS) in neonatal plasma, we studied the relation among plasma DLIS level, blank intensity (BLK-I) value at FPIA measurement and plasma total bilirubin level.. The DLIS levels were measured in 10 neonates with or without jaundice and 10 infants in good health, using fluorescence polarization immunoassay (FPIA) and microparticle enzyme immunoassay (MEIA). BLK-I value and plasma total bilirubin level were also measured simultaneously.. In neonates with jaundice, DLIS using FPIA, BLK-I and total bilirubin level were 0.58 +/-0.13 ng/mL, 2598 +/- 408, and 17.98 +/- 1.13 mg/dL, respectively, before phototherapy, and 0.33 +/-0.06 ng/mL, 1886 +/- 237, and 15.16 +/- 2.07 mg/dL after phototherapy. Corresponding values in neonates without jaundice were (DLIS: 0.34 +/-0.04 ng/mL; BLK-I: 1,764 +/- 278; total bilirubin: 10.37 +/- 4.54 mg/dL); in healthy infants (0.12 +/-0.06 ng/mL, 400.7 +/- 4.6 and 0.42 +/- 0.13 mg/dL, respectively) and in healthy volunteers (0.10 +/-0.07 ng/mL, 403.1 +/- 8.4, and 0.58 +/- 0.30 mg/dL, respectively). Using MEIA, DLIS was not detected in 10 neonates, 10 infants and 20 healthy volunteers.. A fluorescent compound related to bilirubin increased the BLK-I value in the measurement of neonatal plasma using FPIA. The fluorescence was not the result of endogenous digitalis-like factors.

Topics: Bilirubin; Cardenolides; Cardiovascular Agents; Child, Preschool; Digoxin; Female; Fluorescence Polarization Immunoassay; Heart Diseases; Humans; Infant; Infant, Newborn; Jaundice; Male; Phototherapy; Reference Values; Saponins

(E,Z)-3-((2-Aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744) is a novel Na(+)/K(+) pump inhibitor with positive inotropic effects. Compared with digoxin in various experimental models, PST2744 was consistently found to be less arrhythmogenic, thus resulting in a significantly higher therapeutic index. The present work compares the electrophysiological effects of PST2744 and digoxin in guinea pig ventricular myocytes, with the aim to identify a mechanism for their different toxicity. The work showed that 1) the action potential was transiently prolonged and then similarly shortened by both agents; 2) the ratio between Na(+)/K(+) pump inhibition and inotropy was somewhat larger for PST2744 than for digoxin; 3) both agents accelerated inactivation of high-threshold Ca(2+) current (I(CaL)), without affecting its peak amplitude; 4) the transient inward current (I(TI)) induced by a Ca(2+) transient in the presence of complete Na(+)/K(+) pump blockade was inhibited (-43%) by PST2744 but not by digoxin; 5) the conductance of Na(+)/Ca(2+) exchanger current (I(NaCa)), recorded under Na(+)/K(+) pump blockade, was only slightly inhibited by PST2744 (-14%) and unaffected by digoxin; and 6) both agents inhibited delayed rectifier current I(Ks) (

Topics: Animals; Arrhythmias, Cardiac; Calcium Channels; Cardiotonic Agents; Cell Separation; Digoxin; Dose-Response Relationship, Drug; Electrophysiology; Enzyme Inhibitors; Etiocholanolone; Female; Guinea Pigs; Heart Diseases; In Vitro Techniques; Membrane Potentials; Myocardium; Potassium Channels, Inwardly Rectifying; Sodium-Potassium-Exchanging ATPase

The efficacy and safety of amiodarone in the management of atrial fibrillation (AF) or flutter in 108 Japanese patients with heart failure was retrospectively examined. Thirty-four (41%) of the 82 patients who were in sinus rhythm after 1 month of amiodarone administration had their first recurrence, 70% of cases occurring within 1 year of initiation. The cumulative rates of maintenance of sinus rhythm were 0.68, 0.55, and 0.47 at 1, 3, and 5 years, respectively. Amiodarone was more effective in maintaining sinus rhythm in patients with paroxysmal AF or flutter than in those with the persistent form (p<0.05). The cumulative rates for cases that remained in permanent AF were 0.04, 0.11, and 0.14 at 1, 3, and 5 years, respectively. Apart from suppressing AF, the mean heart rate during Holter monitoring was significantly decreased with amiodarone therapy in cases of permanent AF. Adverse effects requiring the discontinuation of amiodarone therapy occurred in 16% of patients. Low-dose amiodarone therapy may prevent AF or flutter in Japanese patients with heart failure.

Topics: Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Cause of Death; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Recurrence; Retrospective Studies; Survival Analysis; Tachycardia, Ventricular; Time Factors; Treatment Outcome

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Heart Diseases; Humans

Topics: Animals; Cardiotonic Agents; Digoxin; Dog Diseases; Dogs; Drug Monitoring; Heart Diseases

Topics: Aged; Anti-Bacterial Agents; Cardiotonic Agents; Clarithromycin; Digoxin; Diuretics; Drug Interactions; Furosemide; Heart Diseases; Humans; Male; Medication Errors; Memory

1. The Na+,K+-ATPase or Na+,K+-pump, mediating the active transport of Na+ and K+, which was first identified 40 years ago, is a central target for acute and long-term regulation, as well as for therapeutic intervention. Acute stimulation of the Na+,K+-pump in skeletal muscle by insulin, catecholamines, beta2-agonists or theophylline increases the intracellular uptake of K+ and accounts for the hypokalaemia elicited by these agents. Conversely, digitalis intoxication elicits hyperkalaemia via acute inhibition of the Na+, K+-pump. 2. Simple and accurate methods have been developed for the quantification of the total concentration of Na+,K+-pumps in small (0.5-5 mg) fresh or frozen biopsies of human skeletal muscle, myocardium or other tissues. This has allowed the identification of several long-term regulatory changes in the concentration of this transport system in human tissues. In skeletal muscle, upregulation is induced by training, thyroid hormones or glucocorticoids. Downregulation is seen in hypothyroidism, cardiac insufficiency, myotonic dystrophy, McArdle disease, K+ deficiency and after muscle inactivity. 3. Since the skeletal muscles contain one of the major pools of Na+,K+-pumps, these changes are important for the ability to counterregulate the hyperkalaemia elicited by exercise or the ingestion of K+. Moreover, downregulation or inhibition of the Na+, K+-pumps in skeletal muscle interferes with contractile performance. Since digitalis glycosides bind to the Na+,K+-pump, the muscles constitute a large distribution volume for these agents and are therefore an important determinant for their plasma level. 4. In cardiac insufficiency, the decrease in the concentration of Na+, K+-pumps in the myocardium is over a wide range correlated to the concomitant reduction in ejection fraction. The regulatory and pathophysiological changes in the activity and concentration of Na+, K+-pumps are important for the contractile function of skeletal muscle and heart as well as for K+ homoeostasis and the response to digitalization.

Topics: Animals; Digoxin; Enzyme Inhibitors; Heart Diseases; Humans; Muscle, Skeletal; Myocardium; Sodium-Potassium-Exchanging ATPase; Thyroid Hormones

This study attempted to identify which group of cardiac patients is most at risk when dental extractions are performed under a local anesthetic with a vasopressor.. Forty cardiac patients who had dental extractions under local anesthesia were connected to a Holter monitor for 24 hours, starting an hour before the procedure. The electrocardiogram was analyzed for the number of premature beats, ST depression, and cardiac rhythm. A mean rate was calculated for the first 2 hours after injection of the local anesthetic and for the subsequent 22 hours. The preoperative electrocardiogram was compared with the electrocardiogram performed 1 week before treatment.. Electrocardiographic changes were observed in 15 patients (37.5%), and all occurred during the first 2 hours after injection of the local anesthetic. Of the 15 patients, eight were being treated with digoxin.. Cardiac patients being treated with digoxin had more electrocardiographic changes after administration of a local anesthetic than other cardiac patients. When the local anesthetic contained a vasopressor, there was a greater incidence of tachycardia but less arrhythmia or ST depression.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Dental; Anesthetics, Local; Arrhythmias, Cardiac; Contraindications; Dental Care for Chronically Ill; Digoxin; Drug Interactions; Electrocardiography, Ambulatory; Epinephrine; Female; Heart Diseases; Humans; Lidocaine; Male; Middle Aged; Myocardial Ischemia; Tooth Extraction; Vasoconstrictor Agents

Topics: Animals; Creatinine; Digoxin; Dog Diseases; Dogs; Echocardiography; Electrocardiography; Heart; Heart Diseases; Heart Murmurs; Heart Rate; Lung; Male; Myocardium; Pulmonary Edema; Radiography; Syncope, Vasovagal; Urea

A group of 65 patients with acute infarction of myocardium (IM) who were not treated with digitalis preparations were subdued to examination to the presence of digitalis-like substances in their urine by means of radioimmuno-analytic method with use of anti-digoxin antibodies. The control group was constituted of 69 healthy subjects. Patients afflicted with IM had significantly increased concentrations of DLS in serum in comparison with health subjects. No significant relations of DLS to the activity of creatinkinase, IM localisation, occurrence of dysrhythmias, heart insufficiency and IM mortality were discovered. An increase in DLS in the blood of patients with acute IM probably coincides with a decreased cardiac output, with the activation of the stress axis and retention of sodium and fluids. The second examined group of patients was constituted of 20 subjects with other severe cardiopathies (inborn and acquired heart defects, chronic ischemic heart disease, inflammatory and degenerative diseases of the heart, and hypertension), who were subdued to catheter examinations. The authors discovered no significant differences of DLS concentrations in the blood during catheterization of individual compartments of inferior vena cava, superior vena cava, and the right ventricle. They were not successful in defining the particular site of DLS secretion on the basis of this examination. The authors pay attention to interaction of DLS during the radioimmuno-analytic examination of the digoxin serum concentration.

Topics: Adult; Aged; Aged, 80 and over; Blood Proteins; Cardenolides; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Myocardial Infarction; Saponins; Sodium-Potassium-Exchanging ATPase

Responses (473) were collated from a questionnaire sent to 5054 veterinarians in Australia enquiring about drug preferences for treating cardiac disease in dogs and cats. When treating a small breed dog with endocardiosis and mild left congestive heart failure, 74% of 472 respondents used a diuretic, 67% a theophylline derivative, 27% a vasodilator and 20% a positive inotrope. Frusemide was the preferred diuretic and digoxin the preferred inotrope, but vasodilator use varied. Low sodium diets were "often recommended" by 71% of respondents. Propranolol was preferred to diltiazem for treating feline hypertrophic cardiomyopathy. Digoxin was clearly preferred for treating supraventricular dysrhythmias, while lignocaine and digoxin were preferred equally for ventricular dysrhythmias. Respondents appeared more willing than US veterinarians to use theophylline derivatives and prasozin, and less inclined to employ nitrates, hydralazine, inotropes other than digoxin, and low sodium diets.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Australia; Cardiotonic Agents; Cardiovascular Agents; Cat Diseases; Cats; Digoxin; Diuretics; Dog Diseases; Dogs; Furosemide; Heart Diseases; Heart Failure; Lidocaine; Propranolol; Surveys and Questionnaires; Vasodilator Agents

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Bupivacaine; Digoxin; Drug Interactions; Heart Diseases; Humans; Resuscitation

Between January 1991 and August 1992, 62 singleton pregnancies with heart disease were managed at the Wadia Maternity Hospital, Bombay. In 51 (82.3%), the heart disease was of rheumatic origin, while in 11 (17.7%), the disease was nonrheumatic. Thirteen cases of rheumatic disease (25.4%) were graded as Class III or IV, as per New York Heart Association (NYHA) classification. Six cases with rheumatic disease had closed mitral commisurotomy done, while none had a prosthetic heart valve. There was no maternal mortality. The average birth weight of neonates born to mothers with Class III or IV rheumatic heart disease was significantly lower (p < 0.05) than the average noted in singleton, normal, uncomplicated, non high risk pregnancies, during this period. There was also a significant difference (p < 0.05) in birth weight between infants born to mothers with NYHA Class I or II and Class III or IV symptoms. No infant had a congenital heart disease. Our findings suggest that though the presence of maternal heart disease did not affect the perinatal outcome, all infants born to mothers with NYHA Class III or IV had intrauterine growth retardation.

Topics: Adult; Digoxin; Embryonic and Fetal Development; Female; Fetal Growth Retardation; Furosemide; Gestational Age; Heart Diseases; Humans; Infant, Low Birth Weight; Infant, Newborn; Mothers; Potassium; Pregnancy; Severity of Illness Index

An attempt has been made to investigate the cardiotoxicity of an interaction of Lead acetate (LA), Aminophylline (APH) and Digoxin (DGN), employing an isolated frog heart preparation. While DGN-Cardiotoxicity was potentiated by LA-preperfusion, it was antagonized by APH-preperfusion as revealed by data reflecting the mean DGN perfusion time (Sec) and mean DGN exposure (microgram/10 mg heart weight) for cardiac arrest. In an experimental group involving interaction of LA, DGN and APH, preperfusion of APH has significantly diminished but not fully abolished LA-induced potentiation of DGN-cardiotoxicity. On the other hand, perfusion of APH after LA resulted not only in annulment of LA-induced potentiation but also in an eventual residual protective effect of APH. It was striking that simultaneous preperfusion of APH and LA led to exacerbation of LA-induced potentiation. The results of this interaction study involving two widely prescribed cardioactive drugs, are considered to be of immense pharmaco-toxicological interest.

Topics: Aminophylline; Animals; Digoxin; Drug Interactions; Drug Synergism; Heart; Heart Diseases; In Vitro Techniques; Lead; Perfusion; Ranidae; Time Factors

The authors provided evidence that the pharmacokinetics of digoxin are influenced by daily rhythms. Using doses of 0.125 mg digoxin by the oral route, after 12 hours they found a statistically higher serum digoxin concentration in the minimum before administration of the morning dose and in the maximum concentration after this dose, as compared with the minimal and maximal concentration before and after administration of the same dose in the evening. The other pharmacokinetic parameters--the area beneath the curve of serum concentrations, the time before the maximum concentration was attained and the total plasma clearance of digoxin did not differ. This chrono-pharmacokinetic relationship in compensated cardiac patients was comparable with data in the literature pertaining to healthy volunteers. To conclude it may be said that on administration of major does in the morning there is a greater risk of serum concentrations beyond the therapeutic range than during the administration of the same amount of digoxin in the evening.

Topics: Aged; Circadian Rhythm; Digoxin; Drug Administration Schedule; Female; Heart Diseases; Humans; Male; Middle Aged

Topics: Adolescent; Computers; Digoxin; Equipment and Supplies; Heart Diseases; Humans; Male; Parents; Patient Compliance; Pediatrics; Phenytoin; Self Administration

1. Despite the fact that numerous studies provide evidence for the existence of an endogenous inhibitor of the cell membrane Na(+)-K+ pump in plasma, little is known about the relationships between this factor and the main haemodynamic parameters. 2. In order to shed some light on this, we attempted to correlate haemodynamic parameters, measured during heart catheterization in a group of 22 cardiopathic subjects, with plasma digitalis-like activity levels, determined by two different procedures. 3. The ability of plasma to inhibit a human renal Na(+)-K(+)-ATPase showed an inverse correlation with cardiac index and a direct correlation with peripheral resistance. Plasma cross-reactivity with digoxin antibodies correlated directly with left atrial pressure. 4. These results furnish confirmation of a number of theoretical assumptions which attribute to the digitalis-like factor the ability to modify the contractility of the cardiovascular system.

Topics: Adult; Aged; Antibodies; Biological Transport, Active; Blood Pressure; Blood Proteins; Cardenolides; Cardiac Catheterization; Digoxin; Female; Heart Diseases; Hemodynamics; Humans; Male; Middle Aged; Potassium; Saponins; Sodium; Sodium-Potassium-Exchanging ATPase; Vascular Resistance

Two patients with atrial fibrillation had abrupt onset of abdominal pain and massive small bowel distension suggesting mesenterial artery embolism. One patient had dilation of the left atrium and ventricle, the other a mitral value prolapse syndrome with a dilated left atrium. Both patients were treated conservatively and gradually recovered. A small bowel series performed several weeks after the acute episode showed loss of normal mucosa and narrowing of a long segment of the small bowel. A control examination in one patient one year later, still revealed jejunal mucosal abnormalities and stenosis, features similar to those occurring in Crohn's disease. Our observations suggest that analogous to ischemic colitis, an entity of acute ischemic small bowel enteritis exists. Mesenteric ischemia apparently can induce a clinical syndrome of "regional enteritis". The radiologic features should not be confused with those of Crohn's disease.

Topics: Aged; Anticoagulants; Digoxin; Heart Diseases; Humans; Intestinal Obstruction; Intestine, Small; Ischemia; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Radiography; Thrombosis

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Creatinine; Digitalis Glycosides; Digoxin; Drug Hypersensitivity; Female; Follow-Up Studies; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Skin Tests; Suicide, Attempted

Non-compliance has a major influence on the successful outcome of a therapeutic regimen. It also unnecessarily increases the costs of health care. In a study involving 137 outpatients receiving digoxin 55 patients (40%) were found to be non-compliant. Patients who experienced communication problems and who lacked a meaningful relationship with their doctor showed a marked deterioration in compliance. An applied pharmacokinetic approach was used to predict the serum digoxin concentration for each patient. The creatinine clearance was determined and the degree of severity of heart failure was assessed. Total body clearance was then calculated. The predicted concentration was also calculated and compared with the measured digoxin concentration enabling an objective assessment of compliance. Twenty-four of the non-compliant patients who had subtherapeutic levels of digoxin (less than 0.8 ng/ml) had signs of cardiac failure. Eighteen of these patients were receiving additional medication (1.7 +/- 0.5 items) for the treatment of cardiac failure.

Topics: Digoxin; Female; Heart Diseases; Humans; Male; Patient Compliance

Topics: Asthma; Digoxin; Drug Therapy; Heart Diseases; Humans; Theophylline

Topics: Child, Preschool; Digoxin; Drug Administration Schedule; Fatigue; Heart Diseases; Humans; Infant; Sleep

Topics: Adult; Aged; Combined Modality Therapy; Depression, Chemical; Digoxin; Heart Diseases; Heart Failure; Hemodynamics; Humans; Middle Aged; Pacemaker, Artificial; Stimulation, Chemical

We studied the inotropic response to dopamine and digoxin in 20 patients with severe sepsis and left ventricular failure. Left ventricular failure was defined as a left ventricular stroke work index less than or equal to 40 g.m/m2 at a pulmonary artery wedge pressure greater than or equal to 15 mm Hg. Hemodynamic assessment was obtained before and following administration of digoxin 10 micrograms/kg IV or dopamine, 5 to 12 micrograms/kg/min IV. Patients treated with digoxin demonstrated a significant increase in LVSWI. The LVSWI increased 13 +/- 10 percent in the dopamine-treated patients compared with 74 +/- 16 percent in the digoxin patients (p less than 0.02). We conclude that digoxin exhibited significant inotropic activity in patients with sepsis.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Blood Circulation; Digoxin; Dopamine; Female; Heart Diseases; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction

Cardiac patients are often on drugs. They invariably benefit from a rehabilitation programme where they may be seen more frequently than in a routine follow-up clinic. Rehabilitation units must keep alert for drug-induced adverse effects or symptomatic deterioration, as well as the more usual psychological and physical benefits they induce.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Calcium Channel Blockers; Cardiovascular Agents; Digoxin; Diuretics; Heart Diseases; Humans; Nitrates; Warfarin

Topics: Adult; Data Interpretation, Statistical; Digoxin; Echocardiography; Exercise; Female; Heart; Heart Diseases; Heart Ventricles; Humans; Male; Medigoxin; Middle Aged; Nifedipine; Propranolol; Stroke Volume

Topics: Digoxin; Heart Diseases; Humans; Monitoring, Physiologic

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.

Topics: Adult; Aged; Aged, 80 and over; Creatinine; Digoxin; Diltiazem; Drug Interactions; Female; Heart Diseases; Heart Rate; Humans; Male; Middle Aged

Quinidine syncope and factors associated with it are well known among adult patients treated for cardiac arrhythmias. To define factors that may influence the occurrence of syncope in children taking quinidine, the clinical, anatomic, electrocardiographic, roentgenographic and pharmacologic data were compared in six patients with syncope (Group A) and 22 patients without syncope (Group B). There was a significant (chi-square = 10.2, p = 0.001) relation between heart disease and quinidine syncope: all six Group A (syncopal) patients had heart disease whereas 15 of the 22 Group B (non-syncopal) patients had no structural heart disease. In contrast, no significant difference was noted between Group A and Group B patients in mean age (11.4 versus 11.4 years), mean quinidine serum concentration (2.9 versus 2.3 micrograms/ml), mean corrected QT interval before quinidine (0.43 versus 0.40 second) or mean corrected QT interval during quinidine therapy (0.46 versus 0.46 second) or between those taking digitalis and those not. Two of the six Group A (syncopal) patients died during therapy, one 6 days after initiating therapy and one suddenly at home 6 months after beginning quinidine. Another two of the six Group A patients exhibited hypokalemia (both 2.9 mEq/liter) at the time of syncope, 2 weeks and 6 months, respectively, after initiation of quinidine therapy; both survived. Syncope occurred within 8 days of initiation of quinidine therapy in three of the six patients. Sustained ventricular tachycardia was observed during quinidine associated arrhythmia in three of six patients with syncope; nonsustained ventricular tachycardia or complex ventricular ectopic activity while on this therapy was observed before syncope in the other three patients in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Child, Preschool; Digitoxin; Digoxin; Drug Administration Schedule; Electrocardiography; Heart Diseases; Hemodynamics; Humans; Quinidine; Syncope

Ten patients with an array of moderate to severe adverse effects resulting from digitalis were effectively treated by hemoperfusion through small columns which contained antidigoxin antibodies bound to polyacrolein microspheres in agarose macrospheres (APAMB). The procedure was well tolerated. There was no detectable damage to formed blood elements and no changes in electrolytes, liver enzymes, or other related biochemical parameters. Despite some theoretic considerations to the contrary, the removal of a relatively small load of digoxin resulted in amelioration of the clinical symptoms and ECG abnormalities associated with digitalis. No rebound phenomena of intoxication or posthemoperfusion increase in digoxin serum levels were noted over the subsequent 5 to 6 days. A further increase in the capacity of the columns may render this method a safe and convenient emergency procedure for patients with digitalis toxicity.

Topics: Acrolein; Aged; Aged, 80 and over; Antibodies; Biocompatible Materials; Digoxin; Female; Heart Diseases; Hemoperfusion; Humans; Male; Microspheres; Middle Aged; Polymers; Sepharose

Derivatives of dihydro-digitoxin (DHD) were studied in the search for a glycoside with a primarily extrarenal clearance and a faster elimination rate than digitoxin. The positive inotropic doses of the derivatives of DHD were higher than those of digitoxin and digoxin. There was no significant difference in the therapeutic margin. After injection of 3H-digoxin in unaesthetized cats, no metabolites were found in the serum which did not bind with the antibody used for the RIA. After injection of 3H-digitoxin and its derivatives, the radioactivity was cleared from the serum at a much lower rate than the concentrations assayed by RIA. The metabolites which did not bind to the digitoxin antibody were hydrophilic and had a low protein binding. Digitoxin-bisdigitoxoside (Dt-2) determined by RIA rapidly disappeared from the serum. The radioactivity remaining after 24 h was eliminated with a half-life of 219 h. Ten min after injection of DHD the serum contained no unchanged DHD, but 36% digitoxin suggesting that the reduction of digitoxin to DHD is reversible and that the conversion of DHD to Dt-2 is the rate limiting step in the metabolism of digitoxin. The total body clearance of digitoxin, its metabolites and derivatives determined by RIA increased in the order DHD-oxime less than or equal to digitoxin less than DHD less than or equal to DHD-acetyloxime less than DHD-methyloxime. The clearance and the elimination rate of DHD-methyloxime were significantly higher than those of digitoxin (P = 0.05).

Topics: Animals; Cats; Digitoxin; Digoxin; Electrocardiography; Female; Heart Diseases; Kinetics; Male; Myocardial Contraction; Protein Binding; Radioimmunoassay; Stimulation, Chemical

The concentration of digoxin-like immunoreactive substance was measured by immunoassay in umbilical venous blood from six normal and 19 fetuses with a variety of cardiac and noncardiac disorders. Fetal blood was obtained either by percutaneous umbilical blood sampling (n = 13) or at delivery (n = 12). Three women received digoxin for fetal indications. Healthy control fetuses had significantly less digoxin-like immunoreactive substance measured (mean concentration below the limit of the assay sensitivity) than was found in ill fetuses whose mothers received digoxin (p less than 0.005). However, the fetal concentrations of immunoreactive digoxin in fetuses with a cardiac abnormality were similar whether the mother had (0.93 +/- 0.4 ng/ml) or had not (1.27 +/- 0.4 ng/ml) received digoxin (p = 0.1452). Although there was a significant negative correlation between digoxin concentration and gestational age (R = -0.5079, p less than 0.01), the youngest fetuses examined were generally the sickest. The correlation with gestational age was not significant if the normal control fetuses were excluded. One fetus with a cardiac tachyarrhythmia was examined during and after transplacental therapy. There was no change. It is possible that previously measured "digoxin" in "treated" fetuses represents digoxin-like immunoreactive substance and that only small amounts of maternally administered digoxin actually reach the ill fetus. Our findings suggest that a randomized trial of maternal digitalization for the treatment of fetal supraventricular tachycardia is essential prior to its acceptance as effective therapy.

Topics: Blood Proteins; Cardenolides; Digoxin; Female; Fetal Blood; Fetal Diseases; Heart Diseases; Humans; Maternal-Fetal Exchange; Pregnancy; Saponins

A retrospective study of 5,100 patients on digoxin, with a four-week follow up after digoxin levels were measured, was done to determine the mortality rate. A significant increase in mortality was correlated with an increasing serum digoxin level, up to 50% at a level of 6.0 ng/mL and more. Clinical toxicity was suspected in only 0.25% of all patients on digoxin, although almost 10% had levels above the therapeutic range. Deliberate digoxin overdoses were fatal in 50% of cases. This study shows a correlation between increasing digoxin levels and increasing mortality rates. We recommend the use of serum digoxin measurements to identify those asymptomatic patients with elevated levels. The physician should seriously consider the indications for initiating or continuing digoxin treatment in any patient because of an increased mortality in patients with levels of more than 1.0 ng/mL.

Topics: Adult; Aged; Digoxin; Electrocardiography; Heart Diseases; Humans; Infant; Middle Aged; Mortality; Retrospective Studies; Suicide; Suicide, Attempted

In guinea-pigs intravenously infused with digoxin, prior immunization using a digoxin-human serum albumin conjugate increased by 3- and 2.4-fold, respectively, the digoxin doses causing the first signs of cardiotoxicity and death. At death, serum digoxin concentration was four times higher in immunized than in control animals. In the immunized guinea-pigs 50% of the serum digoxin was protein bound, presumably mainly to digoxin-specific antibodies, since in the controls the bound fraction was only 1-2%. Generally, tissue digoxin concentrations were not increased to the same extent as the lethal dose, and in the heart and lungs the increase was not significant. With cardiac (ventricle) subcellular fractions, there was no difference between control and immunized animals in the digoxin concentration of the 'microsomal' pellet. This subfraction contains the plasma membrane and the associated sodium pumps which are considered to be the sites at which the pharmacologically active digoxin binds. It seems likely, therefore, that the greater digoxin resistance in the immunized animals can be explained on the basis of reduced drug access to the site of action within the heart.

Topics: Animals; Digoxin; Female; Guinea Pigs; Heart Diseases; Immunization; Tissue Distribution

Digoxin toxicity occurs more commonly in aged than younger individuals. Cardioactive drugs such as quinidine effect digoxin pharmacokinetics so as to increase the potential for digoxin toxicity. The calcium-channel antagonists have become extensively used for cardiac disorders and are often co-administered with digoxin. Despite documented calcium-channel antagonist interactions with digoxin, clinically significant digoxin toxicity associated with their concurrent use is apparently unusual. Two elderly patients receiving digoxin and verapamil simultaneously are presented to demonstrate the clinical importance and potential danger of the concomitant use of these drugs.

Topics: Aged; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Kinetics; Quinidine; Verapamil

Swallow syncope is an often misdiagnosed rare disorder due to enhanced vagal tone during eating in patients with underlying esophageal and/or cardiac abnormalities. We present three cases of this disorder, one related to digitalis toxicity and the other two with diffuse esophageal spasm. The investigation, differential diagnosis, prognosis and management of swallow syncope are discussed.

Topics: Adult; Deglutition; Diagnosis, Differential; Digoxin; Epilepsy; Esophageal Diseases; Female; Heart Diseases; Humans; Male; Middle Aged; Propantheline; Syncope

Congestive heart failure in children is unusual as a presenting problem, and the nonspecific nature of the signs and symptoms in the pediatric population makes recognition difficult. Congenital heart disease is most common in the infant whereas older children most commonly develop congestive heart failure due to cardiomyopathy, myocarditis, electrolyte abnormalities, dysrhythmias, and, more rarely, endocarditis, and rheumatic carditis. Management focuses upon stabilization of the airway and ventilation while improving circulatory function. This is achieved by the use of inotropic agents, combined with attention to the volume and pressure overload, pulmonary problems, dysrhythmias, and ongoing follow-up.

Topics: Cardiotonic Agents; Digoxin; Diuretics; Heart Defects, Congenital; Heart Diseases; Heart Failure; Humans; Infant; Infant, Newborn; Pulmonary Edema; Respiration, Artificial

A major role of therapeutic drug monitoring services is to advise on the dose of a drug which would be required to bring the concentration in the blood to within specific 'therapeutic' limits. Monitoring digoxin usage constitutes a substantial part of the work load. We have examined the potential variability in recommendations for digoxin dosages based on a series of serum digoxin measurements in each of 80 out-patients. In over a third of cases a dose, which seemed to be optimal on the basis of the first assay result, would have produced concentrations outside the conventional therapeutic range when the measurement was repeated. This was despite careful supervision of medication and the timing of the blood sample in relation to its administration. In routine practice the apparent variability in dose requirements would be far greater. Objectives of therapeutic drug monitoring services remain the same, the way forward would seem to lie in their taking on a heavy commitment to counsel and supervise patients before repeated blood sampling. However, effort and resources might be better channelled into producing simple prescribing aids relating the risk of cardiotoxicity directly to the size of the maintenance dose and the individual's renal function.

Topics: Aged; Creatinine; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Monitoring, Physiologic; Probability

Digoxin is clinically useful as a cardiac antiarrhythmic and inotropic agent. Its antiarrhythmic actions are mediated through the cholinergic nervous system. The cholinergic system, when activated, can depress ventricular function. We have sought to further increase the cardiovascular effects of digoxin by blocking its cholinergic effects with atropine. Atropine, 1 mg intravenously, was given to 10 postoperative cardiac patients. The cardiovascular time course was monitored by an ECG, radial arterial line, and pulmonary artery thermodilution catheter for 8 hours. A significant increase (p less than 0.05) in the cardiac output (CO), from 5.98 +/- 0.24 L/min to 6.60 +/- 0.34 L/min, was evident within 2 hours after atropine administration. The CO returned to control levels by 6 hours. There were no significant changes in heart rate, systemic vascular resistance, pulmonary artery wedge pressure, or systemic blood pressure. The results indicate that the cholinergic blockade of digoxin with atropine will acutely increase the cardiac output in postoperative cardiac patients.

Topics: Atropine; Cardiac Output; Cardiovascular System; Digoxin; Heart Diseases; Heart Rate; Heart Ventricles; Hemodynamics; Humans; Male; Middle Aged; Postoperative Care

The importance of cardiovascular system involvement in hyperthyroidism has been recognized for many years. In the middle-aged and elderly patient, often with mild but prolonged elevation of plasma thyroid hormones, symptoms and signs of heart failure and complicating atrial fibrillation may dominate the clinical picture and mask the more classical endocrine manifestations of the disease. Pitfalls in diagnosis and the importance of early recognition and treatment are discussed. Despite experimental evidence for a short-term inotropic action of thyroid hormone excess, clinical data support the existence of a reversible cardiomyopathy in hyperthyroidism with impaired contractile reserve. Enhanced myocardial performance at rest primarily reflects the peripheral actions of thyroid hormone excess. Most, if not all, of the cardiac abnormalities return to normal once a euthyroid state has been achieved, although atrial fibrillation may persist in a minority. Optimum treatment requires rapid and definitive antithyroid therapy, usually using a large dose of radio-iodine, and rapid control of heart failure. Systemic anticoagulation is indicated in the presence of atrial fibrillation and should be continued until sinus rhythm has been present for at least three months, either spontaneously or after cardioversion.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiomyopathies; Digoxin; Drug Therapy, Combination; Heart Diseases; Heart Rate; Hemodynamics; Humans; Hyperthyroidism; Myocardial Contraction; Myocardial Infarction; Sympathetic Nervous System; Thyroid Function Tests; Thyroid Hormones

Topics: Adult; Aged; Digoxin; Heart Diseases; Humans; Middle Aged

The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and practical considerations must be attained before these drugs can be used effectively.

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Digoxin; Diuretics; Dobutamine; Dopamine; Drug Administration Schedule; Edema; Heart Diseases; Heart Failure; Heart Rate; Hemodynamics; Horse Diseases; Horses; Injections, Intravenous; Lidocaine; Procainamide; Propranolol; Quinidine

Topics: Aging; Animals; Blood Circulation; Body Temperature Regulation; Cardiac Output; Digitalis; Digoxin; Dopamine; Embryonic and Fetal Development; Fetal Heart; Heart Diseases; Humans; Infant, Newborn; Infant, Premature; Isoproterenol; Norepinephrine; Oxygen Consumption; Plants, Medicinal; Plants, Toxic; Sheep; Thyroid Hormones

During a nine-month period, July 1980 through March 1981, the mortality rate for patients on the cardiology ward of a children's hospital was 43.1 deaths per 10,000 patient-days, as compared with 11.0 deaths per 10,000 patient-days during the preceding 54 months. Twenty-five (76 per cent) of 33 infant deaths during this nine-month period occurred between midnight and 6:00 a.m., as compared with 1 of 10 infant deaths during a separate 27-month period (P less than 0.001). Although nearly all deaths occurred in patients with serious congenital heart disease, epidemic-period deaths were more likely to have an unexpected timing and a clinical pattern consistent with digoxin toxicity. In four patients, forensic and clinical digoxin measurements suggested that an intravenous overdose of digoxin had been administered shortly before death. Although a review of nursing schedules revealed a strong association (relative risk, 64.6) between infant deaths and the duty times of a particular nurse, the cause of the epidemic remains unclear. The study led to suggestions that the hospital strengthen central control over procedures for dispensing medicines and implement a system for monitoring the occurrence of deaths by time and place within the hospital.

Topics: Digoxin; Epidemiologic Methods; Forensic Medicine; Heart Diseases; Hospital Bed Capacity, 500 and over; Hospital Units; Hospitals, Pediatric; Hospitals, Special; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Medication Errors; Mortality; Ontario; Peer Review; Personnel Staffing and Scheduling; Risk; Space-Time Clustering; Time

Data on monthly totals of cardiac deaths in England and Wales were examined in different ways to see whether there were any unexplained fluctuations in rates both at the time of an unplanned increase in the bioavailability and therefore the potency of the Lanoxin brand of digoxin in May 1972 and also when there was a coordinated increase in the bioavailability of other brands in October 1975. Despite advice to prescribers, dosages were not proportionately reduced in the 600 000 patients who were on treatment. Monthly totals of deaths from cardiac causes were high through the summer of 1972 but not at the end of 1975 and the excess in 1972 seems to be related to a cold summer. There was no evidence of a consistent or specific effect of changes in digoxin potency, either beneficial or harmful, on deaths from all cardiac causes or in specific subgroups in which digoxin treatment was likely to be most common. Although major changes in digoxin potency in England and Wales did not seem to produce a repeatable effect on death rates, data from other countries should also be examined for evidence of such an effect.

Topics: Biological Availability; Digoxin; Dose-Response Relationship, Drug; England; Heart Diseases; Humans; Seasons; Temperature; Wales

The frequency of therapy with digitalis glycosides was determined in 4.143 patients on their first visit at a medical outpatient clinic. 508 (12.3%) patients said to take digitalis. Of 480 (94.5%) patients, a digoxin serum concentration was obtained. It was in 229 (47.7%) patients below, in 31 (6.5%) above, and in 220 (45.8%) within the therapeutic range (0.8-2.0 ng/ml). From the 251 patients with a serum digoxin concentration greater than or equal to 0.8 ng/ml, 220 (87.7%) were not included in a withdrawal trial on the basis of predetermined criteria, mainly because of cardiac diseases (52%). Digitalis therapy was withdrawn in 31 patients. 5 patients started to take the drug again on their own; they were considered drop-outs. In the remaining 26 patients, no symptoms of heart failure appeared during a 3-month observation period; in 2 patients, however, atrial fibrillation requiring intervention occurred. Our results confirm the frequent use of digitalis therapy in Germany, but also the frequent presence of subtherapeutic serum digoxin concentrations. Withdrawal should be considered in patients with a questionable indication for this therapy; the occasional occurrence of supraventricular arrhythmias, and not so much of heart failure, should be anticipated.

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Substance Withdrawal Syndrome

Topics: Digoxin; Heart Diseases; Humans; Intestinal Absorption

To evaluate the effect of puberty on the net renal tubular secretion of digoxin, we measured the ratio of digoxin clearance to creatinine clearance in 23 patients aged 4 to 21 yr and correlated this ratio with both sexual maturity (Tanner stage) and chronologic age. All subjects were at steady-state levels for digoxin treatment; all had normal serum creatinine values for age as well as normal serum potassium levels. Mean ratio for immature children (n = 14, Tanner 1 through 3.5) was 1.45 +/- 0.66. Mean ratio for mature adolescents (n = 9, Tanner 4 through 5) was 0.95 +/- 0.28. The difference between the two groups was significant (P less than 0.05). When patients were regrouped by age using either 13 or 15 yr as a cutoff, the difference in ratios was no longer statistically significant. Based on 45 subjects (new and from our previous study) aged 2 mo to 80 yr, there was a significant decrease in the clearance ratio with increasing age, but when the 23 subjects aged 4 to 21 yr were analyzed separately, the correlation between ratio and age was not significant. It appears that the decrease in net renal tubular secretion of digoxin from childhood to adulthood correlates better with full sexual maturation at puberty (Tanner 4 through 5) than with chronologic age. This observation may represent a developmental change in pharmacokinetics with broader significance than for digoxin disposition alone.

Topics: Adolescent; Adult; Child; Child, Preschool; Creatinine; Digoxin; Female; Heart Diseases; Humans; Immunoenzyme Techniques; Kidney Tubules; Kinetics; Male; Puberty

We performed a study on 96 patients to compare monitoring by immunoenzymologic measurement (EMIT) of digoxinemia. In doing so, we uniquely relied on clinical and electrocardiographic results. Compliance was good because only 9 patients had a digoxinemia equal or below 0.8 ng/ml, but we emphasize that our patients were hospitalized. Correlation between intoxications and plasmatic levels shows that 5 patients presented clinical or electrocardiographic signs indicative of digitalis intoxication with a digoxinemia less than 2.5 ng/ml and 14 patients without intoxication with a digoxinemia higher than 2.5 ng/ml. We point out in this study that for EMIT immunoassay it is better to take 2.5 ng/ml as the concentration limit to be sure to avoid intoxication.

Topics: Adult; Aged; Digoxin; Electrocardiography; Female; Heart Diseases; Humans; Immunoenzyme Techniques; Male; Middle Aged

The increasing use of amiodarone as antiarrhythmic drug has raised the possibilities of dangerous effects from amiodarone-digitalis interaction. We have studied twelve patients who were taking digitalis and to whom amiodarone was administered because of arrhythmias. We found a 75,42% increase of digitalis plasma levels (p less than 0,001) in the early days of amiodarone therapy, and a 52,1% increase (p less than 0,001) in the medium term. An inverse correlation was found (r = -0,65; p less than 0,05) between the plasma levels of digitalis during the steady-state control period and during the following 2-to-6 months evaluation. Acute episodes of cardiac failure caused in our patients an abrupt increase of digitalis plasma levels: in three patients digitalis toxicity occurred. Based on our experience, we recommend that the dose of digitalis be halved when the two drugs are given together in patients with various degree of cardiac failure; moreover digitalis plasma levels should be frequently monitored in these patients. On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digitalis Glycosides; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Male; Medigoxin; Middle Aged

Topics: Adult; Digoxin; Heart Diseases; Humans; Infant

Topics: Aged; Cardiac Glycosides; Digoxin; Dose-Response Relationship, Drug; Drug Hypersensitivity; Electrocardiography; Female; Heart Diseases; Humans; Hypoxia; Lung Diseases, Obstructive; Male; Middle Aged

As part of a blood-pressure survey in Munich, some of its inhabitants aged 30-69 years were asked by questionnaire about any digitalis medication. Chemically defined glycosides were taken by 127 of 1827 persons (7%), two-thirds of them older than 60 years, for clinically compensated chronic heart failure. Using the equation of Cockcroft and Gault to calculate creatinine clearance, it was below 80 ml/min and thus indicative of early impairment of renal function in more than 50%. In 44% the prescribed daily dose of glycoside corresponded to the calculated maintenance dose, 29% had less and 27% had taken more. None had clinical signs of digitalis intoxication. ECG changes possibly due to digitalis were much less common than had been expected. Sinus rhythm was present in 93%. More than 50% did not know why they were taking digitalis and 80% were taking two or more drugs at the same time. Since more than half had signs of early renal function impairment, creatinine clearance should be taken into account when determining the dosage of a digoxin preparation especially in elderly patients; alternatively, digitoxin should be prescribed. The survey also showed that a large number of persons on glycoside medication did not take the drug regularly.

Topics: Acetyldigoxins; Adult; Age Factors; Aged; Creatinine; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Female; Germany, West; Heart; Heart Diseases; Humans; Hypertension; Kidney; Male; Middle Aged; Prospective Studies; Sex Factors

The addition of amiodarone to digoxin therapy in nine children caused a sharp increase in digoxin serum concentrations (68% to 800%) in the presence of preserved serum creatinine and BUN concentrations. Digoxin half-life was prolonged. Digoxin accumulation could be attributed in part to the decrease in the renal clearance of digoxin resulting from inhibited tubular secretion of the drug and to the reduction in the distribution volume of digoxin caused by amiodarone. Creatinine clearance was not affected by amiodarone. This interaction appears to be more acute in children than in adults, presumably because of the more important role of the renal tubular secretion of digoxin in children. Whenever digoxin and amiodarone therapy are combined, the digoxin serum concentration should be monitored carefully, with appropriate reduction of the digoxin dose.

Topics: Adolescent; Amiodarone; Benzofurans; Cardiomyopathy, Dilated; Child; Child, Preschool; Creatinine; Digoxin; Drug Interactions; Heart Defects, Congenital; Heart Diseases; Humans; Infant; Male; Prospective Studies

The value of red blood cell (RBC) sodium/potassium ratio in diagnosing digitalis toxicity was studied in 60 adult patients. The normal ratio was established in 34 healthy volunteers and in 10 patients with heart disease not receiving digoxin (group I). During chronic digoxin therapy, RBC sodium/potassium (Na/K) ratio and plasma digoxin were measured in 50 nontoxic patients (group II), in 10 toxic patients (group III), and in 9 of these 10 toxic patients after resolution of digoxin toxicity. Red cell sodium and RBC Na/K ratio in nontoxic patients were significantly greater than in the control group. Red cell sodium and the RBC Na/K ratio in toxic patients were significantly greater than in nontoxic patients. Despite significant group differences in these variables, however, there was considerable overlap among the subjects studied. After resolution of toxicity, red cell sodium and the RBC Na/K ratio fell to values indistinguishable from those in the nontoxic group. Although there was a statistically significant positive correlation between RBC Na/K ratio and plasma digoxin level, the RBC Na/K ratio had weak predictive value (33%) in determining digoxin toxicity. Plasma digoxin was a better predictor of digoxin toxicity (60%). The combination of plasma digoxin concentration and of RBC Na/K ratio had a higher calculated predictive value (75%), and may be more useful as an indicator of digoxin intoxication.

Topics: Adult; Aged; Digoxin; Drug Interactions; Electrocardiography; Erythrocyte Membrane; Erythrocytes; Female; Heart Diseases; Humans; Male; Middle Aged; Potassium; Quinidine; Sodium; Sodium-Potassium-Exchanging ATPase

Topics: Animals; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Dogs; Drug Interactions; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Macaca mulatta

The relationship between the plasma level of the cardiac glycoside digoxin and performance on a range of cognitive tasks was investigated in a group of cardiac outpatients on maintenance therapy. The cognitive functions assessed were speed of decision-making and recognition memory of nonverbal and verbal material, competitive audio-visual attention performance, visuo-motor-choice reaction time and auditory verbal learning (AVL). Multiple regression analysis of the data revealed a strong relationship between plasma digoxin level at the time of testing and the number of trials to criterion in the AVL task (plasma digoxin level 0.7-1.8 nmol/l). Further data analysis indicated that this association was unlikely to be due to age, education or severity of cardiac disorder. The results strongly suggest that an increasing plasma level of digoxin may produce a progressive deterioration in auditory verbal learning and short-term memory.

Topics: Adult; Aged; Digoxin; Female; Heart Diseases; Humans; Learning Disabilities; Male; Memory Disorders; Middle Aged; Reaction Time

Topics: Adult; Creatinine; Digoxin; Heart Diseases; Humans; Kidney Failure, Chronic; Kinetics

Topics: Adult; Aged; Digoxin; Drug Therapy, Combination; Erectile Dysfunction; Heart Diseases; Humans; Male; Middle Aged; Verapamil

Topics: Aged; Digoxin; Dose-Response Relationship, Drug; Female; Heart Diseases; Humans; Male; Middle Aged; Time Factors

In seven cardiac patients on long-term digoxin therapy, digoxin kinetics were investigated - in the absence and presence of quinidine - after simultaneous administration of an oral digoxin dose and an intravenous 3H-digoxin bolus injection. From 3H-digoxin data quinidine was found to decrease both renal (from 1.19 +/- 0.35 to 0.86 +/- 0.21 ml/min./kg) (P less than 0.02) and extrarenal clearances of digoxin (from 0.85 +/- 0.24 to 0.49 +/- 0.23 ml/min./kg) (P less than 0.02), and to diminish the steady state distribution volume of the drug (from 6.78 +/- 1.23 to 5.63 +/- 1.64 l/kg) (P less than 0.02). Plasma half-life increased from 51.5 +/- 5.4 to 64.4 +/- 14.8 hrs (P less than 0.05), while urinary excretion half-life increased from 54.4 +/- 3.9 to 78.5 +/- 14.1 hrs (P less than 0.01). Pharmacokinetic parameters derived from plasma and urinary digoxin data showed similar changes during quinidine therapy. Reduction in renal 3H-digoxin clearance occurred at subtherapeutic plasma quinidine levels and was independent of plasma quinidine, whereas reductions in extrarenal 3H-digoxin clearance and 3H-digoxin distribution volume were positively correlated to plasma quinidine concentrations (P less than 0.05).

Topics: Creatinine; Digoxin; Glomerular Filtration Rate; Half-Life; Heart Diseases; Humans; Kinetics; Quinidine

Topics: Digoxin; Diuretics; Drug Interactions; Heart Diseases; Humans

M-mode echocardiograms and systolic time intervals were recorded before and six weeks after stopping digoxin in 11 patients in sinus rhythm to see whether the inotropic effect of digoxin was maintained with long-term treatment. Significant changes indicating a reduction in inotropic state on stopping digoxin were observed in the group. Clinical deterioration occurred in only one patient, associated with evidence of initially impaired cardiac function rather than an atypical response to digoxin. This study provides evidence that chronic digoxin treatment does continue to exert a positive inotropic effect.

Topics: Adult; Aged; Digoxin; Drug Administration Schedule; Echocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Myocardial Contraction; Stimulation, Chemical; Systole; Time Factors

Topics: Adult; Digoxin; Drug Interactions; Heart Diseases; Humans; Middle Aged; Verapamil

A patient with acute nonlymphoblastic leukemia in relapse and anthracycline cardiomyopathy was treated with AMSA in combination with cytosine arabinoside and thioguanine (AAT). Induction of remission was accomplished after one course of therapy without development of congestive heart failure. Radionuclide studies done prior to and subsequent to the reinduction with AAT revealed that the combination did not induce further deterioration of myocardial function. Although the exact risk of AMSA causing additional cardiac damage will require more extensive experience, this case suggests that AMSA may be safely given to patients with anthracycline cardiomyopathy and may be the treatment of choice for this group of patients.

Topics: Acute Disease; Adult; Aminoacridines; Amsacrine; Antibiotics, Antineoplastic; Antineoplastic Agents; Digoxin; Female; Furosemide; Heart Diseases; Humans; Leukemia; Naphthacenes

Topics: Aged; Digoxin; Enzyme-Linked Immunosorbent Assay; Heart Diseases; Humans; Immunoenzyme Techniques; Radioimmunoassay

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Electric Countershock; Female; Heart Diseases; Humans; Male; Middle Aged; Tachycardia

Topics: Aged; Digoxin; Heart Diseases; Humans; Kidney Function Tests; Liver Function Tests; Middle Aged

Topics: Digoxin; Drug Interactions; Heart Diseases; Humans; Kinetics; Myocardium; Quinidine

This work undertakes, in a second part, the clinical exploration of 947 serum digoxin levels of 281 hospitalized patients on a cardiology ward. Our results, which coincide with those of other researchers, have led us to draw certain practical conclusions: the posology is determined first of all according to kidney function, weight and age of the patient. When the treatment is insufficient or, on the other hand, poorly tolerated, a serum digoxin level is performed permitting thus: 1) in the case of ineffective treatment: to be sure of the patient's cooperation, to increase the posology if the serum digoxin level is not in the toxic zone, to discover an eventual pharmacokinetic problem; 2) to establish the responsibility of digitalis (when there are signs of intolerance or of intoxication), in case of arrhythmia, in patients with pacemakers, when associated drugs are capable of causing similar adverse effects; 3) to better manage a digitalis treatment in a high risk patient (unstable renal function, advanced myocardial disease, chronic obstructive disease).

Topics: Age Factors; Aged; Body Weight; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Radioimmunoassay

Topics: Adult; Child; Digoxin; Diuretics; Drug Interactions; Furosemide; Heart; Heart Diseases; Hemoperfusion; Humans; Infant; Infant, Newborn; Male; Myocardium; Oxygen Consumption; Quinidine; Spironolactone

Investigations were performed in order to study whether or not quinidine would exert similar effects on the serum digoxin concentration in patients with renal failure as in normal subjects. Fourteen out of fifteen patients showed a significant increase of the serum digoxin level after four days of quinidine application. This indicates, that the quinidine effect is not solely caused by a decrease of the renal digoxin clearance, although nine patients, not being hemodialysed, revealed a correlation between their creatinine clearance and the rise of the serum digoxin concentration after quinidine. As however, the patients on hemodialysis did not show higher digoxin levels than those treated conservatively, it is suggested that the degree of the uremic intoxication might be responsible for the observed correlation.

Topics: Acetyldigoxins; Adult; Aged; Creatinine; Digoxin; Drug Interactions; Electrocardiography; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Quinidine; Renal Dialysis

Topics: Adolescent; Adult; Aged; Digoxin; Female; Heart Diseases; Humans; Kidney Diseases; Male; Middle Aged

The medical records of an elderly woman revealed strong evidence of a lethal digoxin-quinidine interaction. This case and several problems contributing to digitalis toxicity are presented. Physicians should be more aware of the potential toxicities involved in cardioactive drug therapy in the elderly. Current concepts of the quinidine-digoxin interaction are discussed.

Topics: Aged; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Quinidine

Topics: Abortion, Therapeutic; Adult; Aminoglycosides; Digoxin; Eisenmenger Complex; Female; Furosemide; Heart Diseases; Humans; Mitral Valve Prolapse; Mitral Valve Stenosis; Penicillins; Pregnancy; Pregnancy Complications, Cardiovascular

Topics: Binding, Competitive; Digoxin; Drug Synergism; Heart Diseases; Humans; Quinidine; Receptors, Drug

Topics: Aged; Digoxin; Heart Diseases; Heart Rate; Humans

Topics: Aged; Digoxin; Heart Diseases; Humans; Retrospective Studies

Topics: Absorption; Acetyldigoxins; Aged; Digoxin; Female; Heart Diseases; Humans; Male; Medigoxin; Middle Aged

With ever increasing frequency potentially dangerous interactions are reported between Cardiac Glycosides and other drugs, particularly the antiarrhythmic one. The AA, carried out this work with the intent of studying the possible modifications produced by Q and A on the SDL. First of all the AA. retrospectively studied the SDL of patients treated with the associations Q-D and A-D and this SDL was compared with the SDL of patients treated with D alone. Then 10 subjects treated sequentially, at first with D alone and after with the Q-D (5 p.) and A-D (5 p.) association, were studied. The results obtained confirm the data of other AA. regarding the Q-D interaction; in fact, in the presence of this antiarrhythmic drug, the SDL increase significantly following the concomitant pharmacological effects of the Cardiac Glycosides. The SDL on the contrary seem not be influenced by the A-D association. The AA. then reviewed the literature about the mechanism of the Q-D interaction. The majority of the AA. agree outlining a reduction of the Volume of Distribution and of D Clearance, in consequence of the concomitant administration of Q, which would explain the high SDL obtained. In conclusion the AA. suggest, when the Q-D association is mandatory, a 50% reduction of the D maintenance dose and to check periodically the ECG and SDL.

Topics: Adult; Aged; Amiodarone; Benzofurans; Coronary Disease; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Quinidine; Rheumatic Heart Disease

Seven healthy volunteers received a single 1.0-mg dose of intravenous digoxin in a drug-free control trial and again during concurrent therapy with therapeutic doses of quinidine. Digoxin kinetics were determined from multiple serum digoxin concentrations measured during 72 hours after dosage. Compared to the control state, quinidine coadministration reduced mean digoxin volume of distribution (15.1 vs. 12.4 l./kg), prolonged its elimination half-life (47.7 vs. 75.7 hours), and significantly reduced total clearance (6.06 vs. 2.18 ml/min.kg). Both renal and extrarenal digoxin clearances were impaired by quinidine. In nine cardiac patients receiving long-term digoxin therapy (0.25 mg twice daily), quinidine coadministration elevated mean morning digoxin levels from 1.37 to 2.0 ng/ml (P less than 0.001) and evening levels from 1.44 to 1.97 ng/ml (N.S.). If digoxin concentrations at the site of action are increased by quinidine, the interaction is likely to be of clinical importance in many patients.

Topics: Adult; Biotransformation; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Half-Life; Heart Diseases; Humans; Infusions, Parenteral; Kinetics; Male; Middle Aged; Quinidine; Random Allocation

The effect of a kaolin-pectin antidiarrheal mixture on steady-state plasma levels of orally administered digoxin in subjects receiving chronic digoxin therapy was evaluated when the antidiarrheal and the cardiac glycoside were given concomitantly and when two doses of antidiarrheal were given, one 2 hours before and the other 2 hours after digoxin. Although simultaneous administration of both products decreased peak digoxin levels by 36 per cent, 24-hour areas under the curve were reduced by only 15 per cent, indicative of a slight decrease in digoxin bioavailability. In contrast, when their times of administration were separated by 2 hours, no evidence of a drug interaction was noted. Hence, the effect of one or two doses of kaolin-pectin suspension on steady-state plasma levels of digoxin appears inconsequential in patients on chronic digoxin therapy. Saliva levels were poorly correlated with plasma levels, presumably because of complexation in the oral cavity.

Topics: Absorption; Administration, Oral; Adult; Aged; Antidiarrheals; Biological Availability; Digoxin; Drug Administration Schedule; Female; Heart Diseases; Humans; Kaolin; Male; Middle Aged; Pectins

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).

Topics: Adult; Aged; Creatinine; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Muscles; Potassium; Reference Values

Topics: Aged; Autopsy; Digoxin; Diuretics; Female; Forensic Medicine; Heart Diseases; Humans; Hypertension; Iatrogenic Disease; Middle Aged; Water-Electrolyte Imbalance

One hundred and twenty-two patients with cardiac disease were compared with 250 controls with respect to the duration of pregnancy and labour, birth weight percentile and Apgar score. The babies of the patients with cardiac disease were light-for-dates (18% below the 10th percentile); the mothers, if multiparous, delivered at an earlier gestational age. The patients with cardiac disease did not have shorter labours than the control group. Digoxin administration and the severity of heart disease had no significant effect on these variables.

Topics: Apgar Score; Birth Weight; Digoxin; Female; Heart Defects, Congenital; Heart Diseases; Humans; Infant, Low Birth Weight; Infant, Newborn; Labor, Obstetric; Parity; Pregnancy; Pregnancy Complications, Cardiovascular; Rheumatic Heart Disease

Topics: Adult; Aged; Digoxin; Diuretics; Drug Interactions; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Male; Medigoxin; Middle Aged; Radioimmunoassay; Renal Dialysis; Uremia

Topics: Digitalis Glycosides; Digoxin; Drug Tolerance; Heart Diseases; Humans; Time Factors

We investigated the age-specific arrhythmogenic effects of digoxin in the rat. Adult female rats (n = 26) and one-day-old newborns (n = 20) were anesthetized with pentobarbital and injected subcutaneously with varying doses of digoxin. Electrocardiograms (ECG) were monitored continuously for four and one-half hours following digoxin administration. The arrhythmogenic dose 50 (AD50) and lethal dose 50 under anesthesia (LD50) were determined using the method of Litchfield and Wilcoxon. AD50 in adults was 13.0 +/- 1.0 mg/kg (X +/- SD) compared with 2.9 +/- 0.3 mg/kg in the newborns (P less than 0.01), and LD50 in adults was 30.0 +/- 1.9 mg/kg compared with 5.0 +/- 0.2 mg/kg in the newborns (P less than 0.01). Arrhythmias appeared earlier in adults (54 +/- 11.5 minutes after digoxin, X +/- SEM) than in newborns (132.2 +/- 11.0 minutes, P less than 0.01). Paroxysmal atrial tachycardia was the predominant arrhythmia in adults (73%), while transient sinus bradycardia appeared in only 9%. In contrast, all newborns with arrhythmias had severe sinus bradycardia and 69% had profound first degree heart block as well. In conclusion, the newborn rat is more sensitive to digoxin toxicity and develops lethal arrhythmias much more readily than the adult.

Topics: Aging; Animals; Animals, Newborn; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Heart Diseases; Rats

Eighteen neonates in heart failure were investigated to assess whether high or low serum digoxin levels had differing effects on left ventricular function as determined by systolic time intervals obtained by echocardiography. Nine patients had digoxin levels of 1.99 +/- 0.35 ng/ml (group 1). Nine others had levels of 3.62 +/- 0.95 ng/ml (group 2). Systolic time intervals were obtained by echocardiography before and at 5 days after digoxin and correlated with serum levels. The heart rate, preejection period (PEP), left ventricular ejection time (LVET), electromechanical systole (QS2) and the PEP/LVET ratio were measured. LVET and electromechanical systole were indexed. These measurements were analyzed and the two groups were compared using Student's t test. The clinical improvement in both groups was similar and no difference in ECG changes were noted. Therapy with digoxin produced changes in heart rate and systolic time intervals in both groups. Both showed significant shortening of electromechanical systole index; group 1 significantly shortened the LVET index and PEP/LVET ratio, whereas group 2 significantly shortened the PEP. Statistical analysis comparing the two groups showed no difference between them. Digoxin produces measurable changes in the indices of left ventricular function. The magnitude of these changes suggests no therapeutic advantage to the higher levels.

Topics: Digoxin; Echocardiography; Electrocardiography; Heart Diseases; Heart Ventricles; Humans; Infant, Newborn; Infant, Newborn, Diseases; Myocardial Contraction; Systole

The pharmacokinetics of digoxin was studied in 11 subjects before and during quinidine treatment. Renal clearances of digoxin and creatinine were calculated from plasma concentrations and urinary excretions of digoxin and creatinine in subjects on long-term digoxin treatment. The investigations were repeated in the same subjects during administration of quinidine. Renal clearance of digoxin decreased, while plasma concentration of digoxin and renal excretion of digoxin increased in the presence of quididine, indicating substantial changes of digoxin kinetics, induced by quinidine. The reduction in renal clearance of digoxin may be due to a specific inhibition of tubular secretion of digoxin. The considerable rise of the plasma digoxin level and the increased excretion of digoxin support the assumption of a major extrarenal mechanism of interaction.

Topics: Aged; Creatinine; Digoxin; Drug Interactions; Heart Diseases; Humans; Kidney; Kinetics; Middle Aged; Quinidine

Topics: Adult; Age Factors; Aged; Blood Urea Nitrogen; Creatinine; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Furosemide; Heart Diseases; Humans; Male; Metabolic Clearance Rate; Middle Aged; Powders; Protein Binding; Spironolactone; Tablets

Topics: Aged; Digoxin; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Male; Medigoxin; Middle Aged; Stroke Volume

On the patients with moderate and severe heart insufficiency haemodynamic, clinical and electrocardiographic examinations were carried out. After the application of digitoxin at the beginning in the majority of cases no favourable effects on clinical and haemodynamic findings could be proved. In 2 patients with cor pulmonale even a drastic deterioration with increase of the pulmonary pressure and formation of a pulmonary oedema developed. The temporary analysis of the systole and the estimation of the glycoside level did not give any reliable references. The recompensation began only after 2-3 days. In 5 out of 10 patients in whom the cardiac rhythm was continuously controlled by means of a tape storage device, after the application of digoxin ventricular extrasystoles appeared. Also in these cases increased as well as subtherapeutic digoxin-plasma levels were present. In 2 patients with hypertrophic obstructive cardiomyopathy the infundibular gradients were considerably increased by strophantin. The causes of the different reaction patters are to be sought in disease-specific peculiarities, in the degree of severity of the heart insufficiency, in the speed of the flooding of glycoside and several extracardiac factors.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Pressure; Cardiac Complexes, Premature; Cardiomyopathy, Hypertrophic; Digitalis Glycosides; Digoxin; Female; Heart; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Pulmonary Edema; Pulmonary Heart Disease

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Child; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Taiwan

Topics: Adult; Age Factors; Aged; Digoxin; Heart Diseases; Humans; Injections, Intravenous; Middle Aged

Following the development of digoxin radioimmunoassay, we noted that serum digoxin concentrations appeared to rise in patients given quinidine. To further evaluate this important possible interaction between digoxin and quinidine, charts from 863 cardiology patients were reviewed. Ninety two patients received both drugs after having been on digoxin alone; 38 were ineligible for the study because of insufficient data and 27 were excluded because of changing renal function and/or concomitant antiarrhythmic drug therapy, leaving 27. Serum digoxin increased in 25 of the 27 study patients (93%) during quinidine therapy; mean serum digoxin rose from 1.4 ng/ml before quinidine to 3.2 ng/ml during quinidine. Anorexia, nausea and/or vomiting developed in 16 patients (59%) during quinidine therapy, but disappeared in all 10 patients in whom digoxin alone was reduced in dose, suggesting that digoxin had a causative role in the appearance of these symptoms although they developed only after quinidine had begun. Three of thirteen patients with only atrial arrhythmias on digoxin prior to quinidine developed new ventricular premature depolarizations (VPD) after starting quinidine; two of these three as well as four patients with prior VPDs developed new ventricular tachycardia, ventricular fibrillation, asystole, or sudden death. When starting quinidine in patients who are taking digoxin, the clinical course, ECG and serum digoxin should be followed closely.

Topics: Adult; Aged; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Male; Middle Aged; Quinidine; Retrospective Studies

Serum concentrations of digitoxin and digoxin were measured in 145 cases with various heart diseases receiving maintenance doses of digitalis. Digitalis toxicity was seen in only 2 cases (1.4%). Day-to-day variation of serum concentration while taking the same daily dose was small in digitoxin therapy (13.8%), but a considerable variation was seen in digoxin therapy (24.4%). Serum concentrations of both digitoxin and digoxin were measured in the patients receiving digitoxin, and there was a positive correlation between the two (r = 0.66, p less than 0.001). This fact suggested that the effect of digitoxin was the sum of the effects of digitoxin and its metabolite, digoxin. In the patients taking digoxin, digitoxin was not detected in the serum. Serum digitoxin level had a significantly positive correlation to serum albumin level, presumably because digitoxin was retained in serum in the bound form to albumin. Minimal effective level, 10 ng/ml, was however obtained with higher daily dose of digitoxin in patients with lower serum albumin.

Topics: Adolescent; Adult; Aged; Digitoxin; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Radioimmunoassay

Topics: Action Potentials; Adolescent; Adult; Aged; Ajmaline; Bunaftine; Coronary Disease; Diabetes Mellitus; Digoxin; Electrocardiography; Female; Heart; Heart Diseases; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Ventricular Function

Topics: Aged; Cerebrovascular Disorders; Digoxin; Drug Combinations; Drug Evaluation; Female; Heart Diseases; Humans; Male; Middle Aged; Nicotinic Acids; Theobromine

Topics: Adolescent; Adult; Aged; Biological Availability; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Tablets

Serum and salivary digoxin concentrations were measured in 53 children and correlated with ECG variables and serum potassium, calcium and magnesium concentrations. In 73% of patients cardiac failure was controlled, while only 7,5% of patients had serum digoxin concentrations within the 'therapeutic range'. It is proposed that the adult therapeutic range of 1-2 ng/ml is not applicable to children, who can be controlled at lower concentrations and/or that a significant proportion of the children studied no longer required maintenance digoxin therapy.

Topics: Adolescent; Child; Child, Preschool; Digoxin; Electrocardiography; Heart Diseases; Humans; Infant; Saliva

Data from a survey of general-practitioner prescribing from 1967 to 1977 were examined to see how news of the changed potency of "Lanoxin" tablets in 1972 and of unbranded digoxin in 1975 had affected prescribing patterns. A stong downward trend in average daily dose was found, equivalent to a halving in lanoxin, almost as much in digoxin, and a one-fifth fall in prepared digitalis. This trend, however, preceded the publicity on potency and bioavailability, and in the case of lanoxin was apparent during the time that bioavailability fell. It had two components--reduced frequency of tablets per day, and increased popularity of low-dose tablets. From 1972 the proprietary 250 microgram tablet of lanoxin was prescribed increasingly at the expense of unbranded digoxin, but at a lower daily frequency until 1975. The number of people treated with digoxin and lanoxin has risen overall and constitutes perhaps 6% of those over 65. The determinants of prescribing behaviour are complex.

Topics: Aged; Biological Availability; Digoxin; Drug Prescriptions; Family Practice; Heart Diseases; Humans; United Kingdom

Topics: Adult; Biological Availability; Circadian Rhythm; Digoxin; Heart Diseases; Humans; Medigoxin

Topics: Aged; Coronary Disease; Creatinine; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Potassium

Topics: Adult; Biological Availability; Capsules; Coronary Disease; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Myocardial Contraction; Tablets

Topics: Digoxin; Doxorubicin; Electrocardiography; Heart Diseases; Humans

Atrioventricular nodal alternating Wenckebach periods were defined as episodes of 2:1 atrioventricular block in which there was a gradual increase in transmission intervals of conducted beats ending in two or three consecutively blocked atrial impulses. This is one of the mechanisms whereby 2:1 atrioventricular block progresses into 3:1 or 4:1 atrioventricular block. Alternating Wenckebach periods appear during rapid atrial pac,ng (even in the absence of depressed atrioventricular nodal function), provided that the atria can be captured at a rate fast enough to allow for the occurrence of this phenomenon. Treatment of atrial flutter with digoxin and quinidine produces alternating Wenckebach's periods, with associated electrocardiographic changes specific for the type of drug given. In patients with "atrial tachycardia with atrioventricular block" due to digitalis intoxication or with primary disease of the conducting system or with acute myocardial infarction, there are coexisting severe arrhythmias and clinical symptoms requiring almost immediate pharmacologic or electrical therapy. We conclude that atrioventricular nodal alternating Wenckebach's periods are common and frequentyly transient and that they occur in a variety of clinical conditions, most of which are benign; however, contrary to what is commonly accepted, some episodes appear in clinical settings requiring prompt pharmacologic or electrical treatment.

Topics: Acute Disease; Atrial Flutter; Atrioventricular Node; Bundle of His; Digitalis Glycosides; Digoxin; Electrocardiography; Heart Atria; Heart Block; Heart Conduction System; Heart Diseases; Humans; Myocardial Infarction; Pacemaker, Artificial; Purkinje Fibers; Quinidine; Tachycardia

Topics: Digoxin; Doxorubicin; Heart Diseases; Humans

Topics: Adolescent; Adult; Age Factors; Aged; Anesthesia, General; Anesthesia, Intravenous; Child; Creatinine; Digoxin; Diuretics; Female; Heart Diseases; Hemoglobins; Humans; Male; Middle Aged; Premedication; Sex Factors; Thiopental

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Family Practice; Heart Diseases; Humans

Isolated heart muscle preparations are useful in the study of cardiac toxicities of drugs and environmental chemicals: such tissues allow assessment of chemical effects on heart muscle that is free from indirect in vivo influences that can mask or even accentuate cardiac responses measured in the intact animal. In the present study, left atria of guinea pigs were used to demonstrate a direct cardiac depressant effect of greater-than-therapeutic concentrations of several aminoglycoside antibiotics. The toxic effect of these antibiotics seems to be a calcium-dependent event, and may prove useful to characterize contractile responses of the heart. Other antibiotic agents can also depress cardiovascular function, as summarized in this report, but mechanisms of action have not been clearly defined.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Calcium; Digoxin; Gentamicins; Guinea Pigs; Heart Diseases; In Vitro Techniques; Isoproterenol; Male; Myocardial Contraction

All 24 patients on long-term digoxin in a general practice were reviewed. 17 of the 18 patients in sinus rhythm had their digoxin discontinued without any alteration in their cardiovascular signs or symptoms. Other therapy was adjusted as necessary. These results suggest that heart-failure can often be managed without long-term digoxin therapy.

Topics: Aged; Digoxin; Drug Evaluation; Family Practice; Female; Heart Diseases; Humans; Long-Term Care; Male; Middle Aged; Time Factors

Serum digoxin levels were measured in 53 neonates and infants receiving 18-22 microgram/kg/day (high dose) oral maintenance digoxin, and 44 neonates, infants and children receiving less than 18 microgram/kg/day (low dose) oral maintenance digoxin. In both groups, patients under four months of age had significantly higher serum digoxin levels than older patients, in the high dose group 2.6 ng/ml compared with 1.4 ng/ml and in the low dose group 2.2 ng/ml compared with 1.0 ng/ml. Correlation between digoxin dosage and serum level was weak and unaffected by blood urea level. Only two patients in the entire series showed toxic manifestations. Sixteen patients had serum digoxin levels measured before and after corrective cardiac surgery while receiving comparable dosages of digoxin. Despite lower serum digoxin levels postoperatively pulse rates fell significantly, illustrating the influence of changing haemodynamic status on the inter-relationships of digoxin dosage, serum levels and clinical response. Recommended dosage regimens are outlined.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Depression, Chemical; Digoxin; Heart Diseases; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Pulse

Topics: Administration, Oral; Adult; Aged; Biological Availability; Biopharmaceutics; Clinical Competence; Digoxin; Drug Evaluation; Drug Industry; Heart Diseases; Humans; Mathematics; Middle Aged; Quality Control; Solutions; Tablets; Tablets, Enteric-Coated; Time Factors

Topics: Calcium Chloride; Digoxin; Echocardiography; Heart Diseases; Heart Ventricles; Humans; Isoproterenol; Propranolol; Proscillaridin; Verapamil

1. Eight dogs were given two infusions of digoxin 0.1 mg/kg, one over 9 min and the other one over 90 min in a randomized sequence, allowing at least 12 days between each experiment. 2. Digoxin plasma profiles reflected the rate of digoxin infusion, the peak concentration of drug attained at the end of each infusion being considerably higher but more transient after the 9 min than after the 90 min transfusion. 3. Digoxin reduced the amount of acetylstrophanthidin required to produce electrocardiographic evidence of cardiotoxicity. This increase in cardiac sensitivity at 150 and at 360 min after the start of the digoxin infusion was independent of rate of infusion. 4. These results suggest that the development of cardiotoxicity is dependent upon the quantity of digoxin delivered into the systemic circulation regardless of the plasma concentration. 5. By inference, cardiotoxicity is related solely to the amount and not the rate of absorption from a given dose of digoxin.

Topics: Animals; Digoxin; Dogs; Electrocardiography; Female; Heart Diseases; Male; Strophanthins; Time Factors

Twenty-nine patients with gynaecological cancers who received over 400 mg of doxorubicin were monitored electrocardiographically to determine whether cardiac glycosides countered the adverse effects of high total doses of doxorubicin. Minor electrocardiographical changes were noted in five out of six patients who were not receiving a cardiac glycoside and four out of six who were receiving ouabain, and none of the 16 who were receiving digoxin. One other patient on digoxin stopped taking it and developed cardiomyopathy. One patient on ouabain also developed cardiomyopathy. So far nine patients on digoxin have received between 550 and 1000 mg/m2 of doxorubicin without ill effect. Cardiac glycosides are thought to prevent doxorubicin cardiomyopathy by competitively inhibiting doxorubicin at its receptor sites, but ouabain has a much shorter half life than doxorubicin and its metabolites and so is less effective than digoxin.

Topics: Digoxin; Doxorubicin; Electrocardiography; Female; Genital Neoplasms, Female; Heart Diseases; Humans; Ouabain

Topics: Adult; Aged; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Radioimmunoassay

Radioimmunologically determined digoxin and beta methyl digoxin values were the same in cardiopaths with and without clinical and instrumental changes referable to chronic cirrhosis or hepatitis. Lower values, however, were noted when gastroenteric disturbances were present. This was especially true of beta methyl digoxin in subjects with hyperkinetic-hyperchlorhydric syndromes due to depressed gastric pH, with a consequent inhibition of beta methyl digoxin absorption, presumably caused by lability of the molecule as a result of methylation of the terminal digitoxose group.

Topics: Aged; Blood Protein Disorders; Digoxin; Gastrointestinal Diseases; Heart Diseases; Hepatitis; Humans; Liver Cirrhosis; Middle Aged; Radioimmunoassay

Topics: Adult; Aged; Biological Availability; Digoxin; Heart Diseases; Humans; Middle Aged

Topics: Acetyldigoxins; Administration, Oral; Adult; Aged; Biological Availability; Deslanoside; Digoxin; Female; Heart Diseases; Humans; Lanatosides; Male; Middle Aged

Six subjects receiving digoxin therapy for heart disease were studied on two occasions with a single oral dose of 0.5 mg of tritiated digoxin. In every study, all stools and urine were saved for 1 week. Before the second study, treatment with cholestyramine, 4 g every 6 hours, was begun and continued throughout. In three patients, a third study was performed after cholestyramine treatment had been continued for 1 month. Results showed that after cholestyramine administration serum levels, stool output and urinary output of tritiated digoxin varied over a wider range, but cholestyramine had no net short-term effect of any of these variables. After 1 month of cholestyramine administration, there was a small statistically significant increase in stool output of tritiated digoxin and metabolites. In vitro studies suggested that cholestyramine is likely to be a weak digoxin binder in the gut and that changes induced by this resin in digoxin metabolism are not likely to be due to drug binding.

Topics: Administration, Oral; Binding Sites; Cholestyramine Resin; Chronic Disease; Digoxin; Drug Interactions; Drug Therapy, Combination; Heart Diseases; Humans; In Vitro Techniques; Intestinal Absorption; Male; Time Factors

Topics: Adolescent; Child; Digoxin; Heart Diseases; Humans

Topics: Adult; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged

Topics: Acute Disease; Child, Preschool; Digoxin; Diuretics; Heart Diseases; Humans; Infant; Infant, Newborn; Respiratory Tract Infections; Strophanthins

Topics: Child, Preschool; Digoxin; Female; Heart Diseases; Humans; Infant; Male; Pneumonia

Topics: Digoxin; Heart Diseases; Humans; Ventricular Fibrillation

A radioimmunologic assay method was employed for assessing the hematic and urinary levels of beta methyl-digoxin in patients with various degrees of renal function, evaluated by creatinine clearance test. Significantly elevated hematic values and reduced clearance rates of MD were observed only in patients whose creatinine clearance values were below 50 cc/min. A good correlation between values of creatinine and MD clearances and between their ratio and serum albumin levels was verified. The authors stress the usefulness of this ratio as an indirect index for the plasmatic percentage of the free and of the protein- bound fractions of MD.

Topics: Adolescent; Adult; Aged; Creatinine; Digoxin; Female; Heart Diseases; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Serum Albumin

1 As part of a prospective study on the use of digoxin in a general practice, plasma digoxin concentrations were measured in all patients receiving the drug. 2 A low mean plasma digoxin concentration was observed, suggesting a cautious approach to digitalization. 3 The correlation between plasma digoxin concentration and signs or symptoms commonly used in the assessment of digoxin effect was poor. 4 It was concluded that the measurement of plasma digoxin could be of assistance in a variety of clinical settings within a general practice.

Topics: Aged; Digoxin; Female; Heart Diseases; Humans; Kidney; Male; Middle Aged; Radioimmunoassay; Time Factors

The concentration of digoxin in blood was determined by the radio-immunologic method in 41 patients with circulatory insufficiency and permanent form of auricular fibrillation who were treated with the drug. In 85.5% of cases the therapeutic digoxin concentrations did not exceed 2 ng/ml. The therapeutic concentrations ranged from 0.3 to 3.6 ng/ml, the toxic from 0.9 to 6 ng/ml. A relationship was established between the dose of digoxin and its concentration in the blood of patients with normal renal filtration. It is concluded that the blood digoxin concentrations alone, without the clinical data being taken into account, cannot be a reliable criterion in assessment of the level of saturation with cardiac glycosides. Study of the dynamics of blood digoxin concentration in each patient allows its determination to be used to assess the tolerance to the drug, choose the adequate maintenance dose and the time for its correction, and to confirm the clinical signs of digitalis intoxication if the concentration of digoxin is above 2.5 ng/ml.

Topics: Administration, Oral; Adult; Aged; Biological Availability; Digoxin; Dose-Response Relationship, Drug; Heart Diseases; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Adrenergic beta-Antagonists; Aged; Aging; Antihypertensive Agents; Biological Availability; Coronary Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart Diseases; Humans; Hypertension; Hypokalemia; Male; Potassium; Risk

Topics: Adult; Aged; Digoxin; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Diuretics; Drug Therapy, Combination; Heart Diseases; Heart Failure; Humans; Myocardial Infarction; Potassium

Topics: Adult; Age Factors; Aged; Digoxin; Female; Heart Diseases; Humans; Middle Aged

Topics: Animals; Digoxin; Dogs; Heart Diseases; Humans; Time Factors

Topics: Adult; Aged; Body Weight; Digoxin; Heart Diseases; Humans; Middle Aged

Topics: Body Weight; Digoxin; Dose-Response Relationship, Drug; Heart Diseases; Heart Failure; Humans

Topics: Digoxin; Heart Diseases; Humans

Topics: Digoxin; Heart Diseases; Humans

Topics: Adult; Aged; Digoxin; Heart Diseases; Humans; Methods; Middle Aged; Rubidium

A questionnaire was sent to several general practitioners and specialists in an attempt to obtain a consensus on standards of care for patients receiving long-term digoxin treatment. The consultants' suggested standards were slightly more stringent than those of the general practitioners. The records of 42 patients taking digoxin under the care of two general practitioners were studied to see how far their actual care matched up to the suggested standards. The models of management proposed by these patients' doctors were only slightly different from those suggested by other practitioners, but measured against these models the patients' care was in some cases inadequate. Nevertheless, there was little relationship between the recorded levels of care and the health of the patient, and it may have been the standard of recording rather than the care that was inadequate. Measuring plasma digoxin levels in these patients proved to be of little value. Medical audit is thus a useful tool in helping the general practitioner to review his work and improve his knowledge, but it may not be a practical or true way of measuring the quality of care.

Topics: Adult; Aged; Digoxin; Family Practice; Heart Diseases; Humans; Long-Term Care; Medical Audit; Quality of Health Care; Surveys and Questionnaires

Topics: Daunorubicin; Digoxin; Heart; Heart Diseases; Humans; Leukemia, Myeloid, Acute

Topics: Digoxin; Heart Diseases; Humans; Models, Biological

The radioimmunoassay of digoxin is one of the most important services of the nuclear medicine laboratory. Precision and accuracy in the performance of the test are especially critical. A number of commerical kits are available and reliable. Pitfalls to be avoided includelimited availability or delay in performance of the assay; failure to consider senitizing factors; drawing the blood sample too soon after a digoxin dose; failure to consider desensitizing factors; forgetting that renal function is a major determinant of blood and tissue digoxin levels; assuming patient compliance and uniform intestinal absorption (bioavailiability with all digoxin preparations in all patients; attempting to interpret digoxin levels without the necessary clinical information; and failure to deliver the result to the proper person. If one avoids these pitfalls, and important service will be rendered in the evaluation of the patient requiring digitalis therapy.

Topics: Administration, Oral; Aged; Biopharmaceutics; Calcium; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Hypothyroidism; Hypoxia; Kidney Failure, Chronic; Magnesium; Male; Middle Aged; Potassium; Procainamide; Propranolol; Quinidine; Radioimmunoassay

Topics: Adult; Digitalis Glycosides; Digitoxin; Digoxin; Drug Therapy, Combination; Female; Heart Diseases; Heart Failure; Humans; Infusions, Parenteral; Lanatosides; Male; Organomercury Compounds; Time Factors

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Humans; Lanatosides

Topics: Biological Transport, Active; Digoxin; Heart Diseases; Humans; Hypokalemia; Leukocytes; Myocardium; Potassium; Sodium

Topics: Adult; Cardiomegaly; Digoxin; Doxorubicin; Electrocardiography; Female; Heart; Heart Diseases; Heart Failure; Heart Function Tests; Heart Ventricles; Humans; Lymphoma; Male; Middle Aged; Multiple Myeloma; Neoplasms; Prospective Studies

Topics: Administration, Oral; Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Heart Block; Heart Diseases; Heart Failure; Humans; Hyperthyroidism; Injections, Intravenous; Kidney Failure, Chronic; Middle Aged; Obesity; Ventricular Fibrillation

Topics: Age Factors; Aged; Digoxin; Heart Diseases; Humans; Middle Aged; Prenylamine

Topics: Digoxin; Drug Tolerance; Female; Heart Diseases; Humans; Kinetics; Male; Middle Aged

Topics: Biological Availability; Biopharmaceutics; Digoxin; Drug Prescriptions; Drug Utilization; Heart Diseases; Humans; Terminology as Topic

Topics: Coronary Circulation; Digoxin; Heart Diseases; Humans; Myocardium

Topics: Digitoxin; Digoxin; Heart Diseases; Humans; Magnesium; Poisoning; Radioimmunoassay; Spectrum Analysis; Uremia

A 56-year-old male patient diagnosed as a case of procainamide-induced systemic lupus erythematosus (SLE) was found to have a lymphoproliferative disorder at postmortem examination.Contrary to other immune disorders, the association of SLE with neoplasia is a rare occurrence. The present case raises the question of whether a relationship exists between the lupus diathesis and lymphoreticular neoplasia. The study of the incidence of neoplasia in families of patients with SLE may prove helpful in establishing this relationship.

Topics: Aortic Diseases; Autopsy; Blindness; Bone Marrow; Digoxin; Drug Therapy, Combination; Heart Diseases; Heparin; Humans; Immunologic Deficiency Syndromes; Kidney; Lupus Erythematosus, Systemic; Lymph Nodes; Lymphoma; Male; Middle Aged; Procainamide; Quinidine; Retinal Artery; Spleen; Thromboembolism; Warfarin

Topics: Acute Disease; Adult; Aged; Blood Pressure; Cardiac Catheterization; Digoxin; Female; Furosemide; Germany, West; Heart Diseases; Heart Failure; Heart Septum; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Myocardial Infarction; Prognosis; Pulmonary Artery; Pulmonary Edema; Rupture, Spontaneous; Shock, Cardiogenic; Strophanthins

Topics: Adult; Aged; Body Height; Body Weight; Computers; Creatinine; Digoxin; Dose-Response Relationship, Drug; Female; Heart Diseases; Humans; Kidney; Male; Middle Aged; Regression Analysis

Topics: Cardiac Glycosides; Digoxin; Half-Life; Heart Diseases; Humans; Lanatosides; Strophanthins; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Digoxin; Female; Heart Block; Heart Diseases; Humans; Hypertension; Middle Aged; Pacemaker, Artificial; Sinoatrial Node; Syncope

Topics: Administration, Oral; Aged; Digoxin; Female; Heart Diseases; Humans; Injections, Intravenous; Male; Middle Aged; Radioimmunoassay; Tablets; Time Factors

Topics: Calcium; Digoxin; Heart Diseases; Humans; Potassium; Saliva

Topics: Aged; Creatinine; Digoxin; Electrocardiography; Heart Diseases; Humans; Myocardium; Potassium; Pulse; Radioimmunoassay; Urea

Topics: Administration, Oral; Biopharmaceutics; Digoxin; Female; Half-Life; Heart Diseases; Humans; Injections, Intravenous; Intestinal Absorption; Male; Tablets; Therapeutic Equivalency; Time Factors

Topics: Adult; Age Factors; Aged; Bufanolides; Digitalis Glycosides; Digitoxin; Digoxin; Drug Evaluation; Female; Heart Diseases; Humans; Lanatosides; Male; Middle Aged; Plants, Medicinal; Strophanthins; Time Factors

Topics: Adult; Aged; Atrial Fibrillation; Bundle-Branch Block; Cardiac Complexes, Premature; Digoxin; Electrocardiography; Female; Heart Block; Heart Conduction System; Heart Diseases; Heart Failure; Humans; Male; Tachycardia

Topics: Cerebrovascular Disorders; Digoxin; Disulfides; Drug Combinations; Feeding and Eating Disorders; Heart Diseases; Heart Failure; Humans; Pyridoxine

Topics: Biopharmaceutics; Digoxin; Drug Stability; Half-Life; Heart Diseases; Humans; Quality Control; Time Factors

Topics: Adolescent; Adult; Arrhythmia, Sinus; Digoxin; Female; Heart Diseases; Humans; Immune Sera; Methods; Radioimmunoassay; Regression Analysis; Time Factors; Tritium

Topics: Anticoagulants; Digoxin; Heart Diseases; Humans; Spironolactone; Therapeutic Equivalency

Topics: Calcium; Cystic Fibrosis; Digitalis Glycosides; Digoxin; Heart Diseases; Humans; Hyperaldosteronism; Potassium; Prospective Studies; Saliva

Topics: Age Factors; Aged; Body Height; Body Surface Area; Body Weight; Creatinine; Digoxin; Diuretics; Female; Heart Diseases; Humans; Iodine Radioisotopes; Iodohippuric Acid; Kidney Function Tests; Male; Radioimmunoassay

Topics: Administration, Oral; Animals; Digitoxin; Digoxin; Dog Diseases; Dogs; Female; Heart Diseases; Injections, Intravenous; Male; Protein Binding; Tritium

Topics: Adult; Aged; Biological Assay; Cardiac Glycosides; Digitoxin; Digoxin; Female; Heart Diseases; Humans; Male; Methods; Middle Aged; Radioisotopes; Rubidium

Topics: Acidosis; Angiocardiography; Cardiac Catheterization; Cineangiography; Diet Therapy; Digoxin; Diuretics; Electrocardiography; Heart Auscultation; Heart Defects, Congenital; Heart Diseases; Heart Failure; Humans; Infant, Newborn; Infant, Newborn, Diseases; Isoproterenol; Radiography, Thoracic; Respiration, Artificial

Topics: Digoxin; Heart Diseases; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Middle Aged; Tritium

Topics: Animals; Digoxin; Dogs; Heart Diseases

Topics: Coronary Disease; Digoxin; Heart Diseases; Heart Failure; Hemodynamics; Humans; Hypertension; Indicator Dilution Techniques; Indium; Radioisotopes

Topics: Abortion, Therapeutic; Adult; Aortic Valve Insufficiency; Chronic Disease; Digoxin; Drug Combinations; Female; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Long-Term Care; Lynestrenol; Mestranol; Mitral Valve Insufficiency; Mitral Valve Stenosis; Pregnancy; Pregnancy Complications, Cardiovascular

Topics: Adenocarcinoma; Aged; Blood Glucose; Carbutamide; Diabetes Mellitus; Diethylstilbestrol; Digoxin; Drug Interactions; Heart Diseases; Humans; Jaundice; Lipids; Liver Cirrhosis; Liver Function Tests; Male; Nitroglycerin; Prostatic Neoplasms; Triglycerides

Topics: Aged; Agglutinins; Aortic Valve Stenosis; Blood Platelets; Cells, Cultured; Digitoxin; Digoxin; Female; Heart Diseases; Hemagglutination Tests; Humans; Lymphocyte Activation; Lymphocytes; Thrombocytopenia

Topics: Adolescent; Adult; Aged; Coronary Disease; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Tablets

Topics: Arrhythmias, Cardiac; Benzoates; Coronary Disease; Digoxin; Drug Combinations; Heart Diseases; Heart Failure; Humans; Morpholines; Tranquilizing Agents; Verapamil

Topics: Digitalis Glycosides; Digoxin; Heart Diseases; Humans; Kidney

Topics: Administration, Oral; Aged; Digoxin; Heart Diseases; Humans; Injections, Intramuscular; Middle Aged; Nausea; Vomiting

Topics: Digoxin; Heart Diseases; Humans; Kidney Diseases

Topics: Digoxin; Female; Heart Diseases; Humans; Hypertension; Male

Topics: Administration, Oral; Age Factors; Body Weight; Child, Preschool; Digoxin; Heart Diseases; Humans; Infant; Radioimmunoassay

Topics: Administration, Oral; Digitalis; Digitoxin; Digoxin; Heart Diseases; Humans; Lanatosides; Plants, Medicinal; Plants, Toxic

Topics: Aged; Dextrocardia; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged

Topics: Adult; Aged; Angina Pectoris; Arrhythmias, Cardiac; Blood Pressure; Cardiac Complexes, Premature; Coronary Disease; Digoxin; Geriatrics; Heart Diseases; Heart Failure; Humans; Hypertension; Middle Aged; Morpholines; Myocardial Infarction; Phenethylamines; Pulmonary Heart Disease; Pulse; Tachycardia

Topics: Administration, Oral; Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Humans; Intestinal Absorption

Topics: Cardiac Glycosides; Cardiac Output; Digitoxin; Digoxin; Heart Diseases; Heart Rate; Humans; Lanatosides; Methods; Time Factors

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Humans; Myocardial Infarction; Myocardium

Topics: Acetates; Administration, Oral; Digoxin; Electrocardiography; Heart Diseases; Humans

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Drug Synergism; Heart Diseases; Humans; Middle Aged; Nitriles; Tranquilizing Agents

Topics: Arrhythmias, Cardiac; Biliary Tract; Digitalis Glycosides; Digitoxin; Digoxin; Gastrointestinal Diseases; Heart Diseases; Humans; Intestinal Absorption; Kidney; Lanatosides; Liver; Lung; Muscles; Myocardium; Nervous System Diseases; Strophanthins; Vision Disorders

Topics: Adenosine Triphosphatases; Animals; Cardiomegaly; Digoxin; Heart Diseases; Heart Ventricles; Kidney; Male; Microsomes; Myocardium; Ouabain; Plant Poisoning; Potassium; Rats; Sodium

Topics: Aged; Cardiac Glycosides; Digoxin; Electrocardiography; Heart Diseases; Humans; Intensive Care Units; Male; Postoperative Complications; Pulmonary Embolism; Resuscitation; Shock; Surgical Procedures, Operative

Topics: Acute Disease; Bradycardia; Digoxin; Female; Hearing Disorders; Heart Diseases; Heart Failure; Humans; Myocardial Infarction; Nitroglycerin; Vestibular Function Tests

Topics: Administration, Oral; Animals; Cardiac Catheterization; Cardiac Output; Cardiomyopathies; Chagas Disease; Coronary Disease; Digitalis Glycosides; Digoxin; Dogs; Electrocardiography; Heart Diseases; Hemodynamics; Humans; Hypertension; Male; Mitral Valve Insufficiency; Ouabain; Oxygen Consumption; Phonocardiography

Topics: Adolescent; Adult; Aged; Bundle-Branch Block; Cardiac Catheterization; Digoxin; Electrocardiography; Female; Heart Conduction System; Heart Diseases; Humans; Male; Middle Aged; Rheumatic Heart Disease

Topics: Aged; Bradycardia; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Female; Heart Auscultation; Heart Diseases; Hemodynamics; Humans; Male; Middle Aged; Muscle Contraction; Plants, Medicinal

Topics: Adolescent; Adult; Aged; Digoxin; Female; Heart Diseases; Humans; Injections, Intravenous; Male; Middle Aged; Time Factors

Topics: Adenine Nucleotides; Blood Circulation; Cardiovascular Diseases; Coronary Vessels; Digoxin; Female; Heart Diseases; Humans; Middle Aged; Myocardium; Nucleotides

Topics: Adult; Digitoxin; Digoxin; Female; Heart; Heart Diseases; Heart Function Tests; Heart Rate; Humans; Injections, Intravenous; Male; Methods; Middle Aged; Radioisotopes; Rubidium

Topics: Arrhythmias, Cardiac; Coronary Disease; Digoxin; Heart Diseases; Humans

Topics: Aged; Aging; Coronary Circulation; Coronary Vessels; Coumarins; Digoxin; Glycolates; Heart; Heart Diseases; Humans; Myocardium; Vasodilator Agents

Topics: Adult; Aged; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Nausea; Vomiting

Topics: Administration, Oral; Cardiac Glycosides; Digitoxin; Digoxin; Drug Combinations; Heart Diseases; Humans; Injections, Intravenous; Strophanthins

Topics: Adolescent; Aspartic Acid; Brain; Child; Child, Preschool; Clinical Enzyme Tests; Diagnosis, Differential; Digoxin; Electrocardiography; Erythrocytes; Female; Heart Diseases; Humans; Hydro-Lyases; Isomerases; Liver Diseases; Lyases; Male; Methandrostenolone; Muscular Diseases; Muscular Dystrophies; Oxidoreductases; Time Factors; Transferases; Vitamin E

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Diuretics; Electrocardiography; Female; Heart Conduction System; Heart Diseases; Heart Failure; Humans; Lidocaine; Male; Middle Aged; Phenytoin; Potassium; Radiography, Thoracic

Topics: Cardiac Glycosides; Digitoxin; Digoxin; Heart Diseases; Humans; Lanatosides; Strophanthins

Topics: Adult; Aged; Arteriosclerosis; Coronary Disease; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged

Topics: Adult; Aged; Anti-Arrhythmia Agents; Digoxin; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged

Topics: Aged; Coronary Disease; Digoxin; Heart Diseases; Humans; Middle Aged

Topics: Animals; Aorta; Aortography; Arteriovenous Fistula; Blood Pressure; Cardiomegaly; Catheterization; Digoxin; Dogs; Female; Femoral Artery; Heart Diseases; Heart Ventricles; Hypertension, Pulmonary; Male; Oxygen; Pulmonary Artery; Pulmonary Circulation; Regional Blood Flow

Topics: Digoxin; Female; Heart Diseases; Humans; Male

Topics: Cardiomyopathies; Digoxin; Ethiopia; Heart Diseases; Heart Valve Diseases; Humans; Hydrochlorothiazide; Pulmonary Edema; Radiography

Topics: Digoxin; Heart Diseases; Humans

Topics: Adult; Aged; Cardiac Glycosides; Digoxin; Drug Tolerance; Female; Heart Diseases; Humans; Male; Middle Aged

Topics: Chromatography, Thin Layer; Colorimetry; Digoxin; Heart Diseases; Humans; Injections, Intravenous; Intestinal Absorption; Tritium

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Coronary Disease; Digoxin; Female; Heart Defects, Congenital; Heart Diseases; Heart Valve Diseases; Humans; Male; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease; Tachycardia, Paroxysmal

Topics: Aged; Digoxin; Female; Heart Diseases; Humans; Injections, Intravenous; Intestinal Absorption; Vomiting

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electric Countershock; Heart Diseases; Humans

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Child; Child, Preschool; Digoxin; Heart Defects, Congenital; Heart Diseases; Heart Septal Defects, Atrial; Humans; Lanatosides; Middle Aged; Postoperative Complications; Preoperative Care; Retrospective Studies; Tachycardia

Topics: Blood Pressure; Coronary Disease; Digoxin; Heart Diseases; Heart Rate; Humans; Hypertension; Intestinal Absorption; Pulmonary Heart Disease; Pulse; Tablets; Tachycardia, Paroxysmal

Topics: Adolescent; Adult; Aged; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged

Topics: Digoxin; Heart Diseases; Humans; Myocardial Infarction

Topics: Adult; Aged; Digitalis Glycosides; Digoxin; Heart Diseases; Humans; Middle Aged

Topics: Adult; Aged; Aspartic Acid; Cardiac Glycosides; Digoxin; Heart Diseases; Humans; Magnesium; Male; Middle Aged; Plant Extracts; Plants, Medicinal; Potassium; Theophylline; Time Factors

Topics: Adult; Aged; Digoxin; Drug Synergism; Female; Heart Diseases; Humans; Male; Middle Aged; Plant Extracts; Plants, Medicinal; Strophanthins

Topics: Cardiac Catheterization; Cardiomyopathies; Desoxycorticosterone; Diagnosis; Digoxin; Drug Therapy; Edema; Guanethidine; Heart Diseases; Heart Failure; Humans

Topics: Digitalis; Digoxin; Drug Therapy; Geriatrics; Heart Diseases; Iatrogenic Disease; Toxicology

Topics: Abdomen; Adult; Aged; Blood Flow Velocity; Blood Pressure; Blood Volume; Cardiac Output; Digoxin; Heart Diseases; Heart Failure; Heart Rate; Hemodynamics; Humans; Middle Aged

Topics: Cardiac Surgical Procedures; Digoxin; Drug Therapy; Electrocardiography; Embolism; Heart Diseases; Humans; Mitral Valve Stenosis; Penicillins; Radiography, Thoracic; Rheumatic Heart Disease; Thoracic Surgery; Thrombosis; Vectorcardiography

Topics: Adolescent; Biomedical Research; Chemistry, Pharmaceutical; Digitalis; Digitalis Glycosides; Digoxin; Geriatrics; Heart Diseases; Pharmacology; Pharmacy; Toxicology

Topics: Biomedical Research; Digitalis; Digitalis Glycosides; Digoxin; Geriatrics; Glucosides; Heart Diseases; Humans

Topics: Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Humans; Lanatosides; Plant Extracts

Topics: Cardiac Glycosides; Digitalis Glycosides; Digitoxin; Digoxin; Drug Therapy; Glycosides; Heart Diseases; Lanatosides; Strophanthins; Toxicology

Topics: Cardiotonic Agents; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Drug Therapy; Heart Diseases; Humans; Lanatosides

Topics: Digitalis; Digoxin; Exercise; Heart Diseases; Heart Failure; Humans; Metabolism; Oxygen; Oxygen Consumption; Physical Exertion

Topics: Anti-Arrhythmia Agents; Digitalis; Digoxin; Enzyme Inhibitors; Heart Diseases

Topics: Adenosine; Digoxin; Diuretics; Heart Diseases; Humans; Purines; Theobromine; Theophylline

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digitalis; Digoxin; Enzyme Inhibitors; Heart Diseases; Humans

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digitalis; Digoxin; Enzyme Inhibitors; Heart Diseases; Humans

Topics: Child; Digitalis; Digoxin; Heart Diseases; Humans; Infant

Topics: Digitalis; Digitalis Glycosides; Digoxin; Heart; Heart Diseases