digoxin and Drug-Related-Side-Effects-and-Adverse-Reactions

There are currently no universally accepted guidelines for the management of digoxin toxicity. In the absence of clinical practice guidelines, a set of consensus recommendations for management of digoxin toxicity in the clinical setting were developed through a modified Delphi approach. The recommendations highlight the importance of early recognition of signs of potentially life-threatening toxicity that requires immediate treatment with digoxin-specific antibodies. The consensus identifies a straightforward approach to dosing immune antibody fragments according to the presence or absence of signs of life-threatening toxicity. Supportive measures and management of specific signs of toxicity are also covered.

Topics: Consensus; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans

This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.. Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs.. A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF.. The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine.. These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Ivabradine; Male; Mineralocorticoid Receptor Antagonists; Mortality; Practice Guidelines as Topic; Research Design; Research Report; Sex Distribution; Sex Factors; Stroke Volume

The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, we present our results for digoxin.. After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations.. Out of 435 articles screened, 77 met inclusion criteria. Only in-vitro, animal studies, case reports and case series were identified yielding a very low quality of evidence for all recommendations. Based on data from 84 patients, including six fatalities, it was concluded that digoxin is slightly dialyzable (level of evidence = B), and that ECTR is unlikely to improve the outcome of digoxin-toxic patients whether or not digoxin immune Fab (Fab) is administered. Despite the lack of robust clinical evidence, the workgroup recommended against the use of ECTR in cases of severe digoxin poisoning when Fab was available (1D) and also suggested against the use of ECTR when Fab was unavailable (2D).. ECTR, in any form, is not indicated for either suspected or proven digoxin toxicity, regardless of the clinical context, and is not indicated for removal of digoxin-Fab complex.

Topics: Animals; Cardiotonic Agents; Consensus; Delphi Technique; Digoxin; Disease Models, Animal; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Randomized Controlled Trials as Topic; Renal Dialysis

Accidental poisoning or overdoses occur frequently in children. These are difficult to recognise because young children cannot communicate their symptoms; this means that specific symptoms can be missed, which can delay the diagnosis. A 5-month-old boy was accidently given a tenfold dose of digoxin for 5 days. He developed feeding difficulties, vomiting, weight loss, elevated urea and creatinine levels, hyponatraemia, hyperkalaemia and ECG abnormalities. The digoxin plasma concentration was 7.6 µg/l. The patient was given digoxin antibodies, following which the digoxin concentration was < 0.3 µg/l; 12 hours later the digoxin concentration was 3.1 µg/l as a result of redistribution; 2 days after the administration of digoxin antibodies the plasma concentration was within the therapeutic range.

Topics: Antibodies; Cardiotonic Agents; Digoxin; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Hyperkalemia; Infant; Male; Medication Errors

While it is relatively uncommon, an overdose of calcium-channel blockers, beta blockers, or digoxin has a significant morbidity and mortality rate, and its management can be complex. Digoxin toxicity can present with an acute overdose or as chronic toxicity while a patient is on therapeutic dosing, which has implications for diagnosis and management. While the patient's specific clinical presentation may depend on factors such as the time of exposure and the type of agent ingested, the differential diagnosis of the bradycardic and hypotensive patient is narrow, and toxicity from these agents must be considered. This review provides an evidence-based overview of the emergency department management of calcium-channel blocker overdose, beta blocker overdose, and digoxin toxicity.

Topics: Adrenergic beta-Antagonists; Calcium Channel Blockers; Critical Pathways; Digoxin; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Emergency Service, Hospital; Humans; Risk Factors

Digoxin is the oldest cardiac medication used in contemporary medicine. With a complex pharmacokinetic profile and narrow therapeutic index, its use in managing patients with atrial arrhythmias or heart failure can present a challenge to today's clinicians. Digoxin dosing based on patient-specific factors such as age, lean body weight, and renal function will allow practitioners to minimize drug toxicity while maintaining clinical efficacy. The ability to recognize digoxin overdose, which can manifest in both the acute and chronic settings, helps guide the appropriate dosing of digoxin immune globulins to reverse toxicity. Understanding this unique medication is essential for clinicians to ensure digoxin is used safely and effectively in practice.

Topics: Atrial Fibrillation; Cardiotonic Agents; Clinical Protocols; Digoxin; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Heart Failure; Heart Rate; Humans; Immunoglobulin Fab Fragments; Myocardial Contraction

The objective of this review is to characterize the mechanisms, risk factors, and offending pharmacotherapeutic agents that may cause drug-induced arrhythmias in critically ill patients. PubMed, other databases, and citation review were used to identify relevant published literature. The authors independently selected studies based on relevance to the topic. Numerous drugs have the potential to cause drug-induced arrhythmias. Drugs commonly administered to critically ill patients are capable of precipitating arrhythmias and include antiarrhythmics, antianginals, antiemetics, gastrointestinal stimulants, antibacterials, narcotics, antipsychotics, inotropes, digoxin, anesthetic agents, bronchodilators, and drugs that cause electrolyte imbalances and bradyarrhythmias. Drug-induced arrhythmias are insidious but prevalent. Critically ill patients frequently experience drug-induced arrhythmias; however, enhanced appreciation for this adverse event has the potential to improve prevention, treatment, patient safety, and outcomes in this patient population.

Topics: Anesthetics, Inhalation; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Bronchodilator Agents; Cardiotonic Agents; Critical Care; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Long QT Syndrome; Risk Factors; Torsades de Pointes; Water-Electrolyte Balance

Medications are commonly used in the elderly population. Because of a variety of treatments now available, many disease states now have very effective treatment. As a result, our elderly patients often take multiple medications. Due to various changes that occur, the elderly are at increased risk of adverse drug effects and drug toxicity potentially resulting in serious complications. Some medications have a greater potential to cause harm and these should be made aware to those who prescribe to elderly patients. Some of these medications should not be used if at all possible, while others, if used, need to be used with great caution, watching carefully for signs of problems. This article describes a variety of medications which have an increased potential for causing harm in elderly patients and gives alternatives of safer medications consideration.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Barbiturates; Benzodiazepines; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Polypharmacy; Warfarin

Numerous medications can trigger diarrhea. In some cases it is a common side effect, and the relationship is evident (e.g. acarbose, somatostatin analogs and antibiotics). When diarrhea does occur, the therapeutic benefit of the drug should be weighed against the negative results of the side effect. If pseudomembranous colitis is suspected, prompt action is required, since a fatal outcome cannot be excluded. A particular challenge is a suspected drug association in a multimorbid patient taking several drugs, each associated with an only low diarrhea risk. In such a case, it may be necessary to discontinue drugs consecutively, or to replace a drug by another, until the diarrhea ceases, without lessening the effectiveness of the treatment.

Topics: Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Antineoplastic Agents; Antirheumatic Agents; Cardiotonic Agents; Diarrhea; Digoxin; Drug-Related Side Effects and Adverse Reactions; Enterocolitis, Pseudomembranous; Female; Gastrointestinal Motility; Hormones; Humans; Hypoglycemic Agents; Male; Radiography, Abdominal; Ultrasonography

Serum drug concentrations have commonly been described in terms of therapeutic ranges within which most patients have a therapeutic effect and a low incidence of toxicity. However, truly individualized drug dosage regimens cannot be developed without first setting a specific individualized target goal, such as a target serum drug concentration, at a desired target time after the dose (usually at a peak or trough), for each patient. For example, it is well known that the dosage of digoxin, or of any drug with a narrow therapeutic range, should somehow be individualized. One can begin this process by considering each patient as an individual, with his/her own individual need for the drug. If the need is small, so is the upper acceptable risk of toxicity. This would lead to a gently regimen, adjusted to the patient's body weight and renal function, to best achieve that specific target goal. Alternatively, if previous therapy has not sufficed and a significant or urgent need exists, then a higher goal may justifiably be selected, a greater risk of toxicity accepted, and a dosage regimen developed to meet that greater need. After such an individualized target goal is chosen, it should be achieved as precisely as possible. After the regimen is given, serum levels need to be measured and an individualized, patient-specific pharmacokinetic model should be made. Without the model, with only the raw serum level data, one cannot perceive the important exchanges that occur between serum and nonserum compartments of the drug, and we lack the precision given by the combination of the assay and the model to evaluate properly, optimally, the patient's clinical sensitivity to the drug. These concepts have been discussed here for digoxin, but they are general and apply to all drugs. This approach has also been applied to therapy with aminoglycoside antibiotics, vancomycin, lidocaine, theophylline, antiviral agents, a variety of anesthetic agents, psychiatric drugs, and anticancer agents.

Topics: Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Individuality; Pharmaceutical Preparations; Pharmacokinetics

There is limited evidence to suggest that the incidence of adverse drug reactions increases with patient age. Factors which may predispose the elderly to adverse drug reactions include multiple drug therapy and changes in pharmacokinetics and pharmacodynamics associated with ageing. Digoxin, diuretics and psychotropic drugs may be particularly hazardous in this age group.

Topics: Aged; Antidepressive Agents; Benzodiazepines; Cohort Studies; Digoxin; Diuretics; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacokinetics

The ten drugs most frequently prescribed in 1977 are identified according to proprietary and non-proprietary names, pharmaceutical manufacturer, drug class, principal uses, and the ocular side effects which have been reported in the medical literature.

Topics: Acetaminophen; Ampicillin; Brompheniramine; Codeine; Diazepam; Digoxin; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Eye; Eye Diseases; Female; Furosemide; Humans; Hydrochlorothiazide; Methyldopa; Phenylephrine; Phenylpropanolamine; Pregnancy; Propranolol; Tetracyclines; Triamterene

Topics: Administration, Oral; Biopharmaceutics; Digoxin; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmaceutical Preparations; Therapeutic Equivalency

Topics: Adrenal Cortex Hormones; Anesthetics; Animals; Carbonic Anhydrase Inhibitors; Cats; Chymotrypsin; Contraceptives, Oral; Digitalis Glycosides; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Guanethidine; Humans; Hypnotics and Sedatives; Intraocular Pressure; Ouabain; Parasympatholytics; Parasympathomimetics; Pargyline; Propranolol; Rabbits; Sympathomimetics; Tranquilizing Agents; Vasodilator Agents

Recent data suggest that P-glycoprotein may be involved in cellular transport of lacosamide.. To investigate potential drug-drug interactions (DDIs) between lacosamide and digoxin, this phase I, multiple-dose, randomised, double-blind, placebo-controlled, crossover trial assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of digoxin administered in combination with lacosamide or placebo.. Twenty healthy White male volunteers were randomised. After receiving digoxin 0.25 mg three times daily on day 1 (loading dose), participants received digoxin 0.25 mg once daily on days 2-22. Participants received either lacosamide (200 mg twice daily) or placebo on days 8-11 and vice versa on days 18-21, after a 6-day washout. The steady-state area under concentration-time curve over the dosing interval (AUC(24,ss)) and maximum steady-state plasma concentration (C(max,ss)) of digoxin were measured; ratios of these parameters for co-administration of digoxin + lacosamide versus digoxin alone were used to evaluate potential DDIs. Interaction was excluded if the 90 % confidence interval (CI) for the geometric mean ratio of AUC24,ss and C max,ss fell within the acceptance range for bioequivalence (0.8-1.25).. The point estimates (90 % CI) of the geometric mean ratios for co-administration of digoxin with lacosamide versus digoxin alone for AUC(24,ss) [1.024 (0.979-1.071)] and C(max,ss) [1.049 (0.959-1.147)] were within the acceptance range for bioequivalence. Digoxin and lacosamide co-administration was generally well-tolerated. A small numerical increase in the mean PR interval following co-administered digoxin + lacosamide was observed versus digoxin alone and versus pre-treatment baseline values (178.5 vs. 170.4 or 166.8 ms, respectively). The RR interval increased in parallel. The change was not considered clinically relevant.. Co-administration of steady-state digoxin (0.25 mg/day) with multiple-dose lacosamide (400 mg/day) versus digoxin alone revealed no differences in digoxin disposition.

Topics: Acetamides; Adolescent; Adult; Cross-Over Studies; Digoxin; Double-Blind Method; Drug Tolerance; Drug-Related Side Effects and Adverse Reactions; Healthy Volunteers; Humans; Lacosamide; Male; Middle Aged; Placebos; Young Adult

Topics: Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin Fragments; Prospective Studies; Registries; United Kingdom

Digoxin toxicity (plasma digoxin concentration ≥0.9 ng/mL) is associated with worsening heart failure (HF). Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of adverse drug reactions. The present study aimed to construct a flowchart using DT analysis that can be used by medical staff to predict digoxin toxicity. We conducted a multicenter retrospective study involving 333 adult patients with HF who received oral digoxin treatment. In this study, we employed a chi-squared automatic interaction detection algorithm to construct DT models. The dependent variable was set as the plasma digoxin concentration (≥ 0.9 ng/mL) in the trough during the steady state, and factors with p < 0.2 in the univariate analysis were set as the explanatory variables. Multivariate logistic regression analysis was conducted to validate the DT model. The accuracy and misclassification rates of the model were evaluated. In the DT analysis, patients with creatinine clearance <32 mL/min, daily digoxin dose ≥1.6 µg/kg, and left ventricular ejection fraction ≥50% showed a high incidence of digoxin toxicity (91.8%; 45/49). Multivariate logistic regression analysis revealed that creatinine clearance <32 mL/min and daily digoxin dose ≥1.6 µg/kg were independent risk factors. The accuracy and misclassification rates of the DT model were 88.2 and 46.2 ± 2.7%, respectively. Although the flowchart created in this study needs further validation, it is straightforward and potentially useful for medical staff in determining the initial dose of digoxin in patients with HF.

Topics: Adult; Cardiotonic Agents; Creatinine; Digoxin; Drug-Related Side Effects and Adverse Reactions; Heart Failure; Humans; Machine Learning; Retrospective Studies; Stroke Volume; Ventricular Function, Left

Topics: Cardiovascular Agents; Digoxin; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin Fab Fragments

Topics: Cardiovascular Agents; Digoxin; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Humans

Topics: Cardiovascular Agents; Digoxin; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Heart Rate; Hospitalization; Humans; Immunoglobulin Fab Fragments; Potassium

Topics: Digoxin; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Humans; Myocardial Infarction; Phenytoin; Tachycardia

Topics: Cardiovascular Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin Fab Fragments; Poisoning

Topics: COVID-19 Drug Treatment; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans

For acute digoxin poisoning, it has been recommended to give bolus doses of 10-20 vials or potentially larger than needed doses calculated from dose ingested or the measured concentration. However, a recent revision of internal Poisons Information Centre guidelines prompted a change of our recommendations, specifically instead of large boluses, to use titrating repeated low doses of digoxin antibodies(Digoxin-Fab) based on bedside assessment of cardiac toxicity.. This is a prospective observational study of patients with acute digoxin poisoning identified through two Poisons Information Centres and three toxicology units. Patient demographics, signs and symptoms of digoxin toxicity, doses and response to Digoxin-Fab, free and bound serum digoxin concentrations. Outcomes were recorded and analysed.. From September 2013 to September 2020, 23 patients with 25 presentations (median age 56 years, females 56%) were recruited. Median dose ingested was 13 mg(IQR: 9.5-25). Median heart rate (HR) was 41 beats/min before treatment. Initial median digoxin and potassium concentrations were 14.5 nmol/L (IQR: 10.9-20) [11.2 µg/L(IQR: 8.4-15.4)] and 5 mmol/L (IQR: 4.5-5.4 mmol/L), respectively. Gastrointestinal symptoms and acute kidney injury were present in 22 patients (88%) and 5 patients (20%), respectively. Four patients received an initial bolus dose of Digoxin-Fab of 5-20 vials. Twenty-one patients received repeated titrated doses (1-2 vials) of Digoxin-Fab and the median total dose was 4 vials (IQR: 2-7.5). Median maximal change in HR post-Digoxin-Fab was 19 beats/min. The median potassium concentration decrease post-Digoxin-Fab was 0.3 mmol/L. Total dose used in the titration group was 25% and 35% of the predicted doses based on the amount of digoxin ingested or measured serum concentration, respectively. Twelve had free digoxin concentrations measured. Free digoxin concentrations dropped to almost zero after any dose of Digoxin-Fab. Ten patients had a rebound of digoxin >2.6 nmol/L (2 µg/L). There were no deaths from acute digoxin toxicity.. The new practice of using small, titrated doses of Digoxin-Fab led to a considerable reduction in total usage and major savings. The clinical response to titrated doses was safe and acceptable in acute digoxin poisoning.

Topics: Cardiovascular Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Immunoglobulin Fab Fragments; Middle Aged; Poisoning; Potassium

Digoxin is a cardiac glycoside, used to control rapid ventricular rates in atrial fibrillation and to reduce the hospitalizations due to heart failure. Digoxin has a narrow therapeutic range. So, in the treatment of older patients (≥ 65 years), it is important to set the optimal dose of digoxin to prevent toxicity and therapeutic drug monitoring of digoxin trough plasmatic concentration (C0) may be useful.. To assess measured C0, to evaluate age influence on digoxin pharmacokinetic parameters and to report adverse events in patients administered digoxin.. It consisted in a retrospective study. We included all the patients addressed to the department of clinical pharmacology for digoxin C0 measurement by an automated fluorescence polarization immunoassay. Therapeutic ranges of digoxin C0 were: 1 to 2.5 ng.mL-1 in children, 0.8 to 2 ng.mL-1 in adults and 0.5 to 0.9 ng.mL-1 in older adults (≥ 65 years) in atrial fibrillation and heart failure.. We collected 183 samples from 132 patients. Sex ratio M/W was 0.47. Mean age was 60 years and 57% of patients were older adults. Mean dose of digoxin was 0.3 mg.day-1. In older adults, 45% were administered daily doses over 0.125 mg.day-1. Mean digoxin C0 was 1.6 ng.mL-1. There was more supra-therapeutic C0 in older adults than younger ones (p<0.0001).There was no correlation between C0 and daily dose of digoxin. Adverse events, mainly cardiac and digestive, were reported in 47 patients (36%), among this population 47% were older adults.. TDM is useful to prevent toxicity, mainly in older adults where diagnosis may be difficult to establish.

Topics: Adolescent; Adult; Age Factors; Age of Onset; Aged; Aged, 80 and over; Atrial Fibrillation; Child; Child, Preschool; Digoxin; Dose-Response Relationship, Drug; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Male; Middle Aged; Retrospective Studies; Young Adult

We present a man undergoing regular haemodialysis sessions, who presented with non-specific symptoms of nausea, vomiting and light-headedness. He was found to have significantly raised serum digoxin concentrations, as well as a heart rate of 30 beats per minutes. An ECG showed complete heart block. He has a history of non-ischaemic dilated cardiomyopathy with resistant supraventricular and ventricular tachycardias and was on concomitant beta-blockade and digoxin. On questioning, he reported a gradual decline in his residual urine output over the past 6 months. He was reviewed by the cardiology team and required both pharmacological therapy for reversal of digoxin toxicity and temporary pacing in view of significant bradyarrhythmias. The beta-blockade and digoxin were discontinued. He was kept on continuous monitoring at the Cardiac Critical Care Unit. His symptoms resolved spontaneously once digoxin-specific antibody fragments were administered and temporary pacing successfully performed.

Topics: Aged; Anti-Arrhythmia Agents; Bradycardia; Cardiac Pacing, Artificial; Cardiomyopathy, Dilated; Digoxin; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Humans; Immunoglobulin Fab Fragments; Kidney Failure, Chronic; Male; Protective Agents; Renal Dialysis; Risk Adjustment; Tachycardia, Supraventricular; Treatment Outcome

Digoxin is a cardiac glycoside that is used for the treatment of heart failure and atrial fibrillation. Besides its careful close follow-up, toxicity affects nearly 1% of congestive heart failure patients. Cessation of the drug, appropriate electrolyte and rhythm control and digoxin-Fab antibody are the mainstay for toxicity treatment in these patients. As known, hemodialysis and peritoneal dialysis are not effective by the means of digoxin removal. We present a 66-year-old patient who admitted to hospital with digoxin toxicity and severe acute kidney injury. The patient was treated with continuous venovenous hemodialysis because of her hypervolemia, hyperkalemia, cardiac instability, and the thought of probable decrease in digoxin levels concerning the continuous nature of solute clearance. Without the treatment using digoxin-specific Fab antibodies, the patient's digoxin level was decreased successfully with continuous venovenous hemodialysis. In conclusion, continuous venovenous hemodialysis may be a treatment option in digoxin toxicity especially those who suffer from severe renal dysfunction and cannot access digoxin antidote.

Topics: Aged; Continuous Renal Replacement Therapy; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Renal Dialysis

Mutlu M, Aslan Y, Kader Ş, Aktürk-Acar F, Dilber E. Clinical signs and symptoms of toxic serum digoxin levels in neonates. Turk J Pediatr 2019; 61: 244-249. Digoxin is widely used in the treatment of congestive heart failure and some arrhythmias. Digoxin toxicity may occur easily because digoxin has a narrow therapeutic index. This retrospective study was conducted to evaluate the clinical signs and symptoms of toxic serum digoxin levels in neonates. Medical reports of the neonates who had serum digoxin concentrations > 2 nanogram/milliliter (ng/ml) were reviewed in terms of patient demographics, serum digoxin concentrations, signs and symptoms of digoxin toxicity, serum digoxin and electrolyte levels, renal function tests, electrocardiograms, echocardiography, and treatments applied. Digoxin toxic levels were identified in the 13 neonates. Of the 13 neonates with digoxin toxic level, 9 (69%) were term and 8 (62%) were female. Twenty-three percent (3/13) of newborn infants were symptomatic. Symptomatic patients had statistically significantly higher serum digoxin levels, at 7.76±2.76 (5.4-10.8) ng/ml, than asymptomatic patients, at 3.31±1.09 (2.02-4.95) (p=0.036). Symptoms related to toxic digoxin levels were observed in the three neonates with plasma digoxin levels > 5 ng/ml. Gastrointestinal and central nervous system symptoms were the major clinic findings. Despite high digoxin levels, no digoxin-related arrhythmia was observed on electrocardiography, other than sinus bradycardia. Two premature neonates were treated with digoxin-specific antibody Fab fragments (DigiFab®) and hypokalemia developed in both of them. Our data suggests that symptoms related with digoxin toxic levels were observed in neonates with plasma digoxin levels > 5 ng/ml. Serum digoxin levels should be measured in case of signs and symptoms of digoxin toxicity or risk factors for such toxicity.

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Immunoassay; Infant, Newborn; Male; Retrospective Studies; Risk Factors

The aim of the present study was to compare clinical features of patients with elevated serum digoxin concentrations who were treated with digoxin-Fab with those where the immunotherapy was not given by a tertiary hospital toxicology service.. This was a retrospective series of patients with supratherapeutic serum digoxin concentrations referred to the toxicology service from August 2013 to October 2015. Data collected included demographics, presenting complaint, digoxin dose, other medications taken, serum digoxin, potassium and creatinine concentration on presentation and initial and post-digoxin-Fab heart rate.. There were 47 referrals. Digoxin-Fab was administered in 21 cases. It was given more commonly when the heart rate was <51/min or serum potassium was >5.0 mmol/L. Patients receiving digoxin-Fab were more likely to be on maintenance therapy with beta-blockers or calcium channel blockers (95% vs 61%; OR 13.1; 95% CI 1.5-113) and/or potassium-sparing medications (95% vs 54%; OR 17.1; 95% CI 2.0-147). They had elevated serum creatinine (76% vs 42%; OR 8.2; 95% CI 1.9-34), higher serum potassium (median: 5.1 mmol/L vs 4.2 mmol/L, P = 0.02), higher serum digoxin concentration (median: 3.5 nmol/L vs 2.3 nmol/L, P = 0.02) and pretreatment heart rate <51/min (66% vs 31%; OR 4.5; 95% CI 1.3-15). There were no patients with ventricular arrhythmias or hypotension. Median heart rate increased by 10/min 1 and 4 h after digoxin-Fab. However, individual heart rate response to digoxin-Fab was variable.. Digoxin-Fab was more commonly administered when heart rate was <51/min. It had a small effect on increasing heart rate; however, individual response to digoxin-Fab was variable as patients were using other negative chronotropic medications. In symptomatic bradycardic patients on multiple heart failure medications, positive chronotropic and potassium-lowering therapies should be considered in concert with digoxin-Fab.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Cohort Studies; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Heart Rate; Humans; Male; Retrospective Studies; Victoria

Digoxin is a high-alert medication because of its narrow therapeutic range and high drug-to-drug interactions (DDIs). Approximately 50% of digoxin toxicity cases are preventable, which motivated us to improve the treatment outcomes of digoxin. The objective of this study is to apply machine learning techniques to predict the appropriateness of initial digoxin dosage. A total of 307 inpatients who had their conditions treated with digoxin between 2004 and 2013 at a medical center in Taiwan were collected in the study. Ten independent variables, including demographic information, laboratory data, and whether the patients had CHF were also noted. A patient with serum digoxin concentration being controlled at 0.5-0.9 ng/mL after his/her initial digoxin dosage was defined as having an appropriate use of digoxin; otherwise, a patient was defined as having an inappropriate use of digoxin. Weka 3.7.3, an open source machine learning software, was adopted to develop prediction models. Six machine learning techniques were considered, including decision tree (C4.5),

Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Decision Support Systems, Clinical; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Machine Learning; Male; Middle Aged; Young Adult

Topics: Antibodies; Cardiovascular Agents; Chronic Disease; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans

Topics: Cardiovascular Agents; Chronic Disease; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans

Topics: Aged; Atrial Fibrillation; Cardiovascular Agents; Contraindications; Digoxin; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; Heart Failure, Diastolic; Humans; Hypertension; Renal Insufficiency, Chronic; Treatment Outcome; Withholding Treatment

Hospital mortality related to adverse drug reactions (ADRs) is a relevant clinical problem with major health and economic consequences. We conducted a study to assess hospital mortality related to ADRs, the drugs most frequently involved, and the possible risk factors associated with fatal ADRs.. A retrospective observational study was conducted, reviewing the clinical records of 1388 consecutive adult patients (18-101 years) who died during a 22-month period in a tertiary hospital in Southern Europe (Granada, Spain). The main outcome was the prevalence of hospital death suspected to be related to administered drugs.. Out of the 1388 adult deaths studied, 256 (18.4 %) were suspected of being related to drugs. Drugs were suspected of causing death in 146 inpatients (10.5 %) and contributing to death in 110 (7.9 %). Drugs related to death were administered during the hospital stay in 161 cases (11.5 %) and before hospital admission in 95 (6.84 %). The most frequent fatal ADRs were cardiac arrhythmia, gastrointestinal bleeding, and respiratory failure. The drugs most frequently involved in fatal ADRs were antithrombotics (anticoagulants or antiplatelets) (23 %), psychotropic drugs (21.2 %), and digoxin (11.3 %). Independent risk factors for ADR-related death were the presence of ≥4 diseases (OR = 1.43) and the receipt of ≥10 drugs (OR = 3.24), but no significant association with gender or age was found.. A high percentage of hospital deaths were suspected of being associated with ADRs, especially in patients with comorbidity and/or polypharmacy. Antithrombotics, psychotropics, and digoxin were the drugs most frequently associated with in-hospital drug-related deaths.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Fibrinolytic Agents; Hospital Mortality; Humans; Inpatients; Male; Middle Aged; Psychotropic Drugs; Spain; Young Adult

Topics: Acute Kidney Injury; Aged; Agglutinins; Anti-Arrhythmia Agents; Atrial Fibrillation; Bradycardia; Digoxin; Dosage Forms; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Fatigue; Humans; Male; Treatment Outcome; Vision Disorders; Vomiting

Topics: Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin Fab Fragments

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Heart Conduction System; Humans; Hypokalemia; Male

Topics: Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin Fab Fragments

Topics: Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin Fab Fragments

Patients with chronic diseases often receive multiple medications and are associated with increased vulnerability to medication errors. Identifying high-alert medications for them would help to prioritize the interventions with greatest impact for improving medication safety. The aim of this study was to develop a list of high-alert medications for patients with chronic illnesses (HAMC list) that would prove useful to the Spanish National Health Service strategies on chronicity.. The RAND/UCLA appropriateness method was used. Drug classes/drugs candidates to be included on the HAMC list were identified from a literature search in MedLine, bulletins issued by patient safety organizations, incidents recorded in Spanish incident reporting systems, and previous lists. Eighteen experts in patient/medication safety or in chronic diseases scored candidate drugs for appropriateness according to three criteria (evidence, benefit and feasibility of implementing safety practices). Additionally they rated their priority of inclusion on a Likert scale.. The final HAMC list includes 14 drug classes (oral anticoagulants, narrow therapeutic range antiepileptics, antiplatelets - including aspirin -, antipsychotics, β-blockers, benzodiazepines and analogues, corticosteroids long-term use, oral cytostatics, oral hypoglycemic drugs, immunosuppressants, insulins, loop diuretics, nonsteroidal anti-inflammatory drugs, and opioid analgesics), and 4 drugs or pairs of drugs (amiodarone/ dronedarone, digoxin, oral methotrexate and spironolactone/eplerenone).. An initial list of high-alert medications for patients with chronic diseases has been developed, which can be built into the medication management strategies for chronicity to guide the implementation of efficient safety strategies and to identify those patients at greater risk for preventable adverse drug events.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Amiodarone; Analgesics, Opioid; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Cytostatic Agents; Digoxin; Dronedarone; Drug-Related Side Effects and Adverse Reactions; Eplerenone; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Methotrexate; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Spironolactone

Topics: Age Factors; Aged, 80 and over; Aging; Digitoxin; Digoxin; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Half-Life; Humans; Medication Errors; Patient Safety

Drug-induced liver injury is the most common cause of market withdrawal of pharmaceuticals, and thus, there is considerable need for better prediction models for DILI early in drug discovery. We present a study involving 223 marketed drugs (51% associated with clinical hepatotoxicity; 49% non-hepatotoxic) to assess the concordance of in vitro bioactivation data with clinical hepatotoxicity and have used these data to develop a decision tree to help reduce late-stage candidate attrition. Data to assess P450 metabolism-dependent inhibition (MDI) for all common drug-metabolizing P450 enzymes were generated for 179 of these compounds, GSH adduct data generated for 190 compounds, covalent binding data obtained for 53 compounds, and clinical dose data obtained for all compounds. Individual data for all 223 compounds are presented here and interrogated to determine what level of an alert to consider termination of a compound. The analysis showed that 76% of drugs with a daily dose of <100 mg were non-hepatotoxic (p < 0.0001). Drugs with a daily dose of ≥100 mg or with GSH adduct formation, marked P450 MDI, or covalent binding ≥200 pmol eq/mg protein tended to be hepatotoxic (∼ 65% in each case). Combining dose with each bioactivation assay increased this association significantly (80-100%, p < 0.0001). These analyses were then used to develop the decision tree and the tree tested using 196 of the compounds with sufficient data (49% hepatotoxic; 51% non-hepatotoxic). The results of these outcome analyses demonstrated the utility of the tree in selectively terminating hepatotoxic compounds early; 45% of the hepatotoxic compounds evaluated using the tree were recommended for termination before candidate selection, whereas only 10% of the non-hepatotoxic compounds were recommended for termination. An independent set of 10 GSK compounds with known clinical hepatotoxicity status were also assessed using the tree, with similar results.

Topics: Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Decision Trees; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Glutathione; Humans; Liver; Pharmaceutical Preparations; Protein Binding

Drug-induced liver injury (DILI) is a leading cause of drugs failing during clinical trials and being withdrawn from the market. Comparative analysis of drugs based on their DILI potential is an effective approach to discover key DILI mechanisms and risk factors. However, assessing the DILI potential of a drug is a challenge with no existing consensus methods. We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts. The method is transparent and reproducible with a potential to serve as a common practice to study the DILI of marketed drugs for supporting drug discovery and biomarker development.

Topics: Animals; Benchmarking; Biomarkers, Pharmacological; Chemical and Drug Induced Liver Injury; Drug Design; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmaceutical Preparations; Reproducibility of Results; United States; United States Food and Drug Administration

Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60-70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the "Rule of Three" was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Chemical and Drug Induced Liver Injury; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Models, Biological; Predictive Value of Tests

Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity.. This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94).. The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.

Topics: Aged; Aged, 80 and over; Anthraquinones; Case-Control Studies; Constipation; Digoxin; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Male; Middle Aged; Senna Extract; Sennosides

Topics: Digoxin; Drug Combinations; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Imidazoles; Male; Propantheline

The chemical space of registered oral drugs was explored for inhibitors of the human multidrug-resistance associated protein 2 (MRP2; ABCC2), using a data set of 191 structurally diverse drugs and drug-like compounds. The data set included a new reference set of 75 compounds, for studies of hepatic drug interactions with transport proteins, CYP enzymes, and compounds associated with liver toxicity. The inhibition of MRP2-mediated transport of estradiol-17beta-D-glucuronide was studied in inverted membrane vesicles from Sf9 cells overexpressing human MRP2. A total of 27 previously unknown MRP2 inhibitors were identified, and the results indicate an overlapping but narrower inhibitor space for MRP2 compared with the two other major ABC efflux transporters P-gp (ABCB1) and BCRP (ABCG2). In addition, 13 compounds were shown to stimulate the transport of estradiol-17beta-D-glucuronide. The experimental results were used to develop a computational model able to discriminate inhibitors from noninhibitors according to their molecular structure, resulting in a predictive power of 86% for the training set and 72% for the test set. The inhibitors were in general larger and more lipophilic and presented a higher aromaticity than the noninhibitors. The developed computational model is applicable in an early stage of the drug discovery process and is proposed as a tool for prediction of MRP2-mediated hepatic drug interactions and toxicity.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Antipsychotic Agents; Antiviral Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Biological Transport; Cell Line; Computer Simulation; Cytochrome P-450 Enzyme System; Drug-Related Side Effects and Adverse Reactions; Estradiol; Humans; Insecta; Liver; Models, Molecular; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Pharmaceutical Preparations; Pharmacology; Structure-Activity Relationship

We hypothesized that digoxin toxicity has declined in recent years, and that the decline is accompanied by reductions in overall utilization and dose. To analyze trends in digoxin toxicity and utilization from 1991 to 2004, we used surveys from the National Center for Health Statistics and Medicaid data in the United States and The Health Improvement Network (THIN) database in the United Kingdom. There was a significant decline in digoxin toxicity hospitalizations in the United States and a decline in ambulatory digoxin toxicity in the United Kingdom. The study demonstrated a reduction in the use of digoxin in the United States, but found no change in digoxin use in the United Kingdom. Finally, the number of prescriptions written for at least 250 microg decreased in the United States and the United Kingdom. The public health burden of digoxin toxicity declined dramatically from 1991 to 2004 in the United Kingdom and the United States.

Topics: Ambulatory Care; Databases, Factual; Digoxin; Drug-Related Side Effects and Adverse Reactions; Hospitalization; Humans; Public Health; United Kingdom; United States

Older people experience more concurrent illnesses, are prescribed more medications and suffer more adverse drug events than younger people. Many drugs predispose older people to adverse events such as falls and cognitive impairment, thus increasing morbidity and health resource utilization. At the same time, older people are often denied potentially beneficial, clinically indicated medications without a valid reason. We aimed to validate a new screening tool of older persons' prescriptions incorporating criteria for potentially inappropriate drugs called STOPP (Screening Tool of Older Persons' Prescriptions) and criteria for potentially appropriate, indicated drugs called START (Screening Tool to Alert doctors to Right, i.e. appropriate, indicated Treatment).. A Delphi consensus technique was used to establish the content validity of STOPP/START. An 18-member expert panel from academic centers in Ireland and the United Kingdom completed two rounds of the Delphi process by mail survey. Inter-rater reliability was assessed by determining the kappa-statistic for measure of agreement on 100 data-sets.. STOPP is comprised of 65 clinically significant criteria for potentially inappropriate prescribing in older people. Each criterion is accompanied by a concise explanation as to why the prescribing practice is potentially inappropriate. START consists of 22 evidence-based prescribing indicators for commonly encountered diseases in older people. Inter-rater reliability is favorable with a kappa-coefficient of 0.75 for STOPP and 0.68 for START.. STOPP/START is a valid, reliable and comprehensive screening tool that enables the prescribing physician to appraise an older patient's prescription drugs in the context of his/her concurrent diagnoses.

Topics: Abbreviations as Topic; Age Factors; Aged; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Bendroflumethiazide; Clopidogrel; Delphi Technique; Digoxin; Diuretics; Drug Prescriptions; Drug Therapy; Drug Utilization Review; Drug-Related Side Effects and Adverse Reactions; Glomerular Filtration Rate; Health Services for the Aged; Humans; Ireland; Metformin; Practice Patterns, Physicians'; Reproducibility of Results; Risk Factors; Ticlopidine; Time Factors; United Kingdom

We sought to examine the validity of specific hospital discharge codes in identifying drug toxicity precipitating hospitalization, among elderly users of high-risk medications.. We conducted a cross-sectional evaluation assessing the diagnostic test characteristics of International Classification of Diseases-9 External-Cause-of-Injury codes (E-codes) compared with a reference standard of medical record review. This study was nested within a prospective cohort of elders using warfarin, digoxin, or phenytoin as identified in the Pharmaceutical Assistance Contract for the Elderly benefit program.. We identified 4,803 subjects contributing 11,409 person-years of exposure to at least one of three drug groups. Subjects experienced 8,756 hospitalizations, of which 304 were deemed, by expert review, to be a result of an adverse event of warfarin, digoxin, or phenytoin. The sensitivity, specificity, and positive (PPVs) and negative predictive values for drug-specific E-codes were warfarin--25.5%, 98.3%, 46.6%, and 95.7%; digoxin--84.0%, 99.1%, 56.8%, and 99.8%; and phenytoin--86.7%, 98.7%, 59.1%, and 99.7%.. E-codes for digoxin and phenytoin have a high sensitivity, but E-codes for all three medications have poor PPVs, a result that might produce misclassification in studies based solely on discharge coding. Investigators should confirm such rare events via medical record review.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Anti-Arrhythmia Agents; Anticoagulants; Anticonvulsants; Cross-Sectional Studies; Digoxin; Drug-Related Side Effects and Adverse Reactions; Forms and Records Control; Hospitalization; Humans; International Classification of Diseases; Medical Records; Patient Discharge; Pennsylvania; Phenytoin; Warfarin

Reduced renal function requires dose adjustment for certain drugs to avoid toxicity. The aim of this study was to determine whether appropriate dosage adjustments were made for drugs that are nephrotoxic, excreted, or metabolized (TEM medications) by the kidney in patients with renal impairment.. A cross-sectional study of a group of hospitalized patients was carried out at Al-Watni governmental hospital, Nablus, Palestine. All patients with creatinine clearance

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Creatinine; Cross-Sectional Studies; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Hospital Bed Capacity, 100 to 299; Hospitals, Public; Humans; Israel; Male; Medication Errors; Middle Aged; Models, Statistical; Pharmaceutical Preparations; Pharmacokinetics; Ranitidine; Renal Insufficiency

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Cross-Sectional Studies; Digoxin; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Emergency Service, Hospital; Humans; Hypoglycemic Agents; Insulin; Medical Errors; United States; Warfarin

The Beers criteria identify inappropriate use of medications in older adults. The number of and risk for adverse events from these medications are unknown.. To estimate the number of and risk for emergency department visits for adverse events involving Beers criteria medications compared with other medications.. Nationally representative, public health surveillance of adverse drug events and a cross-sectional survey of outpatient medical visits.. National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance System, 2004-2005; National Ambulatory Medical Care Survey, 2004; and National Hospital Ambulatory Medical Care Survey, 2004.. Persons 65 years of age or older seeking emergency department and outpatient care.. Estimated number of and risks for emergency department visits for adverse drug events involving Beers criteria medications and other medications.. Among U.S. patients 65 years of age or older, an estimated 177,504 emergency department visits (95% CI, 100,155 to 254,854 visits) for adverse drug events occurred both years. An estimated 3.6% (CI, 2.8% to 4.5%) of these visits were for adverse events medications considered to be always potentially inappropriate, according to the Beers criteria, and 33.3% (CI, 27.8% to 38.7%) of visits were for adverse events from 3 other medications (warfarin [17.3%], insulin [13.0%], and digoxin [3.2%]). Accounting for outpatient prescription frequency, the risk for emergency department visits for adverse events due to these 3 medications was 35 times (CI, 9.6 to 61) greater than that for medications considered to be always potentially inappropriate.. Adverse events were identified only in emergency departments.. Compared with other medications, Beers criteria medications caused low numbers of and few risks for emergency department visits for adverse events. Performance measures and interventions targeting warfarin, insulin, and digoxin use could prevent more emergency department visits for adverse events.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Cross-Sectional Studies; Digoxin; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Emergency Service, Hospital; Humans; Hypoglycemic Agents; Insulin; Medical Errors; United States; Warfarin

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Female; Heart Failure; Humans; Male

Topics: Aged; Anti-Bacterial Agents; Cardiotonic Agents; Clarithromycin; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Intestinal Mucosa; Treatment Outcome

Depression is a common disorder among hospitalized older adults, and it has been associated with adverse outcomes during hospital stays, including increased risk of morbidity and mortality and reduced recovery rates from illness and disability. The aim of this study was to assess whether depression may be a risk factor for adverse drug reactions (ADRs) among hospitalized older adults.. A total of 3134 older patients admitted to 23 hospitals throughout Italy between May 1 and June 30 and September 1 and October 31, 1998, entered the study. Patients with a short-form Geriatric Depression Scale score of 5 or greater were considered depressed. Adverse drug reactions observed during hospital stays and classified as definite or probable on the basis of the Naranjo algorithm were considered for this study.. During the hospital stays, 192 ADRs were identified in 183 patients (5.8% of the sample). Cardiovascular and arrhythmic complications (20.3% of all ADRs) were the most frequent ADRs, followed by gastrointestinal (18.8%), dermatologic and allergic (12.5%), hemorrhagic (11.5%), and electrolyte (9.9%) disturbances. Adverse drug reactions were recorded in 101 (7.4%) of 1363 depressed patients and in 82 (4.6%) of 1771 nondepressed patients (P =.001). After adjusting for potential confounders, depression was associated with a significantly higher rate of ADRs (odds ratio, 1.58; 95% confidence interval, 1.14-2.20; P =.006). This effect seemed more pronounced in women (odds ratio, 1.85; 95% confidence interval, 1.16-2.95) than in men (odds ratio, 1.38; 95% confidence interval, 0.85-2.34).. In older hospitalized patients, depression seems to be associated with a greater occurrence of ADRs.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Anxiety Agents; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Benzodiazepines; Depression; Digoxin; Diuretics; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Inpatients; Italy; Male; Odds Ratio; Psychiatric Status Rating Scales; Risk Assessment; Risk Factors; Severity of Illness Index

Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized.. To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission.. Three population-based, nested case-control studies.. Ontario, Canada, from January 1, 1994, to December 31, 2000.. All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors).. Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date.. During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively).. Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Asthmatic Agents; Anti-Infective Agents; Antihypertensive Agents; Case-Control Studies; Clarithromycin; Contraindications; Digoxin; Diuretics; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Glyburide; Hospitalization; Humans; Hyperkalemia; Hypoglycemia; Male; Ontario; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the prevalence of adverse drug reaction (ADR)-related hospital admissions in an older population, to describe the most common clinical manifestations and drugs most frequently responsible for ADR-related hospital admissions, and to identify independent factors predictive of these ADRs.. Multicenter pharmacoepidemiology survey conducted between 1988 and 1997.. Eighty-one academic hospitals throughout Italy.. Twenty-eight thousand four hundred eleven patients consecutively admitted to participating centers during the survey periods.. For each suspected ADR at admission, a physician, who coded description, severity, and potentially responsible drugs, completed a questionnaire.. Mean age +/- standard deviation of the patients was 70 +/- 16. One thousand seven hundred four ADRs were identified upon hospital admission. In 964 cases (3.4% of all admissions), ADRs were considered to be the cause of these hospital admissions. Of these, 187 ADRs were coded as severe. Gastrointestinal complaints (19%) represented the most common events, followed by metabolic and hemorrhagic complications (9%). The drugs most frequently responsible for these ADRs were diuretics, calcium channel blockers, nonsteroidal antiinflammatory drugs, and digoxin. Female sex (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.10-1.54), alcohol use (OR = 1.39, 95% CI = 1.20-1.60), and number of drugs (OR = 1.24, 95% CI = 1.20-1.27 for each drug increase) were independent predictors of ADR-related hospital admissions. For severe ADRs, age (OR = 1.50, 95% CI = 1.01-2.23 for age 65-79 and OR = 1.53, 95% CI = 1.00-2.33 for age > or =80, respectively), comorbidity (OR = 1.12, 95% CI = 1.05-1.20 for each point in the Charlson Comorbidity Index), and number of drugs (OR = 1.18, 95% CI = 1.11-1.25 for each drug increase) were the only predisposing factors.. The most important determinant of risk for ADR-related hospital admissions in older patients is number of drugs being taken. When considering only severe ADRs, risk is also related to age and frailty.

Topics: Aged; Alcohol Drinking; Anti-Inflammatory Agents, Non-Steroidal; Calcium Channel Blockers; Comorbidity; Digoxin; Diuretics; Drug-Related Side Effects and Adverse Reactions; Female; Gastrointestinal Diseases; Hemorrhage; Humans; Male; Metabolic Diseases; Patient Admission; Risk Factors; Sex Factors; Surveys and Questionnaires

Topics: Cardiotonic Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; HIV Infections; Humans; Middle Aged

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digitalis; Digoxin; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Heart Conduction System; Humans; Male

The purpose of this study was to document adverse drug reaction (ADR)-related hospitalizations from a nursing facility population.. This 4-year prospective observational study used monthly repeated measures of 332 residents present for 30 or more days. The review included admission and monthly drug regimen review for each resident. Each probable ADR was sent with monthly reports to attending physicians and charge nurses.. There were 64 ADR-associated hospitalizations in 52 of the 332 residents (15.7%). The most common events were for nonsteroidal anti-inflammatory drugs (NSAIDs) (30), psychotropic-related fall with fracture (14), digoxin toxicity (5), and insulin hypoglycemia (4). Five patients had recurrence of the hospitalization for the same problem. A significant factor noted between ADR hospitalized and non-ADR residents was the number of medications per patient (7.9 +/- 2.6 vs 3.3 +/- 1.3) for the same number of problems.. Adverse drug reaction-related hospitalizations may affect as many as one of every seven nursing home residents and appear to be related to polypharmacy as well as inattention to patient history of contraindications and previous ADRs.

Topics: Accidental Falls; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Homes for the Aged; Hospitalization; Humans; Insulin; Male; Nursing Homes; Polypharmacy; Prospective Studies; Psychotropic Drugs

The Adverse Drug Reaction program at CSMC identifies patients whose charts have been encoded with an ICD-9 code of E930 through E949, inclusively. Incidences per drug or drug category have permitted the Department of Pharmacy, acting through the Pharmacy and Therapeutics Committee, to review patient charts, identify trends and risk factors, and subsequently develop usage criteria for DUE studies. It is hoped that these activities will result in an improvement in usage of these drugs and a reduction in adverse drug reactions to them.

Topics: Digoxin; Drug Utilization; Drug-Related Side Effects and Adverse Reactions; Evaluation Studies as Topic; Hospital Bed Capacity, 500 and over; Humans; Los Angeles; Pharmacy and Therapeutics Committee; Product Surveillance, Postmarketing

The use of population-based serum drug concentration cutoff values for several commonly monitored drugs as tests to distinguish toxicity from nontoxicity was studied. Serum drug concentration and response data published in studies of theophylline, digoxin, aminoglycosides, vancomycin, and procainamide were analyzed to determine the prevalence of toxicity in each group of patients. Serum drug concentration cutoff values were then varied, and the following performance characteristics of the cutoffs as tests for predicting toxicity were calculated for each value: sensitivity, specificity, likelihood ratio, predictive value, and ratio of net consequences. At commonly accepted cutoff values, sensitivity was lower than desirable, positive predictive values were less than negative values, and the ratio of net consequences indicated that false-negative errors are implicitly weighted as more risky than false-positive errors. As the cutoff for each drug was increased, specificity increased but sensitivity decreased, positive predictive values increased but negative predictive values decreased, and the ratio of net consequences increased. Therapeutic drug monitoring would improve if practitioners and laboratorians collaborated to (1) conduct prospective studies of the test performance characteristics of drug concentrations, (2) estimate the pretest probability of toxicity for each patient, (3) combine the pretest estimate with the test characteristics to make a posttest estimate, and (4) develop a more patient-specific, Bayesian approach.

Topics: Aminoglycosides; Bayes Theorem; Digoxin; Drug-Related Side Effects and Adverse Reactions; False Negative Reactions; False Positive Reactions; Humans; Pharmacokinetics; Predictive Value of Tests; Probability; Procainamide; Theophylline; Vancomycin

The association between factors that place patients at risk for adverse drug reactions (ADRs) and the occurrence of ADRs was examined, and a therapeutic risk-assessment model was developed. Theoretical risk factors for ADRs to digoxin and theophylline were identified through the literature by researchers at a private tertiary-care hospital. Data were then collected from two groups of 67 patient charts each during a 15-month period. One group of charts represented patients who had experienced an ADR to digoxin or theophylline. The other group represented matched control patients who had not experienced an ADR to either drug. ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modifications) ADR codes were assigned by medical records department personnel, and the ADRs were verified by using the Naranjo algorithm. Seven risk factors for each drug were found to be significantly associated with ADRs. A serum digoxin concentration greater than 2.5 ng/mL and elevated blood urea nitrogen were the two best predictors of an ADR to digoxin. The probability of experiencing an ADR to digoxin was 94.1% for a patient with both of these risk factors. A serum theophylline concentration greater than 25 micrograms/mL was the greatest predictor of an ADR to theophylline; the probability of experiencing an ADR to theophylline was 85.2% if a patient had that risk factor. The sensitivity and specificity of the therapeutic risk-assessment model were 92.9% and 61.8%, respectively, for digoxin and 95.8% and 84.0%, respectively, for theophylline. Several laboratory-based screening criteria demonstrated an ability to predict ADRs to digoxin and theophylline.

Topics: Digoxin; Drug-Related Side Effects and Adverse Reactions; Hospital Bed Capacity, 500 and over; Humans; Models, Theoretical; Ohio; Pharmacy Service, Hospital; Product Surveillance, Postmarketing; Risk Factors; Theophylline

Several side effects of drugs observed in an office of a general practitioner are described. The cause of these side effects, their prevention and their treatment are discussed.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Anaphylaxis; Anti-Inflammatory Agents, Non-Steroidal; Cosyntropin; Diclofenac; Digoxin; Drug Eruptions; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Nitrofurantoin; Penicillin G Procaine; Risk Factors; Verapamil

Topics: Adult; Ambulatory Care Facilities; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Health Maintenance Organizations; Hematologic Tests; Humans; Male; Middle Aged; Phenytoin; Toxicology; United States

The sensitivity and specificity of three methods of detecting adverse drug reactions (ADRs) were determined. Minimal use of a voluntary ADR reporting program prompted this investigation of three ADR detection methods, as follows: screening of laboratory reports, pharmacist screening of medication orders, and voluntary reporting. A total of 98 patients who were receiving oral or i.v. digoxin therapy, oral or i.v. theophylline therapy, or i.v. gentamicin therapy were randomly selected and monitored for possible ADRs. A physician reviewed the charts of patients with suspected ADRs using the Naranjo algorithm to assess causality. The chart review served as the reference method to which the other three methods were compared. Thirteen "true" (i.e., confirmed by the Naranjo algorithm) ADRs were identified in 11 different patient charts, resulting in a 13.3% ADR incidence rate for the 98 sampled patients. For the three ADR detection methods, the decreasing order for level of sensitivity was screening of laboratory reports, pharmacist screening of medication orders, and voluntary reports; however, only the difference between laboratory reports and voluntary reports was significant. For level of specificity, the decreasing order for the three methods was voluntary reports, pharmacist screening of medication orders, and pharmacist screening of laboratory reports; the differences among all three methods were significant. Screening of laboratory reports and pharmacist screening of medication orders are two detection methods that appear to exhibit an appropriate combination of sensitivity and specificity for identifying ADRs; trials with larger sample sizes are needed to confirm the results of this study.

Topics: Algorithms; Computers; Data Collection; Digoxin; Drug-Related Side Effects and Adverse Reactions; Gentamicins; Humans; Laboratories, Hospital; Medical Records; Pharmacy Service, Hospital; Sensitivity and Specificity; Theophylline

The drugs prescribed for 280 women with hip fractures (mean age 83 years) were compared with those prescribed for 145 women controls (mean age 81 years) as recorded in a family practice age-sex register. Thirty-three percent of the fracture patients were taking diuretics compared with 24% of the controls (.10 greater than P greater than .05). Forty-six percent of these diuretics taken by the fracture group (compared with 40% taken by the controls) were either loop or potassium sparing diuretics in combination with another diuretic. Twenty-five percent of the controls (compared with 9% of the fracture patients) were taking nonsteroidal anti-inflammatory drugs (NSAIDs) (P less than .001). The greater use of NSAIDs by control subjects may be due to the small overlap between osteoporosis and osteoarthritis. No significant differences were found for digoxin, anti-hypertensive drugs, and those taking no drugs. Thirty percent of fracture patients were taking sedatives and hypnotics compared with 28% of controls. Within this category, 54% of the fracture patients and 80% controls were receiving drugs (mainly benzodiazepines) with half-lives longer than 24 hours. Thus, this population did not confirm a previously identified association between long-acting sedatives and the risk of fracture. As only 3.5% of fracture patients and 2.1% controls were receiving phenothiazines, a role for these drugs in hip fracture cannot be ruled out. In summary, hip fracture patients were slightly more likely to be taking diuretics and somewhat less likely to be taking NSAIDs than controls but there were no differences with respect to other drugs.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Digoxin; Diuretics; Drug-Related Side Effects and Adverse Reactions; Female; Hip Fractures; Humans; Hypnotics and Sedatives; Risk Factors

Topics: Cephalexin; Digoxin; Drug-Related Side Effects and Adverse Reactions; Educational Measurement; Humans; Meperidine; Nursing Staff, Hospital; Pharmaceutical Preparations

During 1983, 15% of admissions to the medical ward of Kaitaia Hospital resulted from ill effects of prescribed medication. Tranquillisers, digoxin, beta-blockers, other hypotensive drugs, and nonsteroid antiinflammatory drugs were the offending agents in 73% of these admissions. Drug induced illness makes an important contribution to the work-load of a general medical ward, and more care in the prescription of these classes of drugs might substantially reduce this contribution.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Hospitalization; Hospitals, Rural; Humans; Male; Middle Aged; New Zealand; Tranquilizing Agents

Topics: Aged; Aging; Antihypertensive Agents; Antiparkinson Agents; Cathartics; Digoxin; Diuretics; Drug-Related Side Effects and Adverse Reactions; Geriatrics; Humans; Patient Compliance; Psychotropic Drugs; Risk; Social Environment

The probability of experiencing adverse drug reactions increases with age. Polypharmacy, pharmacokinetic changes (altered drug distribution, reduced renal and hepatic drug clearances), unusual pharmacological effects and impaired compensatory mechanisms are the principal reasons for the diminished tolerance of elderly patients to several drugs. Especially neuroleptics, antidepressants, tranquilizers, digoxin, potent diuretics, betablockers, and antiarrhythmics have to be employed with special care. To prevent adverse reactions in geriatric patients, prescriptions should be limited to a few essential drugs, dosage reduced, and dosing regimens simplified. However, therapeutic nihilism can never be justified by old age alone.

Topics: Acute Kidney Injury; Adrenergic beta-Antagonists; Aged; Antidepressive Agents; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Creatine; Digoxin; Diuretics; Drug-Related Side Effects and Adverse Reactions; Female; Geriatrics; Humans; Hypotension; Male

A study was carried out to assess the feasibility of using record linkage for drug monitoring. For two years, three types of records were collected for a total of 43 117 people: (1) details of basic attributes, such as sex and age; (2) details of prescriptions dispensed; and (3) records of hospital admissions, obstetric deliveries, and deaths. The records about each person were linked together, and analyses were performed to reveal associations between drugs and diagnoses. The study suggested that record linkage would be useful both for generating and for testing hypotheses about the adverse effects of drugs. The method would be especially valuable for detection of delayed effects (such as the induction of cancer), sudden deaths outside hospital, and effects of the fetus-all of which are difficult to study by other means. A full-scale project would need to cover a large population, and some of the practical issues that would arise are discussed.

Topics: Aged; Aspirin; Cerebral Hemorrhage; Computers; Delivery, Obstetric; Diarrhea; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infant; Medical Record Linkage; Medical Records; Mortality; Patient Admission; Pregnancy

Topics: Adolescent; Adult; Aged; Aging; Analgesics, Opioid; Benzodiazepines; Digoxin; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Kidney; Liver; Liver Circulation; Metabolic Clearance Rate; Middle Aged; Patient Compliance; Pharmaceutical Preparations; Propranolol

Topics: Aged; Analgesics; Anti-Bacterial Agents; Anticoagulants; Antihypertensive Agents; Digoxin; Diuretics; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hypnotics and Sedatives; Male; Psychotropic Drugs; Quinidine; Theophylline

Topics: Aged; Arrhythmias, Cardiac; Bethanidine; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Furosemide; Humans; Hyperkalemia; Hypotension, Orthostatic; Male; Middle Aged; Spironolactone; Uremia

Topics: Biguanides; Clonidine; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmaceutical Preparations; Poisoning; Radiography; Time Factors; Toxicology

Topics: Aspirin; Child; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Iron; Penicillins; Phenobarbital

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Depression; Digoxin; Diuretics; Drug Hypersensitivity; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Humans; Hypoglycemic Agents; Inflammation; Intestinal Absorption; Pain; Pharmaceutical Preparations; Sleep Initiation and Maintenance Disorders

Topics: Adult; Aged; Creatine; Digoxin; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Middle Aged; Nitrazepam; Penicillin V; Pharmaceutical Preparations; Sulfamerazine

Topics: Adult; Aspirin; Boston; Digoxin; Drug Evaluation; Drug Therapy; Drug Utilization; Drug-Related Side Effects and Adverse Reactions; Hospitalization; Humans; Statistics as Topic; United States

Topics: Age Factors; Blood Urea Nitrogen; Body Height; Body Weight; Creatinine; Diagnosis, Computer-Assisted; Digoxin; Drug-Related Side Effects and Adverse Reactions; Education, Medical, Continuing; Feedback; Half-Life; Humans; Kidney; Kinetics; Pharmaceutical Preparations; Sex Factors; Teaching

Topics: Aged; Dehydration; Digoxin; Drug-Related Side Effects and Adverse Reactions; Furosemide; Guanethidine; Humans; Hypertension; Kidney; Kidney Failure, Chronic; Male; Pharmaceutical Preparations; Tetracycline; Uremia

Topics: Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Kidney Failure, Chronic

Topics: Chlorpropamide; Digoxin; Drug-Related Side Effects and Adverse Reactions; Indomethacin; Penicillins; Prednisone; Streptomycin; Tetracycline; Thiopental; Warfarin

Topics: Aminophylline; Aspirin; Atropine; Cardiomyopathies; Cataract; Child, Preschool; Chloramphenicol; Chlorothiazide; Conjunctivitis; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Iatrogenic Disease; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Ophthalmic Solutions; Pre-Eclampsia; Pregnancy; Purpura, Thrombocytopenic; Substance-Related Disorders; Suppositories

Topics: Birth Weight; Cataract; Cesarean Section; Chloramphenicol; Digoxin; Drug-Related Side Effects and Adverse Reactions; Ductus Arteriosus, Patent; Female; Humans; Infant; Infant, Newborn; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Rubella virus

Topics: Biological Assay; Cardiovascular Agents; Digitalis Glycosides; Digitoxin; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Rabbits; Research; Sex Characteristics; Toxicology

Topics: Digitalis; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans