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

Drugs are the most cost-effective modality of chronic care, and older adults with multiple illnesses often need multiple drugs. Because this may lead to drug interactions, adverse drug effects, and problems with compliance, drug regimens should be individualized and as few drugs as possible used. When a new drug is indicated, it is important for the physician reassess the appropriateness and continued need for the existing regimen. Patients and providers must agree on a particular regimen, its goals, promises, and limitations.

Topics: Aged; Anticonvulsants; Antidepressive Agents; Antihypertensive Agents; Benzodiazepines; Chronic Disease; Digitalis; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Patient Compliance; Plants, Medicinal; Plants, Toxic

Topics: Aged; Animals; Atropine; Carbohydrate Metabolism; Clinical Enzyme Tests; Colchicine; Cortisone; Dietary Carbohydrates; Digitoxin; Drug-Related Side Effects and Adverse Reactions; Ethacrynic Acid; Glycoside Hydrolases; Humans; Infant; Infant, Newborn; Intestinal Absorption; Intestinal Mucosa; Malabsorption Syndromes; Neomycin; Nutrition Disorders; Phenformin; Protein Deficiency; Sympathomimetics; Xylose

The bile salt export pump (BSEP) is expressed at the canalicular domain of hepatocytes, where it serves as the primary route of elimination for monovalent bile acids (BAs) into the bile canaliculi. The most compelling evidence linking dysfunction in BA transport with liver injury in humans is found with carriers of mutations that render BSEP nonfunctional. Based on mounting evidence, there appears to be a strong association between drug-induced BSEP interference and liver injury in humans; however, causality has not been established. For this reason, drug-induced BSEP interference is best considered a susceptibility factor for liver injury as other host- or drug-related properties may contribute to the development of hepatotoxicity. To better understand the association between BSEP interference and liver injury in humans, over 600 marketed or withdrawn drugs were evaluated in BSEP expressing membrane vesicles. The example of a compound that failed during phase 1 human trials is also described, AMG 009. AMG 009 showed evidence of liver injury in humans that was not predicted by preclinical safety studies, and BSEP inhibition was implicated. For 109 of the drugs with some effect on in vitro BSEP function, clinical use, associations with hepatotoxicity, pharmacokinetic data, and other information were annotated. A steady state concentration (C(ss)) for each of these annotated drugs was estimated, and a ratio between this value and measured IC₅₀ potency values were calculated in an attempt to relate exposure to in vitro potencies. When factoring for exposure, 95% of the annotated compounds with a C(ss)/BSEP IC₅₀ ratio ≥ 0.1 were associated with some form of liver injury. We then investigated the relationship between clinical evidence of liver injury and effects to multidrug resistance-associated proteins (MRPs) believed to play a role in BA homeostasis. The effect of 600+ drugs on MRP2, MRP3, and MRP4 function was also evaluated in membrane vesicle assays. Drugs with a C(ss)/BSEP IC₅₀ ratio ≥ 0.1 and a C(ss)/MRP IC₅₀ ratio ≥ 0.1 had almost a 100% correlation with some evidence of liver injury in humans. These data suggest that integration of exposure data, and knowledge of an effect to not only BSEP but also one or more of the MRPs, is a useful tool for informing the potential for liver injury due to altered BA transport.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Biological Transport; Chemical and Drug Induced Liver Injury; Cluster Analysis; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Male; Multidrug Resistance-Associated Proteins; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Risk Assessment; Risk Factors; Toxicity Tests

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

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

Topics: Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antihypertensive Agents; Antineoplastic Agents; Arrhythmias, Cardiac; Digitalis; Diuretics; Drug-Related Side Effects and Adverse Reactions; Humans; Plants, Medicinal; Plants, Toxic; Psychotropic Drugs; Vasodilator Agents

Topics: Aged; Aging; Dementia; Depression; Digitalis; Drug-Related Side Effects and Adverse Reactions; Humans; Kinetics; Patient Compliance; Pharmaceutical Preparations; Plants, Medicinal; Plants, Toxic

Topics: Aged; Aminorex; Anticoagulants; Digitoxin; Drug Evaluation; Drug-Related Side Effects and Adverse Reactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Pulmonary Heart Disease

Topics: Anti-Arrhythmia Agents; Anti-Infective Agents; Antidepressive Agents; Autonomic Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions; Humans; Hypnotics and Sedatives; Mental Disorders; Plants, Medicinal; Plants, Toxic; Steroids

Topics: Chlordiazepoxide; Digitoxin; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hydrochlorothiazide; Hyperkinesis; Hypokalemia; Iatrogenic Disease; Male; Medication Errors; Middle Aged; Nausea; Trifluoperazine

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Digitoxin; Diuretics; Drug-Related Side Effects and Adverse Reactions; Environment; Female; Hospitalization; Humans; Insulin; Male; Middle Aged; Quinidine

Topics: Diagnosis; Digitalis; Digitalis Glycosides; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Heart Diseases; Poisoning; Toxicology

Topics: Calcium; Calcium, Dietary; Digitalis; Digitalis Glycosides; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Poisoning; Potassium; Procainamide; Toxicology

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

Topics: Blood Viscosity; Cardiac Glycosides; Digitoxin; Drug-Related Side Effects and Adverse Reactions; Pharmacology; Strophanthins; Toxicology; Viscosity

Topics: Animal Experimentation; Animals; Arrhythmias, Cardiac; Digitalis; Drug-Related Side Effects and Adverse Reactions; Hypertension; Reserpine

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Gynecomastia; Humans; Male; Plant Extracts

Topics: Animals; Contraceptive Agents, Female; Digitalis; Dogs; Drug-Related Side Effects and Adverse Reactions; Estrogens; Female; Humans; Plant Extracts

Topics: Coronary Vessels; Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Heart; Plant Extracts

Topics: Animals; Cestode Infections; Digitalis; Drug-Related Side Effects and Adverse Reactions; Humans; Plant Extracts; Taenia saginata

Topics: Atrial Flutter; Cardiovascular Agents; Cardiovascular Diseases; Digitalis; Drug-Related Side Effects and Adverse Reactions

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Plant Extracts; Psychoses, Substance-Induced

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Plant Extracts

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Plant Extracts; Potassium

Topics: Biological Factors; Digitalis; Digitoxin; Drug-Related Side Effects and Adverse Reactions

Topics: Calcium; Calcium, Dietary; Cardiovascular Agents; Chelating Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions; Edetic Acid; Humans

Topics: Cardiovascular Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions; Humans; Syncope

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

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

Topics: Cardiovascular Agents; Digitalis; Digitoxin; Drug-Related Side Effects and Adverse Reactions; Lactic Acid; Lactones

Topics: Chlorpromazine; Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Emetics; Plant Extracts; Vomiting

Topics: Blindness; Cardiovascular Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions; Humans

Topics: Animals; Columbidae; Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Leadership; Plant Extracts

Topics: Cardiovascular Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions; Humans; Poisoning

Topics: Digitalis; Drug-Related Side Effects and Adverse Reactions; Heart Failure; Humans; Plant Extracts; Urticaria

Topics: Digitalis; Drug-Related Side Effects and Adverse Reactions; Gynecomastia; Heart Failure; Humans; Liver; Male; Plant Extracts

Topics: Animals; Columbidae; Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Injections; Pharmaceutical Solutions

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Heart; Plant Extracts

Topics: Cardiovascular Diseases; Digitalis; Drug-Related Side Effects and Adverse Reactions; Heart Block; Heart Failure

Topics: Cardiovascular Diseases; Digitalis; Drug-Related Side Effects and Adverse Reactions; Humans; Ventricular Fibrillation

Topics: Cardiovascular Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Plant Extracts

Topics: Asthma; Chronic Disease; Digitalis; Drug-Related Side Effects and Adverse Reactions; Plant Extracts

Topics: Animals; Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Plant Extracts; Rana esculenta

Topics: Cardiovascular Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions

Topics: Cardiovascular Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions

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

Topics: Digitalis; Drug-Related Side Effects and Adverse Reactions; Heart Diseases

Topics: Digitalis; Drug-Related Side Effects and Adverse Reactions; Psychoses, Substance-Induced

Topics: Digitalis; Digitoxin; Drug-Related Side Effects and Adverse Reactions; Vision, Ocular

Topics: Cardiotonic Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions; Heart; Humans

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Humans; Plant Extracts; Procainamide; Procaine; Ventricular Premature Complexes

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Heart; Procainamide; Procaine

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

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

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

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Plant Extracts

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Plant Extracts

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

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

Topics: Animals; Digitalis; Digitoxin; Dogs; Drug-Related Side Effects and Adverse Reactions; Heart; Ouabain; Strophanthins

Topics: Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Plant Extracts; Vision, Low

Topics: Atrioventricular Block; Cardiovascular Agents; Digitalis; Drug-Related Side Effects and Adverse Reactions; Optic Neuritis

Topics: Animals; Cardiotoxicity; Digitalis; Dogs; Drug-Related Side Effects and Adverse Reactions; Humans