demeclocycline and Chemical-and-Drug-Induced-Liver-Injury

Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Drug Labeling; Humans; Pharmaceutical Preparations; Risk

Hyponatremia is the most frequent electrolyte disorder in hospitalized patients. Acute and severe hyponatremia can be a life-threatening condition, but recent evidence indicates that also mild and chronic hyponatremia is associated with neurological and extra-neurological signs, such as gait disturbances, attention deficits, falls and fracture occurrence, and bone loss. The syndrome of inappropriate ADH secretion (SIADH) is the most frequent cause of hyponatremia. Hyponatremia secondary to SIADH may result for instance from ectopic release of ADH in lung cancer, from diseases affecting the central nervous system, from pneumonia or other pneumopathies or as a side-effect of various drugs In SIADH, hyponatremia results from a pure disorder of water handling by the kidney, whereas external sodium balance is usually well regulated. Despite increased total body water, only minor changes of urine output and modest oedema are usually seen. Neurological impairment may range from subclinical to life-threatening, depending on the degree and mostly on the rate of serum sodium reduction. The management of hyponatremia secondary to SIADH is largely dependent on the symptomatology of the patient. This review briefly summarizes the main aspects related to hyponatremia and then discusses the available treatment options for the management of SIADH, including vaptans, which are vasopressin receptor antagonists targeted for the correction of euvolemic hyponatremia, such as that observed in SIADH.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Blood Volume; Body Water; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Demeclocycline; Diabetes Insipidus, Nephrogenic; Disease Management; Drug Interactions; Hospitalization; Humans; Hydrocortisone; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Lithium; Multicenter Studies as Topic; Osmolar Concentration; Paraneoplastic Syndromes; Saline Solution, Hypertonic; Tolvaptan

Topics: Absorption; Acne Vulgaris; Bacteria; Bacteriuria; Bronchial Diseases; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemistry; Chlortetracycline; Demeclocycline; Drug Eruptions; Humans; Infections; Kidney Diseases; Methacycline; Oxytetracycline; Protein Binding; Tetracycline; Tooth Discoloration

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

Topics: Acne Vulgaris; Acute Kidney Injury; Body Weight; Chemical and Drug Induced Liver Injury; Demeclocycline; Diabetes Insipidus; Drug Eruptions; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Infections; Photosensitivity Disorders; Pregnancy; Tetracyclines; Time Factors

Topics: Adolescent; Adult; Animals; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Demeclocycline; Dogs; Female; Humans; Kidney Diseases; Male; Methacycline; Oxytetracycline; Photosensitivity Disorders; Pregnancy; Tetracycline; Tooth Calcification; Tooth Discoloration

Topics: Adult; Chemical and Drug Induced Liver Injury; Demeclocycline; Glomerulonephritis; Humans; Male

Topics: Anti-Bacterial Agents; Black People; Chemical and Drug Induced Liver Injury; Chlortetracycline; Demeclocycline; Female; Hepatitis; Hepatitis A; Humans; Kidney Diseases; Liver; Maternal-Fetal Exchange; Oxytetracycline; Pharmacology; Pregnancy; Pregnancy Complications; Tetracycline; Tetracyclines; Tooth; Toxicology; Urine