oxytetracycline--anhydrous and Drug-Related-Side-Effects-and-Adverse-Reactions

Drug-induced liver injury (DILI) is a leading cause of drugs failing during clinical trials and being withdrawn from the market.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

To evaluate the possible association between all kinds of drug treatments during pregnancy and isolated cleft lip with or without cleft palate (CL/P) and posterior cleft palate (PCP) in the offspring.. The dataset of the large population-based Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996, was evaluated.. One thousand three hundred seventy-four cases with isolated CL/P and 601 with PCP, plus 38,151 population controls (without birth defects) and 20,868 malformed controls with other defects.. In this observation case-control study the data collection was based on prospective medical records particularly prenatal logbook, retrospective maternal data via a self-reported questionnaire, and home visits of nonresponding mothers.. Isolated CL/P and PCP associated with drug treatments during pregnancy.. An increased risk for isolated CL/P was found in cases born to mothers treated with amoxicillin, phenytoin, oxprenolol, and thiethylperazine during the second and third month of pregnancy, i.e., the critical period of isolated CL/P. Risk of isolated PCP was increased in mothers with oxytetracycline and carbamazepine treatment during the third and fourth month of pregnancy, i.e., the critical period of PCP.. This study confirmed the orofacial cleft (OFC) inducing effect of phenytoin, carbamazepine, oxytetracycline, and thiethylperazine and suggested a possible association between OFCs and oxprenolol and amoxicillin. However, drugs may have only a limited role in the origin of isolated OFCs.

Topics: Abnormalities, Drug-Induced; Adrenergic beta-Antagonists; Amoxicillin; Anti-Bacterial Agents; Anticonvulsants; Carbamazepine; Case-Control Studies; Cleft Lip; Cleft Palate; Dopamine Antagonists; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hungary; Oxprenolol; Oxytetracycline; Phenytoin; Population Surveillance; Pregnancy; Pregnancy Trimesters; Prospective Studies; Retrospective Studies; Risk Factors; Thiethylperazine

A total of 167 264 symptoms were recorded in numerical shorthand during a ten years period in a general practice. Computer analysis yielded 1535 adverse reactions with the drug prescribed. Especially prominent were reactions from three antibiotics (13% of all reported reactions), most of which were alimentary symptoms. Ampicillin also induced rashes reported at a rate of 5.2 per thousand prescriptions. Reactions to an oral contraceptive (Minovlar) were the most frequent to a single named drug, being 25.9% of prescriptions for that drug. A worldwide total of around one trillion symptoms seems likely before AD 2000. Computers could be used to detect the unpredictable side effects, as with practolol. Various 'costs' involved are noted, together with wider questions.

Topics: Ampicillin; Computers; Contraceptives, Oral; Contraceptives, Oral, Combined; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Family Practice; Humans; Oxytetracycline; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In a one-year period (July 1, 1975, through June 30, 1976), 130 cases of suspected adverse drug reactions were reviewed in the Veterinary Medical Teaching Hospital, School of Veterinary Medicine, Davis, Ca. Sixty-six of these cases had sufficient evidence to link the reaction to the medication administered. Most of the reactions were attributed to anti-infective agents (antibiotics and parasiticides) and to anesthetics and related drugs. In 28 (42.4%) of the cases, uncomplicated recovery occurred without supportive medication. Four animals (6.1%) died as a direct result of adverse drug reactions. It was concluded that a higher degree of adverse drug reaction awareness is needed in the veterinary profession to enable the accumulation of meaningful data.

Topics: Amphotericin B; Anaphylaxis; Animals; Cat Diseases; Cats; Cattle; Cattle Diseases; Chloral Hydrate; Dextrans; Dog Diseases; Dogs; Droperidol; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Fentanyl; Fluorouracil; Horse Diseases; Horses; Ketamine; Oxytetracycline; Penicillins; Seizures; Sweating

Topics: Ampicillin; Analgesics; Aspirin; Chlorpromazine; Drug-Related Side Effects and Adverse Reactions; Erythema Multiforme; Humans; Indomethacin; International Cooperation; Oxyphenbutazone; Oxytetracycline; Phenylbutazone; Photosensitivity Disorders; Skin Diseases; Stevens-Johnson Syndrome; Tetracycline; World Health Organization

Topics: Ampicillin; Animals; Chloramphenicol; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Extracellular Space; Female; Humans; Infant, Newborn; Kidney; Liver; Maternal-Fetal Exchange; Oxytetracycline; Pharmaceutical Preparations; Phenobarbital; Pregnancy; Streptomycin; Sulfonamides

Topics: Candida; Candidiasis; Chlortetracycline; Disease; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Larynx; Oxytetracycline; Paralysis; Trichomonas Infections; Vagina; Vaginal Diseases

Topics: Chloramphenicol; Chlortetracycline; Drug-Related Side Effects and Adverse Reactions; Oxytetracycline