Drug-induced nephrotoxicity in children is dependent upon the histological, anatomical and physiological features of their kidneys and the structural and functional characteristics of drugs. The kidney is mainly composed of microvascular network and tubulointerstitial tissue, so drug-induced nephrotoxicity is usually manifested by interstitial nephropathy. The mechanisms of drug-induced nephrotoxicity include cytotoxicity (necrosis or apoptosis), ischemic injury, and immunological injury. Individual drugs cause renal damage by various mechanisms due to differences in chemical structure and pharmacology. This article reviews the main features of nephrotoxicity induced by common antibiotics (cephalosporins, aminoglycosides, vancomycin, carbapenems and amphotericin B), non-steroidal anti-inflammatory drugs, and cyclosporine A.
Anti-Bacterial Agents ; toxicity ; Anti-Inflammatory Agents, Non-Steroidal ; toxicity ; Child ; Cyclosporine ; toxicity ; Humans ; Kidney Diseases ; chemically induced

BACKGROUND/AIMS: NSAIDs induce gut damage throughout the entire gastrointestinal tract and bacterial translocation. The aim of this study was to examine if administration of glutamine was able to prevent the NSAID-induced gut damages and bacterial translocation in the animal models. METHODS: Rats were utilized into 5 groups; control group, diclofenac group, and diclofenac with glutamine 0.8, 1.6, and 3.2 g/kg/day group. The animals with glutamine were fed with L-glutamine for 4 days before diclofenac administration. Gut injury was induced by administration of a single dose of diclofenac (80 mg/kg orally). Intestinal permeability (24 hour urinary excretion of phenolsulfonphthalein), enteric aerobic bacterial counts, serum biochemical profiles and bacterial translocation to mesenteric lymph nodes, liver and spleen were measured. RESULTS: Diclofenac caused the increase in intestinal permeability, enteric bacterial count, enteric protein and albumin loss and bacterial translocation. Administration of glutamine reduced the increase in intestinal permeability, protein losing enteropathy, enteric bacterial overgrowth and bacterial translocation induced by diclofenac. CONCLUSIONS: Glutamine may have beneficial effects on NSAID-induced gut damage and bacterial translocation.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/toxicity ; Bacterial Translocation/*drug effects ; Diclofenac/*pharmacology/toxicity ; English Abstract ; Glutamine/*pharmacology ; Intestines/drug effects/*microbiology ; Male ; Rats

BACKGROUND: Due to rapidly growing elderly population, there are increasing numbers of older persons with multiple chronic disorders and geriatric problems arising from polypharmacy. In this study we tried to find out the state of polypharmacy and inappropriate drug prescription and their related factors in community-dwelling elderly by review of drugs taken by older persons visiting a day health center. METHODS: From April 2007 to July 2007, 80 subjects of 65 year-old or over with chronic illness who visited a elderly-wellness and health care center were randomly sampled. All of them were surveyed by structured questionnaires, medical records review, pill counts about all medications they are taking and experience of adverse drug reactions. And all the prescribed medications were reviewed or their drug prescription's appropriateness for each elderly according to Beers criteria. Data results were evaluated by frequency and correlation analyses. RESULTS: The average counts of drugs taken by elderly with chronic disorders were 7.23, minimum 1 to maximum 27 drugs a day. Patients experienced more adverse effects significantly when more prescribed medications were taken (P=0.005), and patients with lack of information about their drugs had taken increased number of medications (P<0.001). Referred to Beers criteria, inappropriate cases of prescription were observed in 26 persons. Those drugs were NSAIDs including aspirin in 17 subjects (21%), amitrityline in 3 (4%), short-acting benzodiazepines in 3 (4%), long acting benzodiazepines in 2 (3%), and anticholinergic antihistamine in 1 (1%). CONCLUSION: Polypharmacy is very common in community-dwelling elderly with chronic disorders. More medications were related to more adverse drug reactions and lack of information about their drugs related to increased number of drug taking. High proportion of inappropriate drug prescriptions was observed in the elderly, which may have resulted from poor education concerning geriatric care of the medical personnels.
Aged ; Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Beer ; Benzodiazepines ; Chronic Disease ; Delivery of Health Care ; Drug Prescriptions ; Drug Toxicity ; Humans ; Medical Records ; Polypharmacy ; Prescriptions ; Surveys and Questionnaires

Over the past century, since the introduction of non steroidal anti-inflammatory drugs (NSAID), antacid, histamine H2-receptor antagonists (H2RA), proton pump inhibitors (PPI), and discovery of Helicobacter pylori infection, the paradigm of peptic ulcer disease has changed with marked decrease in morbidity and mortality. However, peptic ulcer disease still occupies a position as a major health problem with increase of aged population and NSAIDs usage. In daily general practice, the management of peptic ulcer disease is directed according to the presence of bleeding or not. For non-bleeding peptic ulcer disease, proper acid suppression and the correction of underlying causes such as Helicobacter pylori infection and NSAID use is the main stay of treatment. Though a complete understanding of pathophysiology and a perfect treatment strategy are still a challenge, this guideline aims to provide practical recommendations based on evidences or consensus of experts through in-depth literature review and expert meeting.
Antacids/toxicity ; Anti-Inflammatory Agents, Non-Steroidal/toxicity ; Anti-Ulcer Agents/therapeutic use ; Bismuth/therapeutic use ; Helicobacter Infections/diagnosis/drug therapy ; Helicobacter pylori ; Histamine Antagonists/therapeutic use ; Humans ; Peptic Ulcer/*drug therapy ; Proton Pump Inhibitors/therapeutic use

To further understand triptolide, this paper has introduced the pharmacology, pharmacokinetics, toxicity, the clinic application and semi-synthesis of triptolide on basis of importance and significant contents of reference which have been consulted in the past twenty years. Presently triptolide and Tripterygium wilfordii have been a hot spot of modernization of Chinese traditional medicine. It is very important to develop a new dosage form of high effect and low toxicity by making use of advanced technology according to its characteristics.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Antineoplastic Agents, Alkylating ; pharmacology ; Antispermatogenic Agents ; pharmacology ; Diterpenes ; chemical synthesis ; isolation & purification ; pharmacology ; toxicity ; Epoxy Compounds ; Humans ; Immunosuppressive Agents ; pharmacology ; Phenanthrenes ; isolation & purification ; pharmacology ; toxicity ; Tripterygium ; chemistry

To further understand sinomenine, this paper has introduced the abstract technology, assaying, pharmaceutical chemistry, pharmacological action, pharmacotoxicology, pharmacokinetics and clinical application of sinomenine based on the important and significant contents of reference which have been consulted in the past ten years. Sinomenine is a kind of non-steroidal anti-inflammatory drugs with very effective and little side effect and expected it as a good new drug withdrawal medicine in the future.
Animals ; Anti-Arrhythmia Agents ; pharmacology ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Antirheumatic Agents ; pharmacology ; Humans ; Morphinans ; isolation & purification ; pharmacokinetics ; pharmacology ; toxicity ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Sinomenium ; chemistry ; Technology, Pharmaceutical ; methods

BACKGROUND/AIMS: The recent introduction of computerized surveillance systems has promoted the monitoring of adverse drug reactions (ADRs), a feature that facilitates voluntary reports and enables prompt feedback. To investigate the causative agents and severity of ADRs that occurred in a single hospital, we analyzed the features of 980 ADRs that occurred over 14 months after developing a computerized ADR reporting system in Hallym Sacred Heart Hospital. METHODS: ADR data collected prospectively from September 2007 to October 2008 by a computerized reporting system were analyzed. The World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria were used to determinate causality for each ADR. RESULTS: The number of ADR cases reported voluntarily increased rapidly since the introduction of the computerized ADR reporting system. Of the 980 cases, antibiotics (34.5%) were the most common causative drugs, followed by analgesics such as tramadol and its compound (15.2%), radiocontrast media (7.0%), narcotics (5.9%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (5.5%). Fifty-nine (6.0%) and 206 (21.0%) cases were classified as severe and moderate reactions, respectively. The mean age was older in patients with severe ADRs than in patients with non-severe ADRs. The most common clinical features were skin manifestations, such as pruritus, skin eruptions, and urticaria. Gastrointestinal symptoms including nausea, vomiting, and diarrhea were the second most frequently reported ADRs. Among antibiotics, first-generation cephalosporins were the most frequently reported causative drugs, followed by second-generation cephalosporins, penicillin/beta-lactamase inhibitors, and third-generation cephalosporins. While 11.6% of ADRs related to penicillin/beta-lactamase inhibitors were classified as severe, there was only one severe ADR (1.1%) for first-generation cephalosporins. Most ADRs were reported equally in men and women, although female cases constituted about two thirds of ADRs associated with tramadol and NSAIDs. CONCLUSIONS: We believe that a computerized reporting and replying system promoted the monitoring of ADRs. Antibiotics were reported most frequently as the causative agent of ADRs. Elderly patients seemed to be more susceptible to severe ADRs. With the voluntary reporting system, skin manifestations and gastrointestinal symptoms were detected successfully, while laboratory abnormalities without prominent symptoms seemed to be overlooked. Further efforts to screen for automated ADR signals are required.
Aged ; Analgesics ; Anti-Bacterial Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Cephalosporins ; Contrast Media ; Diarrhea ; Drug Toxicity ; Electronics ; Electrons ; Female ; Heart ; Humans ; Male ; Narcotics ; Nausea ; Prospective Studies ; Pruritus ; Skin ; Skin Manifestations ; Tramadol ; Urticaria ; Vomiting ; World Health ; World Health Organization

BACKGROUND/AIMS: The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID. METHODS: Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated. RESULTS: Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively. CONCLUSIONS: Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*toxicity ; Disease Models, Animal ; Gastric Mucosa/*drug effects/enzymology/pathology ; Glucosamine/metabolism ; Indomethacin/*toxicity ; Intestine, Small/*drug effects/pathology ; Male ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors

BACKGROUND/AIMS: The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID. METHODS: Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated. RESULTS: Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively. CONCLUSIONS: Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*toxicity ; Disease Models, Animal ; Gastric Mucosa/*drug effects/enzymology/pathology ; Glucosamine/metabolism ; Indomethacin/*toxicity ; Intestine, Small/*drug effects/pathology ; Male ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na+ concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K+ and Cl- concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/*toxicity ; Benzophenones/administration & dosage/toxicity ; Benzopyrans/administration & dosage/toxicity ; Bromobenzenes/administration & dosage/toxicity ; Cell Movement/drug effects ; Cells, Cultured ; Diclofenac/administration & dosage/toxicity ; Epithelial Cells/drug effects/metabolism/ultrastructure ; Epithelium, Corneal/cytology/*drug effects/metabolism ; Fluorometholone/administration & dosage/toxicity ; Humans ; L-Lactate Dehydrogenase/metabolism ; Microscopy, Electron, Transmission ; Ophthalmic Solutions ; Propionates/administration & dosage/toxicity