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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 64 (1990), S. 210-217 
    ISSN: 1432-0738
    Keywords: Aspirin ; Diclofenac ; Diflunisal ; Ibuprofen ; Indomethacin ; Non-steroidal anti-inflammatory agents ; Gastrointestinal toxicity ; Prostaglandins ; Biliary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aspirin, diclofenac, diflunisal, ibuprofen and indomethacin were given orally or intravenously to fasted or fed rats. The resulting gastric and intestinal damage was assessed using standard methods. The same drugs were administered to rats with biliary fitulas, and the fraction of drug excreted in bile was quantified using HPLC methods. We found that gastric damage occurred only in the fasted animals and was found to be dose-dependent and related to the amount (r=0.871) and solubility (r=0.909) of the individual drug. As far as acute gastric toxicity is concerned, neither the potency of a drug as an inhibitor of cyclo-oxygenase nor the fraction of unchanged or conjugated agent excreted in bile appeared to be relevant. Secondly, ulcerations of the small intestine occurred in fed animals only. The degree of damage was related to the amount of unchanged or conjugated drug excreted in bile and cyclo-oxygenase inhibitory potency (r=0.873). The administered dose (within the range investigated) and drug solubility appeared not to contribute to intestinal toxicity. It is concluded that, in the rat, acute gastric and intestinal toxicity of non-steroidal anti-inflammatory drugs are due to different mechanisms. Whereas gastric toxicity is strongly influenced by the amount of drug dissolved under the pH conditions in the stomach, intestinal toxicity appears to depend on biliary excretion and enterohepatic circulation of a drug as well as on its potency as an inhibitor of prostaglandin synthesis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been claimed that the risk of adverse drug reactions increases with age. However, only limited data exist for disease-group specific risks and none for patients with liver and gastrointestinal diseases.〈section xml:id="abs1-2"〉〈title type="main"〉Aims:To determine the incidence and characteristics of adverse drug reactions and the physicians’ awareness of adverse drug reactions.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:During a 7-month period, a prospective survey of 532 male patients (158 aged 65 years or older; 30%) was conducted on a hepatogastroenterological ward of a tertiary-care university hospital, using intensive bedside and computer-assisted drug surveillance methods.〈section xml:id="abs1-4"〉〈title type="main"〉Results:No difference was found in the overall rate of adverse drug reactions between older and younger patients (25.9% vs. 24.2%) during 6213 treatment days. However, a significantly higher risk for developing adverse drug reactions could be shown for the elderly with biliary tract diseases (P 〈 0.01). Independently of age, patients suffering from gastric ulcers, acute episodes of pancreatitis, cholangitis or inflammatory bowel diseases were at high risk of adverse drug reactions. Adverse drug reaction-associated mortality was encountered in four elderly and none of the younger patients. Secondary pharmacological effects and drug toxicity were the main types of adverse drug reactions for both age groups. Although 75.3% of the adverse drug reactions were predictable, only 37.5% of all adverse drug reactions were recognized by the staff physicians.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusion:In hepatogastroenterological patients, advancing age was not associated with an overall increased risk of adverse drug reactions except for patients with biliary tract diseases. In the elderly, adverse drug reactions were more severe and carried higher mortality. Guidelines and educational programs should be developed to increase the awareness of adverse drug reactions and their prevention, especially in high risk patients and, thus, to improve patient outcomes.
    Type of Medium: Electronic Resource
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