Investigation of interference by nonsteroidal anti-inflammatory drugs in urine tests for abused drugs.
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Anecdotal and uncontrolled studies have suggested that nonsteroidal anti-inflammatory drugs produce false-positive results in immunoassay urine tests for some drugs of abuse. This study was performed in 60 volunteers who took ibuprofen as either a single 400-mg dose, or 200 mg three times a day, or 400 mg three times a day, and in 42 patients taking ibuprofen, naproxyn, or fenoprofen in therapeutic regimens for more than 30 days. Of the 510 urines collected from 102 individuals during these dosage regimens, two gave false-positive tests for cannabinoid by enzyme-mediated immunoassay (EMIA), one after 1200 mg of ibuprofen in three divided doses for one day and one in a patient taking naproxyn on a chronic basis; none was falsely positive for benzodiazepines. Two urines were false-positive for barbiturates by fluorescence polarization immunoassay (FPIA), one in a patient taking ibuprofen and one in a patient taking naproxyn. These data, collected prospectively, demonstrate the small likelihood of a false-positive immunoassay test result for cannabinoids, benzodiazepines, or barbiturates after the acute or chronic ingestion of ibuprofen, or after the chronic ingestion of naproxyn or fenoprofen. (+info)
Depression by fenoprofen of the rebound contractions' elicited by vagal stimulation and arterial infusion of ATP in the rabbit stomach in vivo.
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In the atropine-treated rabbit, vagal stimulation, arterial infusion of ATP or vasoactive intestinal peptide (VIP) caused gastric relaxation. At the end of either vagal stimulation or ATP infusion, but not after VIP, the gastric inhibitory responses were abruptly interrupted by 'rebound contractions'. Administration of fenoprofen depressed or abolished the rebound contraction, thus transforming the brisk relaxant response, elicited by vagal stimulation or ATP, into long-lasting relaxation. Indomethacin depressed the rebound contractions only at high doses and this effect was not always reproducible. (+info)
The propionic acids. Gastrointestinal toxicity in various species.
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The propionic acids represent the largest chemical class of nonsteroidal anti-inflammatory agents (NSAID). Several of them are widely used, both in the United States and internationally. This paper discusses observations made on fenoprofen, flurbiprofen, ibuprofen and naproxen. Of these compounds, three are racemates; the fourth, naproxen, is an enantiomer. As a group, the propionic acids, along with most members of the other classes of NSAID, produce gastrointestinal damage in most species. These lesions vary from erythema, hemorrhage and erosion to ulceration and peritonitis. As might be expected, the degree of gastrointestinal intolerance depends on many factors: the individual compound, the dose-level, the duration of the period of drug administration, and the pharmacokinetics and metabolism in a given species. For example, in our experience the rat is less tolerant of NSAID than is the monkey, and the dog is less tolerant than the rat. Gastrointestinal lesions have been seen following both parenteral and oral administration; these findings suggest that factors other than local irritation play a role in the development of lesions. Most NSAID inhibit prostaglandin cyclo-oxygenase activity, which results in a prostaglandin deficiency at the tissue level. The administration of relevant exogenous prostaglandins, such as 16,16-dimethyl PGE2, has been shown to inhibit the gastrointestinal toxicity accompanying the administration of several NSAID, including some of the propionic acids. (+info)
Time-course study of gastric damages in rats by anti-inflammatory drugs using a gastroscope and its quantification.
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Time-course studies on gastric damages in rats caused by nonsteroidal anti-inflammatory drugs (NSAIDs) were performed using a gastroscope, and the readings were quantified to obtain the Congestion-Hemorrhage Index (CHI) for evaluating the potencies of the damaging properties of NSAID. The correlation between CHI and Ulcer Index (UI), the quantified value obtained by the conventional methods, was highly significant at 6 and 24 hr after forced oral administration of NSAID. The peak CHIs of aspirin (300 mg/kg), indomethacin (60 mg/kg), mefenamic acid (300 mg/kg) and fenoprofen calcium (300 mg/kg) appeared approximately 24 hr after a single forced oral administration of drugs. Thus, it was suggested that an observation at 24 hr in addition to one at 6 to 7 hr might be necessary for the examination of damaged gastric mucosa. Under the present experimental conditions, fenoprofen calcium caused the greatest damages on gastric mucosa among the four NSAIDs. Mefenamic acid showed the least damaging potency on gastric mucosa, having a smaller CHI than that of aspirin. Indomethacin possessed a stronger damaging property than aspirin. (+info)
Drug-induced acute interstitial nephritis: report of 10 cases.
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Between January 1979 and June 1985, 10 patients with acute allergic interstitial nephritis were seen in a clinical nephrology service at a large regional hospital. The onset of renal failure was temporally related to the use of a drug: a nonsteroidal anti-inflammatory agent (NSAID) (in four patients), cimetidine (in three), antibiotics (in two) or allopurinol (in one). The onset of renal failure was acute in three patients and insidious in seven. Two patients also exhibited marked proteinuria. Clinical features such as fever, rash, hematuria, pyuria with or without eosinophiluria, and mild to marked proteinuria had led to suspicion of the disease. The diagnosis was confirmed by renal biopsy findings of inflammatory cells, predominantly lymphocytes, plasma cells and eosinophils. Three patients required hemodialysis; two of them received steroids as well. Steroid therapy was also used in two patients with NSAID-induced proteinuria. Renal function improved in nine patients by 35 days, but one patient continued to have slow but progressive deterioration of renal function. Acute interstitial nephritis can be distinguished from other forms of acute renal failure by heavy renal uptake of gallium 67, maximal 48 hours or more after injection. The improvement in renal function after discontinuation of the implicated drug, the characteristic histopathological findings of allergic interstitial nephritis, and the presence of eosinophils and sometimes IgE in the blood suggest a hypersensitivity reaction. (+info)
Mild analgesics and the accident and emergency department--cost and safety more important than potency?
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A prospective controlled trial involving over 1000 patients did not reveal any difference between four drugs commonly used in accident and emergency departments for the relief of mild to moderate pain. There were no significant variations in therapeutic effect, side-effects or patient compliance. When considering the supply of analgesics which may be no more potent than those available without prescription from retail chemists, cost and safety are more important than analgesic effect. By restricting the choice of analgesics available, the accident and emergency department should be able to increase awareness among its staff of the actions and side-effects of a small number of prescribed drugs and to contain costs. (+info)
Four new anti-inflammatory drugs: responses and variations.
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Ninety patients with rheumatoid arthritis completed a double-blind crossover trial comparing fenoprofen, ibuprofen, ketoprofen, and naproxen. Fenoprofen and naproxen were slightly more effective than the other two drugs but there were striking individual variations in response. Groups of patients could be identified who preferred each of the four drugs. The commonest side effects were those related to the upper gastrointestinal tract; these showed individual variation and seldom occurred with more than one or two of the drugs. Side effects were least common with ibuprofen and naproxen. Since naproxen combined greater effectiveness with a lower incidence of side effects it must be regarded as the first choice among these drugs. It may be necessary to try several drugs before finding the right one for a particular patient. (+info)
Antiproliferative effect of nonsteroidal antiinflammatory drugs against human colon cancer cells.
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Several lines of evidence suggest that nonsteroidal antiinflammatory drugs may be effective in preventing colorectal cancer. These include animal experiments, case-control studies, and clinical experience with sulindac in promoting the regression of adenomatous colon polyps in adenomatous polyposis coli. We determined the antiproliferative activity of various nonsteroidal antiinflammatory drugs, including two sulindac derivatives, against human colon cancer cells in vitro. Ht-29, SW480, and DLD-1 cells were continuously incubated with serial drug dilutions for 6 days prior to fixation. Cell number was determined using the sulforhodamine B assay, and drug concentrations which inhibited cell growth by 50% were estimated for each agent by interpolation. All drugs exhibited antiproliferative activity against Ht-29 and DLD-1 cells, and most inhibited SW480 cells. For Ht-29 cells, the 50% inhibitory concentration varied from 55 microM for diclofenac to 2100 microM for 5-aminosalicylic acid, with three drug groups of high, intermediate, and low potency evident. Inhibition of cell growth by sulindac sulfide was reversible following drug removal. Nonsteroidal antiinflammatory drugs exert an antiproliferative effect against human colon cancer cells with a wide range of potencies. A cytostatic response was demonstrated with sulindac sulfide. These data further support the potential role of these agents for chemoprevention of colorectal neoplasia. (+info)