摘要:

SUMMARYBoth the relative efficacy and inefficacy of non‐steroidal anti‐inflammatory drugs (NSAIDs) contribute to their use in chronic rheumatic diseases. There are also sociological trends in patients, and in the population as a whole, increasing demand for treatment. In view of the risks of such treatment, the most rational approach to prescribing would be the use of a scientific risk‐benefit analysis. Unfortunately, the data, especially those related to symptom relief, are inadequate for such an analysis. Until more meaningful figures are produced, good clinical practise concentrates on the responsibilities of physicians who both start and stop drugs, and makes it essential that strategies to minimize risk are pro

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00760.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYThe design of randomized controlled trials to assess the efficacy of pharmacological measures for the prevention of the gastrointestinal side‐effects of anti‐inflammatory drugs requires an accurate estimate of excess risk under controlled conditions. Photocopies of 952 randomized controlled trial publications were obtained after scanning titles and abstracts of a MEDLINE computer search, 427 were excluded for obvious reasons, and 525 were again photocopied after obliterating source and results. Selection criteria were: the presence of a non‐anti‐inflammatory drug control group; at least 4 days of therapy; at least 3 days without anti‐inflammatory drugs before randomization; no complicating background drugs; mention of side‐effects; and a clear differentiation of gastrointestinal complications. Observer error, with two independent readings, for inclusion suitability in the study was 19% for Methods and 9% for Results. For the 44 aspirin trials, the mean therapy duration was 357 days; the unweighted rate difference between therapy and control groups (± 1 S.E.M.) for ulcer was 0.006 ± 0.003, for gross haemorrhage 0.006 ± 0.002 and for unspecified gastric symptoms 0.03 ± 0.01. In 123 non‐aspirin non‐steroidal anti‐inflammatory drug (NA—NSAID) trials, the mean duration was 67 days; the unweighted rate difference for ulcer was 0.0005 ± 0.0003, for gross haemorrhage 0.007 ± 0.004 and for unspecified gastric symptoms 0.02 ± 0.005. Risk differences were also pooled using the DerSimonian and Laird method, which weights studies inversely according to variance. Using this method, only the unspecified gastric symptoms for non‐aspirin non‐steroidal anti‐inflammatory drugs (NA—NSAIDs) and the haemorrhage for aspirin were found to be statistically significant. Longer studies have higher risk differences. Randomized control trials to determine prophylactic efficacy against haemorrhage (that is, to demonstrate a reduction of ulcer rate in the therapy group to the rate of controls) would require 190 patients in each group for NA—NSAIDs in studies of 2–6 months; 950 subjects would be needed to detect a 50% reduction. Randomized control trials to determine a reduction in ulcer rate to that of controls in patients on aspirin for more than 6 months would require 700 subjects in each group; 3346 subjects would be needed to detect a 50

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00761.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYThe H+, K+‐ATPase inhibitor omeprazole has been made available on a compassionate basis for patients with Zollinger—Ellison syndrome considered resistant to, or with side‐effects on, histamine Hz‐receptor antagonists. By December 1985, the first 80 patients, from 46 centres in 11 countries, had been treated for periods of 2 days to 4 years. Basal acid output was decreased to the desired level of less than 10 mmol · hour1, and symptoms were rapidly relieved. Acid secretion and laboratory variables were checked regularly and endoscopic examinations made at intervals. Dosage was adjusted primarily on the basis of basal acid output, but also if symptoms recurred. The starting dose was generally 60 mg daily and the median dose ranged between 60 and 70 mg daily over the study period. There was no evidence of tachyphylaxis. More than 90 % of the patients were successfully controlled on total daily doses of 120 mg or less; one‐third of patients required divided doses. Tolerance was good: there were no obvious drug‐related effects on laboratory variables, including fasting serum gastrin, and there were very few adverse events. Thirteen patients died (11 of the primary disease and two of other causes), four underwent successful tumour resection, six underwent total gastrectomy (though acid secretion was controlled in five), four patients’ treatment was changed to other medical therapy, and one was lost to follow‐up. Omeprazole thus appears to be both safe and very effective in controlling acid hypersecretion in this group of patients, and to provide a suitable alternative to t

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00667.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYGastroenterologists believe that non‐steroidal anti‐inflammatory drugs (NSAIDs) cause dyspepsia, may cause ulcers to developde novoand cause ulcer bleeding and perforation. Regulatory authorities are aware that NSAID‐associated adverse events are reported more often than for any other drug class, and that gastrointestinal events are most common and often serious. A case‐control study in the UK indicates that those who use NSAIDs may be between two and four times as liable to gastrointestinal bleeding and probably perforation as non‐users, particularly if elderly. It has further been suggested that the chances of dying of ulcer complications are very high in NSAID users. By contrast, studies in the USA conducted prospectively and post‐marketing surveillance in the UK have appeared to show little risk. Differences may be partially, if not completely, explained by the variable methodologies employed. Dispute also exists about the rank order and significance of toxic effects among the var

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00762.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYIt is difficult to ascertain the incidence of gastrointestinal side‐effects associated with intake of non‐steroidal anti‐inflammatory drugs (NSAIDs). In retrospective studies, some NSAIDs have been reported to be associated with a higher incidence of gastrointestinal side‐effects than others. However, this has not been verified either in a prospective casereview study or in a large double‐blind study. Serious side‐effects, such as bleeding, perforation and heart failure, occur in approximately 1 % of patients using NSAIDs. One‐third of all patients receiving NSAIDs will have gastrointestinal complaints. Since at least 10% of patients terminate treatment with NSAIDs as a result of side‐effects, even reduction of those that are not life‐threatening would be of great benefit. H2‐receptor antagonists have proved effective in ulcer treatment, and their use as prophylaxis against the side‐effects of NSAIDs is being widely studied. In a recent study, 63 patients who had experienced serious upper gastrointestinal side‐effects were given cimetidine while continuing their NSAID therapy. All but 4 of the 47 who had gastric or duodenal ulcer on first admission were healed at 8 weeks, and none of the remaining 16 with diffuse bleeding gastritis experienced further clinical episodes of bleeding or

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00763.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00669.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYConcepts are reviewed of the effects of anti‐ulcer agents in counteracting the biochemical and cellular pathology of gastrointestinal injury by non‐steroidal anti‐inflammatory drugs (NSAIDs). While some measure of control of NSAID‐induced mucosal damage is achieved in the upper gastrointestinal tract by the currently available anti‐ulcer drugs, none can effectively counteract the major biochemical changes induced by NSAIDs. Some experimental approaches, which have been developed from recent studies in laboratory animals, are considered as a possible basis towards developing improvements in preventive procedures against NSAID‐induced gastrointestinal in

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00764.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYIn a double‐blind placebo‐controlled trial of patients undergoing elective abdominal surgery (n=91), a single intravenous infusion of ceruletide (2.5 ng kg−’min−1’for 1 hour) resulted in audible bowel sounds in 42/47 patients as opposed to 30/44 receiving placebo (P<0.025). Excessive bowel sounds were noted in 16 patients in the ceruletide group and four receiving placebo (P<0.01). Significantly more patients (P<0.01) in the ceruletide group (22/45 versus 9/44) passed flatusper rectumbetween the second and third post‐operative day. Ceruletide infusion was accompanied by a significant increase in the incidence of nausea and vomiting (P<0.005,P<0.0025) but these side effects were short‐lived. These results indicate that ceruletide is likely to be a useful therapeutic agent for acute intestinal adynamic mot

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00671.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYThe effect of two ranitidine intravenous infusion regimens on intragastric pH was studied in 134 critically ill patients admitted to 15 intensive care units. Intragastric pH was determined hourly for 30 hours. Those patients whose intragastric acidity fell below pH 4.0 for 3 or more of the first 6 hours were considered ‘at risk’ of developing stress‐related gastric lesions and randomized to receive a 50 mg bolus of ranitidine together with a continuous intravenous infusion of either 0.125 or 0.25 mg kg—1h—1ranitidine for 24 hours. The maximal elevation in intragastric pH was achieved within 12 hours. The median intragastric pH for the last 20 hours of the infusion period was 5.9 for the higher dose group and 5.6 for the lower dose group. The increase in intragastric pH achieved by the two dosage regimens did not differ significantly throughout the 24 hour period. Patients having two or more of five major risk factors (head injury, major trauma, sepsis, respiratory failure/insufficiency and major surgery) had better overall control of intragastric pH on the higher dose of ranitidine than those receiving the lower dose. The majority of intensive care patients are likely to receive satisfactory treatment with the lower dosage regimen that was tested (0.125 mg kg—1h—1). Those with multiple risk factors may, however, require treatment with higher doses of ranitidine (0.2

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00672.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYProstaglandins have numerous mucosal protective properties, impairment of which contribute to NSAID injury. It is not clear which is the most important injurious factor affecting patients taking NSAIDs. Is it the NSAID itself, either by topical toxidty and/or production of toxic mediators or does the patient become more sensitive to NSAIDs as a result of some other luminal component, such as acid or bile acids, food (by physical or chemical mechanisms) or accompanying alcohol? Intrinsic irritancy/toxicity probably accounts for the greater mucosal toxicity of aspirin, although it is not clear whether this is due to a direct (non‐prostaglandin‐dependent) effect on mucus or bicarbonate secretion, membrane integrity, interference with intermediary metabolism or the production of toxic products. Similarly, the relationship of irritancy to the symptom of dyspepsia, to which patients on aspirin are prone, is as yet not well understood. While strategies for short‐term protection of experimental animals and humans are well established, protection against important, but relatively rare clinical events, is more difficult to study and much less well understood. In particular, the importance of the ability of NSAIDs to exacerbate bleeding, independent of injury, has been largely neglected in the context of presentation with haematemesis and me

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00765.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY