Nonsteroidal antiinflammatory drugs and their effects.
TL;DR: A brief review of several of the newly described effects of the NSAIDs and the possible implications of the experimentally observed COX-2-selective effects of these clinically useful antiinflammatory agents are presented.
Abstract: New information about the mechanisms of action of nonsteroidal antiinflammatory drugs (NSAIDs) offers potential opportunities to minimize the complications of these commonly used drugs. Traditionally, the accepted mode of action of the NSAIDs has been the inhibition of prostaglandin synthesis through either reversible or irreversible binding to cyclooxygenase (COX). However, drugs that are weak prostaglandin synthesis inhibitors in vitro have been demonstrated to be equally as effective in vivo as other "stronger" COX inhibitors in treating inflammatory diseases, suggesting the importance of other actions of these drugs. Various NSAIDs have been used for years to palliate pain and inflammation in many different disease processes; unfortunately, they have not been demonstrated to alter the natural history of disease such as rheumatoid arthritis. Perhaps that is because prostaglandins do not play a large role in most inflammatory diseases; alternatively, it might be attributable to the inability of NSAIDs to exert their full effects because of their potential toxic reactions.An understanding of the effects of cyclooxygenase inhibition has been further complicated by the recently described second isoenzyme of prostaglandin synthase. One form of cyclooxygenase appears to be important in the maintenance of normal physiologic functions (COX-1), whereas the other form is induced primarily in sites of inflammation (COX-2). Even if inhibition of cyclooxygenase is only one mechanism of action for these drugs, with only some of the potential toxic effects modulated by the inhibition of prostaglandin synthesis such as inhibition of COX-1, an understanding of the actions of the two isoforms of cyclooxygenase is an important step in further delineating the inflammatory cascade. Ideally, the treatment of inflammation could be improved by inhibiting the effects of COX-2 without inhibiting COX-1 activity. Thus, some potential side effects of the NSAIDs might be alleviated. The presently available NSAIDs all affect both COX-1 and COX-2, although not equally. There are also data describing some of the NSAIDs as less toxic to the gastrointestinal mucosa because of their chemical composition. These data are typically based on in vitro experiments that use varying methodologies, making it difficult to compare the effects of any one NSAID between studies.This paper presents a brief review of several of the newly described effects of the NSAIDs and concentrates on the possible implications of the experimentally observed COX-2-selective effects of these clinically useful antiinflammatory agents.
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TL;DR: Understanding of the pharmacologic basis for the differential actions of NSAIDs when prescribing them for pain and inflammation is important so that physicians can critically evaluate the basis for, and the emerging data on, COX-2-specific inhibitors and their potential role in clinical medicine.
314 citations
TL;DR: Preliminary data from cyclooxygenase-2-selective inhibitors suggest that they also affect renal prostaglandins, and the same cautions should be exercised with their use as with traditional NSAIDs.
256 citations
TL;DR: The data indicate that administration of valdecoxib offers similar efficacy for the treatment of osteoarthritis but improved upper-gastrointestinal safety compared with the conventional NSAIDs, ibuprofen and diclofenac, based on the significantly lower incidence of gastroduodenal ulcers detected by endoscopy.
Abstract: OBJECTIVE: To determine whether valdecoxib, at chronic arthritis doses, has the characteristics of a cyclo-oxygenase 2 (COX-2) specific inhibitor, as measured by a reduced incidence of upper-gastrointestinal ulceration compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: This double-blind, multicentre, placebo-controlled, parallel-group study compared the incidence of gastroduodenal ulcers associated with valdecoxib 10 mg daily (q.d.) and 20 mg q.d. with that of ibuprofen 800 mg three times daily (t.i.d.) or diclofenac 75 mg twice daily (b.i.d.) when administered over a 12-week period. The incidence of gastroduodenal ulcers was assessed by upper-gastrointestinal endoscopy, performed at baseline and again at the end of week 12 (or at early study termination). Efficacy assessments were performed at baseline and at weeks 2, 6 and 12 using Patient's and Physician's Global Assessments of Arthritis. RESULTS: A total of 1052 osteoarthritis patients were enrolled into the trial. The incidence of gastroduodenal ulcers over 12 weeks was 5% in patients receiving valdecoxib 10 mg q.d., 4% in patients receiving valdecoxib 20 mg q.d., 7% in patients receiving placebo, 16% in patients receiving ibuprofen 800 mg t.i.d. (P <0.05 v. placebo), and 17% in patients receiving diclofenac 75 mg b.i.d. (P <0.05 v. placebo). The incidence of gastroduodenal ulcers at week 12 seen in the ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. groups was significantly higher than that in the valdecoxib 10 mg q.d. and valdecoxib 20 mg q.d. groups (P <0.05). The incidence rates of gastroduodenal ulcers were not significantly different between the valdecoxib treatment groups or between valdecoxib- and placebo-treated patients. Efficacy responses to valdecoxib 10 mg and 20 mg q.d. were significantly greater than placebo and comparable with both ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. CONCLUSIONS: The results of the study demonstrate that valdecoxib has an upper-gastrointestinal safety profile typical of a COX-2 specific inhibitor. Overall, the data indicate that administration of valdecoxib offers similar efficacy for the treatment of osteoarthritis but improved upper-gastrointestinal safety compared with the conventional NSAIDs, ibuprofen and diclofenac, based on the significantly lower incidence of gastroduodenal ulcers detected by endoscopy.
104 citations
TL;DR: This review will summarize the known information defining the mechanisms by which these renal syndromes and related cardiovascular NSAIDs-induced side effects evolve and will characterize the “at-risk” NSAID consumer populations, together with approaches to the prevention and management of these diverse NSAID-related side effects.
101 citations
TL;DR: The evidence from the available clinical trials is of limited amount and quality, but it weakly supports the proposal that the addition of an NSAIDs to WHO Step III opioids can improve analgesia or reduce opioid dose requirement.
Abstract: Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are used widely in the management of mild to moderate cancer pain and are frequently combined with opioids in the treatment of moderate to severe pain.Aim: To perform a systematic literature review of the evidence of the efficacy and toxicity of NSAIDs or paracetamol added to WHO Step III opioid treatment for cancer pain.Design and data sources: A systematic literature review of MedLine, EMBASE and Cochrane Central register of controlled trials database was carried out using both text words and MeSH/EMTREE terms.Results: Seven eligible papers were retrieved from the new search and five from the Cochrane review. Five of seven studies showed an additive effect of NSAIDs when combined with opioids either by improving analgesia (three studies) or by reducing the opioid dose (two studies). Paracetamol was only marginally effective in one of five trials. The study designs were not adequate to assess differences in side effects between the...
86 citations