Nonsteroidal anti-inflammatory drug gastropathy

Hawkey, Christopher J.

doi:10.1053/gast.2000.9561

Cited by 308 publications

(212 citation statements)

References 115 publications

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“…7 In the United States, about 16 500 people die per year as a result of NSAIDassociated gastrointestinal complications. 8 We recently suggested that direct cytotoxic effects of NSAIDs (such as induction of apoptosis), that is, COX-independent are involved in NSAID-induced gastric lesions in vivo.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

et al. 2004

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Apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs) is involved not only in the production of NSAIDinduced gastric lesions but also in the antitumor activity of these drugs. The endoplasmic reticulum (ER) stress response is a cellular mechanism that aids in protecting the ER against ER stressors and is involved in ER stressor-induced apoptosis. Here, we examine the relationship between this response and NSAID-induced apoptosis in cultured guineapig gastric mucosal cells. Exposure of cells to indomethacin, a commonly used NSAID, induced GRP78 as well as CHOP, a transcription factor involved in apoptosis. Three factors that positively regulate CHOP expression (ATF6, ATF4 and XBP-1) were activated and/or induced by indomethacin. NSAIDs other than indomethacin (diclofenac, ibuprofen and celecoxib) also induced CHOP. Monitoring of the transcriptional activities of ATF6 and CHOP by luciferase assay revealed that both were stimulated in the presence of indomethacin. Furthermore, indomethacin-induced apoptosis was suppressed in cultured guinea-pig gastric mucosal cells by expression of the dominant-negative form of CHOP, or in peritoneal macrophages from CHOP-deficient mice. These results suggest that ER stress response-related proteins, particularly CHOP, are involved in NSAID-induced apoptosis.

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Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

et al. 2004

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“…These agents continue to serve as the mainstay of treatment despite their association with clinically significant gastrointestinal (GI) complications, including nonulcer dyspepsia, symptomatic ulcers, ulcer hemorrhages, and ulcer perforations (3). The economic impact of these adverse events is significant: they result in Ͼ100,000 hospitalizations annually at a cost of $1.6 billion (1,4).…”

Section: Introductionmentioning

confidence: 99%

Minimizing complications from nonsteroidal antiinflammatory drugs: Cost‐effectiveness of competing strategies in varying risk groups

Spiegel¹,

Chiou²,

Ofman³

2005

Arthritis & Rheumatism

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Objective. To appraise the cost-effectiveness of competing therapeutic strategies in patient cohorts eligible for aspirin prophylaxis with varying degrees of gastrointestinal (GI) and cardiovascular risk. Methods. Cost-effectiveness and cost-utility analyses were performed to evaluate 3 competing strategies for the management of chronic arthritis: 1) a generic nonselective nonsteroidal antiinflammatory drug (NSAID NS ) alone; 2) NSAID NS plus a proton pump inhibitor (PPI); and 3) a cyclooxygenase 2-selective inhibitor (coxib) alone. Cost estimates were from a third-party payer perspective. The outcomes were incremental cost per ulcer complication avoided and incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analysis was performed to evaluate the impact of varying patient GI risks and aspirin use. Results. In average-risk patients, the NSAID NS ؉ PPI strategy costs an incremental $45,350 per additional ulcer complication avoided and $309,666 per QALY gained compared with the NSAID NS strategy. The coxib strategy was less effective and more expensive than the NSAID NS ؉ PPI strategy. Sensitivity analysis revealed that the NSAID NS ؉ PPI strategy became the dominant approach in patients at high risk for an NSAID adverse event (i.e., patients taking aspirin with >1 risk factor for a GI complication). Conclusion. Generic nonselective NSAIDs are most cost-effective in patients at low risk for an adverse event. However, the addition of a PPI to a nonselective NSAID may be the preferred strategy in patients taking aspirin or otherwise at high risk for a GI or cardiovascular adverse event.

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“…1,2 Progress towards safer analgesic and antiinflammatory therapy has been aided by the identification of two isoforms of the enzyme cyclo-oxygenase (COX): COX-1 and COX-2. [3][4][5] Although COX-1 is constitutively expressed in most tissues (e.g.…”

Section: Introductionmentioning

confidence: 99%

The pharmacological properties and clinical use of valdecoxib, a new cyclo‐oxygenase‐2‐selective inhibitor

Alsalameh

Burian

Mahr

et al. 2003

Aliment Pharmacol Ther

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SUMMARYCyclo-oxygenase-2-selective inhibitors produce less gastric damage than conventional non-steroidal antiinflammatory drugs. Valdecoxib is a new orally administered cyclo-oxygenase-2-selective inhibitor, recently approved for use in osteoarthritis, rheumatoid arthritis and primary dysmenorrhoea in the USA. The drug has been evaluated in more than 60 clinical studies involving more than 14 000 patients and healthy volunteers. The analgesic efficacy of valdecoxib at a dose of 10 mg once daily in both osteoarthritis and rheumatoid arthritis is superior to that of placebo and similar to that of traditional non-steroidal anti-inflammatory drugs. Valdecoxib is effective in single doses of up to 40 mg for the alleviation of acute menstrual pain and has a rapid onset of action (within 30 min) and a long duration of analgesia (up to 24 h). Valdecoxib is well tolerated and has safety advantages compared with traditional non-steroidal anti-inflammatory drugs in terms of less gastrointestinal toxicity and a lack of an effect on platelet function. The incidence of adverse effects involving the kidney (fluid retention, oedema and hypertension) is similar to that of non-selective, nonsteroidal anti-inflammatory drugs.

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Nonsteroidal anti-inflammatory drug gastropathy

Cited by 308 publications

References 115 publications

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

Minimizing complications from nonsteroidal antiinflammatory drugs: Cost‐effectiveness of competing strategies in varying risk groups

The pharmacological properties and clinical use of valdecoxib, a new cyclo‐oxygenase‐2‐selective inhibitor

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