Aspirin-induced peptic ulcer and genetic polymorphisms.
ABSTRACT There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.
- SourceAvailable from: John Lawrence Wallace[show abstract] [hide abstract]
ABSTRACT: As we approach the 100th year since the introduction of aspirin to the marketplace, the association of gastrointestinal damage with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) remains the major limitation to their use. Although various approaches have been taken to producing NSAIDs with reduced gastrointestinal toxicity, few have significantly reduced the incidence of clinically significant adverse reactions (perforation or hemorrhage). In this review, the mechanisms contributing to the mucosal injury caused by NSAIDs in the stomach, small intestine, and colon are reviewed. In addition, several recent strategies for developing NSAIDs that spare the gastrointestinal tract of injury are discussed. These include selective inhibitors of cyclooxygenase 2, nitric oxide-releasing NSAIDs, and NSAIDs preassociated with zwitterionic phospholipids.Gastroenterology 04/1997; 112(3):1000-16. · 12.82 Impact Factor
Article: Aspirin.Journal of the American Pharmaceutical Association 03/1977; 17(2):107-12.
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ABSTRACT: Aspirin products are known to cause irritation and injury to the gastric mucosa. The belief that enteric-coated and buffered varieties are less likely to occasion major upper-gastrointestinal bleeding (UGIB) than plain aspirin was tested in data from a multicentre case-control study. 550 incident cases of UGIB admitted to hospital with melaena or haematemesis and confirmed by endoscopy, and 1202 controls identified from population census lists, were interviewed about use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) during the 7 days before the onset of bleeding (cases) or interview (controls). Relative risks of UGIB for each type of aspirin used regularly (at least every other day) were calculated overall, and according to dose, by multiple logistic regression, with control for age, sex, marital status, date, education, cigarette smoking, alcohol use, and use of NSAIDs. The relative risks of UGIB for plain, enteric-coated, and buffered aspirin at average daily doses of 325 mg or less were 2.6, 2.7, and 3.1, respectively. At doses greater than 325 mg, the relative risk was 5.8 for plain and 7.0 for buffered aspirin; there were insufficient data to evaluate enteric-coated aspirin at this dose level. There were no important differences in risk attributable to the three aspirin forms according to bleeding site (gastric vs duodenal), or when users of NSAIDs were excluded. Use of low doses of enteric-coated or buffered aspirin carries a three-fold increase in the risk of major UGIB. The assumption that these formulations are less harmful than plain aspirin may be mistaken.The Lancet 12/1996; 348(9039):1413-6. · 39.06 Impact Factor