Pharmacological approach to the prevention of non-steroidal anti-inflammatory drug-induced gastropathy.
Non-steroidal anti-inflammatory drugs can provoke gastric damage by multiple interactive mechanisms. These processes include topical irritant actions that disrupt the epithelial barrier, which allows the back-diffusion of acid into the mucosa. The inhibition of the cyclo-oxygenase isoform, cyclo-oxygenase-1 also promotes gastric injury, such effects involving the microcirculation. These mechanisms of mucosal damage synergistically interact to cause more extensive injury, which can be attenuated by antisecretory agents or by mucosal protective agents such as the synthetic prostanoid, misoprostil. In addition, agents that release nitric oxide may prevent such mucosal damage. However, the development of the novel anti-inflammatory drugs, the cyclo-oxygenase-2 selective agents, that inhibit the formation of prostanoids at inflammatory sites, but not the endogenous protective prostanoids in the stomach formed by cyclo-oxygenase-1, has provided a highly effective therapeutic approach to minimising of gastric damage.
Whittle
B J
BJ
William Harvey Research Institute, St. Bartholomew's, London, England, UK. B.J.whittle@mds.qmw.ac.uk
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D011379:Prognosis; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000517:prevention & control*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors