T1977 Rand Appropriateness Study with Development of Recommendations for NSAID Treatment

Abstract

NH4Cl prepulse followed by a Na+-free solution. Alkalinization in Na+-free solution represents intracellular acid production and eliminates the possibility of contribution by the Na+/ H+ proteins. Studies were done in the presence or absence of indomethacin (100μM) or acetylsalicylic acid (ASA) (100-500μM). Results: In the presence of indomethacin, a rapid decrease in pHi is seen upon the removal of Na+, followed by an immediate rise in pHi, approaching pH of 7.0. In the absence of indomethacin, no alkalinization was observed until Na+ was added back to the solution. In a separate series of experiments, a similar result was observed with ASA. In the presence of ASA, a rapid alkalinization was observed in the Na+-free solution, representing intracellular acid production. This effect was not seen in the absence of drug. Conclusions: This study suggests that indomethacin and ASA have a direct effect on activation of acid secretion in the parietal cell. This is a novel mechanism in which NSAID use may increase risk of PUD. The direct stimulatory effect on acid secretion provides evidence for a rapid onset of PUD via the decreased barrier function coupled with enhanced acid secretion that occurs in the absence of secretagogues.