• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文会议>International Symposium on Cell/Tissue Injury and Cytoprotection/Organoprotection: Focus on GI Tract >NSAID-Mucosal Injury: Roles of Drug Chemistry in Pathogenesis
【24h】

NSAID-Mucosal Injury: Roles of Drug Chemistry in Pathogenesis

机译：nsaid-mucosal损伤：药物化学在发病机制中的作用

获取原文
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Although extensive studies have been performed on the cellular and molecular aspects pathogenesis of gastrointestinal (Gl) injury from non-steroidal anti-inflammatory drugs (NSAIDs), there has been relatively little attention to the chemical features of these drugs which cause cellular injury. The chemical properties of most NSAIDs as organic acids accounts for their irritant properties which are achieved by their uptake through mucosal membranes as non-ionized acids and subsequent entrapment in mucosal cell in their ionized state. Our studies have shown that there is a direct relationship between drug acidity (pKa) of the drugs and their Lanza scores of human gastric mucosal injury, with less of a component attributed to lipophilicity (log P). Data are presented here from studies in a rat model of ulcer formation (cold exposed) and in mice (in which acid and pepsin secretion are stimulated by administration of the cholinomimetic, bethanechol chloride) and show that the relationships between pKa and log P (or the distribution coefficient, log D) are., with the exception of data on pKa in mice, not associated with ulcerogenicity as shown in humans. It is suggested that the differences between data in humans and those in rats or mice may relate to the marked increase in sensitivity of the mucosae of the animal models to the ulcerogenic effects of the drugs. Various additional factors particularly the steric, electronic and quantum chemistry of NSAIDs may markedly influence their ulcerogenic potential. These factors play an important role in determining the potential of pro-drugs to be less ulcerogenic than their parent NSAIDs.
机译：虽然大量的研究已经进行了胃肠（GI）损伤的细胞和分子发病机制方面的非甾体类抗炎药（NSAIDs）进行，出现了相对很少注意这些药物引起的细胞损伤的化学特性。大多数的NSAIDs如有机酸的化学性质占它们通过它们的摄取通过粘膜作为非离子化的酸，并在其离子化状态在粘膜细胞随后的截留实现它们的刺激性。我们的研究表明，有毒品和人胃粘膜损伤的Lanza评分的药物酸度（pKa值）之间的直接关系，归结为亲脂性（日志P）的组件更少。数据是这里提出从研究中溃疡形成的大鼠模型中（冷曝光）和在小鼠中（其中酸和胃蛋白酶的分泌是通过的拟胆碱，氯贝胆碱给药刺激的）和表明的pKa之间和日志P上的关系（或的分配系数，对数d）是，与数据的上pKa值在小鼠除外，如图人类不与ulcerogenicity相关联。有人建议，在人体和数据没有在大鼠或小鼠之间的差异可以涉及在动物模型中对药物的溃疡作用的粘膜的灵敏度的显着增加。各种附加因素尤其NSAID的空间，电子和量子化学可以显着地影响它们的溃疡的潜力。这些因素决定的前药的潜力会比他们的父母的NSAIDs溃疡少发挥重要作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号