UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
Med Res Rev. 2017 Jul;37(4):802-859. doi: 10.1002/med.21424. Epub 2016 Dec 22.
The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) against inflammation, pain, and fever has been supporting their worldwide use in the treatment of painful conditions and chronic inflammatory diseases until today. However, the long-term therapy with NSAIDs was soon associated with high incidences of adverse events in the gastrointestinal tract. Therefore, the search for novel drugs with improved safety has begun with COX-2 selective inhibitors (coxibs) being straightaway developed and commercialized. Nevertheless, the excitement has fast turned to disappointment when diverse coxibs were withdrawn from the market due to cardiovascular toxicity. Such events have once again triggered the emergence of different strategies to overcome NSAIDs toxicity. Here, an integrative review is provided to address the breakthroughs of two main approaches: (i) the association of NSAIDs with protective mediators and (ii) the design of novel compounds to target downstream and/or multiple enzymes of the arachidonic acid cascade. To date, just one phosphatidylcholine-associated NSAID has already been approved for commercialization. Nevertheless, the preclinical and clinical data obtained so far indicate that both strategies may improve the safety of nonsteroidal anti-inflammatory therapy.
非甾体抗炎药（NSAIDs）在抗炎、止痛和退热方面的疗效一直支持着它们在治疗疼痛和慢性炎症性疾病方面的全球应用。然而，长期使用 NSAIDs 很快就与胃肠道不良事件的高发率相关联。因此，人们开始寻找具有更好安全性的新型药物，COX-2 选择性抑制剂（coxibs）随即被开发并商业化。然而，当由于心血管毒性而将多种coxibs 撤出市场时，这种兴奋很快变成了失望。这些事件再次引发了克服 NSAIDs 毒性的不同策略的出现。在这里，提供了一个综合综述，以解决两种主要方法的突破：（i）将 NSAIDs 与保护介质联合使用，以及（ii）设计针对花生四烯酸级联下游和/或多种酶的新型化合物。迄今为止，只有一种与磷脂酰胆碱相关的 NSAID 已经获得商业化批准。然而，到目前为止获得的临床前和临床数据表明，这两种策略都可能提高非甾体抗炎治疗的安全性。
