Department of Medicine and Center of Excellence on Aging, Gabriele d'Annunzio University, School of Medicine, and Gabriele d'Annnunzio University Foundation, Ce.S.I., Via dei Vestini 31, 66013 Chieti, Italy.
Pharmacol Rep. 2005;57 Suppl:66-85.
Prostanoids act leading roles in a myriad of physiologic and pathologic processes because these autacoids participate in the amplification of biological responses induced by innumerable stimuli. The formation of prostanoids is operated by two synthases named cyclooxygenase(COX)-1 and COX-2. Traditional nonsteroidal antiinflammatory drugs (tNSAIDs) and COX-2 inhibitors (coxibs) give rise to antipyretic, analgesic, and antiinflammatory actions, through their reversible clogging of the COX channel of COX-2 - apart from aspirin which modifies irreversibly the catalytic activity of COX-2. tNSAIDs and COX-2 inhibitors resulted clinically equivalent for the relief of acute pain and symptoms of arthropathies but they failed to modify disease progression. Clinical evidence of the possible contribution of COX-1 in inflammation and pain in some occasion - as suggested by experimental and pharmacology studies - is orphan because none efficacy trial with COX inhibitors was designed to establish it. COX-2 inhibitors were developed with the aim to reduce the incidence of serious gastrointestinal (GI) adverse effects associated with the administration of tNSAIDs ensued as a consequence of the inhibition of cytoprotective COX-1-derived prostanoids. However, the reduced incidence of serious GI adverse effects compared to tNSAIDs demonstrated for 2 COX-2 inhibitors (e.g. rofecoxib and lumiracoxib) has been countered by an increased incidence of myocardial infarction and stroke detected in 5 placebo controlled trials involving the COX-2 inhibitors celecoxib, rofecoxib and valdecoxib. The future of COX-2 inhibitors will be an example of personalised medicine as their use will be restricted to patients who do not respond to tNSAIDs or with increased risk of GI complications.
前列腺素在无数生理和病理过程中发挥着主导作用，因为这些自体活性物质参与了无数刺激引起的生物反应的放大。前列腺素的形成是由两种称为环加氧酶 (COX)-1 和 COX-2 的合成酶操作的。传统的非甾体抗炎药 (tNSAIDs) 和 COX-2 抑制剂 (coxibs) 通过可逆地堵塞 COX-2 的 COX 通道产生解热、镇痛和抗炎作用——除了阿司匹林，它不可逆地改变 COX-2 的催化活性。tNSAIDs 和 COX-2 抑制剂在缓解急性疼痛和关节炎症状方面在临床上等效，但它们未能改变疾病进展。实验和药理学研究表明 COX-1 在某些情况下炎症和疼痛中可能发挥作用的临床证据是孤儿的，因为没有设计 COX 抑制剂的疗效试验来确定这一点。COX-2 抑制剂的开发旨在降低与 tNSAIDs 给药相关的严重胃肠道 (GI) 不良反应的发生率，这是由于抑制细胞保护 COX-1 衍生的前列腺素所致。然而，与 tNSAIDs 相比，两种 COX-2 抑制剂（例如罗非昔布和鲁米昔布）显示出严重 GI 不良反应发生率降低的情况，被涉及 COX-2 抑制剂塞来昔布、罗非昔布和伐地昔布的 5 项安慰剂对照试验中检测到的心肌梗死和中风发生率增加所抵消。COX-2 抑制剂的未来将是个性化医学的一个例子，因为它们的使用将仅限于对 tNSAIDs 无反应或有增加 GI 并发症风险的患者。
