Laufer S
Institute of Pharmacy, University of Tübingen, Tübingen, Germany.
Rheumatology (Oxford). 2004 Feb;43 Suppl 1:i9-15. doi: 10.1093/rheumatology/keh103.
Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors are commonly used to control pain and inflammation in osteoarthritis. However, these agents have been associated with gastrointestinal, renal and cardiovascular adverse effects. Together, these complications indicate a clear unmet need in the safety of current treatment options for the management of osteoarthritis. NSAIDs are known to have adverse gastrointestinal effects, and more recently it has been suggested that some selective COX-2 inhibitors are also associated with serious gastrointestinal complications. Selective COX-2 inhibitors have a similar capacity to NSAIDs to delay ulcer healing, and may not significantly decrease the incidences of perforation, ulceration and bleeding (the most clinically relevant gastrointestinal endpoints) compared with NSAIDs. These effects may be due to overlapping roles of COX-1 and COX-2 in physiological and pathophysiological processes. Furthermore, as COX-2 is integrally involved in renal homeostasis, selective COX-2 inhibitors are associated with negative effects on kidney function similar to those seen with NSAIDs. Electrolyte disturbances, oedema and hypertension have been correlated with the use of both drug classes. Additionally, selective COX-2 inhibitors have the potential to increase cardiovascular events, although further research is required to clearly determine such a risk. With the current unmet needs in the treatment of osteoarthritis, the opportunity exists for the development of new therapies. Novel agents include the COX-inhibiting nitric oxide donors and the lipoxygenase (LOX)/COX inhibitor licofelone. Initial results suggest that these therapies may have tolerability advantages over the NSAIDs and selective COX-2 inhibitors.
非甾体抗炎药（NSAIDs）和选择性环氧化酶（COX）-2抑制剂常用于控制骨关节炎的疼痛和炎症。然而，这些药物与胃肠道、肾脏和心血管不良反应有关。这些并发症共同表明，目前骨关节炎治疗方案的安全性存在明显未满足的需求。已知NSAIDs具有不良胃肠道作用，最近有人提出，一些选择性COX-2抑制剂也与严重的胃肠道并发症有关。选择性COX-2抑制剂与NSAIDs具有相似的延迟溃疡愈合的能力，与NSAIDs相比，可能不会显著降低穿孔、溃疡和出血（临床上最相关的胃肠道终点）的发生率。这些作用可能是由于COX-1和COX-2在生理和病理生理过程中的重叠作用。此外，由于COX-2在肾脏内环境稳定中起着不可或缺的作用，选择性COX-2抑制剂与NSAIDs类似，对肾功能有负面影响。电解质紊乱、水肿和高血压与这两类药物的使用都有关联。此外，选择性COX-2抑制剂有可能增加心血管事件，尽管需要进一步研究来明确确定这种风险。鉴于目前骨关节炎治疗存在未满足的需求，开发新疗法的机会是存在的。新型药物包括COX抑制性一氧化氮供体和脂氧合酶（LOX）/COX抑制剂利考昔芬。初步结果表明，这些疗法可能比NSAIDs和选择性COX-2抑制剂具有耐受性优势。
