Naesdal Jørgen, Brown Kurt
AstraZeneca R&D, Mölndal, Sweden.
Drug Saf. 2006;29(2):119-32. doi: 10.2165/00002018-200629020-00002.
NSAIDs are central to the clinical management of a wide range of conditions. However, NSAIDs in combination with gastric acid, which has been shown to play a central role in upper gastrointestinal (GI) events, can damage the gastroduodenal mucosa and result in dyspeptic symptoms and peptic lesions such as ulceration.NSAID-associated GI mucosal injury is an important clinical problem. Gastroduodenal ulcers or ulcer complications occur in up to 25% of patients receiving NSAIDs. However, these toxicities are often not preceded by indicative symptoms. Data obtained from the Arthritis, Rheumatism, and Aging Medical Information System have shown that 50-60% of NSAID-associated peptic ulcer cases can remain clinically silent and do not present until complications occur. Therefore, prophylactic treatment to prevent GI complications may be necessary in a substantial proportion of NSAID users, especially those in groups associated with a high risk of developing these complications. Use of cyclo-oxygenase (COX)-2 selective NSAIDs, also known as 'coxibs', substantially reduces the incidence of upper GI toxicities seen with non-selective NSAIDs. However, there are concerns regarding the cardiovascular safety of coxibs. For this reason, the US FDA recommends minimal use of coxibs and only when strictly necessary. Additionally, rofecoxib has been removed from the US market and sales of valdecoxib have been suspended. Furthermore, upper GI toxicities still occur in patients receiving coxibs. Therefore, cotherapies are required to prevent and/or heal upper GI effects associated with NSAID use. Effective prophylactic and treatment strategies include misoprostol, histamine H(2) receptor antagonists and proton pump inhibitors (PPIs). The key role that gastric acid plays in upper GI adverse events among NSAID users suggests that it is important to choose the most effective agent for acid control to alleviate symptoms, heal mucosal erosions and improve the reduced quality of life in this patient population. PPIs provide effective acid suppression, which is essential to avoid GI mucosal injury, and they are, therefore, capable of dramatically decreasing the morbidity and mortality associated with this disorder. Since many serious GI complications are not heralded by any previous symptoms, physicians need to be aware of risk factor profiles that predispose patients to serious GI problems. Physicians also need to initiate the appropriate preventative acid suppressive therapy to minimise the burden of NSAID-associated GI adverse effects.
非甾体抗炎药(NSAIDs)在多种疾病的临床管理中至关重要。然而,NSAIDs与胃酸共同作用时(胃酸在上消化道(GI)事件中已被证明起核心作用),会损害胃十二指肠黏膜,导致消化不良症状和消化性病变,如溃疡。NSAID相关的胃肠道黏膜损伤是一个重要的临床问题。在接受NSAIDs治疗的患者中,高达25%会发生胃十二指肠溃疡或溃疡并发症。然而,这些毒性反应往往没有先兆症状。从关节炎、风湿病和老年医学信息系统获得的数据表明,50 - 60%的NSAID相关消化性溃疡病例在临床上可能无症状,直到出现并发症才被发现。因此,在相当一部分NSAID使用者中,尤其是那些发生这些并发症风险较高的人群,可能需要进行预防性治疗以预防胃肠道并发症。使用环氧化酶(COX)-2选择性NSAIDs,也称为“昔布类药物”,可大幅降低非选择性NSAIDs所致上消化道毒性反应的发生率。然而,人们对昔布类药物的心血管安全性存在担忧。因此,美国食品药品监督管理局(FDA)建议尽量少用昔布类药物,仅在严格必要时使用。此外,罗非昔布已从美国市场撤出,伐地昔布的销售也已暂停。而且,接受昔布类药物治疗的患者仍会出现上消化道毒性反应。因此,需要联合治疗来预防和/或治愈与NSAID使用相关的上消化道不良反应。有效的预防和治疗策略包括米索前列醇、组胺H2受体拮抗剂和质子泵抑制剂(PPIs)。胃酸在NSAID使用者上消化道不良事件中所起的关键作用表明,选择最有效的抑酸药物以缓解症状、治愈黏膜糜烂并改善该患者群体下降的生活质量非常重要。PPIs能有效抑制胃酸,这对于避免胃肠道黏膜损伤至关重要,因此,它们能够显著降低与该疾病相关的发病率和死亡率。由于许多严重的胃肠道并发症没有任何先前症状的预示,医生需要了解使患者易患严重胃肠道问题的风险因素概况。医生还需要启动适当的预防性抑酸治疗,以尽量减少NSAID相关胃肠道不良反应的负担。