Coron Emmanuel, Hatlebakk Jan G, Galmiche Jean-Paul
Department of Gastroenterology and Hepatology, University Hospital, Nantes, France.
Curr Opin Gastroenterol. 2007 Jul;23(4):434-9. doi: 10.1097/MOG.0b013e328159f001.
Proton pump inhibitors remain the mainstay of medical therapy in gastroesophageal reflux disease. Despite their increasing use, up to 40% of patients are not fully satisfied with their antireflux therapy. Recent data on efficacy and safety are reviewed and causes of failure are discussed.
Several randomized studies and a metaanalysis have shown marginal differences in efficacy between various proton pump inhibitor regimens. In subgroups, however, such as severe esophagitis, esomeprazole may be superior. Poor compliance is one of the main causes of failure. Nonacid reflux is likely to play an important role, especially in patients with regurgitation or cough persisting on therapy. Genetic polymorphisms involved in proton pump inhibitor metabolism, Helicobacter pylori infection or nocturnal acid breakthrough during therapy are probably less important than initially suspected. Recent pharmacological developments include new proton pump inhibitor isomers, potassium competitive acid blockers and inhibitors of transient lower esophageal sphincter relaxations.
There are still important unmet needs in the treatment of gastroesophageal reflux disease. Optimizing acid control is unlikely to improve the condition of the majority of patients with incomplete proton pump inhibitor response. Inhibition of transient lower esophageal sphincter relaxations remains the major pharmacological target for future drug development.
质子泵抑制剂仍然是胃食管反流病药物治疗的主要手段。尽管其使用越来越广泛,但仍有高达40%的患者对其抗反流治疗不完全满意。本文综述了近期有关疗效和安全性的数据,并讨论了治疗失败的原因。
多项随机研究和一项荟萃分析表明,不同质子泵抑制剂治疗方案之间在疗效上存在微小差异。然而,在亚组分析中,如重度食管炎患者,埃索美拉唑可能更具优势。依从性差是治疗失败的主要原因之一。非酸性反流可能起重要作用,尤其是在治疗后仍有反流或咳嗽的患者中。质子泵抑制剂代谢相关的基因多态性、幽门螺杆菌感染或治疗期间的夜间酸突破可能没有最初认为的那么重要。近期的药理学进展包括新型质子泵抑制剂异构体、钾离子竞争性酸阻滞剂和一过性下食管括约肌松弛抑制剂。
胃食管反流病的治疗仍存在重要的未满足需求。优化胃酸控制不太可能改善大多数对质子泵抑制剂反应不完全的患者的病情。抑制一过性下食管括约肌松弛仍然是未来药物研发的主要药理学靶点。