Eastern Virginia Medical School, Gastroenterology, 885 Kempsville Rd, Norfolk, VA 23502, USA.
Expert Opin Pharmacother. 2010 Jun;11(9):1541-8. doi: 10.1517/14656566.2010.482932.
Despite the clinical success of proton pump inhibitors to treat gastroesophageal reflux disease (GERD), for the majority of patients in both gastroenterology and primary care clinics there is still a substantial group of patients (up to 40% in some studies) who do not completely respond symptomatically to a standard dose of proton pump inhibitors (PPIs). Specific explanations for these PPI noncomplete responders included transient lower esophageal sphincter relaxations (TLESRs), sensitivity to weakly acidic and/or alkaline reflux, large volume of reflux and esophageal hypersensitivity. There is a clear need for GERD therapies beyond the PPIs.
These drug classes include the GABA(B) receptor agonists (including lesogaberan and arbaclofen placarbil), mGluR5 receptor antagonists, P-CABs, cholecystokinin(2) antagonists and add-on therapies to PPIs including mosapride and rikkunshito.
Both physicians and patients are eagerly awaiting the development and FDA approval of a new class of anti-GERD medications targeting distinct mechanisms. This article provides information on pharmacologic strategies, clinical trials and side-effect profiles on several of the most promising and heavily researched compounds being developed today for the treatment of GERD symptoms and inflammation. Hopefully, this important research will help a large group of PPI noncomplete responding patients receive symptomatic relief and reduce esophageal inflammation through a unique pharmacologic mechanism in the near future.
The treatment of GERD has greatly improved with the PPI class of therapy. Despite excellent success, there is a sizeable population of patients who do not have adequate response to therapies directed only at acid suppression. Emerging new pharmacologic treatment options show promise in further advancing the treatment success of GERD.
尽管质子泵抑制剂 (PPI) 在治疗胃食管反流病 (GERD) 方面取得了临床成功，但在胃肠病学和初级保健诊所的大多数患者中，仍有相当一部分患者（在某些研究中高达 40%）对标准剂量的质子泵抑制剂 (PPI) 不能完全缓解症状。这些 PPI 不完全应答者的具体解释包括短暂性食管下括约肌松弛 (TLESRs)、对弱酸性和/或碱性反流的敏感性、反流量大和食管高敏性。显然需要超越 PPI 的 GERD 治疗方法。
这些药物类别包括 GABA(B) 受体激动剂（包括 lesogaberan 和 arbaclofen placarbil）、mGluR5 受体拮抗剂、P-CAB、胆囊收缩素 (2) 拮抗剂以及 PPI 的附加治疗方法，包括 mosapride 和 rikkunshito。
医生和患者都在急切地等待着针对不同机制的新一代抗 GERD 药物的开发和 FDA 批准。本文提供了有关几种最有前途和研究最多的化合物的药理学策略、临床试验和副作用概况的信息，这些化合物目前正在开发用于治疗 GERD 症状和炎症。希望这项重要的研究能够帮助大量的 PPI 不完全应答患者通过独特的药理学机制在不久的将来获得症状缓解和减轻食管炎症。
PPI 类治疗极大地改善了 GERD 的治疗。尽管取得了优异的成功，但仍有相当一部分患者对仅针对酸抑制的治疗反应不佳。新兴的新药理治疗选择有望进一步提高 GERD 的治疗成功率。
