Hunt Richard H, Scarpignato Carmelo
Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
Curr Treat Options Gastroenterol. 2018 Dec;16(4):570-590. doi: 10.1007/s11938-018-0206-y.
Acid suppression treatment has revolutionized the management of the acid-related disorders since the introduction of the H-receptor antagonists (H-RAs) and the proton pump inhibitors (PPIs). However, there has been increasing identification of needs for improvement in antisecretory therapy, especially in gastroesophageal reflux disease (GERD), the eradication of Helicobacter pylori (H. pylori), protection from aspirin (ASA) and non-steroidal inflammatory drug (NSAID) injury and the management of upper gastrointestinal (UGI) bleeding. There have also been increasing publications addressing safety concerns of antisecretory drugs.
The needs have been identified as shortcomings of the pharmacology of the delayed release-PPIs (DR-PPIs), which have short plasma half-lives, required to be given before a meal and show poor control of nocturnal acid secretion. New-generation PPIs have been developed, including dexlansoprazole modified release (MR), instant release omeprazole (IR-omeprazole), while metered release preparations such as Durasec™ or novel molecules such as tenatoprazole have also been developed and achieve superior control of intragastric pH especially at night. The major advance has been the development of the potassium channel acid blocking drugs, which block the K,H-ATPase K channel, are food independent, reversible, have a rapid onset of action, and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan, the first P-CAB, has so far been introduced only into a small number of Asian countries. Safety issues have been extensively addressed in numerous publications. This review sets the needs, individual new drug classes and key individual new treatments into clinical context. Acid suppression treatment is reviewed including the pharmacology, the unmet clinical needs across the acid-related disorders, the place of new drug treatments, and where superiority exists. The safety of antisecretory drugs is broadly summarized with reference to several recent comprehensive reviews and set within the clinical context of patient management, particularly those on long-term treatment who are the greatest risk of some adverse events.
自H受体拮抗剂（H-RAs）和质子泵抑制剂（PPIs）问世以来，抑酸治疗彻底改变了酸相关性疾病的管理方式。然而，人们越来越认识到抗分泌治疗需要改进，尤其是在胃食管反流病（GERD）、幽门螺杆菌（H. pylori）根除、预防阿司匹林（ASA）和非甾体类抗炎药（NSAID）损伤以及上消化道（UGI）出血管理方面。关于抗分泌药物安全性问题的出版物也越来越多。
已确定这些需求是延迟释放型PPIs（DR-PPIs）药理学的缺点，其血浆半衰期短，需要在饭前给药，且对夜间胃酸分泌控制不佳。新一代PPIs已研发出来，包括右兰索拉唑缓释剂（MR）、即释型奥美拉唑（IR-奥美拉唑），同时也开发了如Durasec™的控释制剂或如替那拉唑的新型分子，它们能更好地控制胃内pH值，尤其是在夜间。主要进展是钾通道酸阻断药物的研发，这类药物可阻断K，H-ATP酶钾通道，不受食物影响，具有可逆性，起效迅速，并能使胃内pH值持续长时间升高。沃克，首个钾竞争性酸阻滞剂（P-CAB），目前仅在少数亚洲国家上市。众多出版物广泛讨论了安全性问题。本综述将需求、各类新药和关键的个别新疗法置于临床背景中。对抑酸治疗进行了综述，包括药理学、酸相关性疾病中未满足的临床需求、新药治疗的地位以及优势所在。参考近期几篇全面综述，广泛总结了抗分泌药物的安全性，并将其置于患者管理的临床背景中，特别是那些长期治疗且发生某些不良事件风险最高的患者。
