Bell N J, Hunt R H
Division of Gastroenterology, McMaster University Medical Centre, Hamilton, Ontario, Canada.
Yale J Biol Med. 1992 Nov-Dec;65(6):649-57;discussion 689-92.
The proton pump, a H+/K(+)-ATPase located on the secretory canalicular membrane of the parietal cell, forms the final pathway for gastric acid secretion. Omeprazole is concentrated in the secretory canaliculus, where it is converted to its active form, which binds covalently with the H+/K(+)-ATPase, thus inhibiting acid secretion arising from any stimulus. Meta-analysis has defined the primary determinants for peptic ulcer healing as the degree of acid suppression, the duration of suppression over 24 hours, and the length of treatment. The longer duration of acid suppression with omeprazole, particularly during the day, when food is ingested and H2-receptor antagonists are less effective, is reflected in the clinical superiority for symptom relief and ulcer healing and especially for the treatment of erosive esophagitis. Extensive clinical experience has proved omeprazole to be safe, and concerns over hypergastrinemia, ECL-cell hyperplasia, and carcinoid formation have not been substantiated in humans. Recent evidence has shown that omeprazole suppresses Helicobacter pylori and, in combination with antibiotics, can eradicate this organism in a substantial proportion of patients. This effect may result from enhancement of antibiotic bioavailability and optimizing host defense mechanisms.
质子泵是一种位于壁细胞分泌小管膜上的H⁺/K⁺-ATP酶，它构成了胃酸分泌的最终途径。奥美拉唑在分泌小管中浓集，在那里它转化为活性形式，与H⁺/K⁺-ATP酶共价结合，从而抑制任何刺激引起的胃酸分泌。荟萃分析已将消化性溃疡愈合的主要决定因素定义为胃酸抑制程度、24小时内抑制持续时间以及治疗时长。奥美拉唑胃酸抑制持续时间更长，尤其是在摄入食物且H₂受体拮抗剂效果较差的白天，这体现在其在缓解症状和促进溃疡愈合方面的临床优势上，特别是在治疗糜烂性食管炎方面。广泛的临床经验已证明奥美拉唑是安全的，对高胃泌素血症、肠嗜铬样细胞增生和类癌形成的担忧在人类中尚未得到证实。最近的证据表明，奥美拉唑可抑制幽门螺杆菌，并且与抗生素联合使用时，能在相当比例的患者中根除该菌。这种作用可能是由于提高了抗生素的生物利用度并优化了宿主防御机制。
