Karnes W E, Walsh J H
Division of Gastroenterology, UCLA.
J Clin Gastroenterol. 1990;12 Suppl 2:S7-12.
Newer potent and long-acting inhibitors of acid secretion, such as the proton pump inhibitor omeprazole, are becoming available for general use. These drugs promise to control acid-peptic disease effectively in patients who do not respond adequately to conventional short-acting H2-receptor antagonists. The safety of chronic administration of these drugs has come into question, however. Lifelong profound inhibition of acid secretion in rats induced by superpotent inhibitors of acid secretion or subtotal fundectomy is associated with the development of carcinoid tumors of enterochromaffin-like (ECL) cells in the gastric corpus. Available evidence supports a role of gastrin, which becomes chronically elevated in animals subjected to prolonged and profound hypochlorhydria. In humans, hypergastrinemic states such as Zollinger-Ellison syndrome and atrophic gastritis are associated with an increased risk of ECL-cell carcinoid tumors. Such observations have raised concern that humans may also be susceptible to carcinoid tumor formation in response to potent inhibitors of acid secretion. To date, however, no cases of carcinoid tumor have been attributed to the use of omeprazole in humans. If achlorhydric doses are not used, significant hypergastrinemia can be avoided while effectiveness of treatment is maintained. Such measures should minimize any risk of ECL-cell carcinoid tumors in humans taking potent long-term antisecretory drugs.
新型强效长效胃酸分泌抑制剂，如质子泵抑制剂奥美拉唑，已开始广泛应用。这些药物有望有效控制那些对传统短效H2受体拮抗剂反应欠佳的患者的酸相关性疾病。然而，这些药物长期服用的安全性已受到质疑。大鼠长期接受超强效胃酸分泌抑制剂或胃底大部切除术导致终身胃酸分泌被深度抑制，这与胃体部肠嗜铬样（ECL）细胞类癌肿瘤的发生有关。现有证据支持胃泌素的作用，在长期严重胃酸过少的动物中，胃泌素会持续升高。在人类中，高胃泌素血症状态，如卓艾综合征和萎缩性胃炎，与ECL细胞类癌肿瘤的风险增加有关。这些观察结果引发了人们的担忧，即人类可能也容易因强效胃酸分泌抑制剂而发生类癌肿瘤。然而，迄今为止，尚无人类使用奥美拉唑导致类癌肿瘤的病例报道。如果不使用导致胃酸缺乏的剂量，在维持治疗效果的同时可以避免显著的高胃泌素血症。这些措施应能将服用强效长期抗分泌药物的人类发生ECL细胞类癌肿瘤的风险降至最低。
