Sabesin S M
Rush Presbyterian St Luke's Medical Center, Chicago 60612.
Aliment Pharmacol Ther. 1993;7 Suppl 2:35-40. doi: 10.1111/j.1365-2036.1993.tb00597.x.
H2-receptor antagonist therapy is associated with a low incidence of adverse reactions. Adverse events reported in clinical trials of ranitidine in daily doses of up to 1200 mg include headache, tiredness and mild gastrointestinal disturbances, but the incidence is similar to or less than that for placebo. High doses of cimetidine (> 5 g/day) can cause reversible impotence or gynaecomastia. While ranitidine exhibits no clinically significant drug-drug interactions, cimetidine interacts with many drugs metabolized by cytochrome P450. In contrast to ranitidine and cimetidine, where safety data are available for up to 10 years of continuous therapy, experience with famotidine and nizatidine is limited. The safety of long-term H2-receptor antagonist therapy needs to be considered in relation to the potential consequences of prolonged acid suppression, including the risk of proliferation of gastric flora and the risk of developing enterochromaffin-like cell hyperplasia, which could in turn, theoretically, lead to gastric malignancy. Such problems have not been observed in patients during long-term therapy at low or full doses of H2-receptor antagonists. Standard doses of currently available H2-receptor antagonists permit acid secretion in response to food and other stimuli, and this daily acid tide prevents persistent bacterial colonization.
H2受体拮抗剂治疗的不良反应发生率较低。雷尼替丁日剂量高达1200毫克的临床试验中报告的不良事件包括头痛、疲倦和轻度胃肠道不适，但发生率与安慰剂相似或低于安慰剂。高剂量西咪替丁（>5克/天）可导致可逆性阳痿或男子女性型乳房。虽然雷尼替丁未表现出具有临床意义的药物相互作用，但西咪替丁与许多经细胞色素P450代谢的药物相互作用。与雷尼替丁和西咪替丁不同，法莫替丁和尼扎替丁的安全性数据仅来自长达10年的持续治疗经验，其经验有限。长期H2受体拮抗剂治疗的安全性需要结合胃酸分泌长期受抑制的潜在后果来考虑，包括胃内菌群增殖的风险以及肠嗜铬样细胞增生的风险，理论上这可能进而导致胃癌。在长期接受低剂量或全剂量H2受体拮抗剂治疗的患者中未观察到此类问题。目前可用的H2受体拮抗剂标准剂量允许对食物和其他刺激产生胃酸分泌，这种每日的胃酸潮可防止细菌持续定植。
