体征/症状 虽然罕见,但质子泵抑制剂引起的低胃酸可影响铁和钴胺素的吸收。[68]Hutchinson C, Geissler CA, Powell JJ, et al. Proton-pump inhibitors suppress absorption of dietary non-haem iron in hereditary hemochromatosis. Gut. 2007;56:1291-1295.http://www.ncbi.nlm.nih.gov/pubmed/17344278?tool=bestpractice.com[69]Sharma VR, Brannon MA, Carloss EA. Effect of omeprazole on oral iron replacement in patients with iron deficiency anemia. South Med J. 2004;97:887-889.http://www.ncbi.nlm.nih.gov/pubmed/15455980?tool=bestpractice.com[79]Den Elzen WP, Groeneveld Y, De Ruijter W, et al. Long-term use of proton pump inhibitors and vitamin B12 status in elderly individuals. Aliment Pharmacol Ther. 2008;27:491-497.http://www.ncbi.nlm.nih.gov/pubmed/18194503?tool=bestpractice.com有报告称,长期使用质子泵抑制剂的患者骨折发生率升高,原因可能是钴胺素、钙和/或维生素 D 吸收不良。[11]Richards JB, Goltzman D. Proton-pump inhibitors: balancing the benefits and potential fracture risks. CMAJ. 2008;179:306-307.http://www.cmaj.ca/content/179/4/306.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18695170?tool=bestpractice.com[12]Yang YX, Lewis JD, Epstein S, et al. Long-term proton-pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947-2953.http://www.ncbi.nlm.nih.gov/pubmed/17190895?tool=bestpractice.com[13]Targownik LE, Lix LM, Metge CJ, et al. Use of proton-pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179:319-326.http://www.cmaj.ca/content/179/4/319.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18695179?tool=bestpractice.com[123]O'Connell MB, Madden DM, Murray AM, et al. Effects of proton-pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med. 2005;118:778-781.http://www.ncbi.nlm.nih.gov/pubmed/15989913?tool=bestpractice.com
质子泵抑制剂选择性抑制壁细胞 H+/K+ ATPase,质子泵负责酸分泌的最后步骤,从而抑制基础和刺激后的胃酸分泌。[1]Schubert ML, Peura DA. Control of gastric acid secretion in health and disease. Gastroenterology. 2008;134:1842-1860.http://www.ncbi.nlm.nih.gov/pubmed/18474247?tool=bestpractice.com[40]Fellenius E, Berglindh T, Sachs G. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+K+)ATPase. Nature. 1981;290:159-161.http://www.ncbi.nlm.nih.gov/pubmed/6259537?tool=bestpractice.com因为它们的半衰期约为 1 小时,且新的质子泵不断产生,所以患者并未出现胃酸缺乏,且 24 小时胃 pH 值中位数约为 4.0 至 5.0。[38]Miner P Jr, Katz PO, Chen Y, et al. Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study. Am J Gastroenterol. 2003:98:2616-2620.http://www.ncbi.nlm.nih.gov/pubmed/14687806?tool=bestpractice.com[39]Shi S, Klotz U. Proton-pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol. 2008;64:935-951.http://www.ncbi.nlm.nih.gov/pubmed/18679668?tool=bestpractice.com低胃酸导致约 20% 的患者出现胃泌素水平升高,通常低于 2 至 4 倍。但是,约 5% 的患者的胃泌素水平可能超过 400 pg/mL。[75]Klinkenberg-Knol EC, Festen HP, Jansen JB, et al. Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med. 1994;121:161-167.http://www.ncbi.nlm.nih.gov/pubmed/8017742?tool=bestpractice.com[76]McCloy RF, Arnold R, Bardhan KD, et al. Pathophysiological effects of long-term acid suppression in man. Dig Dis Sci. 1995;40:96S-120S.http://www.ncbi.nlm.nih.gov/pubmed/7859587?tool=bestpractice.com[77]Hung PD, Schubert ML, Mihas AA. Zollinger-Ellison syndrome. Curr Treat Options Gastroenterol. 2003;6:163-170.http://www.ncbi.nlm.nih.gov/pubmed/12628075?tool=bestpractice.com