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Open Access 01-05-2017 | Review

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

Authors: Li-Yuan Yu, Lu-Ning Sun, Xue-Hui Zhang, Yue-Qi Li, Lei Yu, Zi-Qing-Yun Yuan, Ling Meng, Hong-Wen Zhang, Yong-Qing Wang

Published in: Advances in Therapy | Issue 5/2017

Abstract

Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H⁺/K⁺-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.

Feng S, Cleary Y, Parrott N, Hu P, Weber C, Wang Y, et al. Evaluating a physiologically based pharmacokinetic model for prediction of omeprazole clearance and assessing ethnic sensitivity in CYP2C19 metabolic pathway. Eur J Clin Pharmacol. 2015;71(5):617–24. doi:10.1007/s00228-015-1834-y.CrossRefPubMed

Wang Y, Zhang H, Meng L, Wang M, Yuan H, Ou N, et al. Influence of CYP2C19 on the relationship between pharmacokinetics and intragastric pH of omeprazole administered by successive intravenous infusions in Chinese healthy volunteers. Eur J Clin Pharmacol. 2010;66(6):563–9. doi:10.1007/s00228-010-0821-6.CrossRefPubMed

Wang Y, Yuan Y, Meng L, Fan H, Xu J, Zhang H, et al. Study of the pharmacokinetics and intragastric pH of rabeprazole given as successive intravenous infusion to healthy Chinese volunteers. Eur J Clin Pharmacol. 2011;67(1):25–31. doi:10.1007/s00228-010-0949-4.CrossRefPubMed

Li Y, Zhang W, Guo D, Zhou G, Zhou H, Xiao Z. Pharmacokinetics of the new proton pump inhibitor ilaprazole in Chinese healthy subjects in relation to CYP3A5 and CYP2C19 genotypes. Clinica Chimica Acta. 2008;391(1–2):60–7. doi:10.1016/j.cca.2008.02.003.CrossRef

Abe Y, Sasaki Y, Yagi M, Yaoita T, Nishise S, Ueno Y. Diagnosis and treatment of eosinophilic esophagitis in clinical practice. Clin J Gastroenterol. 2017;10(2):87–102.CrossRefPubMed

Lipka S, Muhammad A, Champeaux A, Richter JE. Case report of proton pump inhibitor responsive esophageal eosinophilia: why 2 months of proton pump inhibitors is required. Dis Esophagus. 2016;29(6):700–3. doi:10.1111/dote.12237.CrossRefPubMed

Gonzálezcervera J, Lucendo AJ. Eosinophilic esophagitis: an evidence-based approach to therapy. J Investig Allergol Clin Immunol. 2016;26(1):8.CrossRef

Lipka S, Kumar A, Miladinovic B, Richter JE. Systematic review with network meta-analysis: comparative effectiveness of topical steroids vs. PPIs for the treatment of the spectrum of eosinophilic oesophagitis. Aliment Pharmacol Ther. 2016;43(6):663–73.CrossRefPubMed

Cheng E. Translating new developments in eosinophilic esophagitis pathogenesis into clinical practice. Curr Treat Options Gastroenterol. 2015;13(1):30–46.CrossRefPubMedPubMedCentral

10.

Orel R, Murch S, Amil DJ, Vandenplas Y, Homan M. Eosinophilic esophagitis that develops during therapy with proton pump inhibitors: case series and possible mechanisms. Acta Gastroenterol Belg. 2016;79(2):245–50.PubMed

11.

Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet (London, England). 2008;372(9636):392–7. doi:10.1016/s0140-6736(08)61159-9.CrossRef

12.

Iwahi T, Satoh H, Nakao M, Iwasaki T, Yamazaki T, Kubo K, et al. Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related compounds have selective activity against Helicobacter pylori. Antimicrob Agents Chemother. 1991;35(3):490–6.CrossRefPubMedPubMedCentral

13.

Gatta L, Perna F, Figura N, Ricci C, Holton J, D’Anna L, et al. Antimicrobial activity of esomeprazole versus omeprazole against Helicobacter pylori. J Antimicrob Chemother. 2003;51(2):439–42.CrossRefPubMed

14.

Kawakami Y, Akahane T, Yamaguchi M, Oana K, Takahashi Y, Okimura Y, et al. In vitro activities of rabeprazole, a novel proton pump inhibitor, and its thioether derivative alone and in combination with other antimicrobials against recent clinical isolates of Helicobacter pylori. Antimicrob Agents Chemother. 2000;44(2):458–61.CrossRefPubMedPubMedCentral

15.

Nakao M, Malfertheiner P. Growth inhibitory and bactericidal activities of lansoprazole compared with those of omeprazole and pantoprazole against Helicobacter pylori. Helicobacter. 1998;3(1):21–7.CrossRefPubMed

16.

Zhao S, Lv Y, Zhang JB, Wang B, Lv GJ, Ma XJ. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori. World J Gastroenterol. 2014;20(28):9321–9. doi:10.3748/wjg.v20.i28.9321.PubMedPubMedCentral

17.

Zhang Z, Liu ZQ, Zheng PY, Tang FA, Yang PC. Influence of efflux pump inhibitors on the multidrug resistance of Helicobacter pylori. World J Gastroenterol. 2010;16(10):1279–84.CrossRefPubMedPubMedCentral

18.

Saito Y, Serizawa H, Kato Y, Nakano M, Nakamura M, Saito H, et al. First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype. World J Gastroenterol. 2015;21(48):13548–54. doi:10.3748/wjg.v21.i48.13548.CrossRefPubMedPubMedCentral

19.

Liou JM, Wu MS, Lin JT. Treatment of Helicobacter pylori infection: where are we now? J Gastroenterol Hepatol. 2016;31(12):1918–26. doi:10.1111/jgh.13418.CrossRefPubMed

20.

Rimbara E, Fischbach LA, Graham DY. Optimal therapy for Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol. 2011;8(2):79–88. doi:10.1038/nrgastro.2010.210.CrossRefPubMed

21.

Chuah SK, Tsay FW, Hsu PI, Wu DC. A new look at anti-Helicobacter pylori therapy. World J Gastroenterol. 2011;17(35):3971–5. doi:10.3748/wjg.v17.i35.3971.CrossRefPubMedPubMedCentral

22.

Gisbert JP, Calvet X. Review article: non-bismuth quadruple (concomitant) therapy for eradication of Helicobater pylori. Aliment Pharmacol Ther. 2011;34(6):604–17. doi:10.1111/j.1365-2036.2011.04770.x.CrossRefPubMed

23.

Liou JM, Chen CC, Chen MJ, Chen CC, Chang CY, Fang YJ, et al. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet (London, England). 2013;381(9862):205–13. doi:10.1016/s0140-6736(12)61579-7.CrossRef

24.

Hsu PI, Lin PC, Graham DY. Hybrid therapy for Helicobacter pylori infection: a systemic review and meta-analysis. World J Gastroenterol. 2015;21(45):12954.CrossRefPubMedPubMedCentral

25.

Hsu PI, Wu DC, Chen WC, Tseng HH, Yu HC, Wang HM, et al. Randomized controlled trial comparing 7-day triple, 10-day sequential, and 7-day concomitant therapies for Helicobacter pylori infection. Antimicrob Agents Chemother. 2014;58(10):5936–42. doi:10.1128/aac.02922-14.CrossRefPubMedPubMedCentral

26.

Hsu PI, Kao SS, Wu DC, Chen WC, Peng NJ, Yu HC, et al. A randomized controlled study comparing reverse hybrid therapy and standard triple therapy for Helicobacter pylori infection. Medicine. 2015;94(48):e2104. doi:10.1097/md.0000000000002104.CrossRefPubMedPubMedCentral

27.

Zullo A, De Francesco V, Hassan C, Morini S, Vaira D. The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis. Gut. 2007;56(10):1353–7. doi:10.1136/gut.2007.125658.CrossRefPubMedPubMedCentral

28.

Li H, Meng L, Liu F, Wei JF, Wang YQ. H⁺/K⁺-ATPase inhibitors: a patent review. Expert Opin Ther Pat. 2013;23(1):99–111. doi:10.1517/13543776.2013.741121.CrossRefPubMed

29.

Moormann AEBDP, Flynn DL, Hui LI, Villamil CI, Inventor method of using (H⁺/K⁺)ATPase inhibitors as antiviral agents. United States1999 Jun. 14, 2005.

30.

Sasaki T, Yamaya M, Yasuda H, Inoue D, Yamada M, Kubo H, et al. The proton pump inhibitor lansoprazole inhibits rhinovirus infection in cultured human tracheal epithelial cells. Eur J Pharmacol. 2005;509(2–3):201–10. doi:10.1016/j.ejphar.2004.12.042.CrossRefPubMed

31.

Long J, Wright E, Molesti E, Temperton N, Barclay W. Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry. F1000Research. 2015;4:30. doi:10.12688/f1000research.6085.2.PubMedPubMedCentral

32.

Sasaki T, Nakayama K, Yasuda H, Yoshida M, Asamura T, Ohrui T, et al. A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc. 2009;57(8):1453–7. doi:10.1111/j.1532-5415.2009.02349.x.CrossRefPubMed

33.

Vanfleteren LE, Spruit MA, Wouters EF, Franssen FM. Management of chronic obstructive pulmonary disease beyond the lungs. Lancet Respir Med. 2016;4(11):911–24. doi:10.1016/s2213-2600(16)00097-7.CrossRefPubMed

34.

Sasaki T, Nakayama K, Yasuda H, Yamaya M. A new strategy with proton pump inhibitors for the prevention of acute exacerbations in COPD. Ther Adv Respir Dis. 2011;5(2):91–103. doi:10.1177/1753465810392264.CrossRefPubMed

35.

Becker JC, Grosser N, Waltke C, Schulz S, Erdmann K, Domschke W, et al. Beyond gastric acid reduction: proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells. Biochem Biophys Res Commun. 2006;345(3):1014–21. doi:10.1016/j.bbrc.2006.04.170.CrossRefPubMed

36.

Dimango E, Walker P, Keating C, Berdella M, Robinson N, Langfelderschwind E, et al. Effect of esomeprazole versus placebo on pulmonary exacerbations in cystic fibrosis. BMC Pulm Med. 2014;14(1):1–7.CrossRef

37.

Kim YJ, Lee JS, Hong KS, Chung JW, Kim JH, Hahm KB. Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression. Cancer Prev Res (Philadelphia, Pa). 2010;3(8):963–74. doi:10.1158/1940-6207.capr-10-0033.CrossRef

38.

De Milito A, Iessi E, Logozzi M, Lozupone F, Spada M, Marino ML, et al. Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species. Can Res. 2007;67(11):5408–17. doi:10.1158/0008-5472.can-06-4095.CrossRef

39.

Yeo M, Kim DK, Park HJ, Cho SW, Cheong JY, Lee KJ. Blockage of intracellular proton extrusion with proton extrusions with proton pump inhibitor induces apoptosis in gastric cancer. Cancer Sci. 2008;99(1):185.

40.

Marino ML, Fais S, Djavaheri-Mergny M, Villa A, Meschini S, Lozupone F, et al. Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells. Cell Death Dis. 2010;1:e87. doi:10.1038/cddis.2010.67.CrossRefPubMedPubMedCentral

41.

Udelnow A, Kreyes A, Ellinger S, Landfester K, Walther P, Klapperstueck T, et al. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One. 2011;6(5):e20143. doi:10.1371/journal.pone.0020143.CrossRefPubMedPubMedCentral

42.

Canitano A, Iessi E, Spugnini EP, Federici C, Fais S. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma. Cancer Lett. 2016;376(2):278–83. doi:10.1016/j.canlet.2016.04.015.CrossRefPubMed

43.

Lee YY, Jeon HK, Hong JE, Cho YJ, Ryu JY, Choi JJ, et al. Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma. Oncotarget. 2015;6(33):35040–50. doi:10.18632/oncotarget.5319.PubMedPubMedCentral

44.

Spugnini EP, Buglioni S, Carocci F, Francesco M, Vincenzi B, Fanciulli M, et al. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors. J Transl Med. 2014;12:225. doi:10.1186/s12967-014-0225-y.CrossRefPubMedPubMedCentral

45.

Wang BY, Zhang J, Wang JL, Sun S, Wang ZH, Wang LP, et al. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J Experimen Clin Cancer Res. 2015;34:85. doi:10.1186/s13046-015-0194-x.CrossRef

46.

Falk GW, Buttar NS, Foster NR, Ziegler KL, Demars CJ, Romero Y, et al. A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E(2) in patients with Barrett’s esophagus. Gastroenterology. 2012;143(4):917–26. doi:10.1053/j.gastro.2012.06.044.CrossRefPubMedPubMedCentral

47.

Penman ID, el-Omar E, McGregor JR, Hillan KJ, O’Dwyer PJ, McColl KE. Omeprazole inhibits colorectal carcinogenesis induced by azoxymethane in rats. Gut. 1993;34(11):1559–65.

48.

Wang J, Barbuskaite D, Tozzi M, Giannuzzo A, Sorensen CE, Novak I. Proton pump inhibitors inhibit pancreatic secretion: role of gastric and non-gastric H⁺/K⁺-ATPases. PLoS One. 2015;10(5):e0126432. doi:10.1371/journal.pone.0126432.CrossRefPubMedPubMedCentral

49.

Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York, NY). 2009;324(5930):1029–33. doi:10.1126/science.1160809.CrossRef

50.

Hashimoto S, Ishisaki A, Yamato K, Aiko K, Amagasa T, Nishihara T. Intracellular apoptosis-inducing factor is induced by a vacuolar type H⁺-ATPase inhibitor in B lineage cells. J Cell Physiol. 2001;186(1):65–72. doi:10.1002/1097-4652(200101)186:1<65:aid-jcp1000>3.0.co;2-x.CrossRefPubMed

51.

Shchepina LA, Pletjushkina OY, Avetisyan AV, Bakeeva LE, Fetisova EK, Izyumov DS, et al. Oligomycin, inhibitor of the F0 part of H⁺-ATP-synthase, suppresses the TNF-induced apoptosis. Oncogene. 2002;21(53):8149–57. doi:10.1038/sj.onc.1206053.CrossRefPubMed

52.

Shen Y, Chen M, Huang S, Zou X. Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2. Oncol Lett. 2016;11(1):717–22. doi:10.3892/ol.2015.3912.PubMed

53.

McCarty MF, Whitaker J. Manipulating tumor acidification as a cancer treatment strategy. Alter Med Rev. 2010;15(3):264–72.

54.

Glunde K, Guggino SE, Solaiyappan M, Pathak AP, Ichikawa Y, Bhujwalla ZM. Extracellular acidification alters lysosomal trafficking in human breast cancer cells. Neoplasia (New York, NY). 2003;5(6):533–45.

55.

Boyd MR, Farina C, Belfiore P, Gagliardi S, Kim JW, Hayakawa Y, et al. Discovery of a novel antitumor benzolactone enamide class that selectively inhibits mammalian vacuolar-type (H⁺)-atpases. J Pharmacol Exp Ther. 2001;297(1):114–20.PubMed

56.

Schempp CM, von Schwarzenberg K, Schreiner L, Kubisch R, Muller R, Wagner E, et al. V-ATPase inhibition regulates anoikis resistance and metastasis of cancer cells. Mol Cancer Ther. 2014;13(4):926–37. doi:10.1158/1535-7163.mct-13-0484.CrossRefPubMed

57.

Jin UH, Kim SB, Safe S. Omeprazole inhibits pancreatic cancer cell invasion through a nongenomic aryl hydrocarbon receptor pathway. Chem Res Toxicol. 2015;28(5):907–18. doi:10.1021/tx5005198.CrossRefPubMedPubMedCentral

58.

Zlobec I, Molinari F, Kovac M, Bihl MP, Altermatt HJ, Diebold J, et al. Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients. Br J Cancer. 2010;102(1):151–61. doi:10.1038/sj.bjc.6605452.CrossRefPubMed

59.

Kim DJ, Li Y, Reddy K, Lee MH, Kim MO, Cho YY, et al. Novel TOPK inhibitor HI-TOPK-032 effectively suppresses colon cancer growth. Can Res. 2012;72(12):3060–8. doi:10.1158/0008-5472.can-11-3851.CrossRef

60.

Matsuo Y, Park JH, Miyamoto T, Yamamoto S, Hisada S, Alachkar H, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Sci Trans Med. 2014;6(259):259ra145. doi:10.1126/scitranslmed.3010277.CrossRef

61.

Raghunath AS, O’Morain C, McLoughlin RC. Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther. 2005;22(Suppl 1):55–63. doi:10.1111/j.1365-2036.2005.02611.x.CrossRefPubMed

62.

Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016;176(2):172–4. doi:10.1001/jamainternmed.2015.7927.CrossRefPubMed

63.

Wilhelm SM, Rjater RG, Kale-Pradhan PB. Perils and pitfalls of long-term effects of proton pump inhibitors. Expert Rev Clin Pharmacol. 2013;6(4):443–51. doi:10.1586/17512433.2013.811206.CrossRefPubMed

64.

Parikh N, Howden CW. The safety of drugs used in acid-related disorders and functional gastrointestinal disorders. Gastroenterol Clin North Am. 2010;39(3):529–42. doi:10.1016/j.gtc.2010.08.009.CrossRefPubMedPubMedCentral

65.

Abraham NS. Proton pump inhibitors: potential adverse effects. Curr Opin Gastroenterol. 2012;28(6):615–20. doi:10.1097/MOG.0b013e328358d5b9.CrossRefPubMed

66.

Eom CS, Jeon CY, Lim JW, Cho EG, Park SM, Lee KS. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183(3):310–9. doi:10.1503/cmaj.092129.CrossRefPubMedPubMedCentral

67.

Johnstone J, Nerenberg K, Loeb M. Meta-analysis: proton pump inhibitor use and the risk of community-acquired pneumonia. Aliment Pharmacol Ther. 2010;31(11):1165–77. doi:10.1111/j.1365-2036.2010.04284.x.CrossRefPubMed

68.

Filion KB, Chateau D, Targownik LE, Gershon A, Durand M, Tamim H, et al. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut. 2014;63(4):552–8. doi:10.1136/gutjnl-2013-304738.CrossRefPubMed

69.

Ogielska M, Lanotte P, Le Brun C, Valentin AS, Garot D, Tellier AC, et al. Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature. Int J Infect Dis. 2015;37:36–41. doi:10.1016/j.ijid.2015.06.007.CrossRefPubMed

70.

Eyal A, Sueissa A, Braun E, Naffaa ME. From hypomagnesaemia to Zollinger-Ellison syndrome: an adverse effect of a proton pump inhibitor. BMJ case reports. 2014. doi:10.1136/bcr-2014-205165.

71.

Park CH, Kim EH, Roh YH, Kim HY, Lee SK. The association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis. PLoS One. 2014;9(11):e112558. doi:10.1371/journal.pone.0112558.CrossRefPubMedPubMedCentral

72.

Atkinson NS, Reynolds DJ, Travis SP. ‘Lemonade Legs’: why do some patients get profound hypomagnesaemia on proton-pump inhibitors? Intest Res. 2015;13(3):227–32. doi:10.5217/ir.2015.13.3.227.CrossRefPubMedPubMedCentral

73.

Mackay JD, Bladon PT. Hypomagnesaemia due to proton-pump inhibitor therapy: a clinical case series. QJM. 2010;103(6):387–95. doi:10.1093/qjmed/hcq021.CrossRefPubMed

74.

Furlanetto TW, Faulhaber GA. Hypomagnesemia and proton pump inhibitors: below the tip of the iceberg. Arch Intern Med. 2011;171(15):1391–2. doi:10.1001/archinternmed.2011.199.CrossRefPubMed

75.

Bai JP, Hausman E, Lionberger R, Zhang X. Modeling and simulation of the effect of proton pump inhibitors on magnesium homeostasis. 1. Oral absorption of magnesium. Mol Pharm. 2012;9(12):3495–505. doi:10.1021/mp300323q.CrossRefPubMed

76.

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947–53. doi:10.1001/jama.296.24.2947.CrossRefPubMed

77.

Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179(4):319–26. doi:10.1503/cmaj.071330.CrossRefPubMedPubMedCentral

78.

Jo Y, Park E, Ahn SB, Jo YK, Son B, Kim SH, et al. A proton pump inhibitor’s effect on bone metabolism mediated by osteoclast action in old age: a prospective randomized study. Gut liver. 2015;9(5):607–14. doi:10.5009/gnl14135.CrossRefPubMed

79.

Eom CS, Park SM, Myung SK, Yun JM, Ahn JS. Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med. 2011;9(3):257–67. doi:10.1370/afm.1243.CrossRefPubMedPubMedCentral

80.

O’Connell MB, Madden DM, Murray AM, Heaney RP, Kerzner LJ. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med. 2005;118(7):778–81. doi:10.1016/j.amjmed.2005.02.007.CrossRefPubMed

81.

Serfaty-Lacrosniere C, Wood RJ, Voytko D, Saltzman JR, Pedrosa M, Sepe TE, et al. Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans. J Am Coll Nutr. 1995;14(4):364–8.CrossRefPubMed

82.

Boyce BF. Stomaching calcium for bone health. Nat Med. 2009;15(6):610–2. doi:10.1038/nm0609-610.CrossRefPubMed

83.

Costa-Rodrigues J, Reis S, Teixeira S, Lopes S, Fernandes MH. Dose-dependent inhibitory effects of proton pump inhibitors on human osteoclastic and osteoblastic cell activity. FEBS J. 2013;280(20):5052–64. doi:10.1111/febs.12478.CrossRefPubMed

84.

Antoniou T, Macdonald EM, Hollands S, Gomes T, Mamdani MM, Garg AX, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015;3(2):E166–71. doi:10.9778/cmajo.20140074.CrossRefPubMedPubMedCentral

85.

Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86(4):837–44. doi:10.1038/ki.2014.74.CrossRefPubMedPubMedCentral

86.

Praga M, Sevillano A, Aunon P, Gonzalez E. Changes in the aetiology, clinical presentation and management of acute interstitial nephritis, an increasingly common cause of acute kidney injury. Nephrol Dial Transplant. 2015;30(9):1472–9. doi:10.1093/ndt/gfu326.CrossRefPubMed

87.

Klassen S, Krepinsky JC, Prebtani AP. Pantoprazole-induced acute interstitial nephritis. CMAJ. 2013;185(1):56–9. doi:10.1503/cmaj.120954.CrossRefPubMedPubMedCentral

88.

Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol. 2016;27(10):3153–63. doi:10.1681/asn.2015121377.CrossRefPubMed

89.

Praga M, Gonzalez E. Acute interstitial nephritis. Kidney Int. 2010;77(11):956–61. doi:10.1038/ki.2010.89.CrossRefPubMed

90.

Qi X, Cai Y, Gong L, Liu L, Chen F, Xiao Y, et al. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid. Toxicol Appl Pharmacol. 2007;222(1):105–10. doi:10.1016/j.taap.2007.03.029.CrossRefPubMed

91.

Schillinger W, Teucher N, Sossalla S, Kettlewell S, Werner C, Raddatz D, et al. Negative inotropy of the gastric proton pump inhibitor pantoprazole in myocardium from humans and rabbits: evaluation of mechanisms. Circulation. 2007;116(1):57–66. doi:10.1161/circulationaha.106.666008.CrossRefPubMed

92.

Sossalla S, Schotola H, Schmitto J, Toischer K, Sohns C, Schworer H, et al. Effects of different proton pump inhibitors on cardiac contractility in isolated human failing myocardium. J Cardiovasc Surg. 2011;52(3):437–44.

93.

Shah NH, LePendu P, Bauer-Mehren A, Ghebremariam YT, Iyer SV, Marcus J, et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One. 2015;10(6):e0124653. doi:10.1371/journal.pone.0124653.CrossRefPubMedPubMedCentral

94.

Takebayashi K, Inukai T. Effect of proton pump inhibitors on glycemic control in patients with diabetes. World J Diabetes. 2015;6(10):1122–31. doi:10.4239/wjd.v6.i10.1122.CrossRefPubMedPubMedCentral

95.

Bezabeh S, Mackey AC, Kluetz P, Jappar D, Korvick J. Accumulating evidence for a drug-drug interaction between methotrexate and proton pump inhibitors. Oncologist. 2012;17(4):550–4. doi:10.1634/theoncologist.2011-0431.CrossRefPubMedPubMedCentral

96.

Ogawa R, Echizen H. Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet. 2010;49(8):509–33. doi:10.2165/11531320-000000000-00000.CrossRefPubMed

97.

Andersson T, Nagy P, Niazi M, Nylander S, Galbraith H, Ranjan S, et al. Effect of esomeprazole with/without acetylsalicylic acid, omeprazole and lansoprazole on pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. Am J Cardiovasc Drugs. 2014;14(3):217–27. doi:10.1007/s40256-014-0073-4.CrossRefPubMed

98.

Frelinger AL 3rd, Lee RD, Mulford DJ, Wu J, Nudurupati S, Nigam A, et al. A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. J Am Coll Cardiol. 2012;59(14):1304–11. doi:10.1016/j.jacc.2011.12.024.CrossRefPubMed

99.

Leonard CE, Bilker WB, Brensinger CM, Flockhart DA, Freeman CP, Kasner SE, et al. Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors. Stroke. 2015;46(3):722–31. doi:10.1161/strokeaha.114.006866.CrossRefPubMedPubMedCentral

Title: A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors
Authors: Li-Yuan Yu
Lu-Ning Sun
Xue-Hui Zhang
Yue-Qi Li
Lei Yu
Zi-Qing-Yun Yuan
Ling Meng
Hong-Wen Zhang
Yong-Qing Wang
Publication date: 01-05-2017
Publisher: Springer Healthcare
Published in: Advances in Therapy / Issue 5/2017
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI: https://doi.org/10.1007/s12325-017-0532-9

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STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

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