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DOI

http://dx.doi.org/10.18590/mjm.2016.vol2.iss3.9

Abstract

Proton-Pump Inhibitors (PPIs) have changed the therapy of numerous upper gastrointestinal tract disorders; but their use is not without risk of adverse effects. Recent studies suggest more serious adverse events with chronic use of PPIs. Because of these risks, clinicians should reassess individual patient’s needs for chronic PPI therapy.

Conflict(s) of Interest

N/A

References with DOI

1. McQuaid KR. Drugs used in the treatment of gastrointestinal diseases. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology.McGraw Hill, 2009: 1067-1101.

2. Katz PO, Gerson LB, Vela MF. Corrigendum: guidelines for the diagnosis and management of gastroesophageal reflux disease. The American journal of gastroenterology. 2013 Oct 1;108(10):1672-. https://doi.org/10.1038/ajg.2013.314

3. MacLaren R, Campbell J. Cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients*. Critical care medicine. 2014 Apr 1;42(4):809-15. https://doi.org/10.1097/ccm.0000000000000032

4. Gøtzsche PC. Our prescription drugs kill us in large numbers. PolskieArchiwumMedycynyWewnetrznej. 2013 Dec;124(11):628-34.

5. Eid SM, Boueiz A, Paranji S, Mativo C, BA RL, Abougergi MS. Patterns and predictors of proton pump inhibitor overuse among academic and non-academic hospitalists. Internal medicine. 2010;49(23):2561-8. https://doi.org/10.2169/internalmedicine.49.4064

6. Metz D. Proton pump inhibitor therapy: safety issues. Advances in digestive disease. AGA Institute Press, Bethesda, MD. 2007:3-14.

7. Klotz U. Impact of CYP2C19 polymorphisms on the clinical action of proton pump inhibitors (PPIs). European journal of clinical pharmacology. 2009 Jan 1;65(1):1-2. https://doi.org/10.1007/s00228-008-0571-x

8 Metz D. Proton pump inhibitor therapy: safety issues. Advances in digestive disease. AGA Institute Press, Bethesda, MD. 2007:3-14.

9. Metz DC, Inadomi JM, Howden CW, Van Zanten SJ, Bytzer P. On-demand therapy for gastroesophageal reflux disease. The American journal of gastroenterology. 2007 Mar 1;102(3):642-53. https://doi.org/10.1111/j.1572-0241.2006.00998.x

10. Rotman SR, Bishop TF. Proton pump inhibitor use in the US ambulatory setting, 2002–2009. PloS one. 2013 Feb 13;8(2):e56060. https://doi.org/10.1371/journal.pone.0056060

11. Lai PS, Wong YY, Low YC, Lau HL, Chin KF, Mahadeva S. Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors. PeerJ. 2014 Jun 26;2:e451. https://doi.org/10.7717/peerj.451

12. Moran N, Jones E, O'Toole A, Murray F. The appropriateness of a proton pump inhibitor prescription. Irish medical journal. 2014.

13. Heidelbaugh JJ, Inadomi JM. Magnitude and economic impact of inappropriate use of stress ulcer prophylaxis in non-ICU hospitalized patients. The American journal of gastroenterology. 2006 Oct 1;101(10):2200-5. https://doi.org/10.1111/j.1572-0241.2006.00839.x

14. Chia CT, Lim WP, Vu CK. Inappropriate use of proton pump inhibitors in a local setting. Singapore medical journal. 2014 Jul;55(7):363. https://doi.org/10.11622/smedj.2014087

15. Rotman SR, Bishop TF. Proton pump inhibitor use in the US ambulatory setting, 2002–2009. PloS one. 2013 Feb 13;8(2):e56060. https://doi.org/10.1371/journal.pone.0056060

16. Parkman HP, Urbain JC, Knight LC, Brown KL, Trate DM, Miller MA, Maurer AH, Fisher RS. Effect of gastric acid suppressants on human gastric motility. Gut. 1998 Feb 1;42(2):243-50. https://doi.org/10.1136/gut.42.2.243

17. Zedtwitz-Liebenstein K, Wenisch C, Patruta S, Parschalk B, Daxböck F, Graninger W. Omeprazole treatment diminishes intra-and extracellular neutrophil reactive oxygen production and bactericidal activity*. Critical care medicine. 2002 May 1;30(5):1118-22. https://doi.org/10.1097/00003246-200205000-00026

18. Ruigómez A, Johansson S, Wernersson B, FernándezCantero O, García Rodríguez LA. Gastroesophageal reflux disease in primary care: Using changes in proton pump inhibitor therapy as an indicator of partial response. Scandinavian journal of gastroenterology. 2012 Jul 1;47(7):751-61.

19. Inadomi JM, McIntyre L, Bernard L, Fendrick AM. Step-down from multiple-to single-dose proton pump inhibitors (PPIs): a prospective study of patients with heartburn or acid regurgitation completely relieved with PPIs. The American journal of gastroenterology. 2003 Sep 1;98(9):1940-4. https://doi.org/10.1111/j.1572-0241.2003.07665.x

20. Sheikh I, Waghray A, Waghray N, Dong C, Wolfe MM. Consumer use of over-the-counter proton pump inhibitors in patients with gastroesophageal reflux disease. The American journal of gastroenterology. 2014 Jun 1;109(6):789-94. https://doi.org/10.1038/ajg.2013.421

21. Thomson AB, Sauve MD, Kassam N, Kamitakahara H. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. 2010 May 21;16(19):2323-30. https://doi.org/10.3748/wjg.v16.i19.2323

22. Brunner G, Athmann C, Schneider A. Long‐term, open‐label trial: safety and efficacy of continuous maintenance treatment with pantoprazole for up to 15 years in severe acid‐peptic disease. Alimentary pharmacology & therapeutics. 2012 Jul 1;36(1):37-47. https://doi.org/10.1111/j.1365-2036.2012.05106.x

23. Labenz J, Petersen KU, Rösch W, Koelz HR. A summary of Food and Drug Administration‐reported adverse events and drug interactions occurring during therapy with omeprazole, lansoprazole and pantoprazole. Alimentary pharmacology & therapeutics. 2003 Apr 1;17(8):1015-9. https://doi.org/10.1046/j.1365-2036.2003.01550.x

24. McDonald EG, Lee TC, Loo VG, Bourgault AM, Poirier L. Clostridium difficile Infection. The New England journal of medicine. 2015 Jul 16;373(3):286-8.

25. Bourne C, Charpiat B, Charhon N, Bertin C, Gouraud A, Mouchoux C, Skalli S, Janoly-Dumenil A. [Emergent adverse effects of proton pump inhibitors]. Presse medicale (Paris, France: 1983). 2013 Feb;42(2):e53-62.

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

27. Cardoso RN, Benjo AM, DiNicolantonio JJ, Garcia DC, Macedo FY, El-Hayek G, Nadkarni GN, Gili S, Iannaccone M, Konstantinidis I, Reilly JP. Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated metaanalysis. Open heart. 2015 Jun 1;2(1):e000248. https://doi.org/10.1136/openhrt-2015-000248

28. Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, Grams ME. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA internal medicine. 2016 Jan:238-46. https://doi.org/10.1001/jamainternmed.2015.7193

29. Gomm W, von Holt K, Thomé F, Broich K, Maier W, Fink A, Doblhammer G, Haenisch B. Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA neurology. 2016 Feb 15. http://dx.doi.org/10.1001/jamaneurol.2015.4791

30. Shah NH, LePendu P, Bauer-Mehren A, Ghebremariam YT, Iyer SV, Marcus J, Nead KT, Cooke JP, Leeper NJ. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One. 2015 Jun 10;10(6):e0124653. http://dx.doi.org/10.1371/journal.pone.0124653

31. Howell MD, Novack V, Grgurich P, Soulliard D, Novack L, Pencina M, Talmor D. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Archives of internal medicine. 2010 May 10;170(9):784-90. http://dx.doi.org/10.1001/archinternmed.2010.89

32. Berrington A, Borriello SP, Brazier J, Duckworth G, Foster K, Freeman R. National Clostridium difficile standards group: report to the Department of Health. J Hosp Infect. 2004 Feb 1;56(Suppl 1):1- 38. http://dx.doi.org/10.1016/j.jhin.2003.10.016

33. Beaugerie L, Flahault A, Barbut F, Atlan P, Lalande V, Cousin P, Cadilhac M, Petit JC. Antibiotic‐associated diarrhoea and Clostridium difficile in the community. Alimentary pharmacology & therapeutics. 2003 Apr 1;17(7):905-12. http://dx.doi.org/10.1046/j.1365-2036.2003.01531.x

34. Thorens J, Froehlich F, Schwizer W, Saraga E, Bille J, Gyr K, Duroux P, Nicolet M, Pignatelli B, Blum AL, Gonvers JJ. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study. Gut. 1996 Jul 1;39(1):54-9. http://dx.doi.org/10.1136/gut.39.1.54

35. Estborn L, Joelson S. Occurrence of community-acquired respiratory tract infection in patients receiving esomeprazole. Drug safety. 2008 Jul 1;31(7):627-36. http://dx.doi.org/10.2165/00002018-200831070-00008

36. Dial MS. Proton pump inhibitor use and enteric infections. The American journal of gastroenterology. 2009 Mar 1;104:S10-6. http://dx.doi.org/10.1038/ajg.2009.46

37. DePestel DD, Aronoff DM. Epidemiology of Clostridium difficile infection. Journal of pharmacy practice. 2013 Oct 1;26(5):464-75. http://dx.doi.org/10.1177/0897190013499521

38. Zedtwitz-Liebenstein K, Wenisch C, Patruta S, Parschalk B, Daxböck F, Graninger W. Omeprazole treatment diminishes intra-and extracellular neutrophil reactive oxygen production and bactericidal activity*. Critical care medicine. 2002 May 1;30(5):1118-22. http://dx.doi.org/10.1097/00003246-200205000-00026

39. Dial S, Alrasadi K, Manoukian C, Huang A, Menzies D. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case–control studies. Canadian Medical Association Journal. 2004 Jul 6;171(1):33-8. http://dx.doi.org/10.1503/cmaj.1040876

40. Al-Tureihi FI, Hassoun A, Wolf-Klein G, Isenberg H. Albumin, length of stay, and proton pump inhibitors: key factors in Clostridium difficile-associated disease in nursing home patients. Journal of the American Medical Directors Association. 2005 Apr 30;6(2):105-8. http://dx.doi.org/10.1016/j.jamda.2005.01.003

41. McDonald EG, Milligan J, Frenette C, Lee TC. Continuous proton pump inhibitor therapy and the associated risk of recurrent Clostridium difficile infection. JAMA internal medicine. 2015 May 1;175(5):784-91. http://dx.doi.org/10.1001/jamainternmed.2015.42

42. Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. The American journal of gastroenterology. 2012 Jul 1;107(7):1011-9. http://dx.doi.org/10.1038/ajg.2012.108

43. Neal KR, Scott HM, Slack RC, Logan RF. Omeprazole as a risk factor for campylobacter gastroenteritis: case-control study. Bmj. 1996 Feb 17;312(7028):414-5. http://dx.doi.org/10.1136/bmj.312.7028.414

44. Kader SA, Mansour AM, Mohran Z, El-Taoil A, Abdalla KF. A study on the relation between proton pump inhibitor and gastric giardiasis. Journal of the Egyptian Society of Parasitology. 1998 Apr;28(1):149-57.

45. Rodríguez LA, Ruigómez A, Panés J. Use of acid-suppressing drugs and the risk of bacterial gastroenteritis. Clinical Gastroenterology and Hepatology. 2007 Dec 31;5(12):1418-23. http://dx.doi.org/10.1016/j.cgh.2007.09.010

46. Food US. Drug Information. FDA Drug Safety Communication: Abnormal heart rhythms associated with use of Anzemet (dolasetronmesylate).2011.

47. Yu EW, Bauer SR, Bain PA, et al. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med 2011;124:519-26. http://dx.doi.org/10.1016/j.amjmed.2011.01.007

49. Targownik LE, Lix LM, Leung S, Leslie WD. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology. 2010 Mar 31;138(3):896-904. http://dx.doi.org/10.1053/j.gastro.2009.11.014

50. Corley DA, Kubo AI, Zhao W, Quesenberry C. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology. 2010 Jul 31;139(1):93-101. http://dx.doi.org/10.1053/j.gastro.2010.03.055

51. Metz DC, Pilmer BL, Han C, Perez MC. Withdrawing PPI therapy after healing esophagitis does not worsen symptoms or cause persistent hypergastrinemia: analysis of dexlansoprazole MR clinical trial data. The American journal of gastroenterology. 2011 Nov 1;106(11):1953-60. http://dx.doi.org/10.1038/ajg.2011.220

52. Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009 Jul 31;137(1):80- 7. http://dx.doi.org/10.1053/j.gastro.2009.03.058

53. Niklasson A, Lindström L, Simrén M, Lindberg G, Björnsson E. Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial. The American journal of gastroenterology. 2010 Jul 1;105(7):1531-7. http://dx.doi.org/10.1038/ajg.2010.81

54. Fossmark R, Johnsen G, Johanessen E, Waldum HL. Rebound acid hypersecretion after long‐term inhibition of gastric acid secretion. Alimentary pharmacology & therapeutics. 2005 Jan 1;21(2):149-54. http://dx.doi.org/10.1111/j.1365-2036.2004.02271.x

55. Qvigstad G, Waldum H. Rebound hypersecretion after inhibition of gastric acid secretion. Basic & clinical pharmacology & toxicology. 2004 May 1;94(5):202-8. http://dx.doi.org/10.1111/j.1742-7843.2004.pto940502.x

56. Williams MP, Sercombe J, Hamilton MI, Pounder RE. A placebo-controlled trial to assess the effects of 8 days of dosing with rabeprazole versus omeprazole on 24-h intragastric acidity and plasma gastrin concentrations in young healthy male subjects. Alimentary Pharmacology and Therapeutics. 1998 Nov 1;12(11):1079-90. http://dx.doi.org/10.1046/j.1365-2036.1998.00418.x

57. Varannes S, Levy P, Lartigue S, Dellatolas F, Lemaire M, Galmiche JP. Comparison of lansoprazole with omeprazole on 24‐hour pH, acid secretion and serum gastrin in healthy volunteers. Alimentary pharmacology & therapeutics. 1994 Jun 1;8(3):309-14. http://dx.doi.org/10.1111/j.1365-2036.1994.tb00293.x

58. Koop H, Kuly S, Flug M, Schneider A, Rose K. Comparison of 24-h intragastric pH and 24-h gastrin profiles during therapy with the proton pump inhibitors pantoprazole and omeprazole. Gut. 1994;35(Suppl 4):A79.

59. Poulsen AH, Christensen S, McLaughlin JK, Thomsen RW, Sørensen HT, Olsen JH, Friis S. Proton pump inhibitors and risk of gastric cancer: a population-based cohort study. British journal of cancer. 2009 May 5;100(9):1503-7. http://dx.doi.org/10.1038/sj.bjc.6605024

60. Modlin IM, Sandor A, Tang LH, Kidd M, Zelterman D. A 40-year analysis of 265 gastric carcinoids. American Journal of Gastroenterology. 1997 Apr 1;92(4).

61. Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump inhibitor therapy. Digestive diseases and sciences. 2011 Apr 1;56(4):931-50. http://dx.doi.org/10.1007/s10620-010-1560-3

62. Poulsen AH, Christensen S, McLaughlin JK, Thomsen RW, Sørensen HT, Olsen JH, Friis S. Proton pump inhibitors and risk of gastric cancer: a population-based cohort study. British journal of cancer. 2009 May 5;100(9):1503-7. http://dx.doi.org/10.1038/sj.bjc.6605024

63. Hayashi H, Taniai E, Morita R, Hayashi M, Nakamura D, Wakita A, Suzuki K, Shibutani M, Mitsumori K. Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and β-naphthoflavone. The Journal of toxicological sciences. 2012;37(5):969-85. http://dx.doi.org/10.2131/jts.37.969

64. Zelter A, Fernández JL, Bilder C, Rodríguez P, Wonaga A, Dorado F, Galich M, Viola LA. Fundic gland polyps and association with proton pump inhibitor intake: a prospective study in 1,780 endoscopies. Digestive diseases and sciences. 2011 Jun 1;56(6):1743-8. http://dx.doi.org/10.1007/s10620-010-1493-x

65. Hayashi H, Shimamoto K, Taniai E, Ishii Y, Morita R, Suzuki K, Shibutani M, Mitsumori K. Liver tumor promoting effect of omeprazole in rats and its possible mechanism of action. The Journal of toxicological sciences. 2012;37(3):491-501. http://dx.doi.org/10.2131/jts.37.491

66. Jalving M, Koornstra JJ, Wesseling J, Boezen HM, De Jong S, Kleibeuker JH. Increased risk of fundic gland polyps during long‐term proton pump inhibitor therapy. Alimentary pharmacology & therapeutics. 2006 Nov 1;24(9):1341-8. http://dx.doi.org/10.1111/j.1365-2036.2006.03127.x

67. Fossmark R, Jianu CS, Martinsen TC, Qvigstad G, Syversen U, Waldum HL. Serum gastrin and chromogranin A levels in patients with fundic gland polyps caused by long-term proton-pump inhibition. Scandinavian journal of gastroenterology. 2008 Jan 1;43(1):20-4. http://dx.doi.org/10.1080/00365520701561959

68. Jalving M, Koornstra JJ, Wesseling J, Boezen HM, De Jong S, Kleibeuker JH. Increased risk of fundic gland polyps during long‐term proton pump inhibitor therapy. Alimentary pharmacology & therapeutics. 2006 Nov 1;24(9):1341-8. http://dx.doi.org/10.1111/j.1365-2036.2006.03127.x

69. Jalving M, Koornstra JJ, Götz JM, van der Waaij LA, de Jong S, Zwart N, Karrenbeld A, Kleibeuker JH. High-grade dysplasia in sporadic fundic gland polyps: a case report and review of the literature. European journal of gastroenterology & hepatology. 2003 Nov 1;15(11):1229-33. http://dx.doi.org/10.1097/00042737-200311000-00013

70. Choudhry U, Boyce Jr HW, Coppola D. Proton pump inhibitor-associated gastric polyps: a retrospective analysis of their frequency, and endoscopic, histologic, and ultrastructural characteristics. American journal of clinical pathology. 1998 Nov;110(5):615-21. http://dx.doi.org/10.1093/ajcp/110.5.615

71. Lambert AA, Lam JO, Paik JJ, Ugarte-Gil C, Drummond MB, Crowell TA. Risk of communityacquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and metaanalysis. PloS one. 2015 Jun 4;10(6):e0128004. http://dx.doi.org/10.1371/journal.pone.0128004

72. Sultan N, Nazareno J, Gregor J. Association between proton pump inhibitors and respiratory infections: a systematic review and meta-analysis of clinical trials. Canadian Journal of Gastroenterology. 2008 Sep;22(9):761. http://dx.doi.org/10.1155/2008/821385

73. Estborn L, Joelson S. Occurrence of community-acquired respiratory tract infection in patients receiving esomeprazole. Drug safety. 2008 Jul 1;31(7):627-36. http://dx.doi.org/10.2165/00002018-200831070-00008

74. Murray LJ, Gabello M, Rudolph DS, Farrell CP, Morgan M, Martin AP, Underwood JC, Valenzano MC, Mullin JM. Transmucosal gastric leak induced by proton pump inhibitors. Digestive diseases and sciences. 2009 Jul 1;54(7):1408-17. http://dx.doi.org/10.1007/s10620-008-0528-z

75. Luk CP, Parsons R, Lee YP, Hughes JD. Proton Pump Inhibitor–Associated Hypomagnesemia: What Do FDA Data Tell Us? Annals of Pharmacotherapy. 2013 Jun 1;47(6):773-80. http://dx.doi.org/10.1345/aph.1r556

76. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm 245275.

77. Lemon TI. Proton pump inhibitors and hypomagnesemia monitoring. International journal of general medicine. 2013;6:675. http://dx.doi.org/10.2147/ijgm.s51547

78. Chen J, Yuan YC, Leontiadis GI, Howden CW. Recent safety concerns with proton pump inhibitors. Journal of clinical gastroenterology. 2012 Feb 1;46(2):93-114. http://dx.doi.org/10.1097/mcg.0b013e3182333820

79. Cundy T, Mackay J. Proton pump inhibitors and severe hypomagnesaemia. Current opinion in gastroenterology. 2011 Mar 1;27(2):180-5. http://dx.doi.org/10.1097/mog.0b013e32833ff5d6

80. Famularo G, Gasbarrone L, Minisola G. Hypomagnesemia and proton-pump inhibitors. Expert opinion on drug safety. 2013 Sep 1;12(5):709-16. http://dx.doi.org/10.1517/14740338.2013.809062

81. Danziger J, William JH, Scott DJ, Lee J, Lehman LW, Mark RG, Howell MD, Celi LA, Mukamal KJ. Proton-pump inhibitor use is associated with low serum magnesium concentrations. Kidney international. 2013 Apr 1;83(4):692-9. http://dx.doi.org/10.1038/ki.2012.452

82. McColl KE. Effect of proton pump inhibitors on vitamins and iron. The American journal of gastroenterology. 2009 Mar 1;104:S5-9. http://dx.doi.org/10.1038/ajg.2009.45

83. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. Jama. 2013 Dec 11;310(22):2435-42. http://dx.doi.org/10.1001/jama.2013.280490

84. Neal K, Logan R. Potential gastrointestinal effects of long‐term acid suppression with proton pump inhibitors. Alimentary pharmacology & therapeutics. 2001 Jul 9;15(7):1085-. http://dx.doi.org/10.1046/j.1365-2036.2001.0994a.x

85. Murray LJ, Gabello M, Rudolph DS, Farrell CP, Morgan M, Martin AP, Underwood JC, Valenzano MC, Mullin JM. Transmucosal gastric leak induced by proton pump inhibitors. Digestive diseases and sciences. 2009 Jul 1;54(7):1408-17. http://dx.doi.org/10.1007/s10620-008-0528-z

86. Merwat SN, Spechler SJ. Might the Use of Acid-Suppressive Medications Predispose to the Development of Eosinophilic Esophagitis. The American journal of gastroenterology. 2009 Aug 1;104(8):1897-902. http://dx.doi.org/10.1038/ajg.2009.87

87. Maggio M, Corsonello A, Ceda GP, Cattabiani C, Lauretani F, Buttò V, Ferrucci L, Bandinelli S, Abbatecola AM, Spazzafumo L, Lattanzio F. Proton pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA internal medicine. 2013 Apr 8;173(7):518-23. http://dx.doi.org/10.1001/jamainternmed.2013.2851

88. Katz MH. Failing the acid test: benefits of proton pump inhibitors may not justify the risks for many users. Arch Intern Med, 2010. 170(9): p. 747–8. http://dx.doi.org/10.1001/archinternmed.2010.64

89. Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, Leiper J, Cooke JP. An unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor ADMA. Circulation. 2013 Jul 3:CIRCULATIONAHA-113. http://dx.doi.org/10.1161/circulationaha.113.003602

90. Tran CT, Leiper JM, Vallance P. The DDAH/ADMA/NOS pathway. Atherosclerosis Supplements. 2003 Dec 31;4(4):33-40. http://dx.doi.org/10.1016/s1567-5688(03)00032-1

91. Wilson A, Shin D, Weatherby C, Harada R, Ng M, Nair N, Cooke JP. Asymmetric dimethylarginine correlates with measures of disease severity, major adverse cardiovascular events and all-cause mortality in patients with peripheral arterial disease. Vascular medicine. 2010 May 19. http://dx.doi.org/10.1177/1358863x10364552

92. Lu TM, Chung MY, Lin MW, Hsu CP, Lin SJ. Plasma asymmetric dimethylarginine predicts death and major adverse cardiovascular events in individuals referred for coronary angiography. International journal of cardiology. 2011 Dec 1;153(2):135-40. http://dx.doi.org/10.1016/j.ijcard.2011.06.120

93. Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, Leiper J, Cooke JP. An unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor ADMA. Circulation. 2013 Jul 3:CIRCULATIONAHA-113. http://dx.doi.org/10.1161/circulationaha.113.003602

94. Sierra F, Suarez M, Rey M, Vela MF. Systematic review: proton pump inhibitor‐associated acute interstitial nephritis. Alimentary pharmacology & therapeutics. 2007 Aug 1;26(4):545-53. http://dx.doi.org/10.1111/j.1365-2036.2007.03407.x

95. Rossert J. Drug-induced acute interstitial nephritis. Kidney international. 2001 Aug 31;60(2):804-17. http://dx.doi.org/10.1046/j.1523-1755.2001.060002804.x

96. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney international. 2012 Mar 1;81(5):442-8. http://dx.doi.org/10.1038/ki.2011.379

97. 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 Nov 13;9(11):e112558. http://dx.doi.org/10.1371/journal.pone.0112558

98. Tin A, Grams ME, Maruthur NM, Astor BC, Couper D, Mosley TH, Selvin E, Coresh J, Kao WH. Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease. Kidney international. 2015 Apr 1;87(4):820-7. http://dx.doi.org/10.1038/ki.2014.331

99. Cheng FC, Ho YF, Hung LC, Chen CF, Tsai TH. Determination and pharmacokinetic profile of omeprazole in rat blood, brain and bile by microdialysis and high-performance liquid chromatography. Journal of Chromatography A. 2002 Mar 8;949(1):35-42. http://dx.doi.org/10.1016/s0021-9673(01)01225-0

100. Rojo LE, Alzate-Morales J, Saavedra IN, Davies P, Maccioni RB. Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer's disease. Journal of Alzheimer's Disease. 2010 Jan 1;19(2):573-89.

101. Badiola N, Alcalde V, Pujol A, Münter LM, Multhaup G, Lleó A, Coma M, Soler-López M, Aloy P. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PloS one. 2013 Mar 8;8(3):e58837. http://dx.doi.org/10.1371/journal.pone.0058837

102. Dubois B, Feldman HH, Jacova C, Cummings JL, DeKosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S. Revising the definition of Alzheimer's disease: a new lexicon. The Lancet Neurology. 2010 Nov 30;9(11):1118-27. http://dx.doi.org/10.1016/s1474-4422(10)70223-4

103. Majumdar A, Cruz D, Asamoah N, Buxbaum A, Sohar I, Lobel P, Maxfield FR. Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils. Molecular biology of the cell. 2007 Apr 1;18(4):1490-6. http://dx.doi.org/10.1091/mbc.e06-10-0975

104. Mattsson JP, Väänänen K, Wallmark B, Lorentzon P. Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H+-translocating ATPases. BiochimicaetBiophysicaActa (BBA)-Biomembranes. 1991 Jun 18;1065(2):261-8. http://dx.doi.org/10.1016/0005-2736(91)90238-4

105. Fallahzadeh MK, BorhaniHaghighi A, Namazi MR. Proton pump inhibitors: predisposers to Alzheimer disease?. Journal of clinical pharmacy and therapeutics. 2010 Apr 1;35(2):125-6. http://dx.doi.org/10.1111/j.1365-2710.2009.01100.x

106. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. Jama. 2013 Dec 11;310(22):2435-42. http://dx.doi.org/10.1001/jama.2013.280490

107. O'Leary F, Allman-Farinelli M, Samman S. Vitamin B 12 status, cognitive decline and dementia: a systematic review of prospective cohort studies. British Journal of Nutrition. 2012 Dec 14;108(11):1948-61. http://dx.doi.org/10.1017/s0007114512004175

108. Reynolds E. Vitamin B12, folic acid, and the nervous system. The lancet neurology. 2006 Nov 30;5(11):949-60.

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