PROTON PUMP INHIBITORS: PROLONGED INTAKE  AND ADVERSE EFFECTS.

Anna Dominiczak; Agata Janczak; Martyna Wołek; Katarzyna Mazurek; Maciej Bara

doi:10.56782/pps.226

Published : 2024-11-06

Vol. 22 No. 4 (2024)

Proton pump inhibitors: prolonged intake and adverse effects

Anna Dominiczak

Agata Janczak

Martyna Wołek

Katarzyna Mazurek

Maciej Bara

DOI: https://doi.org/10.56782/pps.226

Abstract

Proton pump inhibitors (PPIs) are commonly used medicines in the management of the upper gastrointestinal (GI) tract diseases. The perception of PPIs as relatively safe contributes to their frequent overprescription and misuse. One of the main reasons for PPIs overprescription is unjustified prophylaxis of bleeding in the course of non-steroidal anti-inflammatory drugs therapy. Prolonged PPIs intake is associated with several adverse effects due to intestinal dysbiosis, including increased risk of GI and respiratory infections, as well as small intestine bacterial overgrowth (SIBO). Other reported reactions include malabsorption of vitamins and micro- and macroelements, hypergastrinemia, neurological, cardiovascular and renal complications, and stomach cancer. The aim of this paper was to assess the scale of misuse and overuse of PPIs and to look closely on potential issues regarding prolonged PPIs’ treatment. However, during the review of the available literature, many of the analyzed studies yielded conflicting results, indicating the need for further in-depth research to draw reliable conclusions.

Keywords:

proton pump inhibitor (PPI), misuse, prolonged intake, adverse effects

Similar Articles

Mateusz Sobczyk, Daria Żuraw, Paulina Oleksa, Kacper Jasiński, Mikołaj Porzak, Michał Dacka, SGLT2 inhibitors and their possible use in prevention and treatment of neurological diseases , Prospects in Pharmaceutical Sciences: Vol. 22 No. 1 (2024)
Helena E. Makulska-Nowak, ALCOHOL VERSUS CANNABIS - COMPARISON OF RISK , Prospects in Pharmaceutical Sciences: Vol. 11 No. 6 (2013)
Adam Piasecki, Magdalena Sitnik, Jakub Olszewski, Maciej Bara, Katarzyna Herjan, Piotr Armański, The changing landscape of mineralocorticoid receptor antagonists – finerenone in cardiovascular and renal health , Prospects in Pharmaceutical Sciences: Vol. 22 No. 1 (2024)
Katarzyna Herjan, Piotr Armański, Jakub Olszewski, Magdalena Sitnik, Maciej Bara, Positive impact of tranexamic acid in various medical settings , Prospects in Pharmaceutical Sciences: Vol. 22 No. 3 (2024)
Maciej Stępień, Stanisław Anczyk, Cytokine-targeted treatment in alopecia areata - new possibilities? , Prospects in Pharmaceutical Sciences: Vol. 21 No. 2 (2023)
Ewa Napiórkowska, Thiamine: overview of history of discovery, mechanism of action, role and deficiency , Prospects in Pharmaceutical Sciences: Vol. 21 No. 3 (2023)
Agnieszka Sienicka, Krzysztof Kubasik, Agata Pisula, The glucagon-like peptide-1 analogues therapy in the non-diabetic patients , Prospects in Pharmaceutical Sciences: Vol. 21 No. 1 (2023)
Dominika Łaszczyca, Paradowska Paradowska, Katerina Makarova, ENVIRONMENTAL CONTAMINATION WITH BISPHENOL A , Prospects in Pharmaceutical Sciences: Vol. 13 No. 1 (2015)
Krzysztof Kubica, Aleksander Mazurek, VEMURAFENIB AS A SELECTIVE INHIBITOR OF THE SERINE/THREONINE-PROTEIN KINASE B-RAF, USED IN THE TREATMENT OF MELANOMA , Prospects in Pharmaceutical Sciences: Vol. 14 No. 8 (2016)
Aleksandra Mikulska, Arkadiusz Kocur, Pharmacotherapy with high doses of methotrexate (HDMTX) in oncology – how should chemotherapy be conducted based on therapeutic drug monitoring? , Prospects in Pharmaceutical Sciences: Vol. 21 No. 4 (2023)

1 2 3 4 5 6 > >>

You may also start an advanced similarity search for this article.

Details

References

Statistics

Authors

Download files

PDF (Język Polski)

Citation rules

Dominiczak, A., Agata Janczak, Martyna Wołek, Katarzyna Mazurek, & Maciej Bara. (2024). Proton pump inhibitors: prolonged intake and adverse effects . Prospects in Pharmaceutical Sciences, 22(4), 51–58. https://doi.org/10.56782/pps.226

Altmetric indicators

Cited by / Share

Licence

This work is licensed under a Creative Commons Attribution 4.0 International License.

References

1. Ward, R.M.; Kearns, G.L. Proton pump inhibitors in pediatrics : mechanism of action, pharmacokinetics, pharmacogenetics, and pharmacodynamics. Paediatr. Drugs. 2013, 15(2), 119-131. doi: 10.1007/s40272-013-0012-x

2. Wedemeyer, R.S.; Blume, H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014, 37(4), 201-11. doi: 10.1007/s40264-014-0144-0

3. Stedman, C.A.; Barclay, M.L. Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment. Pharmacol. Ther. 2000, 14(8), 963-78. doi: 10.1046/j.1365-2036.2000.00788.x

4. Crafa, P.; Franceschi, M.; Rodriguez-Castro, K.I.; Franzoni, L.; Russo, M.; Brandimarte, G.; Tursi, A.; Rugge, M.; Di Mario, F. PPIs and gastric cancer: any causal relationship? Acta Biomed. 2023, 94(3), Art. No: e2023096. doi: 10.23750/abm.v94i3.14105

5. Kazberuk, M.; Brzósko, S.; Hryszko, T.; Naumnik, B. Nadużywanie inhibitorów pompy protonowej i jego konsekwencje. Postepy Hig. Med Dosw. 2016, 70(null), 1112-1116. doi: 10.5604/17322693.1222106

6. Chudek, J. Stosowanie inhibitorów pompy protonowej w profilaktyce choroby wrzodowej u chorych leczonych niesteroidowymi lekami przeciwzapalnymi. Gastroenterologia Kliniczna 2012, 4(1), 33-39.

7. Ahmed, A.; Clarke, J.O.; Proton Pump Inhibitors (PPI). [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557385/

8. Shanika, L.G.T.; Reynolds, A.; Pattison, S.; Braund, R. Proton pump inhibitor use: systematic review of global trends and practices. Eur. J. Clin. Pharmacol. 2023, 79(9), 1159-1172. doi: 10.1007/s00228-023-03534-z

9. ClinCalc.com. Available online: https://clincalc.com/About.aspx (accessed on 30 June 2024).

10. El Rouby, N.; Lima, J.J.; Johnson, J.A. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin. Drug Metab. Toxicol. 2018, 14(4), 447-460. doi: 10.1080/17425255.2018.1461835

11. Gendre, P.; Mocquard, J.; Huon, J.F. Appropriateness of proton pump inhibitors prescription in patient admitted to hospital: An observational study. Ann. Pharm. Fr. 2023, 81(4), 596-603. doi: 10.1016/j.pharma.2022.11.003

12. Ahrens, D.; Behrens, G.; Himmel, W.; Kochen, MM.; Chenot, J.F. Appropriateness of proton pump inhibitor recommendations at hospital discharge and continuation in primary care. Int. J. Clin. Pract. 2012, 66(8), 767-773. doi: 10.1111/j.1742-1241.2012.02973.x

13. Gendre, P.; Mocquard, J.; Artarit, P.; Chaslerie, A.; Caillet, P.; Huon, J.F. (De)Prescribing of proton pump inhibitors: what has changed in recent years? an observational regional study from the French health insurance database. BMC Prim. Care. 2022, 23(1), Art. No: 341. doi: 10.1186/s12875-022-01941-2

14. Buda, V.; Prelipcean, A.; Cristescu, C.; Roja, A.; Dalleur, O.; Andor, M.; Danciu, C.; Ledeti, A.; Dehelean, C.A.; Cretu, O. Prescription Habits Related to Chronic Pathologies of Elderly People in Primary Care in the Western Part of Romania: Current Practices, International Recommendations, and Future Perspectives Regarding the Overuse and Misuse of Medicines. Int. J. Environ. Res. Public Health. 2021, 18(13), Art. No: 7043. doi: 10.3390/ijerph18137043

15. Blume, H.; Donath, F.; Warnke, A.; Schug, B.S. Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Saf. 2006, 29(9), 769-84. doi: 10.2165/00002018-200629090-00002

16. Ustawa z dnia 6 września 2001 r. Prawo farmaceutyczne. Dz.U. 2001 nr 126 poz. 1381. Available online: https://isap.sejm.gov.pl/isap.nsf/DocDetails.xsp?id=WDU20011261381 (accessed on 07 October 2024)

17. Zhang, J.; Zhang, C.; Zhang, Q.; Yu, L.; Chen, W.; Xue, Y.; Zhai, Q. Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota. BMC Microbiol. 2023, 23(1), 171. doi: 10.1186/s12866-023-02895-w

18. Kwok, C.S.; Arthur, A.K.; Anibueze, C.I.; Singh, S.; Cavallazzi, R.; Loke, Y.K.; Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am. J. Gastroenterol. 2012, 107(7), 1011-9. doi: 10.1038/ajg.2012.108

19. McDonald, E.G.; Milligan, J.; Frenette, C.; Lee, T.C. Continuous Proton Pump Inhibitor Therapy and the Associated Risk of Recurrent Clostridium difficile Infection. JAMA Intern. Med. 2015, 175(5), 784–791. doi:10.1001/jamainternmed.2015.42

20. Haastrup, P.F.; Thompson, W.; Søndergaard, J.; Jarbøl, D.E. Side Effects of Long-Term Proton Pump Inhibitor Use: A Review. Basic Clin. Pharmacol. Toxicol. 2018, 123(2), 114-121. doi: 10.1111/bcpt.13023

21. Nelis, G.F.; Engelage, A.H.; Samson, G. Does long-term inhibition of gastric acid secretion with omeprazole lead to small intestinal bacterial overgrowth? Neth. J. Med. 1994, 45, 93–100.

22. Pereira, S.P.; Gainsborough, N.; Dowling, R.H. Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly. Aliment. Pharmacol. Ther. 1998, 12, 99–104. doi: 10.1046/j.1365-2036.1998.00275.x

23. Su, T.; Lai, S.; Lee, A.; He, X.; Chen, S. Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth. J. Gastroenterol. 2018, 53(1), 27-36. doi: 10.1007/s00535-017-1371-9

24. Weitsman, S.; Celly, S.; Leite, G.; Mathur, R.; Sedighi, R.; Barlow, G.M. Effects of proton pump inhibitors on the small bowel and stool microbiomes. Dig. Dis. Sci. 2022, 67, 224–232. doi: 10.1007/s10620-021-06857-y.

25. Othman, F.; Crooks, C.J.; Card, T.R. Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study. BMJ 2016, 355, i5813. doi: 10.1136/bmj.i5813

26. de Jager, C.P.; Wever, P.C.; Gemen, E.F.; van Oijen, M.G.; van Gageldonk-Lafeber, A.B.; Siersema, P.D.; Kusters, G.C.; Laheij, R.J. Proton pump inhibitor therapy predisposes to community-acquired Streptococcus pneumoniae pneumonia. Aliment. Pharmacol. Ther. 2012, 36(10), 941-949. doi: 10.1111/apt.12069

27. Lambert, A.A.; Lam, J.O.; Paik, J.J.; Ugarte-Gil, C.; Drummond, M.B.; Crowell, T.A. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PLoS One. 2015, 10(6), Art. No: e0128004. doi: 10.1371/journal.pone.0128004

28. Waldum, H.L.; Qvigstad, G.; Fossmark, R.; Kleveland, P.M.; Sandvik, A.K. Rebound acid hypersecretion from a physiological, pathophysiological and clinical viewpoint. Scand. J. Gastroenterol. 2010, 45(4), 389-394. doi: 10.3109/00365520903477348

29. 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, 137(1), 80-87.e1. doi: 10.1053/j.gastro.2009.03.058

30. Lødrup, A.B.; Reimer, C.; Bytzer, P. Systematic review: symptoms of rebound acid hypersecretion following proton pump inhibitor treatment. Scand. J. Gastroenterol. 2013, 48(5), 515-522. doi: 10.3109/00365521.2012.746395

31. Fallahzadeh, M.K.; Borhani Haghighi, A.; Namazi, M.R. Proton pump inhibitors: predisposers to Alzheimer disease? J. Clin. Pharm. Ther. 2010, 35(2), 125-126. doi: 10.1111/j.1365-2710.2009.01100.x

32. Wu, B.; Hu, Q.; Tian, F.; Wu, F.; Li, Y.; Xu, T. A pharmacovigilance study of association between proton pump inhibitor and dementia event based on FDA adverse event reporting system data. Sci. Rep. 2021, 11(1), 10709. doi: 10.1038/s41598-021-90108-7

33. Dinesh, D.; Lee, J.S.; Scott, T.M.; Tucker, K.L.; Palacios N. Proton Pump Inhibitor Use and Cognitive Function in the Boston Puerto Rican Health Study. J. Gerontol. A. Biol. Sci. Med. Sci. 2023, 78(8), 1461-1470. doi: 10.1093/gerona/glac231

34. Ahn, N.; Wawro, N.; Baumeister, S.E.; Nolde, M.; Gerlach, R.; Tauscher, M.; Günter, A.; Güntner, F.; Rückert-Eheberg, I.M.; Meisinger, C.; Linseisen, J. Time-Varying Use of Proton Pump Inhibitors and Cognitive Impairment and Dementia: A Real-World Analysis from Germany Drugs Aging. 2023, 40(7), 653-663. doi: 10.1007/s40266-023-01031-7

35. Castellana, C.; Pecere, S.; Furnari, M.; Telese, A.; Matteo, M.V.; Haidry, R.; Eusebi, L.H. Side effects of long-term use of proton pump inhibitors: practical considerations. Pol. Arch. Intern. Med. 2021, 131(6), 541-549. doi: 10.20452/pamw.15997

36. Langan, R.C.; Goodbred, A.J. Vitamin B12 Deficiency: Recognition and Management. Am. Fam. Physician 2017, 96(6), 384-389.

37. Swarnakari, K.M.; Bai, M.; Manoharan, M.P.; Raja, R.; Jamil, A.; Csendes, D.; Gutlapalli, S.D.; Prakash, K.; Desai, D.M.; Desai, A.; Khan, S. The Effects of Proton Pump Inhibitors in Acid Hypersecretion-Induced Vitamin B12 Deficiency: A Systematic Review (2022). Cureus. 2022, 14(11), Art. No: e31672. doi: 10.7759/cureus.31672

38. Losurdo, G.; Caccavo, N.L.B.; Indellicati, G.; Celiberto, F.; Ierardi, E.; Barone, M.; Di Leo, A. Effect of Long-Term Proton Pump Inhibitor Use on Blood Vitamins and Minerals: A Primary Care Setting Study. J. Clin. Med. 2023, 12(8), Art. No: 2910. doi: 10.3390/jcm12082910

39. Gommers, L.M.M.; Hoenderop, J.G.J.; de Baaij, J.H.F. Mechanisms of proton pump inhibitor-induced hypomagnesemia. Acta Physiol. (Oxf). 2022, 235(4), Art. No: e13846. doi: 10.1111/apha.13846

40. Paudel, Y.; Najam, B.; Desai, H.N.; Illango, J.; Seffah, K.D.; Kumar, M.; Naveen, N.; Pachchipulusu, V.K.; Penumetcha, S.S. Use of Proton Pump Inhibitors and Risk of Fracture in Adults: A Review of Literature. Cureus 2023, 15(12), Art. No: e49872. doi: 10.7759/cureus.49872

41. Dado, D.N.; Loesch, E.B.; Jaganathan, S.P. A Case of Severe Iron Deficiency Anemia Associated with Long-Term Proton Pump Inhibitor Use. Curr. Ther. Res. Clin. Exp. 2017, 84, 1-3. doi: 10.1016/j.curtheres.2017.01.003

42. Imai, R.; Higuchi, T.; Morimoto, M.; Koyamada, R.; Okada, S. Iron Deficiency Anemia Due to the Long-term Use of a Proton Pump Inhibitor. Intern. Med. 2018, 57(6), 899-901. doi: 10.2169/internalmedicine.9554-17

43. Ariel, H.; Cooke, J.P. Cardiovascular Risk of Proton Pump Inhibitors. Methodist Debakey Cardiovasc. J. 2019, 15(3), 214-219. doi: 10.14797/mdcj-15-3-214.

44. Shiraev, T.P.; Bullen, A. Proton Pump Inhibitors and Cardiovascular Events: A Systematic Review. Heart Lung Circ. 2018, 27(4), 443-450. doi: 10.1016/j.hlc.2017.10.020

45. Song, H.J.; Seo, H.J.; Jiang, X.; Jeon, N.; Lee, Y.J.; Ha, I.H. Proton pump inhibitors associated with an increased risk of mortality in elderly: a systematic review and meta-analysis. Eur. J. Clin. Pharmacol. 2024, 80(3), 367-382. doi: 10.1007/s00228-023-03606-0

46. Parmar, M.P.; Kaleem, S.; Samuganathan, P.; Ishfaq, L.; Anne, T.; Patel, Y.; Bollu, S.; Vempati, R. Impact of Proton Pump Inhibitors on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review. Cureus 2023, 15(12), Art. No: e49883. doi: 10.7759/cureus.4988

47. Hart, E.; Dunn, T.E.; Feuerstein, S.; Jacobs, D.M. Proton pump inhibitors and risk of acute and chronic kidney disease: a retrospective cohort study. Pharmacotherapy. 2019, 39, 443-453. doi: 10.1002/phar.2235

48. Malavade, P.; Hiremath, S. Proton Pump Inhibitors: More Indigestion than Relief? Indian J. Nephrol. 2017, 27(4), 249-257. doi: 10.4103/0971-4065.202824

49. Kamiński, T.; Michałowska, M.; Pawlak, D. Receptor węglowodorów aromatycznych (AhR) i jego endogenny agonista – siarczan indoksylu w przewlekłej chorobie nerek. Postepy Hig. Med. Dosw. 2017, 71, 624-632. doi: 10.5604/01.3001.0010.3843

50. Banoglu, E.; Jha, G.G.; King, R.S. Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. Eur. J. Drug Metab. Pharmacokinet. 2001, 26(4), 235-240. doi: 10.1007/BF03226377

51. Song, H.; Zhu, J.; Lu, D. Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions. Cochrane Database Syst. Rev. 2014, 2014(12), Art. No: CD010623. doi: 10.1002/14651858.CD010623.pub2

52. Tran, T.H.; Myung, S.K.; Trinh, TTK. Proton pump inhibitors and risk of gastrointestinal cancer: A meta‑analysis of cohort studies. Oncol. Lett. 2023, 27(1), Art. No: 28. doi: 10.3892/ol.2023.14161

53. Kim, G.H. Proton Pump Inhibitor-Related Gastric Mucosal Changes. Gut Liver. 2021, 15(5), 646-652. doi: 10.5009/gnl20036

Anna Dominiczak

amdominiczak@gmail.com

Affiliation:

a:1:{s:5:"en_US";s:28:"Medical University of Warsaw";} Poland