Abstract

Direct inhibition of H+ ion excretion to the gastric lumen makes proton pump inhibitors (PPI) the most effective drugs against gastric acid-related diseases. Over recent years usage of proton pump inhibitors has increased dramatically. Due to the low costs, high efficacy and rarity of adverse effects, their use is prevalent and often it does not correspond with existing medical guidelines. The literature lists stress ulcer prophylaxis among patients with low risk of bleeding, routine ‘gastroprotective’ medication during treatment and non-specific abdominal symptoms as the most common patterns of off-label PPI use. This article summarizes the influence of PPI therapy on gastric mucosa, absorption and occurrence of adverse effects. The authors note that their low awareness among physicians contributes to wide and imprudent use of drugs of this group.

References

• 1. Ahrens D., Chenot J.F., Behrens G., Grimmsmann T., Kochen M.M.:Appropriateness of treatment recommendations for PPI in hospitaldischarge letters. Eur. J. Clin. Pharmacol., 2010; 66: 1265-1271
  Google Scholar
• 2. Akram F., Huang Y., Lim V., Huggan P.J., Merchant R.A.: Protonpump inhibitors: are we still prescribing them without valid indications?Australas. Med. J., 2014; 7: 465-470
  Google Scholar
• 3. Albugeaey M., Alfaraj N., Garb J., Seiler A., Lagu T.: Do hospitalistsoveruse proton pump inhibitors? Data from a contemporary cohort.J. Hosp. Med., 2014; 9: 731-733
  Google Scholar
• 4. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHPCommission on Therapeutics and approved by the ASHP Board ofDirectors on November 14, 1998. Am. J. Health. Syst. Pharm., 1999;56: 347-379
  Google Scholar
• 5. Ayuk J., Gittoes N.J.: Contemporary view of the clinical relevanceof magnesium homeostasis. Ann. Clin. Biochem., 2014; 51: 179-188
  Google Scholar
• 6. Barletta J.F., Lat I., Micek S.T., Cohen H., Olsen K.M., Haas C.E.:Off-label use of gastrointestinal medications in the intensive careunit. J. Intensive Care Med., 2015; 30: 217-225
  Google Scholar
• 7. Bashford J.N., Norwood J., Chapman S.R.: Why are patients prescribedproton pump inhibitors? Retrospective analysis of link betweenmorbidity and prescribing in the General Practice ResearchDatabase. BMJ, 1998; 317: 452-456
  Google Scholar
• 8. Cook D.J., Fuller H.D., Guyatt G.H., Marshall J.C., Leasa D., HallR., Winton T.L., Rutledge F., Todd T.J., Roy P., Lacroix J., Griffith N.,Willan A.: Risk factors for gastrointestinal bleeding in critically illpatients. Canadian Critical Care Trials Group. N. Engl. J. Med., 1994;330: 377-381
  Google Scholar
• 9. Cunningham R., Dale B., Undy B., Gaunt N.: Proton pump inhibitorsas a risk factor for Clostridium difficile diarrhoea. J. Hosp. Infect.,2003; 54: 243-245
  Google Scholar
• 10. De Vries F., Cooper A.L., Cockle S.M., van Staa T.P., Cooper C.:Fracture risk in patients receiving acid-suppressant medicationalone and in combination with bisphosphonates. Osteoporos. Int.,2009; 20: 1989-1998
  Google Scholar
• 11. Deane A.M., Guyatt G.H.: Primum non nocere and challengingconventional treatment. Intensive Care Med., 2015; 41: 933-935
  Google Scholar
• 12. Dial S., Alrasadi K., Manoukian C., Huang A., Menzies D.: Risk ofClostridium difficile diarrhea among hospital inpatients prescribedproton pump inhibitors: cohort and case-control studies. CMAJ,2004; 171: 33-38
  Google Scholar
• 13. Dial S., Delaney J.A., Barkun A.N., Suissa S.: Use of gastric acidsuppressiveagents and the risk of community-acquired Clostridiumdifficile-associated disease. JAMA, 2005; 294: 2989-2995
  Google Scholar
• 14. Eid S.M., Boueiz A., Paranji S., Mativo C., Landis R., AbougergiM.S.: Patterns and predictors of proton pump inhibitor overuseamong academic and non-academic hospitalists. Intern. Med., 2010;49: 2561-2568
  Google Scholar
• 15. Fashner J., Gitu A.C.: Common gastrointestinal symptoms: risksof long-term proton pump inhibitor therapy. FP Essent., 2013; 413:29-39
  Google Scholar
• 16. Fraser L.A., Leslie W.D., Targownik L.E., Papaioannou A., AdachiJ.D.: The effect of proton pump inhibitors on fracture risk: reportfrom the Canadian Multicenter Osteoporosis Study. Osteoporos. Int.,2013; 24: 1161-1168
  Google Scholar
• 17. Geevasinga N., Coleman P.L., Webster A.C., Roger S.D.: Protonpump inhibitors and acute interstitial nephritis. Clin. Gastroenterol.Hepatol., 2006; 4: 597-604
  Google Scholar
• 18. Heidelbaugh J.J.: Proton pump inhibitors and risk of vitaminand mineral deficiency: evidence and clinical implications. Ther.Adv. Drug Saf., 2013; 4: 125-133
  Google Scholar
• 19. Hollingworth S., Duncan E.L., Martin J.H.: Marked increase inproton pump inhibitors use in Australia. Pharmacoepidemiol. DrugSaf., 2010; 19: 1019-1024
  Google Scholar
• 20. Howden C.W., Hunt R.H.: Relationship between gastric secretionand infection. Gut, 1987; 28: 96-107
  Google Scholar
• 21. Kelly O.B., Dillane C., Patchett S.E., Harewood G.C., Murray F.E.:The inappropriate prescription of oral proton pump inhibitors inthe hospital setting: a prospective cross-sectional study. Dig. Dis.Sci., 2015; 60: 2280-2286
  Google Scholar
• 22. Khalili H., Huang E.S., Jacobson B.C., Camargo C.A.Jr., FeskanichD., Chan A.T.: Use of proton pump inhibitors and risk of hip fracturein relation to dietary and lifestyle factors: a prospective cohortstudy. BMJ, 2012; 344: e372
  Google Scholar
• 23. Krag M., Perner A., Wetterslev J., Wise M.P., Hylander Møller M.:Stress ulcer prophylaxis versus placebo or no prophylaxis in criticallyill patients. Intensive Care Med., 2014; 40: 11-22
  Google Scholar
• 24. Labenz J., Petersen K.U., Rösch W., Koelz H.R.: A summary ofFood and Drug Administration-reported adverse events and drug interactionsoccurring during therapy with omeprazole, lansoprazoleand pantoprazole. Aliment. Pharmacol. Ther., 2003; 17: 1015-1019
  Google Scholar
• 25. Laheij R.J., Sturkenboom M.C., Hassing R.J., Dieleman J., StrickerB.H., Jansen J.B.: Risk of community-acquired pneumonia and use ofgastric acid-suppressive drugs. JAMA, 2004; 292: 1955-1960
  Google Scholar
• 26. Lanas A., Ferrandez A.: Inappropriate prevention of NSAID-inducedgastrointestinal events among long-term users in the elderly.Drugs Aging, 2007; 24: 121-131
  Google Scholar
• 27. Leonard C.E., Freeman C.P., Newcomb C.W., Reese P.P., HerlimM., Bilker W.B., Hennessy S., Strom B.L.: Proton pump inhibitorsand traditional nonsteroidal anti-inflammatory drugs and the riskof acute interstitial nephritis and acute kidney injury. Pharmacoepidemiol.Drug Saf., 2012; 21: 1155-1172
  Google Scholar
• 28. Leri F., Ayzenberg M., Voyce S.J., Klein A., Hartz L., Smego R.A.:Four-year trends of inappropriate proton pump inhibitor use afterhospital discharge. South. Med. J., 2013; 106: 270-273
  Google Scholar
• 29. Leven C., Hudier L., Picard S., Longuet H., Lorcy N., Cam G.,Boukerroucha Z., Dolley-Hitze T., Le Cacheux P., Halimi J.M., CornecLe Gall E., Hanrotel-Saliou C., Arreule A., Massad M., DuveauA. i wsp.: Prospective study of drug-induced interstitial nephritisin eleven French nephrology units. Presse Med., 2014; 43: 369-376
  Google Scholar
• 30. Liang J.F., Chen Y.T., Fuh J.L, Li S.Y., Chen T.J., Tang C.H., Wang S.J.:Proton pump inhibitor-related headaches: a nationwide populationbasedcase-crossover study in Taiwan. Cephalalgia, 2015; 35: 203-210
  Google Scholar
• 31. Lin L.M., Chen L.W., Liu Y.C., Hsu K.H., Hsieh C.Y., Chen H.Y.: Riskfor hospital-acquired pneumonia from proton pump inhibitor or sucralfatein intensive care units. J. Food Drug Anal., 2012; 20: 570-576
  Google Scholar
• 32. Lundell L., Havu N., Miettinen P., Myrvold H.E., Wallin L.,Julkunen R., Levander K., Hatlebakk J.G., Liedman B., Lamm M., MalmA., Walan A.: Changes of gastric mucosal architecture during longtermomeprazole therapy: results of a randomized clinical trial. Aliment.Pharmacol. Ther., 2006; 23: 639-647
  Google Scholar
• 33. Marlicz W, Łoniewski I, Grimes D.S., Quigley E.M.: Nonsteroidalanti-inflammatory drugs, proton pump inhibitors, and gastrointestinalinjury: contrasting interactions in the stomach and smallintestine. Mayo Clin Proc., 2014; 89: 1699-1709
  Google Scholar
• 34. Nishtala P.S., Soo L.: Proton pump inhibitors utilisation in olderpeople in New Zealand from 2005 to 2013. Intern. Med. J., 2015; 45:624-629
  Google Scholar
• 35. Nørsett K.G., Laegreid A., Kusnierczyk W., Langaas M., YlvingS., Fossmark R., Myhre S., Falkmer S., Waldum H.L., Sandvik A.K.:Changes in gene expression of gastric mucosa during therapeuticacid inhibition. Eur. J. Gastroenterol. Hepatol., 2008; 20: 613-623
  Google Scholar
• 36. Ramirez E., Lei S.H., Borobia A.M., Piñana E., Fudio S., MuñozR., Campos A., Carcas A.J., Frias J.: Overuse of PPIs in patients at admission,during treatment, and at discharge in a tertiary Spanishhospital. Curr. Clin. Pharmacol., 2010; 5: 288-297
  Google Scholar
• 37. Ray S., Delaney M., Muller A.F.: Proton pump inhibitors andacute interstitial nephritis. BMJ, 2010; 341: c4412
  Google Scholar
• 38. Reimer C., Søndergaard B., Hilsted L., Bytzer P.: Proton-pumpinhibitor therapy induces acid-related symptoms in healthy volunteersafter withdrawal of therapy. Gastroenterology, 2009; 137: 80-87
  Google Scholar
• 39. Sanders S.W.: Pathogenesis and treatment of acid peptic disorders:comparison of proton pump inhibitors with other antiulceragents. Clin. Ther., 1996; 18: 2-34
  Google Scholar
• 40. Shah N.H., LePendu P., Bauer-Mehren A., Ghebremariam Y.T.,Iyer S.V., Marcus J., Nead K.T., Cooke J.P., Leeper N.J.: Proton pumpinhibitor usage and the risk of myocardial infarction in the generalpopulation. PLoS One, 2015; 10: e0124653
  Google Scholar
• 41. Spirt M.J., Stanley S.: Update on stress ulcer prophylaxis in criticallyill patients. Crit. Care Nurse, 2006; 26: 18-20
  Google Scholar
• 42. Stollman N., Metz D.C.: Pathophysiology and prophylaxis of stressulcer in intensive care unit patients. J. Crit. Care, 2005; 20: 35-45
  Google Scholar
• 43. Suzuki H., Hibi T.: Novel effects other than antisecretory actionand off-label use of proton pump inhibitors. Expert Opin. Pharmacother.,2005; 6: 59-67
  Google Scholar
• 44. Targownik L.E., Leslie W.D., Davison K.S., Goltzman D., Jamal S.A.,Kreiger N., Josse R.G., Kaiser S.M., Kovacs C.S., Prior J.C., Zhou W.:The relationship between proton pump inhibitor use and longitudinalchange in bone mineral density: a population-based study [corrected]from the Canadian Multicentre Osteoporosis Study (CaMos).Am. J. Gastroenterol., 2012; 107: 1361-1369
  Google Scholar
• 45. Thomson A.B., Sauve M.D., Kassam N., Kamitakahara H.: Safetyof the long-term use of proton pump inhibitors. World J. Gastroenterol.,2010; 16: 2323-2330
  Google Scholar
• 46. Väkeväinen S., Tillonen J., Salaspuro M., Jousimies-Somer H.,Nuutinen H., Färkkilä M.: Hypochlorhydria induced by a protonpump inhibitor leads to intragastric microbial production of acetaldehydefrom ethanol. Aliment. Pharmacol. Ther., 2000; 14: 1511-1518
  Google Scholar
• 47. Waldum H.L., Arnestad J.S., Brenna E., Eide I., Syversen U., SandvikA.K.: Marked increase in gastric acid secretory capacity afteromeprazole treatment. Gut, 1996; 39: 649-653
  Google Scholar
• 48. Woerkom M. van, Piepenbrink H., Godman B., Metz J. de, CampbellS., Bennie M., Eimers M., Gustafsson L.L.: Ongoing measures toenhance the efficiency of prescribing of proton pump inhibitorsand statins in the Netherlands: influence and future implications.J. Comp. Eff. Res., 2012; 1: 527-538
  Google Scholar
• 49. Wolfe M.M., Sachs G.: Acid suppression: optimizing therapyfor gastroduodenal ulcer healing, gastroesophageal reflux disease,and stress-related erosive syndrome. Gastroenterology, 2000; 118(Suppl. 1): 9-31
  Google Scholar

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