Proton pump inhibitors – new mole-cules, new knowledge


Authors: J. Špičák
Authors‘ workplace: Institut klinické a experimentální medicíny, Praha ;  Klinika hepatogastroenterologie ;  Přednosta: prof. MUDr. Julius Špičák, CSc.
Published in: Prakt. Lék. 2013; 93(5): 207-216
Category: Reviews

Overview

Proton pump inhibitors are the most important drugs in the treatment of acid-related diseases. All proton pump inhibitors are weak bases selectively metabolized in an acid environment and blocking active proton pump function. Proton pump inhibitors provide effective treatment of gastroesophageal reflux disease, Helicobacter pylori eradication, functional dyspepsia, and NSAID-associated gastropathy. First-generation proton pump inhibitors include omeprazole, pantoprazole, and lansoprazole, with second-generation ones represented by esomeprazole and rabeprazole. While proton pump inhibitors differ in their pharmacokinetic properties, these differences do not necessarily have clinically relevant sequels. Generally, second-generation proton pump inhibitors provide a faster onset of effect, longer gastric secretion inhibition and, specifically, the effect of rabeprazole is less dependent on the route of administration and has a smaller effect on cytochrome P450 function. The effect of proton pump inhibitors, especially the first-generation ones, is modified by genetic variability of the CYP2C19 enzyme being significantly lower with rapid metabolizers. Proton pump inhibitors are very safe and immediate complications are exceptional. They can cause progression of gastritis in Helicobacter infection. Despite hypergastrinemia, they do not have a malignant potential. Their long-term use is associated with an increased risk of pelvic and hip fractures, community-acquired pneumonia, and clostridium infection. Proton pump inhibitors may reduce the effect of antiplatelet therapy with clopidogrel thus increasing the risk of recurrent cardiovascular events. Package leaflets for patients are generally not well structured and often lack important information.

Keywords:
proton pump inhibitors (PPI) – H2 receptor antagonists (H2RA) – physiology – equipotent doses – oesophageal reflux disease – Helicobacter pylori eradication – NSAID gastropathy – complications – interactions


Sources

1. Hatlebakk JG, Katz PO, Camacho-Lobato J, et al. Proton pump inhibitors: better acid supression when taken before a meal than without a meal. Aliment Pharmacol Ther 2000; 14(10): 1267–1272.

2. Sachs G. Proton pump inhibitors and acid-related diseases. Pharmacotherapy 1997; 17(1): 22–37.

3. Huang JQ, Hunt RH. Pharmacological and pharmacodynamic essentials of H2-receptor antagonists and proton pump inhibitors for the practicing physicians. Best Pract Res Clin Gastroenterol 2001; 15(3): 355–370.

4. Rackoff A, Agrawal A, Hilla A, et al. Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy. Dis Esophagus 2005; 18(6): 370–373.

5. Martínek J, Lukáš M. Inhibitory protonové pumpy – up to date. Gastroent Hepatol 2011; 65(6): 331–342.

6. Andersson T, Weidolf L. Stereoselective disposition of proton pump inhibitors. Clin Drug Investig 2008; 28(5): 263–279.

7. Sachs G. Improving on PPI-based therapy of GORD. Eur J Gastroenterol Hepatol 2001; 13 Suppl. 1: S35–41.

8. Besancon M, Simon A, Sachs G, et al. Sites of reaction of the gastric H, K – ATP-ase with extracytoplasmic thiol reagents. J Biol Chem 1997; 272(36): 22438–22446.

9. Horn J. Review article: understanding the pharnacodynamic and pharmacokinetic differences between proton pump inhibitors – focus on pKa and metabolism. Aliment Pharmacol Ther 2006; 2(2): 340–350.

10. Morelli G, Chen H, Rossiter G, et al. An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers. Aliment Pharmacol Ther 2011; 33(7): 845–854.

11. Li XQ, Andersson TB, Ahlström M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole on human P450 activities. Drug Metab Dispos 2004; 32(8): 821–827.

12. Friedlander EA, Pallentino J, Miller SK, et al. The evolution of proton pump inhibitors for the treatment of gastroesophageal reflux disease. J Am Acad Nurse Pract 2010; 22(12): 674–683.

13. Kirchheiner J, Glatt S, Fuhr U, et al. Relative potency on proton-pump inhibitors-comparison of effects on intragastric pH. Eur J Clin Pharmacol 2009; 65(1): 19–31.

14. Klotz U. Clinical impact of CYP2C19 polymorphism on the action of proton pump inhibitors: a review of a special problem. Int J Clin Pharmacol Ther 2006; 44(7): 297–302.

15. Katz PO, Tutuian R. Histamine receptor antagonists, proton pump inhibitors and their combination in the treatment of gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol 2001; 15(3): 371–384.

16. Pace F, Sonnenberg A, Bianchi Porro G. The lessons learned from randomized clinical trials of GERD. Dig Liver Dis 2007; 39(11): 993–1000.

17. Chiba N, De Gara CJ, Wilkinson JM, et al. Speed of healing and symptom relief in grade II to IV gastroesopohageal reflux disease: a metaanalysis. Gastroenterology 1997; 112(6): 1798–1810.

18. Vakil N, Fennerty MB. Direct comparative trials of the efficacy of proton pump inhibitors in the management of gastroesophageal reflux disease and peptic ulcer disease. Aliment Pharmacol Ther 2003; 18(6): 559–568.

19. Holtmann G, Bytzer P, Metz M, et al. A randomized, double-blind, comparative study of standard-dose rabeprazole and high dose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002; 16(3): 479–485.

20. Maiti R, Jaida J, Israel PL, et al. Rabeprazole and esomeprazole in mild-to-moderate erosive gastroesophageal reflux disease: A comparative study of efficacy and safety. J Pharmacol Pharmacother 2011; 2(3): 150–157.

21. Altman KW, Prufer N, Vaezi MF. A review of clinical practice guidelines for reflux disease: toward creating a clinical protocol for the otolaryngologist. Laryngoscope 2011; 121(4): 717–723.

22. McNicholl AG, Linares PM, Nyssen OP, et al. Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther 2012; 36(5): 414–425.

23. Tang HL, Li Y, Hu YF, et al. Effects of CYP2C19 Loss-of-function variants on the eradication of H. pylori infection in patients treated with proton pump inhibitor-based triple therapy regimens: A meta-analysis of randomized clinical trials. PLoS One 2013; 8(4):e62162. doi: 10.1371/journal.pone.0062162.

24. Tamura T, Kurata M, Inoue S, et al. Improvements in Helicobacter pylori eradication rates through clinical CYP2C19 genotyping. Nagoya J Med Sci 2011; 73(1-2): 25–31.

25. Selgrad M, Bornschein J, Malfertheiner P, et al. Guidelines for treatment of Helicobacter pylori in the East and West. Expert Rev Anti Infect Ther 2011; 9(8): 581–588.

26. Tielemans MM, Eikendal T, Jansen JB, et al. Identification of NSAID users at risk for gastrointestinal complications: a systematic review of current guidelines and consensus agreements. Drug Saf 2010; 33(6): 443–453.

27. Iwamoto J, Saito Y, Honda A, et al. Clinical features of gastroduodenal injury associated with long-term low dose aspirin therapy. World J Gastroenterol 2013; 19(11): 1673–1682.

28. Laine L. Review article: gastrointestinal bleeding with low-dose aspirin-what´s the risk? Aliment Pharmacol Ther 2006; 24(6): 897–908.

29. Lanza FL, Chan FK, Quigley EM, et al. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 2009; 104(3): 728–738.

30. Wallace JL. NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies. Br J Pharmacol 2012; 165(1): 67–74.

31. Vakil N. Proton pump inhibitors for dyspepsia. Dig Dis 2008; 26(3): 215–217.

32. Ford AC, Moayyedi P. Current guidelines for dyspepsia management. Dig Dis 2008; 26(3): 225–230.

33. Veldhuyzen Van Zante SJ, Chiba N, Armstrong B, et al. A randomized trial comparing omeprazole, ranitidine, cisapride or placebo in Helicobacter pylori negative, primary care patiens with dyspepsia: The CADET-HN study. Am J Gastroenterol 2005; 100(7): 1477–1488.

34. Thomson AB, Sauve MD, Kassam N, et al. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol 2010; 16(19): 2323–2330.

35. Lodato F, Azzaroli F, Turco L, et al. Adverse effects of proton pump inhibitors. Best Pract Res Clin Gastroenterol 2010; 24(2): 193–201.

36. Lamberts R, Brunner G, Solcia E, et al. Effects of very long (up to 10 years) proton pump blockade on human gastric mucosa. Digestion 2001; 64: 205–213

37. Malfertheiner P, Megraud F, O´Morain C, et al. Management of Helicobacter pylori infection: the Maastricht IV/ Florance consensus report. Gut 2012; 61(5): 646–664.

38. Fiocca R, Mastracci L, Attwood SE, et al. Gastric exocrine and endocrine cell morfology under prolonged acid inhibition therapy: results of 5-year follow-up in the LOTUS trial. Aliment Pharmacol Ther 2012; 36(10): 959–971.

39. Jalving M, Koornstra JJ, Wesseling J, et al. Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy. Aliment Pharmacol Ther 2006; 24(9): 1341–1348.

40. 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(6): 519–526.

41. Shabajee N, Lamb EJ, Sturgess I, et al. Omeprazole and refractory hypomagnesaemia. BMJ 2008; 337(7662): a425.

42. The U.S. Food and Drug Administration. FDA Drug Safety Communication. Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs)[online]. 2011-02-03 [cit. 2013-05-10]. Dostupný na: www.fda.gov/Drugs/DrugSafety/ucm245011.htm

43. Sultan N, Nazareno J, Gregor J, et al. Association between proton pump inhibitors and respiratory infections: A systematic review and meta-analysis of clinical trials. Can J Gastroenterol 2008; 22(9): 761–766.

44. Eom CH-S, Jeon ChY, Lim J-W, et al. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ 2011; 183(3): 310–319.

45. Giuliano C, Wilhem SM, Kale-Pradhan PB. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev Clin Pharmacol 2012; 5(3): 337–344.

46. Cunningham R, Dale B, Undy B, et al. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. J Hosp Infect 2003; 54(3): 243–245.

47. Deshpande A, Pant Ch, Pasupuleti V, et al. Association between proton pump inhibitor therapy and clostridium difficile in a meta-analysis. Clin Gastroenterol Hepatol 2012; 10(3): 225–233.

48. Ogawa R, Echizen H. Drug-drug interactions profiles of proton pump inhibitors. Clin Pharmacokinet 2010; 49(8): 509–533.

49. Drepper MD, Spahr L, Frossard JL. Clopidogrel and proton pump inhibitors – where do we stand in 2012? World J Gastroenterol 2012; 18(18): 2161–2171.

50. Chen J, Yuan YC, Leontiadis GI, et al. Recent safety concerns with proton pump inhibitors. J Clin Gastroenterol 2012; 46(2): 93–114.

51. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363(20): 1909–1917.

52. Hulot JS, Collet JP, Silvain J, et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor coadministration. J Am Coll Cardiol 2010; 56(2): 134–143.

53. Uotani T, Sugimoto M, Nishino M, et al. Ability od rabeprazole to prevent gastrin mucosal damage from clopidogrel and low doses of aspirin depends on CYP2C19. Clin Gastroenterol Hepatol 2012; 10(8): 879–885.

54. El-Halabi MM, Zgheib N, Mansour NM, et al. CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the anti-platelet action of clopidogrel. J Cardiovasc Pharmacol 2013 Mar 7. [Epub ahead of print].

55. DeVault KR, Talley NJ. Insights into the future of gastric acid suppression. Nat Rev Gastroenterol Hepatol 2009; 6: 524–532.

56. Sachs G, Shin JM, Hunt R. Novel approaches to inhibition of gastric acid secretion. Curr Gastroenterol Rep 2010; 12: 437–447.

Labels
General practitioner for children and adolescents General practitioner for adults
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account