Proton pump inhibitor treatment

Czech version

Authors: J. Špičák
Authors‘ workplace: Klinika hepatogastroenterologie, Institut klinické a experimentální medicíny, Praha
Published in: Kardiol Rev Int Med 2014, 16(3): 214-218
Category: Internal Medicine

Overview

PPIs are weak bases metabolized in an acid environment and blocking the function of active proton pumps. They provide effective treatment for oesophageal reflux disease, Helicobacter pylori infection, functional dyspepsia and non‑steroidal anti‑inflammatory drug‑induced gastropathy. The first generation includes omeprazole, pantoprazole and lansoprazole; the second one consists of esomeprazole and rabeprazole. The pharmacokinetic differences between different PPIs do not always result in relevant clinical consequences. Generally, the second generation PPIs provide a more rapid effect and a more prolonged inhibition of the gastric secretion. The effect of rabeprazole, especially, is less dependent on the method of administration and has a lower influence on the cytochrome P450 function. The effectiveness of first‑ generation PPIs is influenced by the genetic variability of the CYP2C19 enzyme, being significantly lower in rapid metabolizers. PPIs are very safe and immediate complications are exceptional. In Helicobacter pylori infection they cause a worsening of gastritis. Although PPIs cause hypergastrinaemia, they do not exhibit any malignant potential. Their long‑term administration is associated with an increased risk of spine and hip fractures, community pneumonia and clostridium bowel infection. They can lower the effectiveness of antiplatelet therapy with clopidogrel, with a consequent increased risk of cardiovascular events.

Keywords:
proton pump inhibitors – histamine- 2 receptor antagonists – gastric secretion physiology – equipotency – oesophageal reflux disease – Helicobacter pylori eradication – non‑steroid anti‑inflammatory drug‑induced gastropathy – complications – interactions

Sources

1. Sachs G. Proton pump inhibitors and acid‑related diseases. Pharmacotherapy 1997; 17: 22– 37.

2. 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: 355– 370.

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

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

5. Sachs G. Improving on PPI‑based therapy of GORD. Eur J Gastroenterol Hepatol 2001; 13 (Suppl 1): S35– S41.

6. Horn J. Review article: understanding the pharmacodynamic and pharmacokinetic differences between proton pump inhibitors – focus on pKa and metabolism. Alimentary Pharmacology & Therapeutics Symposium Series 2006; 2: 340– 350. doi: 10.1111/ j.1746‑ 6342.2006.00065.x.

7. 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: 821– 827.

8. 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: 19– 31. doi: 10.1007/ s00228‑ 008‑ 0576‑ 5.

9. 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: 674– 683. doi: 10.1111/ j.1745‑ 7599.2010.00578.x

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

11. 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: 717– 723. doi: 10.1002/ lary.21429.

12. 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: 414– 425. doi: 10.1111/ j.1365‑ 2036.2012.05211.x.

13. 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: 581– 588. doi: 10.1586/ eri.11.80.

14. 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: 443– 453. doi: 10.2165/ 11534590‑ 000000000‑ 00000.

15. Lanza FL, Chan FK, Quigley EM et al. Guidelines for prevention of NSAID‑related ulcer complications. Am J Gastroenterol 2009; 104: 728– 738. doi: 10.1038/ ajg.2009.115.

16. Vakil N. Proton pump inhibitors for dyspepsia. Dig Dis 2008; 26: 215– 217. doi: 10.1159/ 000121349.

17. Lodato F, Azzaroli F, Turco L et al. Adverse effects of proton pump inhibitors. Best Pract Res Clin Gastroenterol 2010; 24: 193– 201. doi: 10.1016/ j.bpg.2009.11.004.

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

19. Malfertheiner P, Megraud F, O’Morain C et al. Management of Helicobacter pylori infection: the Maastricht IV/ Florance consensus report. Gut 2012; 61: 646– 664. doi: 10.1136/ gutjnl‑ 2012‑ 302084.

20. 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– 526. doi: 10.1016/ j.amjmed.2011.01.007.

21. Shabajee N, Lamb EJ, Sturgess I et al. Omeprazole and refractory hypomagnesaemia. BMJ 2008; 337: a425. doi: 10.1136/ bmj.39505.738981.BE.

22. Eom CS, Jeon CY, Lim JW et al. Use of acid‑ suppressive drugs and risk of pneumonia: a systematic review and meta‑analysis. CMAJ 2011; 183: 310– 319. doi: 10.1503/ cmaj.092129.

23. 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: 225– 233. doi: 10.1016/ j.cgh.2011.09.030.

24. Drepper MD, Spahr L, Frossard JL. Clopidogrel and proton pump inhibitors – where do we stand in 2012? World J Gastroenterol 2012; 18: 2161– 2171. doi: 10.3748/ wjg.v18.i18.2161.

25. Chen J, Yuan YC, Leontiadis GI et al. Recent safety concerns with proton pump inhibitors. J Clin Gastroenterol 2012; 46: 93– 114. doi: 10.1097/ MCG.0b013e3182333820.

26. Sachs G, Shin JM, Hunt R. Novel approaches to inhibition of gastric acid secretion. Curr Gastroenterol Rep 2010; 12: 437– 447. doi: 10.1007/ s11894‑ 010‑ 0149‑ 5.