Proton pump inhibitor

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In medicine, proton pump inhibitors (PPI) are medications that "inhibit H(+)-K(+)-exchanging atpase. They are used as anti-ulcer agents and sometimes in place of histamine H2 antagonists for gastroesophageal reflux."[1] They are also used as part of curative therapy for Helicobacter pylori, in combination with antibiotics.

Metabolism

Proton pump inhibitors are metabolized by the CYP2C19 isoenzyme of cytochrome P-450. This may be less true for pantoprazole and esomeprazole.[2]

Adverse effects

Proton pump inhibitors may be associated with spontaneous bacterial peritonitis.[3] Recent starting of these drugs may also be associated with pneumonia acquired in the community[4] or hospital[5]. These drugs may be associated with Clostridium difficile diarrhea, and fractures.

Starting proton pump inhibitors in healthy volunteers may induce acid-related symptoms PPIs are stopped[6] This is problematic considering how often PPIs are incorrectly prescribed.[7]

Drug interactions

Randomized controlled trials[8][9]
Trial Patients Intervention Comparison Outcome Results
Intervention Control
Retrospective cohort study from the Cardiac Care Follow-up Clinical Study[8] 8205 subjects with acute coronary syndrome 64% were taking PPIs:
(0.2% used pantoprazole)
  Subjects not taking PPIs    
Cohort study taken from TRITON-TIMI 38 randomized controlled trial[9] 6795 subjects with acute coronary syndrome who were randomized to the clopidogrel arm of the trial 33% were taking PPIs:
(41% used pantoprazole)
  Subjects not taking PPIs    

Proton pump inhibitors (especially inhibitors other than pantoprazole[10]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[8] or may not[9] increase adverse cardiac events when given to patients taking clopidogrel for coronary heart disease.

References

  1. Anonymous (2024), Proton pump inhibitor (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B (January 2009). "Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel". Am. Heart J. 157 (1): 148.e1–5. DOI:10.1016/j.ahj.2008.09.017. PMID 19081411. Research Blogging.
  3. Bajaj JS, Zadvornova Y, Heuman DM, et al. (May 2009). "Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites". Am. J. Gastroenterol. 104 (5): 1130–4. DOI:10.1038/ajg.2009.80. PMID 19337238. Research Blogging.
  4. Sarkar M, Hennessy S, Yang YX. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Ann Intern Med. 2008 Sep 16;149(6):391-8. PMID 18794558
  5. Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009 May 27;301(20):2120-8. PMID 19470989
  6. Reimer C, Søndergaard B, Hilsted L, Bytzer P (2009). "Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy.". Gastroenterology 137 (1): 80-7, 87.e1. DOI:10.1053/j.gastro.2009.03.058. PMID 19362552. Research Blogging.
  7. Wohlt PD, Hansen LA, Fish JT (2007). "Inappropriate continuation of stress ulcer prophylactic therapy after discharge.". Ann Pharmacother 41 (10): 1611-6. DOI:10.1345/aph.1K227. PMID 17848420. Research Blogging.
  8. 8.0 8.1 8.2 Ho PM, Maddox TM, Wang L, et al. (March 2009). "Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome". JAMA 301 (9): 937–44. DOI:10.1001/jama.2009.261. PMID 19258584. Research Blogging.
  9. 9.0 9.1 9.2 O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al. (2009). "Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials.". Lancet 374 (9694): 989-97. DOI:10.1016/S0140-6736(09)61525-7. PMID 19726078. Research Blogging.
  10. Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635