Proton pump inhibitor
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
| Trial | Patients | Intervention | Comparison | Outcome | Results | |
|---|---|---|---|---|---|---|
| PPI | Control | |||||
| Nested case-control study[8] | 13,636 subjects taking clopidogrel after myocardial infarction | 782 subjects readmitted for myocardial infarction | 2057 subjects not readmitted | Rate of PPI usage other than pantoprazole | Odds ratio = 1.40 (95% CI 1.10–1.77) | |
| Retrospective(?) cohort study from the Cardiac Care Follow-up Clinical Study[9] | 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[10] | 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[8]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[9] or may not[10] increase adverse cardiac events when given to patients taking clopidogrel for coronary heart disease.
References
- ↑ Anonymous (2024), Proton pump inhibitor (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ 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.
- ↑ 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.
- ↑ 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
- ↑ 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
- ↑ 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.
- ↑ 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.
- ↑ 8.0 8.1 8.2 Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al. (2009). "A population-based study of the drug interaction between proton pump inhibitors and clopidogrel.". CMAJ 180 (7): 713-8. DOI:10.1503/cmaj.082001. PMID 19176635. PMC PMC2659819. Research Blogging. Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13 Review in: Evid Based Med. 2009 Oct;14(5):154
- ↑ 9.0 9.1 9.2 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.
- ↑ 10.0 10.1 10.2 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.