Proton Pump Inhibitor

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Mechanism-of-action 8 More General Terms 9 References

More Specific Terms

• dexlansoprazole (Kapidex, Dexilant)
• lansoprazole (Prevacid)
• omeprazole (Prilosec, Zegerid, Losec, Medral)
• pantoprazole (Protonix)
• rabeprazole (Aciphex)

Indications

• peptic ulcer [5]; more effective than H2 blockers
• short-term treatment of severe erosive esophagitis
• short-term treatment of gastroesophageal reflux disease
• pathologic hypersecretory conditions
• long-term antiplatelet therapy if: [7]

• history of peptic ulcer or gastrointestinal bleeding
• dual antiplatelet therapy or concomitant anticoagulation
• additional risk factors (age >= 60, steroid use, dyspepsia, or gastroesophageal reflux)

Contraindications

• probably not indicated for routine treatment of asthma [9]
• probably overprescribed [14]
• not effective in infants [16]; may be effective in children & adolescents

Dosage

• (administration)
• administer in AM, 20-45 minutes before 1st meal
• pantoprazole ( Protonix) available for IV injection
• omeprazole may be available for IV injection

Pharmacokinetics

• bioavailability 35-90%
• highly protein bound (90-97%)
• rapidly metabolized in the liver ( cyt P450)
• elimination 1/2life of 1-1.5 hours
• duration of acid inhibition: 48-72 hours

Adverse-effects

• increased risk of C difficile colitis [4,17]
• increased risk of nosocomial pneumonia (HR=2.5) [11,12]
• increased risk of spontaneous bacterial peritonitis in cirrhotic patients with ascites [10]
• rebound gastric hyperacidity may occur in patients when proton pump inhibitor is stopped after 2 months of use; best managed with antiacids [13]
  
• drug adverse effects of proton pump inhibitors

Mechanism-of-action

• covalent binding to cysteine residues of the H+/K+ ATPase ( proton pump)
• inhibition of the proton pump & gastric acid secretion
• esomeprazole (active stereoisomer of omeprazole) may be most effective PPI [3]
• more effecting than H2 blockers to peptic ulcer bleeding [5]
• PPIs don't provide continuous acid suppression... even with BID dosing - nighttime acid breakthrough occurs in > 70% of patients
• acid secretion triggered by histamine may not be effectively inhibited by proton pump inhibitors [6]

More General Terms

• enzyme inhibitor
• antiulcer agent

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Barkun A et al, Ann Intern Med 139:843, 2003 PMID: [1]
3. Journal Watch 24(2):19, 2004 Miner P et al, Am J Gastroenterol 98:2616, 2003 PMID: [2]
4. Prescriber's Letter 11(8): 2004 Proton Pump Inhibitors Associated with Increased Risk of Clostridium difficile Diarrhea Detail-Document#: [3] (subscription needed) [4]
5. Journal Watch 25(10):80, 2005 Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ. 2005 Mar 12;330(7491):568. Epub 2005 Jan 31. Review. <PubMed> PMID: [5] <Internet> [6]
6. Prescriber's Letter 14(3): 2007 What You Should Know About Proton Pump Inhibitors Detail-Document#: [7] (subscription needed) [8]
7. Prescriber's Letter 16(3): 2009 Comparison of Proton Pump Inhibitors Detail-Document#: [9] (subscription needed) [10]
8. Bhatt DL et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Am J Gastroenterol 2008 Nov; 103:2890.
   - Bhatt DL et al, ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2008 Oct 28;52(18):1502-17. PMID: &dopt=Abstract
   - Bhatt DL et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation 2008 Oct 28; 118:1894. PMID: [11]
9. Prescriber's Letter 16(6): 2009 Do Proton Pump Inhibitors (PPIs) Improve Asthma? Detail-Document#: [12] (subscription needed) [13]
10. Bajaj JS et al Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites. Am J Gastroenterol 2009 May; 104:1130. PMID: [14]
11. Herzig SJ et al, Acid-Suppressive Medication Use and the Risk for Hospital- Acquired Pneumonia JAMA. 2009;301(20):2120-2128 PMID: [15]
12. Prescriber's Letter 16(7): 2009 Overuse of Acid Suppressing Drugs in the Hospital Detail-Document#: [16] (subscription needed) [17]
13. Reimer C et al. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology 2009 Jul; 137:80. PMID: [18]
    - McColl KEL and Gillen D. Evidence that proton-pump inhibitor therapy induces the symptoms it is used to treat. Gastroenterology 2009 Jul; 137:20. PMID: [19]
14. Yachimski PS et al Proton Pump Inhibitors for Prophylaxis of Nosocomial Upper Gastrointestinal Tract Bleeding Arch Intern Med. 2010;170(9):779-783. <PubMed> PMID: [20] <Internet> [21]
    - Katz MH Failing the Acid Test: Benefits of Proton Pump Inhibitors May Not Justify the Risks for Many Users Arch Intern Med. 2010;170(9):747-748. <PubMed> PMID: [22] <Internet> [23]
15. Prescriber's Letter 17(7): 2010 COMMENTARY: Proton Pump Inhibitors: Appropriate Use and Safety Concerns CHART: Comparison of Proton Pump Inhibitors PATIENT HANDOUT: What You Should Know About Proton Pump Inhibitors Detail-Document#: [24] (subscription needed) [25]
16. van der Pol RJ et al. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: A systematic review. Pediatrics 2011 May; 127:925. PMID: [26]
17. FDA MedWatch: 02/08/2012 Proton Pump Inhibitors (PPIs) - Drug Safety Communication: Clostridium Difficile-Associated Diarrhea (CDAD) Can be Associated With Stomach Acid Drugs [27]

proton pump inhibitor