Gastroenterology Book

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Proton Pump InhibitorAka: PPI Therapy, Pantoprazole, Protonix, Rabeprazole, Aciphex, Omeprazole, Prilosec, Lansoprazole, Prevacid, Esomeprazole, Nexium

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  1. Indications
    1. Peptic Ulcer Disease
    2. Gastroesophageal Reflux
  2. Contraindications
    1. Hypersensitivity to proton pump inhibitors
    2. Use with caution in severe liver disease
  3. Pregnancy and Lactation
    1. Pregnancy Category C: Omeprazole
    2. Pregnancy Category B: Other agents
    3. Avoid PPI agents in Lactation
  4. Mechanism
    1. Benzimidazole proton pump inhibitors
    2. Binds proton pump of parietal cell
    3. Inhibits >90% of total daily gastric acid production
    4. PPIs irreversibly bind proton pump
  5. Pharmacokinetics
    1. All PPIs have short plasma half life of 1-2 hours
  6. Dosing (Take 30 minutes prior to a meal)
    1. Omeprazole (Prilosec)
      1. Duodenal Ulcer or erosive esophagitis: 20 mg po qd
      2. Gastric Ulcer: 40 mg po qd
      3. Generic in 2002
    2. Lansoprazole (Prevacid)
      1. Duodenal Ulcer or erosive esophagitis: 15 mg po qd
      2. Gastric Ulcer: 30 mg po qd
    3. Pantoprazole (Protonix)
      1. Duodenal Ulcer or erosive esophagitis: 40 mg PO qd
      2. Parenteral dosing available
    4. Rabeprazole (Aciphex)
      1. Erosive esophagitis: 20 mg PO qd
    5. Esomeprazole (Nexium)
      1. Erosive esophagitis: 20 to 40 mg PO qd
  7. Efficacy
    1. Gastroesophageal Reflux treatment with Omeprazole
      1. Patients with healed esophagitis (n=175)
      2. Treated with 1 of 3 drugs to prevent recurrence
        1. Ranitidine: 49% Remission
        2. Ranitidine and Cisapride: 66% Remission
        3. Cisapride: 54% Remission
        4. Omeprazole 80% Remission
        5. Omeprazole and Cisapride: 89% Remission
    2. References
      1. Vigneri (1995) N Engl J Med 333:1106
  8. Adverse Effects
    1. Headache
    2. Diarrhea
    3. Abdominal Pain
    4. Nausea
  9. Drug Interactions
    1. Decreased Absorption (due to increased gastric pH)
      1. Griseofulvin
      2. Ketoconazole
      3. Itraconazole
      4. Iron Salts
      5. Vitamin B12
      6. Cefpodoxime
      7. Enoxacin
    2. Increased Absorption (due to increased gastric pH)
      1. Nifedipine (Procardia)
      2. Digoxin
    3. Drug level increases specific to Prilosec (CYP 450)
      1. Carbamazepine (Tegretol)
      2. Diazepam (Valium)
      3. Phenytoin (Dilantin)
      4. Warfarin (Coumadin)
      5. Methotrexate
    4. Drug level decreases specific to Prevacid (CYP 450)
      1. Theophylline
  10. Relative Potency
    1. General
      1. Potency and outcomes appear to be similar for all PPI
      2. Literature appears to offer conflicting results
      3. Most potent agents appear to be
        1. Rabeprazole (Aciphex)
        2. Esomeprazole (Nexium)
    2. References
      1. Dammann (1999) Eur J Gastroenterol Hepatol 11:1277
      2. Williams (1999) Aliment Pharmacol Ther 13(suppl 3):3
      3. Hartmann (1996) Aliment Pharmacol Ther 10(3):359
      4. Bastaki (2000) J Physiol Paris 94(1):19
      5. Florent (1997) Eur J Gastroenterol Hepatol 9(2):195
      6. Spencer (2000) Drugs 60:321
  11. Risks
    1. Vitamin B12 Deficiency
      1. Bradford (1999) Pharmacother 33:641
    2. Gastric Carcinoma
      1. Originally bi-annual Gastrin Levels recommended
      2. Routine Gastrin Levels not currently necessary
    3. Community Acquired Pneumonia
      1. Risk increases with PPI dosage
      2. H2-Blockers also conferred risk, but less than PPI
      3. Laheij (2004) JAMA 292:1955
  12. References
    1. (2001) Med Lett Drugs Ther 43(1103):36
    2. Vanderhoff (2002) Am Fam Physician 66(2):273

Omeprazole (C0028978)

Definition (MSH)A highly effective inhibitor of gastric acid secretion used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-EXCHANGING ATPASE) in the proton pump of GASTRIC PARIETAL CELLS.
Definition (CSP)substituted benzimidazole used as a gastric acid secretion inhibitor.
Definition (NCI)A drug that inhibits gastric acid secretion.
Definition (PDQ)A benzimidazole with selective and irreversible proton pump inhibition activity. Omeprazole forms a stable disulfide bond with the sulfhydryl group of the hydrogen-potassium (H+ - K+) ATPase found on the secretory surface of parietal cells, thereby inhibiting the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen and suppressing gastric acid secretion. This agent exhibits no anticholinergic properties and does not antagonize histamine H2 receptors. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42309&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42309&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C716" NCI Thesaurus)
Definition (NCI)A benzimidazole derivative and a selective proton pump inhibitor with an anti-ulcer property. Upon entering the parietal cell, omeprazole is protonated and converted to its active form by acid in the stimulated parietal cell of the stomach. The active form irreversibly binds to the proton pump (H+/K+ ATPase) located on the parietal cells, thereby inhibiting the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen and suppressing gastric acid secretion.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishOMEP, Omeprazole, OMEPRAZOLE PREPARATION
Spanishomeprazol
CreditsDerived from the NIH UMLS (Unified Medical Language System)


lansoprazole (C0050940)

Definition (NCI)A substituted benzimidazole prodrug with selective and irreversible proton pump inhibitor activity. Lansoprazole prodrug is converted to an active sulfonamide derivative in the acidic environment of the gastric parietal cell; the sulfonamide derivative binds to the gastric proton pump H+/K+ ATPase and forms a stable disulfide bond with the sulfhydryl group near the potassium-binding site on the luminal side, resulting in inactivation of the ATPase and a reduction in gastric acid secretion. This agent does not have anticholinergic or histamine H2 -receptor antagonistic properties.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
Englishlansoprazole, LANSOPRAZOLE PREPARATION, lanzoprazole
Spanishlansoprazol
CreditsDerived from the NIH UMLS (Unified Medical Language System)


pantoprazole (C0081876)

Definition (NCI)A substituted benzimidazole and proton pump inhibitor with antacid activity. Pantoprazole is a lipophilic weak base that crosses the parietal cell membrane and enters the acidic parietal cell canaliculus where it becomes protonated, producing the active metabolite sulphenamide, which forms an irreversible covalent bond with two sites of the H+/K+-ATPase enzyme located on the gastric parietal cell, thereby inhibiting both basal and stimulated gastric acid production.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
Englishpantoprazole, PANTOPRAZOLE PREPARATION
Spanishpantoprazol
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Prevacid (C0286036)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishAbbot Brand of Lansoprazole, Ogastro, Prevacid, TAP Brand of Lansoprazole
CreditsDerived from the NIH UMLS (Unified Medical Language System)


rabeprazole (C0378482)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
Englishrabeprazole, RABEPRAZOLE PREPARATION
Spanishrabeprazol
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Prilosec (C0700777)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishPrilosec
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Aciphex (C0875952)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishAciphex
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Protonix (C0876139)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishProtonix
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Esomeprazole (C0937846)

Definition (MSH)The S-isomer of omeprazole
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishEsomeprazole, ESOMEPRAZOLE PREPARATION
Spanishesomeprazol
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Nexium (C0939400)

Definition (MSH)Esomeprazole trade name.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishNexium
CreditsDerived from the NIH UMLS (Unified Medical Language System)



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