PROTON-PUMP INHIBITORS

 
Drug Duodenal Ulcer Gastric Ulcer H. pylori tx GERD
Omeprazole (Prilosec) 20mg QD x 4wks 20-40mg QD x 4-8wks 20mg QD 20-60mg QD
Esomeprazole* (Nexium)       20-40mg QD
Lansoprazole (Prevacid) 15mg QD x 4wks 30mg QD x 4-8wks 30mg QD 15-30mg QD
Rabeprazole (Aciphex) 20mg QD x 4wks 20-40mg QD x 4-8wks 20mg QD  
Pantoprazole (Protonix)       40mg QD

*--Esomeprazole is the s-isomer of omeprazole

  1. Pharmacology
    1. Reduce HCl secretion more than H2-blockers
    2. Omeprazole inhibits cytochrome p-450 enzymes (see above under "Cimetidine")
  2. Adverse effects
    1. Can cause some nausea, abd. pain, constipation or diarrhea; acute interstitial nephritis has been reported
    2. May increase risk of pneumonia
      1. In a prospective study of a population of 364,000 pts over 3y, use of either H2-blockers or PPIs were ass'd with RR 4.5 for incidence of community-acquired pneumonia (JAMA 292:1955, 2004--JW)
      2. In a case-control study in 63,878 adult non-ICU inpatients hospitalized for 3d or longer, of whom 27,000 received PPIs and 7,500 received H2-blockers, incidence of hospital-acquired pneumonia was sig. higher in pts receiving acid suppression (4.9% vs. 2.0%).  After adjustment for potential confounders, OR was 1.3; all excess risk was associated with PPI use (JAMA 301:2120, 2009-JW)
    3. Cause hyperplasia of gastric enterochromaffin-like cells in animals & humans and neuroendocrine cell tumors and hepatocellular carcinoma in animals
    4. May accelerate the progression of Osteoporosis by interfering with calcium absorption
      1. In a retrospective study of about 400,000 pts who received at least one prescription for a PPI and/or H2 blocker, after adjustment for potential confounders, pts on a PPI for > 1y had sig. increased incidence of hip fracture (RR 1.44) c/w pts who did not use any acid-suppression therapy. No sig. diff. between users of H2 blockers and non-users. There was evidence of a dose- and duration-dependent effect (JAMA 296:2947, 2006--JW)
    5. Some evidence for rare association with Acute Interstitial Nephritis in children from retrospective studies (Clin. Gastroent. Hepatol. 4:597, 2006--JW)
    6. Some association with risk of Clostridium dificile colitis in case-control studies (JAMA 294:2989, 2005--JW)
  3. See section on NSAIDs for info on use of PPI's for prevention of NSAID-induced ulcers