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10 Day Use of Proton Pump Inhibitors in The Primary Care Setting
10 Day Use of Proton Pump Inhibitors in The Primary Care Setting
10 Day Use of Proton Pump Inhibitors in The Primary Care Setting
Background
Medical complications
Pregnancy
Mechanism of Action
How effective is PPI therapy and is it better
than other available agents for GI
related diseases?
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% heartburn free/week
Placebo
P<0.05
P<0.05
Chiba et al. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1998; 112: 1798-810
Wang et al. Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: a meta-analysis. World J Gastroenterology 2005; 11:4067-77 Chiba N et al. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997; 112: 1801
Control basal and food produced acid secretion Empiric treatment of Esophageal strictures
to a much greater degree GERD
Ulcerations
Endoscopy negative
Produce longer lasting acid suppression Functional dyspepsia
reflux disease
Barretts esophagus
H. pylori eradication
Tachyphylaxis not observed
Savarino V et al. Proton pump inhibitors in GORD. An overview of their pharmacology, efficacy, and safety. Pharmacological Research 2009; 59: 137
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Day 7
Time pH <4 in Supine
80
Position (%)
60
Day 1 P <0.05 vs
40 Omeprazole
20 mg BID
20
0
No Rx Omeprazole
Omeprazole 20 mg BID
Median 20 mg BID
& Ranitidine 300 mg QHS
99.3% Median 42.8%
*Crossover data from 16 GERD patients. Niklasson et al. Dyspeptic symptom development after discontinuation of a proton pump inhibitor:
Fackler WK, et al. Gastroenterology. 2002;122:624632. A double blind placebo-controlled trial. AJG 2010; 105: 1534
acid secretion
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Acid and Bones Whats the PPI Therapy and Fracture Risk
Connection? Short term use of PPIs has been modestly linked to
Acidic environment aids in the release of ionized an increased fracture risk
British study demonstrated an increased risk with each
calcium from insoluble calcium salts
consecutive year of PPI therapy (OR 1.2 1.6 over 1-4
Ca2+ carbonate disintegration and dissolution is a pH years)
dependent process Kaiser study illustrated that the risk of hip fracture increased
by 30% in people who used PPIs for > 2 years
PPIs can act on bones independent of calcium
absorption Strength of association was higher with increasing
Inhibit osteoclastic H+/K+
ATPase pumps doses of PPI therapy
Hypergastrinemia enhances bone resorption via
parathyroid gland hyperplasia H2 RA therapy also had positive, but weaker
Ali et al. Long-term safety concerns with proton pump inhibitors. The American Journal of Medicine 2009; 122:896-903. association with hip fracture
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>2
PPI use not associated with the development of
>3
osteoporosis at the hip or lumbar spine
>4
No significant decrease in BMD
>5
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Gulmez
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Gill et al. The safety of proton pump inhibitors (PPIs) in pregnancy: A meta-analysis. American Journal of Gastroenterology 2009; 104: 1541-1545
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Risk of birth defects increased in women taking PPIs Lifestyle modifications and OTC antacids should still
4 weeks before conception (OR 1.4) be first line approach in treating GERD during
Only Prevacid was statistically significant pregnancy
Pasternak B, Hiviid A. Use of proton pump inhibitors in early pregnancy and the risk of birth defects. NEJM 2010; 362: 2114-23
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Sibbing D et al. Risk of combining PPIs with thienopyridines: fact or fiction? Lancet; 374: 953
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Conclusions Conclusions
PPI usage modifies risk for infectious processes
PPIs are commonly used and effective at Elevated risk for developing some forms of bacterial
treating a multitude of diseases and symptoms gastroenteritis
Evidence for CAP is less compelling
Risk of developing GI associated malignancies
on PPI therapy is low PPI use is safe in the first trimester of pregnancy, but a
risk may exist in the pre-conception phase
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