PPI when and where
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PPI's work by inhibiting gastric H+K+-ATPase and decreasing acid secretion. They are indicated for peptic ulcer disease, gastroesophageal reflux disease, and other acid-related conditions. Common side effects include diarrhea and headache. Long-term PPI use has been associated with nutrient deficiencies, increased risk of fractures, community-acquired pneumonia, and small intestinal bacterial overgrowth. PPIs also interact with some drugs by affecting CYP enzyme metabolism.
PPI when and where
- 1. PPI’S – AN OVERVIEW DR S.VADIVEL KUARAN CONSULTANT MEDICAL GASTROENTEROLOGIST AND HEPATOLOGIST KAUVERY HOSPITAL,ALWARPET CHENNAI
- 4. INTRODUCTION • Decrease gastric acid secretion by inhibiting gastric H⁺K⁺-ATPase . • Omeprazole first PPI- 1989. • PPI’s are weak bases that concentrate in acidic spaces with pKa1- 3-8 to 4.5.
- 5. • PPI’s are metabolised by CYP2C19 and CYP3A4. • Rabeprazole has higher affinity for CYP3A4. • Conc. of PPI in secretory canaliculus is 100000 to 1000000 higher than in blood. • All PPI bind to cysteine 813. • Omeprazole- cysteine 892 Lansoprazole- cysteine 321 Pantoprazole – cysteine 822
- 6. INDICATIONS • PEPTIC ULCER DISEASE • TREATMENT AND PREVENTION OF GASTRODUODENAL ULCERS DUE TO NASAID. • ERADICATION OF H.PYLORI • ZOLLINGER ELLISON SYNDROME • BARRETT’S METAPLASIA • GASTROESOPHAGEAL REFLUX DISEASE • ESOPHAGEAL STRICTURES • EXTRAESOPHAGEAL MANIFESTATIONS
- 7. pKa?? • It refers to degree of willingness of compoud to accept or donate a proton. • Compound with pKa of 5 is 10 fold more basic than compound with pKa of 4.
- 10. SITE OF ACTION
- 11. GASTRIC H⁺K-ATPase • Found in parietal cells and small amounts in renal medulla. • It has α and β subunits. • 3 types F, V1, P1 and P2.
- 15. COMMON SIDE EFFECTS • 2812 pts on OMEPRAZOLE Headache(2.4%) Diarrhea (1.9%) Nausea(0.9%) Rash( 1.1%) • 5669 pts on Lansoprazole Diarrhea(4.1%) Headache(2.9%). Nausea( 2.6%)
- 16. ADVERSE EFFECTS • Physiological Hypergastrinemia • Fundic gland Polyposis • Drug interactions • Vit B12 metabolism and pernicious anemia • Osteopenia and osteoporosis • Community acquired pneumonia • Bacterial overgrowth
- 17. HYPERGASTRINEMIA • PPI’s cause physiological hypergastrinemia. • Hypergastrinemia causing ECL Hyperplasia is controversial. • Only one published report of ECL Hyperplasia and gastric malignancy in ZES pt treated with high dose PPI.
- 18. FUNDIC GLAND POLYPOSIS(FGP) • PPI use leads to 4 fold risk of Fundic gland polyposis. • H.pylori also increases risk of FGP. • Eradication of H.pylori or stopping PPI leads to regression of polyposis. • It doesn’t lead to Adenocarcinoma.
- 19. DRUG INTERACTIONS • All PPI’s metabolized by CYP2C19 except Rabeprazole high affinity for CYP3A4. • Reduce absorption and bioavailability of ketoconazole, Itraconazole and sucralfate. • All PPI’s except Pantoprazole affect the effectiveness of clopidogrel- 40% risk of coronary stent occlusion.
- 20. IRON & B12 • To small extent affect iron absorption. • Elderly and ZES pts on high dose PPI have reduced B12 concentration.
- 21. PPI and Metabolic bone disease??? • PPI > 5 yrs risk of osteoporosis by 1.62 fold • PPI > 7 yrs risk of osteoporosis by 4.55 fold. • Rarely osteoporotic fractures reported even with 6- 12 months of high dose PPI.
- 22. CAP • PPI use leads to bacterial colonization of stomach and pulmonary micro aspirations. • Odd’s ratio is 1.89 for current PPI use , 1.55 for past PPI use. • On contrary PPI do not increase risk of HAP.
- 23. PPI & SIBO?? • PPI postulated as one of etiological factor for SIBO due to reduced acid provacating bacterial colonization of GIT. • Clostridium difficile infection.
- 24. RABEPRAZOLE
- 27. “CAPRIE/CREDO”
- 28. Trials favouring Gastros • PLATO TRIAL • COGENT TRIAL • TRITON TRIAL
- 30. ADD PPI- PANTO/RABE/LANSO/DEXLANSO ANY OF FOLLOWING ADVANCED AGE/ H.PYLORI/ NSAID USE YES NO PATIENT TAKING CLOPIDOGREL HISTORY OF GI BLEED
- 31. NOVEL STRATEGIES • TENATOPRAZOLE • DEXLANSOPRAZOLE MR • “VECAM”
- 32. TAKE HOME MESSAGE • PPI TO BE ADMINISTERED 30 MIN BEFORE BREAKFAST. • TWICE DOSAGE FOR MAXIMAL ACID SUPPRESSION. • RABEPRAZOLE ACID LABILE, RAPID ONSET OF ACTION. • RATIONALIZE CONCOMITANT USE OF PPI AND ANTIPLATELETS. • RCT’S – OMEPRAZOLE & ESOMEPRAZOLE MORE INTERACTIONS WITH ANTIPLATELETS