PPI when and where

PPI usage

1. PPI’S – AN OVERVIEW DR S.VADIVEL KUARAN CONSULTANT MEDICAL GASTROENTEROLOGIST AND HEPATOLOGIST KAUVERY HOSPITAL,ALWARPET CHENNAI

2. 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.

3. 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

4. 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

5. 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.

6. SITE OF ACTION

7. 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.

8. 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%)

9. ADVERSE EFFECTS Physiological Hypergastrinemia Fundic gland Polyposis Drug interactions Vit B12 metabolism and pernicious anemia Osteopenia and osteoporosis Community acquired pneumonia Bacterial overgrowth

10. 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.

11. 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 .

12. 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.

13. IRON & B12 To small extent affect iron absorption. Elderly and ZES pts on high dose PPI have reduced B12 concentration.

14. 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.

15. 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.

16. PPI & SIBO?? PPI postulated as one of etiological factor for SIBO due to reduced acid provacating bacterial colonization of GIT. Clostridium difficile infection.

17. RABEPRAZOLE

18. “CAPRIE/CREDO”

19. Trials favouring Gastros PLATO TRIAL COGENT TRIAL TRITON TRIAL

20. NOVEL STRATEGIES TENATOPRAZOLE DEXLANSOPRAZOLE MR “VECAM”

21. 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

22. COGENT – Clopidogrel and optimization of gastrointestinal events. TRITON – CAPRIE- CLOPIDOGREL VS ASPIRIN INPTS AT RISK OF ISCHEMIC EVENTS. CREDO- CLOPIDOGREL FOR REDUCTION OF EVENTS DURING OBSERVATION.