ppi when and where

PPI’S – AN OVERVIEW

DR S.VADIVEL KUARANCONSULTANT MEDICAL GASTROENTEROLOGIST

AND HEPATOLOGIST

KAUVERY HOSPITAL,ALWARPETCHENNAI

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.

• 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

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

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.

SITE OF ACTION

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.

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%)

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

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.

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.

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.

IRON & B12

• To small extent affect iron absorption.

• Elderly and ZES pts on high dose PPI have reduced B12 concentration.

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.

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.

PPI & SIBO??

• PPI postulated as one of etiological factor for SIBO due to reduced acid provacating bacterial colonization of GIT.

• Clostridium difficile infection.

RABEPRAZOLE

“CAPRIE/CREDO”

Trials favouring Gastros• PLATO TRIAL

• COGENT TRIAL

• TRITON TRIAL

ADD PPI-PANTO/RABE/LANSO/DEXLAN

SO

ANY OF FOLLOWINGADVANCED AGE/ H.PYLORI/ NSAID USE

YES NO

PATIENT TAKING CLOPIDOGREL

HISTORY OF GI BLEED

NOVEL STRATEGIES• TENATOPRAZOLE• DEXLANSOPRAZOLE MR• “VECAM”

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