L22- GIT Drugs I (PPIs)

Question 1

PPIs in terms of strength of gastric acid suppression in comparison to other drugs (quantifiable)

Answer 1

most potent inhibitor –> inhibits 90-98% of 24hr secretion

Question 2

PPIs MOA

Answer 2

irreversibly binds / inhibits H+/K+ ATPase on parietal cells (common pathway for all stimulators of secretion –> therefore most potent inhibitor)

Question 3

PPI effect on basal and meal-time gastric acid secretion

Answer 3

very strong inhibition of both

Question 4

list the PPIs

Answer 4

• omeprazole
• esomeprazole
• lansoprazole
• rabeprazole
• pantoprazole

Question 5

list the indications of PPI use (hint- many)

Answer 5

• patients who failed H2RA po bid therapy
• severe GERD
• PUD: H. pylori eradication, NSAID injury, prevent rebleeding
• gastroma
• non-ulcer dyspepsia
• prophylaxis against stress related gastritis

Question 6

describe the general adverse effects of PPIs

Answer 6

(generally safe)

-<5%: diarrhea, abdominal pain, HA

Question 7

list the adverse effects with some association with PPI use

Answer 7

• B12 deficiency (reduced pepsin function)
• inc in CA-pneumonias and C. diff. colitis (inc pH –> inc pathogen survival)
• hypomagnesemia
• osteopenia –> fractures (reduced Ca absorption OR osteoclast inhibition)

Question 8

list the main additional adverse effect from omeprazole

Answer 8

CYP450 inhibitor:

-inc concentration of Warfarin, Diazepam, Phenytoin

Question 9

Some PPIs, (1), will inhibit CYP2C19, which has the function of activating (2) prodrug, therefore (3) drugs are preferred.

Answer 9

(note this is a theory, not many reports from patients of this intolerance)
1- omeprazole, esomeprazole, lansoprazole

2- clopidogrel

3- pantoprazole, rabeprazole