MOA: Competitive antagonism of H2 receptors (high specificity) Histamine acts on GsPCR → increased AC → increased cAMP → increased protein kinase → increased activity of H/K antiporter

- The proton pump on the basal membrane of the parietal cell is the final common pathway for acid secretion
- It consists of an ATP dependent H/K antiporter
- PPIs irreversibly bind the proton pump to suppress basal and stimulated acid secretion
- PPIs are prodrugs and weak bases that diffuse into acidic environments well, where they become ionized and activated

GIT: Raised gastric pH. No effect on gastric emptying or LOS tone

CVS: Arrhythmias may occur after rapid injection (Cardiac H2-R)

↓acidity/gastric secretions
no change emptying/LOS tone

Absorbed in small bowel
BA 50%

Weak base with pKA 4
- Coated capsules or IV to allow absorption in SI
- High bioavailability

Crosses BBB, placenta and breast milk

20% PB

95% PB

Large Vd

Vd 0.3L/Kg

50% Hepatic metabolism by CYP450

Hepatic metabolism by oxidation, reduction and hydroxylation

50% excreted in urine unchanged

80% renally excreted, 20% bile

T1/2= 1.5-2.5 hours

T1/2= 0.5-1.5 hours but irreversible binding means effects >24 hours

1. Porphyria
2. Thrombocytopenia and leukopenia
3. VAP

1. Inhibits CYP2C19 → prevents prodrug clopidogrel’s activation/ decreased metabolism of diazepam
2. Interstitial nephritis
3. VAP
4. Osteoporosis with long term use

H2 Receptor Antagonist

Proton Pump Inhibitor

-

Level 3

decreased gastric pH and decreased gastric secretions

decreased gastric pH and decreased gastric secretions