Core pharmacology

Class Group

Proton Pump Inhibitor

Legacy Cicm Level

Level 3

Main Action

decreased gastric pH and decreased gastric secretions

Mechanism of action

- 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

Physiological effects

↓acidity/gastric secretions
no change emptying/LOS tone

Adverse Effects Toxicity

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

Absorption

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

Protein binding

95% PB

Volume of distribution

Vd 0.3L/Kg

Metabolism

Hepatic metabolism by oxidation, reduction and hydroxylation

Excretion

80% renally excreted, 20% bile

Half-life

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