- Examples of PPIs are omeprazole, pantoprazole and rabeprazole
- They are lipophilic weak bases that are administered as inactive prodrugs with an enteric coating.
- The enteric coating is dissolved in the small intestine. The pro-drug is then absorbed and circulated to the entire body.
- The prodrug then preferentially diffuses into acidified compartments, where they are converted to their active form and irreversibly inhibit H+/K+ ATPase.
- Adverse effects
- Common side effects are nausea, vomiting and diarrhea.
- Rare but serious side effects are rhabdomyolysis and drug induced acute interstitial nephritis.
- It is theoretically more advantageous to administer PPIs as an infusion than as a bolus because they only inhibit pumps that are actively secreting acid (only a small proportion of pumps are active at a time while the patient is fasting, so administration as an infusion leads to more pumps being inhibited)
- Can be administered PO or IV
- It is only administered as a prodrug. It should be given 1 hour before meals as the bioavailability is reduced by 50% due to crushing of enteric coating.
- It is also inactivated by stomach acid.
- T ½ is short, but the proton pumps are irreversibly inhibited and need 18 hours to regenerate (the drug has a short T ½ but a long duration of effect). Full acid inhibition occurs in 3-4 days.