Suffix: -prazole (i.e. omeprazole, esomeprazole, pantoprazole, rabeprazole).

MOA:

• PPIs are inactivated prodrugs (weak bases) that require activation in an acidic niche, specifically the canaliculi of the parietal cells of the stomach. In the canaliculi, PPIs accumulate and undergo proton driven conversion to sulfenic acid and tetracyclic sulfenamide. The activated tetracyclic sulfenamide covalently binds to the sulfhydryl groups of cysteines on the H+/K+ ATPase This irreversibly inhibits the H+/K+ ATPase enzyme (proton pump) which resides on the luminal surface of the parietal cell.
• This results in the desired effects of:
  • Reduced gastric acid secretion.
  • Increased gastric pH.
• By targeting the final stage of gastric acid production, both stimulated and basal acid production is suppressed.
• In addition, by 1) accumulating in the canaliculi and 2) irreversibly inhibiting the H+/K+ ATPase enzyme, the antisecretory effect of PPIs persists for 24 to 48 hours. Acid secretion only resumes upon H+/K+ ATPase enzyme replacement.

Indications

• PUD.
• GORD.
• Dyspepsia.
• Zollinger-Ellison Syndrome.
• H. pylori eradication.
• Prevention and/or treatment of upper GIT adverse effects of NSAIDs.
• In selected patients for stress ulcer prophylaxis, acute upper GIT bleeding and prevention of acid aspiration.

Contraindications/ Precautions

• Gastric carcinomas (exclude before starting treatment for gastric ulcers; PPIs may mask symptoms and delay diagnosis).
• Hepatic: Monitor for adverse effects in those with hepatic impairment.
• Surgery: Can be continued perioperatively.
• Elderly: Risk of electrolyte disturbance may be increased.