Pathophysiology of GERD and PUD & Acid Suppression Pharmacology continued

What is the mechanism of action (MOA) of PPIs?

PPIs irreversibly inhibit the H+/K+-ATPase (proton pump) in parietal cells.

Name some common members of the PPI drug class.

Pantoprazole, Lansoprazole, Rabeprazole, Esomeprazole, Dexlansoprazole, Omeprazole.

What is the activation mechanism for PPIs?

PPIs are prodrugs activated in the acidic secretory canaliculi of parietal cells.

Why do PPIs require enteric coating or bicarbonate?

PPIs are unstable in stomach acid and must be protected until they reach the small intestine.

How long does it take for parietal cells to regain baseline H+ secretion after stopping PPIs?

Parietal cells are turned over rapidly, taking 3–7 days to regain function.

What is the MOA of PCABs such as Vonoprazan?

PCABs competitively inhibit K+ binding to the H+/K+ pump in parietal cells.

How does the quiescent phase differ between PPIs and PCABs?

PPIs require acid activation, while PCABs like Vonoprazan are stable in acid and act faster.

What are the advantages of PCABs over PPIs?

PCABs work faster and are stable in acid but take longer to leave the body.

What is a key difference in pharmacokinetics between PPIs and PCABs?

PPIs take time to start working but leave the body quickly, whereas PCABs act quickly but have a longer half-life.

What is the MOA of Sucralfate?

Sucralfate forms a physical barrier over erosive lesions to protect them.

What is a concern with the aluminum content of Sucralfate?

Aluminum can accumulate, especially in CKD patients, leading to toxicity.

What is the MOA of Misoprostol?

Misoprostol stimulates mucus and bicarbonate secretion and enhances gastric blood flow.

Why is Misoprostol contraindicated in pregnancy?

Misoprostol can cause abortions due to its prostaglandin analog properties.

What is the role of Bismuth Subsalicylate?

Bismuth coats ulcers, gastric erosions, and has antimicrobial effects on H. pylori.

What drugs are used in triple therapy for H. pylori eradication?

PPI + Amoxicillin + Clarithromycin.

What drugs are used in quadruple therapy for H. pylori eradication?

PPI + Bismuth Subsalicylate + Metronidazole + Tetracycline (or Doxycycline).

What are the mechanisms of Amoxicillin and Clarithromycin in H. pylori therapy?

Amoxicillin inhibits bacterial cell wall synthesis; Clarithromycin inhibits bacterial protein synthesis.

What is the MOA of Metronidazole in H. pylori therapy?

Metronidazole causes DNA damage in bacteria.

How does Tetracycline work in H. pylori therapy?

Tetracycline is bacteriostatic and inhibits protein synthesis.