A patient with GERD refractory to standard-dose PPI is switched to vonoprazan. This drug differs from PPIs because it:

• A Irreversibly inhibits H+/K+-ATPase by forming a covalent disulfide bond with cysteine residues
• B Blocks histamine H2 receptors on parietal cells, reducing cAMP-mediated acid secretion
• C Competitively and reversibly inhibits the H+/K+-ATPase pump in a potassium-competitive manner without requiring acid activation ✓
• D Neutralizes gastric acid directly and buffers luminal pH above 4 for 24 hours

Explanation

Vonoprazan is a potassium-competitive acid blocker (P-CAB). Unlike PPIs, which are prodrugs requiring acid-activated conversion to sulfenamide to irreversibly bind cysteine residues on the H+/K+-ATPase, vonoprazan is a lipophilic weak base that directly and reversibly inhibits the pump by competing with K+ at its binding site on the enzyme. Because it does not require acid activation, vonoprazan has a faster onset of action, more predictable acid suppression (even on the first dose), and activity unaffected by CYP2C19 polymorphisms. It provides stronger, more sustained acid suppression than conventional PPIs, particularly relevant in Helicobacter pylori eradication regimens.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.