lansoprazole

**Class/Mechanism:** Substituted benzimidazole PPI. It is a prodrug that is activated in the acidic canaliculi of parietal cells. The active sulfenamide forms covalent disulfide bonds with cysteine residues on the H+/K+ ATPase (proton pump), irreversibly inhibiting the final common pathway of acid secretion (regardless of histamine, ACh, or gastrin stimulation). Acid secretion returns only after new pumps are synthesized (about 24-48 h or more). Because only actively secreting pumps are inhibited, take 30-60 min before meals (typically before breakfast) to maximize efficacy.

**Pharmacokinetics:** Delayed-release capsule/ODT (enteric-coated because it is acid-labile). Hepatic metabolism by CYP2C19 (major) and CYP3A4. Short plasma half-life (~1-2 h), but the effect lasts much longer because of irreversible binding. Full effect takes several days of dosing.

**Indications:** - GERD and erosive esophagitis - Peptic ulcer disease (duodenal and gastric ulcers), including NSAID-induced ulcers and prophylaxis - H. pylori eradication: triple therapy = PPI + clarithromycin + amoxicillin (or metronidazole if penicillin allergic). Bismuth quadruple therapy = PPI + bismuth + tetracycline + metronidazole. - Zollinger-Ellison syndrome (gastrinoma) and other pathologic hypersecretory states - Stress ulcer prophylaxis (ICU) in some settings

**Adverse effects (high-yield):** - Increased risk of C. difficile infection and other enteric infections (reduced gastric acid barrier) - Community-acquired pneumonia (possible) - Decreased absorption of: iron, calcium carbonate (needs acid), vitamin B12, and magnesium - Hypomagnesemia (can cause hypocalcemia, QT prolongation, arrhythmias) - Osteoporosis/fractures with long-term use - Acute interstitial nephritis and possible chronic kidney disease - Rebound acid hypersecretion after stopping - Fundic gland polyps and possible increased risk of enterochromaffin-like (ECL) hyperplasia (hypergastrinemia) - Possible vitamin B12 deficiency with long-term use

**Drug interactions:** Reduces absorption of drugs that need an acidic environment (ketoconazole, itraconazole, atazanavir, levothyroxine). Omeprazole/esomeprazole inhibit CYP2C19 and can reduce activation of clopidogrel (lansoprazole has less effect, but pantoprazole is preferred when a PPI is needed with clopidogrel). May increase levels of warfarin, diazepam, phenytoin, and methotrexate (reduced clearance).

**Comparisons:** - vs H2 blockers (ranitidine, famotidine, cimetidine): PPIs are more effective at suppressing acid and healing erosive esophagitis. H2 blockers act by competitive antagonism of H2 receptors on parietal cells (cimetidine has anti-androgen effects and CYP inhibition). - Other PPIs: omeprazole, esomeprazole, pantoprazole, rabeprazole, dexlansoprazole (the R-enantiomer of lansoprazole, dual delayed-release formulation).

**Board pearls:** - "-prazole" = PPI. - First-line for GERD with alarm features and for healing erosive esophagitis. - Chronic PPI use plus hypomagnesemia, C. diff, and B12/iron deficiency are favorite exam associations. - In Zollinger-Ellison syndrome, high-dose PPIs are the treatment of choice (along with tumor localization and resection if possible). - In patients with suspected GI bleeding from ulcers, IV PPI is used after endoscopic therapy.