Peptic Ulcer Disease — Anti-ulcer Drugs, H. pylori & GERD

Introduction & pathophysiology

• Acid-peptic disorders — comprise GERD, peptic ulcer disease (PUD) (gastric + duodenal) and stress-related mucosal injury; mucosal ulceration arises when aggressive factors (acid, pepsin, NSAIDs, H. pylori, bile) overwhelm defensive factors (mucus–bicarbonate, prostaglandins, NO, mucosal blood flow, restitution).
• Peptic ulcer — a mucosal break ≥5 mm penetrating the muscularis mucosae, in the acid-/pepsin-exposed stomach and duodenum — deeper than an erosion.
• Two-pronged therapeutic logic — (a) reduce gastric acidity (antacids, H₂ antagonists, PPIs, P-CABs) and (b) enhance mucosal defence (misoprostol, sucralfate, bismuth); GERD adds a third lever — raising LES tone / improving motility.
• Central paradigm shift — recognising H. pylori as the cause of most ulcers turned a chronically relapsing disease into a curable one through eradication — >90% of peptic ulcers are caused by H. pylori or NSAIDs/aspirin.
• DU vs GU pathophysiology — duodenal ulcer — acid high or normal (basal/nocturnal hypersecretion), acid-dominant; gastric ulcer — acid normal/low, impaired mucosal defence predominates; but "no acid, no ulcer" holds for both.
• H. pylori mechanism — spiral microaerophilic gram-negative rod; high urease generates ammonia for acid survival; antral-predominant gastritis ↓somatostatin → hypergastrinaemia → DU; corpus gastritis → GU, atrophy and cancer (WHO class-I carcinogen — chronic gastritis, PUD, MALT lymphoma, adenocarcinoma).
• NSAID mechanism — mainly systemic — COX-1 inhibition suppresses protective PGE₂/PGI₂; risk is additive with low-dose aspirin, corticosteroids, anticoagulants (GI-bleed up to ~20× with warfarin) and co-existing H. pylori; COX-2-selective agents spare GI toxicity.