STEPTRACKERPHARMACOLOGY | GASTROINTESTINAL | HIGH-YIELD REVIEW

Acid Suppression & Ulcer Drugs

The parietal cell has three stimulating receptors and one final pump — drugs block a receptor, the pump, neutralize the acid, or shield the mucosa.

FOCUS ON

Parietal cell: histamine (H2, Gs, ↑ cAMP), gastrin (CCK-B, Gq) and ACh (M3, Gq) → H⁺/K⁺-ATPase. PPIs (omeprazole, pantoprazole, esomeprazole): irreversibly inhibit the pump (activated in acid, take before meals); most potent; GERD, PUD, H. pylori, Zollinger-Ellison. Long term: ↑ C. difficile and pneumonia, hip fractures, ↓ Mg²⁺, ↓ B12, ↓ iron, ↓ Ca²⁺ absorption, interstitial nephritis; omeprazole ↓ clopidogrel activation. H2 blockers (famotidine, cimetidine): reversible; cimetidine — CYP inhibitor, antiandrogen (gynecomastia), crosses placenta/BBB. Antacids: Al(OH)₃ constipation, hypophosphatemia; Mg(OH)₂ diarrhea; CaCO₃ hypercalcemia, milk-alkali, rebound acid; all chelate drugs. Sucralfate: coats ulcer base in acid. Bismuth: H. pylori, black tongue/stool. Misoprostol (PGE₁): NSAID ulcer prevention; diarrhea; abortifacient. H. pylori: bismuth quadruple or clarithromycin triple therapy.

DRUG

MECHANISM

USE

ADVERSE · NOTES

PPIs

omeprazole, pantoprazole, lansoprazole

Irreversible H⁺/K⁺-ATPase inhibition (prodrug activated by acid)

GERD, PUD, H. pylori, ZES, NSAID protection, stress ulcer prophylaxis

C. difficile, pneumonia, fractures, ↓ Mg²⁺, ↓ B12, AIN

Famotidine · cimetidine

Reversible H2 antagonists → ↓ basal and nocturnal acid

Mild GERD, PUD, urticaria (add-on)

Cimetidine: CYP inhibition, gynecomastia, ↑ creatinine (secretion block)

Aluminum hydroxide

Neutralizes acid

Heartburn; phosphate binding

Constipation, hypophosphatemia, osteomalacia, neurotoxicity in CKD

Magnesium hydroxide

Neutralizes acid

Heartburn, laxative

Diarrhea, hypermagnesemia (↓ reflexes) in CKD

Calcium carbonate

Neutralizes acid

Heartburn, calcium supplement

Hypercalcemia, milk-alkali syndrome, rebound acid

Sucralfate

Polymerizes in acid → binds ulcer base

PUD, stress ulcer prophylaxis

Needs acid (don't give with PPI/antacid); constipation, Al toxicity

Bismuth subsalicylate

Coats ulcer, antimicrobial vs H. pylori

H. pylori quadruple therapy, traveler's diarrhea

Black stool and tongue, salicylate effects

Misoprostol

PGE₁ analog → ↑ mucus and bicarbonate, ↓ acid

NSAID-ulcer prevention, labor induction, abortion, PPH

Diarrhea, cramps; contraindicated in pregnancy (unless intended)

Octreotide

Somatostatin analog

Variceal bleeding, ZES, carcinoid, VIPoma

Gallstones

H. pylori — triple

PPI + clarithromycin + amoxicillin (or metronidazole)

Low clarithromycin resistance areas

14 days; confirm eradication

H. pylori — quadruple

PPI + bismuth + metronidazole + tetracycline

First-line in many settings, penicillin allergy

Disulfiram reaction with alcohol (metronidazole)

Vonoprazan

Potassium-competitive acid blocker

Erosive esophagitis, H. pylori

Faster onset than PPIs

Mechanism — the parietal cell

Histamine → H2↑ cAMP (famotidine blocks)

Gastrin → CCK-B↑ Ca²⁺

ACh → M3↑ Ca²⁺

H⁺/K⁺-ATPaseFinal common step — PPIs block

→

H⁺ into lumenAntacids neutralize

Antacid side effects

ANTACID

BOWEL

ELECTROLYTE

Aluminum

Constipation

↓ Phosphate

Magnesium

Diarrhea

↑ Mg²⁺ (CKD)

Calcium

Constipation

↑ Ca²⁺, alkalosis

How it's tested

COMMON CONFUSIONPPIs are prodrugs needing acid activation — take 30–60 min before a meal; they irreversibly inhibit pumps, so effect outlasts plasma levels.

THE TRAPRecurrent C. difficile, hypomagnesemia or a hip fracture in an elderly patient → look for long-term PPI use and deprescribe.

YOUR APPROACHSymptom severity → antacid / H2 / PPI → treat cause (H. pylori, NSAID) → watch long-term risks and interactions.

If you see… think…

Gynecomastia and ↑ warfarin effect on an ulcer drug → cimetidine

Hypomagnesemia, C. difficile, hip fracture → long-term PPI

NSAID-ulcer prevention, contraindicated in pregnancy → misoprostol

Black tongue after ulcer therapy → bismuth

Diarrhea after antacid → magnesium hydroxide

Constipation and low phosphate after antacid → aluminum hydroxide

Ulcer drug that needs an acid environment → sucralfate

Clopidogrel less effective with this acid drug → omeprazole

Refractory ulcers, high gastrin → Zollinger-Ellison → high-dose PPI

Hypercalcemia, alkalosis, renal injury with heartburn tablets → milk-alkali syndrome