Parietal cells in the stomach secrete hydrochloric acid through the proton pump (H⁺/K⁺-ATPase), the final step of acid secretion. Histamine (H2 receptors), acetylcholine, and gastrin stimulate the pump. The stomach lining is protected by mucus, bicarbonate, and blood flow — all supported by prostaglandins. Ulcers form when acid and pepsin overwhelm these defenses, mainly because of Helicobacter pylori infection or NSAIDs (including low-dose aspirin).

Ranitidine was removed from the US market in 2020 because of contamination with a probable carcinogen (NDMA); famotidine is the usual H2RA.

H. pylori eradication (ACG 2024)

• First-line: optimized bismuth quadruple therapy for 14 days — PPI twice daily + bismuth + tetracycline + metronidazole
• Clarithromycin-based triple therapy is no longer recommended as empiric first-line because of widespread resistance; use only when the strain is known to be susceptible
• Alternatives: vonoprazan–amoxicillin dual therapy, rifabutin-based triple therapy
• Test of cure for everyone treated, at least 4 weeks after antibiotics and after PPIs have been stopped for 2 weeks

Upper GI bleeding: IV PPI (bolus and infusion or intermittent dosing) after endoscopic hemostasis for high-risk ulcers.

Antacids — depend on the cation:

H2RAs: headache, dizziness; confusion or delirium in older adults and in kidney impairment; cimetidine — gynecomastia, many CYP450 interactions.

PPIs: headache, diarrhea, abdominal pain. Long-term use: vitamin B12 deficiency, hypomagnesemia (can cause dysrhythmias and seizures), fractures, Clostridioides difficile infection and pneumonia risk, acute interstitial nephritis, fundic gland polyps, rebound acid hypersecretion on stopping.

Sucralfate: constipation, aluminum accumulation in kidney failure, raised glucose (suspension) in diabetes, bezoars in delayed gastric emptying.

Misoprostol: diarrhea and abdominal cramping (common, dose-related); uterine contractions — miscarriage, uterine rupture, birth defects.

Bismuth subsalicylate: harmless black stools and dark tongue; salicylate effects (tinnitus with high doses).

Antacids

• Chelation: antacids (and calcium, iron, magnesium) bind tetracyclines, fluoroquinolones, levothyroxine, iron, and bisphosphonates — separate by at least 1–2 hours (longer for some drugs; follow the label)
• Changing gastric pH alters absorption of drugs such as azole antifungals
• Avoid magnesium- and aluminum-containing products in kidney failure; avoid sodium bicarbonate in heart failure and hypertension

H2RAs: reduce the dose with kidney impairment; cimetidine raises levels of warfarin, phenytoin, theophylline, and lidocaine.

PPIs

• Omeprazole and esomeprazole reduce activation of clopidogrel — pantoprazole is preferred when a PPI is needed with clopidogrel
• Reduced absorption of drugs that need acid: ketoconazole/itraconazole, iron, some HIV drugs (rilpivirine is contraindicated; atazanavir restricted), dasatinib and other kinase inhibitors
• Raised methotrexate levels with high-dose methotrexate
• Masking of gastric cancer symptoms — alarm features (weight loss, dysphagia, bleeding, anemia, age over 60 with new symptoms) need endoscopy
• Pregnancy: PPIs and H2RAs are generally considered acceptable when needed

Sucralfate: binds other drugs (warfarin, digoxin, phenytoin, fluoroquinolones, levothyroxine) — give other drugs 2 hours before; do not give antacids within 30 minutes; caution in kidney failure and diabetes.

Misoprostol: contraindicated in pregnancy for ulcer prevention; people who can become pregnant need a negative pregnancy test and reliable contraception, and start on day 2 or 3 of the next normal period (label).

Bismuth subsalicylate: avoid with aspirin allergy, in children and teenagers with viral illness (Reye syndrome), and with anticoagulants or high-dose aspirin (bleeding, salicylate toxicity).

H. pylori regimen drugs: metronidazole — avoid alcohol during therapy and for 72 hours after (labeling), raises INR with warfarin; tetracycline — not in pregnancy or young children, separate from dairy and antacids; clarithromycin — QT prolongation, strong CYP3A4 inhibitor.

1. Watch for GI bleeding first: hematemesis, coffee-ground emesis, melena, dizziness, tachycardia, falling blood pressure, falling hemoglobin — report at once; IV access, type and crossmatch per protocol
2. Timing
   • PPI 30–60 minutes before breakfast (and before the evening meal when twice daily)
   • Sucralfate 1 hour before meals and at bedtime; other drugs 2 hours before sucralfate
   • Antacids 1 hour after meals and at bedtime; separate from other oral drugs by 1–2 hours
3. Administration
   • Do not crush delayed-release PPI capsules or tablets; some capsules may be opened and sprinkled on applesauce, or given through a tube with the specific product method
   • IV pantoprazole: reconstitute and give over the time on the label, through a dedicated line or flushed line
4. Long-term PPI review: use the lowest effective dose; review ongoing need; periodic magnesium (normal about 1.7–2.2 mg/dL (0.7–0.9 mmol/L); check especially with diuretics or digoxin) and vitamin B12; ask about fractures and new diarrhea
5. Kidney function for H2RAs (dose adjustment) and before magnesium or aluminum antacids
6. Older adults on H2RAs: assess for new confusion
7. Misoprostol: confirm negative pregnancy test and contraception
8. H. pylori therapy: confirm allergy history (amoxicillin), count doses with the client, schedule the test of cure

• Take the PPI before breakfast; do not stop long-term therapy suddenly without advice (rebound heartburn can occur for a few weeks)
• Lifestyle for reflux: raise the head of the bed, avoid lying down within 2–3 hours of meals, lose weight if overweight, stop smoking, limit trigger foods
• Avoid NSAIDs and aspirin unless prescribed; use acetaminophen/paracetamol for pain if suitable
• Antacids: shake suspensions; separate from other medicines; do not use for more than 2 weeks without seeing a provider
• H. pylori therapy: take every dose for the full 14 days; expect black stools with bismuth; no alcohol with metronidazole during and for 72 hours after; separate tetracycline from dairy and antacids; return for the test of cure
• Report black tarry stools, vomiting blood, severe abdominal pain, difficulty or pain with swallowing, unintended weight loss
• Misoprostol: do not use if pregnant or planning pregnancy; do not share with others

• Hypermagnesemia (magnesium antacids in kidney failure): hypotension, weakness, loss of deep tendon reflexes, bradycardia, respiratory depression → stop magnesium; IV calcium gluconate as an antagonist; dialysis if severe
• Milk-alkali syndrome (large calcium carbonate intake): hypercalcemia, metabolic alkalosis, kidney injury → stop calcium, IV fluids
• Hypomagnesemia from long-term PPI: tremor, muscle cramps, dysrhythmias, seizures → replace magnesium; stop the PPI if possible
• C. difficile infection: frequent watery stools, fever, abdominal pain → contact precautions, soap-and-water hand hygiene, report
• Salicylate toxicity from large amounts of bismuth subsalicylate (tinnitus, rapid breathing, confusion) → poison center, supportive care
• Misoprostol exposure in pregnancy: heavy bleeding and cramping → urgent assessment
• PPI and H2RA overdose is usually mild; supportive care. No specific antidotes

• PPIs = strongest acid suppression; 30–60 minutes before breakfast
• Long-term PPI → B12 deficiency, low magnesium, fractures, C. difficile
• Omeprazole/esomeprazole reduce clopidogrel activation — pantoprazole preferred
• H2RAs: reduce dose in kidney impairment; confusion in older adults
• Aluminum = constipation; magnesium = diarrhea; avoid both in kidney failure
• Antacids chelate tetracyclines and fluoroquinolones — separate doses
• Sucralfate: before meals; other drugs 2 hours before; constipation
• Misoprostol: prevents NSAID ulcers; contraindicated in pregnancy
• H. pylori first-line: bismuth quadruple therapy 14 days; confirm cure
• Bismuth → black stools (not melena); Reye syndrome risk in children