What it is:An ulcer crater in the stomach or duodenum that breaks through the mucosa because acid and pepsin overwhelmed the mucosa's defenses. Three drivers cause almost every case: H. pylori, NSAIDs, and stress-related mucosal damage (SRMD)in the critically ill. Everything else (Zollinger-Ellison, cirrhosis, CKD, Crohn's, radiation, chemo) is a distant fourth.
The core problem:It's a balance sheet. Aggressive factors (acid, pepsin, H. pylori, NSAIDs) push one way; protective factors (mucus, bicarbonate, blood flow, prostaglandins) push the other. An ulcer means the aggressive side won.
What you do about it:Figure out which of the three drivers caused it, then treat that driver specifically. Test-and-treat H. pylori if present. Stop the NSAID if that's the cause. Prophylax the ICU patient before the ulcer ever forms.
PUD is not one disease with one treatment, it's one final common pathway with three different upstream causes. The exam (and real practice) is really asking "which of the three is it" first, because the entire regimen changes depending on the answer. Don't reach for a PPI reflexively before you've identified the driver.
Gastric ulcers cluster in the antrum and lesser curvature. Duodenal ulcers cluster in the duodenal bulb, the first part of the duodenum right past the pylorus. Different locations, different acid physiology: duodenal ulcers usually go with increasedacid secretion, while gastric ulcer patients often have normal or even reducedacid output (hypochlorhydria). That's a classic distractor. Don't assume "ulcer" automatically means "too much acid."
| Driver | Mechanism | Why the treatment follows |
|---|---|---|
| H. pylori | Spiral gram-negative bacterium. Urease converts urea to ammonia to neutralize local acid so it can survive; catalase lets it dodge phagocyte killing. Bacterial adherence and virulence factors trigger chronic gastric inflammation in essentially everyinfected person, but only 10-20% develop an actual ulcer and about 1% get gastric cancer. | You have to physically kill the organism with antibiotics; acid suppression alone never cures it. |
| NSAIDs | Two hits: direct topical irritation of the epithelium, plus systemic inhibition of COX-1-derived prostaglandins (the dominant mechanism). Prostaglandins normally drive mucus and bicarbonate secretion and mucosal blood flow. | Replacing the missing prostaglandin (misoprostol) or suppressing acid (PPI) both work; switching to a COX-2-selective agent avoids the mechanism altogether. |
| SRMD | Critical illness (especially mechanical ventilation) drops splanchnic blood flow, so the mucosa is ischemic and can't keep up its own defenses even though acid levels are normal. | Prophylactic PPI, given beforeinjury occurs, not after. |
H. pylori and NSAIDs attack mucosal defensethrough different doors (direct bacterial injury vs. lost prostaglandin), while SRMD attacks the mucosa's blood supply. That's why H. pylori needs antibiotics, NSAID ulcers need prostaglandin replacement or acid suppression, and SRMD needs prophylaxis rather than "cure."
Psychological stresshas not been shown to cause PUD on its own, though it can worsen how patients experience it. Spicy food, coffee, tea, carbonated drinks, beer, milkcan trigger dyspepsia symptoms but don't increase actual ulcer risk. Alcoholin high concentrations causes acute mucosal damage and can cause bleeding, but isn't a clearly established cause of ulcers themselves. Smoking, on the other hand, is a real risk factor: it's linked to PUD, impairs healing, and promotes recurrence, with risk proportional to how much someone smokes. Corticosteroids alonedon't raise ulcer risk, but combined with an NSAID, risk doubles.
Epigastric pain is the headline symptom, usually described as burning, gnawing, or hunger-like, though it can just be vague fullness or cramping. Classic teaching point: nocturnal pain, waking the patient between midnight and 3 AM, is a hallmark. Antacids give rapid relief in most patients.
| Duodenal ulcer | Gastric ulcer | |
|---|---|---|
| Pain and food | Occurs 1-3 hours after eating, usually relievedby food | Food can trigger or worsenpain |
| N/V, anorexia | Less common | More common, can signal a complication |
Duodenal = eat and feel better. Gastric = eat and feel worse (or the same).This single distinction is a favorite test item precisely because it's backwards from what people intuitively guess.
Absence of pain doesn't rule out an ulcer, and healing doesn't guarantee the patient is symptom-free. Older patients in particular can present silentlywith a complication (bleeding, perforation) as the first sign, with no preceding pain at all. Don't anchor on "no pain, no problem" in this population.
Physical exam may show epigastric tenderness between the umbilicus and xiphoid, sometimes radiating to the back. On its own, that's not enough for a diagnosis. Routine blood tests don't establish PUD, hematocrit, hemoglobin, and fecal occult blood are used specifically to check for bleeding, not to diagnose the ulcer itself.
Upper endoscopyis the procedure of choice: it directly visualizes the crater and lets you intervene right there if there's active bleeding. It has replaced barium radiography for this reason.
Only test if you actually plan to treat. Endoscopic (biopsy-based) and nonendoscopic options exist: urea breath test (UBT), fecal antigen, and serologic antibodytesting. If endoscopy isn't planned, serology is a reasonable option to establish status.
To verify H. pylori is actually gone (with UBT, fecal antigen, or biopsy), you must wait at least 4 weeks after finishing antibioticsAND at least 2 weeks off the PPI. Test too early and you'll get a false negative because you're detecting drug-suppressed bacteria, not eradicated bacteria. This is one of the most testable facts in the chapter. Antibody serology should notbe used to confirm cure, since antibodies can linger long after the organism is gone.
PPIs and bismuth can both cause false negativeson UBT by suppressing (not killing) the bacteria enough to blunt urease activity. That's the mechanistic reason for the washout windows above.
Across all etiologies, the goals are the same: relieve pain, heal the ulcer, prevent recurrence, and prevent complications.The specific pathway to get there depends entirely on the cause.
Active ulcer, prior documented ulcer (unless eradication already confirmed), MALT lymphoma, or post-resection gastric cancer are all indications to treat.
Stop the NSAID if at all possible. If it must continue, add protection.
Critically ill patients, especially those on mechanical ventilation for respiratory failure.
All medications except the PPI should be taken with meals and at bedtime; the PPI itself should be taken 30-60 minutes before a mealso it's active when acid secretion ramps up.
PPI + clarithromycin + amoxicillin (or metronidazole) is no longer recommendedanywhere that clarithromycin resistance exceeds 15%, and that's all of North America. It only remains an option in regions with documented low resistance and no prior macrolide exposure. If a question asks for first-line empiric therapy in the US, this is the wrong answer even though it's the "classic" regimen people remember.
PPI (or H2RA) + bismuth subsalicylate + metronidazole + tetracyclinefor 10-14 days. This is the regimen your course study guide flags as "memorize the drugs, not the doses." Mean eradication around 90%at 10 days. Downsides: four-times-daily dosing for three of the four drugs hurts adherence, and minor side effects (dark stool/tongue from bismuth, GI upset) are common. PPIs generally out-eradicate H2RAs in this role, so PPI is preferred when there's a choice.
| Regimen | Duration | Drugs | Notes |
|---|---|---|---|
| First-line options | |||
| Bismuth quadruple | 10-14 days | PPI (or H2RA) BID + bismuth subsalicylate + metronidazole + tetracycline, all QID | Preferred first-line. Suitable for penicillin allergy. Avoid with salicylate allergy, photosensitivity, pregnancy. |
| Non-bismuth ("concomitant") quadruple | 10-14 days | PPI + clarithromycin + amoxicillin + metronidazole, all given together BID | All four drugs the entire duration, unlike sequential. Lacks North American validation data. |
| PCAB dual (Voquenza DualPak) | 10-14 days | Vonoprazan 20 mg BID + amoxicillin 1 g TID | FDA-approved 2022. No clarithromycin, so resistance is less of an issue. |
| PCAB triple (Voquenza TriplePak) | 10-14 days | Vonoprazan 20 mg BID + clarithromycin 500 mg BID + amoxicillin 1 g BID | FDA-approved 2022. |
| Rifabutin triple (Talicia) | 14 days | Omeprazole 40 mg TID + amoxicillin 1 g TID + rifabutin 50 mg TID | Conditional recommendation, low resistance rates. Avoid with penicillin allergy. |
| Other regimens (conditional / require validation in the US) | |||
| Clarithromycin triple | 14 days | PPI + clarithromycin + amoxicillin or metronidazole | Avoid if local clarithromycin resistance >15% (all of North America) or prior macrolide exposure. |
| Sequential therapy | 10 days | PPI + amoxicillin days 1-5, then PPI + clarithromycin + metronidazole days 6-10 | Rationale: knock down bacterial load with a low-resistance drug first, then hit survivors with a second combination. |
| Hybrid therapy | 14 days | PPI + amoxicillin days 1-7, then PPI + amoxicillin + clarithromycin + metronidazole days 7-14 | Combines concomitant and sequential logic. |
| Levofloxacin triple | 10-14 days | PPI BID + levofloxacin + amoxicillin | Fluoroquinolone risks apply: tendonitis, resistance. |
| LOAD | 7-10 days | Levofloxacin + high-dose PPI + nitazoxanide + doxycycline | Not currently recommended, high cost, weak efficacy data. |
Salvage therapy should (1) avoid antibiotics used in the failed regimen, (2) be guided by resistance data where available, and (3) run the full 10-14 days. Patients who fail clarithromycin triple can move to bismuth quadruple or levofloxacin triple. Also: get penicillin allergy testing before ruling out amoxicillin-containing regimens, most patients who report a penicillin allergy aren't actually allergic, and losing amoxicillin as an option meaningfully narrows your choices.
| Class / Drug | Brand | Initial dose | Usual range |
|---|---|---|---|
| Proton pump inhibitors | |||
| Omeprazole | Prilosec | 40 mg daily | 20-40 mg/day |
| Omeprazole/sodium bicarbonate | Zegerid | 40 mg daily | 20-40 mg/day |
| Lansoprazole | Prevacid | 30 mg daily | 15-30 mg/day |
| Rabeprazole | Aciphex | 20 mg daily | 20-40 mg/day |
| Pantoprazole | Protonix | 40 mg daily | 40-80 mg/day |
| Esomeprazole | Nexium | 40 mg daily | 20-40 mg/day |
| Dexlansoprazole | Dexilant | 30-60 mg daily | 30-60 mg/day |
| H2-receptor antagonists | |||
| Cimetidine | Tagamet | 300 mg QID, 400 mg BID, or 800 mg QHS | 800-1600 mg/day divided |
| Famotidine | Pepcid | 20 mg BID or 40 mg QHS | 20-40 mg/day |
| Nizatidine | Axid | 150 mg BID or 300 mg QHS | 150-300 mg/day |
| Ranitidine | Zantac | No longer available in the US | |
| Mucosal protectants | |||
| Sucralfate | Carafate | 1 g QID or 2 g BID | 2-4 g/day |
| Misoprostol | Cytotec | 100-200 mcg QID | 400-800 mcg/day |
| Upper GI bleed, hospital dosing | |||
| PPI (UGIB) | - | BID, total daily dose 80-160 mg, x at least 3 days | |
MOA:prodrugs that irreversibly inhibit the H+/K+-ATPase (the proton pump) on gastric parietal cells, shutting down acid secretion at the final common step. Because they're prodrugs that need an acidic environment to activate, they're dosed 30-60 minutes before breakfast or the largest meal, timed to when the most pumps are actively secreting.
Duration:typical PUD/GERD courses run about 8 weeks. Adverse effects at that timeframe are usually mild: headache, diarrhea, nausea, abdominal pain.
Short-term:community-acquired pneumonia, enteric infections, and C. difficileinfection, all downstream of losing gastric acid's antimicrobial barrier. Long-term:vitamin B12 deficiency, iron deficiency, hypomagnesemia, hypocalcemia, osteoporosis and fracture risk. This is exactly why PPIs shouldn't be continued indefinitely without a real ongoing indication, and why "just leave them on it" is the wrong reflex.
Drug interactions:reduced absorption of ketoconazole and itraconazole (both need acid to dissolve). Omeprazole specifically can blunt clopidogrel's antiplatelet effect via CYP2C19 inhibition, since clopidogrel needs 2C19 to convert to its active form.
MOA:reversibly block H2 receptors on parietal cells, reducing acid secretion (less complete blockade than a PPI, since histamine is only one of three secretagogues alongside gastrin and acetylcholine). Typically BID dosing, and courses can run over a month.
Adverse effects:headache, fatigue, constipation or diarrhea, and tachyphylaxis(tolerance develops with continued use, a distinguishing weakness versus PPIs). Older patients can develop delirium or dementia-like effects, cimetidine especially.
Cimetidineis the one to watch: it's a potent CYP inhibitor with interactions affecting warfarin, phenytoin, nifedipine, and propranolol, and it uniquely causes gynecomastia (weak antiandrogen activity). If you see an H2RA choice on an exam involving polypharmacy or a drug interaction, cimetidine is almost never the right pick.
Bismuth subsalicylatehas direct antibacterial activity against H. pylori and coats the ulcer, which is why it's the backbone of quadruple therapy. Expect dark/black stool and tongue discoloration, a benign but alarming side effect worth counseling on up front so the patient doesn't think it's melena.
Sucralfateforms a protective barrier that binds to the ulcer crater. It's minimally absorbed, so it has essentially no systemic adverse effects, but it needs an acidic environment to activate and doesn't reliably prevent NSAID-induced ulcers.
Misoprostolis a prostaglandin E1 analog that directly replaces what NSAIDs suppress, restoring mucus/bicarbonate secretion and mucosal blood flow. QID dosing tanks adherence, and GI adverse effects (diarrhea, cramping, nausea) are common, which is exactly why it's underused despite solid efficacy data. It's also an abortifacient (uterotonic), so it's contraindicated in pregnancy and needs clear counseling in anyone who could become pregnant.
COX-1 inhibition is the driver, so both the topical irritation and the loss of protective prostaglandins stack against the mucosa. COX-2 selective inhibitors carry lower ulcer riskthan nonselective NSAIDs, but adding aspirin to a COX-2 inhibitor erases most of that ulcer-sparing benefit while still raising ulcer risk, since aspirin independently hits COX-1.
Age >65, prior peptic ulcer, concurrent H. pylori infection, smoking, alcohol use, high-dose or multiple NSAIDs, and concurrent steroids or anticoagulants.
Test every patient with an NSAID-induced ulcer for H. pylori statusbefore deciding the regimen. H. pylori positive:start a first-line eradication regimen. H. pylori negative:stop the NSAID and treat with a PPI, H2RA, or sucralfate, with PPI preferred for faster symptom relief and healing.
| Strategy | Effectiveness |
|---|---|
| PPI co-therapy | Effective, once-daily, best tolerated. First choice in practice. |
| Misoprostol co-therapy | Effective and more so than H2RA, but QID dosing and GI side effects limit real-world use, so it's chosen less often despite the data favoring it. |
| High-dose H2RA | May help prevent duodenal ulcers but does notreliably prevent gastric ulcers. |
| Sucralfate | Not effective for NSAID ulcer prevention. Common wrong-answer trap. |
| Switch to COX-2 inhibitor | Lowers but doesn't eliminate risk; reserve for patients at low cardiovascular risk since COX-2 selectivity raises CV risk in exchange for lower GI risk. |
COX-2 selectivity buys you lower GI risk at the cost of higher cardiovascular risk, this is a straight tradeoff, not a free upgrade. That's why COX-2 inhibitors are reserved for patients with low CV riskbut meaningful GI risk. High CV risk plus high GI risk is the hardest patient to manage and usually means avoiding NSAIDs altogether if possible.
Unlike typical PUD, NSAID-induced ulcers are frequently asymptomaticuntil a complication (bleeding, perforation) shows up. Don't wait for pain as your trigger to worry in a chronic NSAID user.
This is a critically-ill-patient problem, not an outpatient one. Reduced gastric blood flow from critical illness causes mucosal ischemia, and the mucosa loses the ability to protect itself even though acid levels aren't necessarily elevated. Respiratory failure requiring mechanical ventilationis the classic setup your course material calls out specifically.
One of your professors put it bluntly in lecture: prophylactic PPI use in the hospital is often "a CYA (cover your... self) kind of thing." Translation: stress ulcer prophylaxis gets ordered reflexively in a lot of ICU patients who may not truly need it. Know the actual high-risk population (mechanically ventilated, critically ill) so you can recognize when prophylaxis is genuinely indicated versus habitually ordered.
Treatment/prevention:PPI once daily, given prophylactically before the ulcer forms, not as a reactive treatment after symptoms appear.
One of the most common GI emergencies, and often the first sign that brings an ulcer patient to the ED.
| Intervention | Trigger / dosing |
|---|---|
| Red blood cell transfusion | Hgb <7 g/dL |
| PPI | IV, BID, total daily dose 80-160 mg, for at least 3 days |
| Endoscopy | Both diagnostic and therapeutic (can directly control the bleeding site) |
| Surgical intervention | Reserved for bleeding not controlled endoscopically |
The 80-160 mg/day IV dosing in acute bleeding is dramatically higher than routine oral PUD dosing (20-40 mg/day). The goal in the acute setting is to keep gastric pH consistently above 6, since a stable clot needs a much less acidic environment than ordinary ulcer healing does. Don't confuse acute UGIB dosing with maintenance PPI dosing on an exam.
| Parameter | When | Watching for |
|---|---|---|
| Symptom relief | Days after stopping NSAID; within 7 days of starting antiulcer therapy | Uncomplicated PUD patients should be essentially symptom-free after any recommended regimen |
| Persistent/recurrent symptoms | Within 14 days after finishing treatment | Failed healing, failed H. pylori eradication, or a different diagnosis entirely (e.g., GERD) |
| H. pylori eradication test | ≥4 weeks post-antibiotics AND ≥2 weeks off PPI | True eradication vs. drug-suppressed false negative |
| Hgb/Hct, stool guaiac | Any suspicion of bleeding | Occult or overt GI blood loss |
| Signs of bleeding, obstruction, penetration, perforation | Ongoing in any NSAID user, especially high-risk patients | Complication requiring escalation, not just a dose adjustment |
| Follow-up endoscopy | Frequent recurrence, refractory disease, complications, suspected hypersecretory state | Confirm nonhealing, exclude malignancy, reassess H. pylori status |
An ulcer that doesn't heal despite a complete standard PPI course gets double the PPI dose, or a switch to a different PPI, alongside repeat endoscopy to rule out malignancy and reassess H. pylori.