Peptic Ulcer Disease

What is peptic ulcer disease (PUD)?

A mucosal break that extends into the submucosa

How large are peptic ulcers generally?

≥5 mm

How does PUD differ from gastritis?

Ulcers are larger and extend deeper into the muscularis mucosa

What are the 3 most common causes of PUD?

- H. pylori

- NSAIDs

- Stress-related mucosal damage (SRMD)

What are the 2 major locations of peptic ulcers?

Stomach and duodenum

What conditions are associated with chronic peptic ulcers?

- Cirrhosis

- CKD

- COPD

- Cardiovascular disease

- Organ transplantation

How does cigarette smoking affect PUD?

- Higher ulcer prevalence in H. pylori-infected patients

- Impairs ulcer healing

- Promotes recurrence

- Increases ulcer risk

How does diet affect PUD?

Certain foods may worsen dyspepsia but do not appear to directly increase PUD risk, including

What is the role of alcohol in PUD?

Alcohol may cause acute gastric mucosal damage and upper GI bleeding, but it is unclear whether it directly causes ulcers

What are the characteristics of H.pylori induced ulcers?

- Chronic

- Duodenum > stomach

- More acid/pH dependent

- Usually epigastric pain

- Superficial ulcers

- Less-severe bleeding from a single vessel

What are the characteristics of NSAID induced ulcers?

- Chronic

- Stomach > duodenum

- Less pH dependent

- Often asymptomatic

- Deep ulcers

- More-severe bleeding from a single vessel

What are the characteristics of stress-related mucosal damage ulcers?

- Acute or critically ill patients

- Stomach > duodenum

- Less pH dependent

- Usually asymptomatic

- Most superficial ulcers

- More-severe bleeding from superficial mucosal capillaries

What are the common symptoms of PUD?

- Dyspepsia/mild epigastric abdominal pain

- Burning, aching, gnawing, fullness, or cramping

- Heartburn

- Belching/bloating

- Nausea/vomiting

How does food affect gastric vs duodenal ulcer pain?

- Gastric ulcer: food aggravates pain

- Duodenal ulcer: food relieves pain

What is the diagnostic test of choice for suspected PUD?

Upper EGD (inspects visualizations of erosions and active bleeding)

How does uncomplicated PUD differ from complicated PUD?

- Uncomplicated: typically mild epigastric pain

- Complicated: acute upper GI complication such as bleeding, obstruction, or perforation

What are the major complications of chronic PUD?

- Upper GI bleed

- Gastric perforation

- Obstruction

What are the key characteristics of H. pylori?

- Gram-negative

- Spiral-shaped

- Produces urease, catalase, and oxidase

- Can survive in acidic environments

How is H. pylori transmitted?

- Fecal → oral

- Gastric → oral

How does H. pylori cause gastric mucosal injury?

- H. pylori binds gastric-type epithelium

- Bacterial enzymes and virulence factors cause mucosal injury and inflammation

- End result is Altered host inflammatory response, hypergastrinemia, and increased acid secretion

What is associated with H. pylori colonization of the antrum and corpus?

Gastric ulcer and gastric cancer

What is the gold-standard endoscopic test for H. pylori?

Histology

When is H. pylori culture generally used?

After failure of second-line therapy, because it allows sensitivity testing for antibiotic resistance.

What is the test of choice for H. pylori when the patient is already undergoing endoscopy?

Biopsy Urease

Which test for H.pylori detects the DNA, is highly sensitive, and considered a research technique?

PCR

What are the preferred noninvasive tests for active H. pylori infection?

- Urea breath test

- Fecal antigen test

Which test is recommended to confirm H. pylori eradication after treatment?

Urea Breath Test

What medications must be held before a urea breath test?

- PPIs/H2RAs: 1-2 weeks

- Bismuth/antibiotics: 4 weeks

Which non-endoscopic H.pylori test may be used post-treatment to confirm eradication, but patients may have reluctance to obtain stool samples?

Fecal antigen

What GI damage can chronic NSAID use cause?

- Upper GI tract injury

- PUD

- Gastritis

- Superficial erosion

What can continued NSAID exposure cause superficial mucosal damage/intramucosal hemorrhage to progress to?

Erosions

Which NSAIDs are classified as nonselective COX-2 inhibitors?

- Ibuprofen

- Naproxen

- Ketorolac

- Diclofenac

- Indomethacin

Which NSAIDs are classified as selective COX-2 inhibitors?

- Meloxicam

- Celecoxib

- Etodolac

- Nabumetone

What increases the risk of NSAID-induced PUD?

- Age >65

- Previous peptic ulcer

- Previous ulcer-related upper GI complication

- High-dose NSAIDs• Multiple NSAIDs

- Longer treatment duration

- Type of NSAID/COX selectivity

- Chronic debilitating disease

- H. pylori

- Smoking

- Alcohol

Which concomitant medications further increase NSAID ulcer risk?

- Low-dose aspirin

- Oral bisphosphonates

- Systemic corticosteroids

- Anticoagulants

- Antiplatelets

- SSRIs

How do NSAIDs cause gastric injury?

Local mechanisms:

• Acidic properties

• Topical irritation

• Reduce hydrophobic nature of mucus gel layer

Systemic mechanism:

• COX enzyme inhibition

• Reduces protective mucosal defenses

What is the difference between COX-1 and COX-2 inhibition?

- COX-1 inhibition: undesirable ↓ gastric mucosal protection

- COX-2 inhibition: desirable analgesic and anti-inflammatory effects

What is the GI ulceration associated with hospitalization in critically ill patients, most commonly in the stomach?

Stress-Related Mucosal Damage (SRMD)

What are the two major risk factors for SRMD?

- Mechanical ventilation >48 hours

- Coagulopathy

What qualifies as coagulopathy as a risk factor for SRMD?

- INR >1.5

- Platelets <50,000

What are additional risk factors for SRMD?

• ICU admission >7 days

• Hypotension/sepsis

• Hepatic failure

• Acute renal failure

• High-dose corticosteroids >250 mg/day hydrocortisone equivalent

• Severe burns >35% TBSA

• Head/spinal cord injury

• History of GI bleeding

• Major surgery

What are the goals of PUD treatment?

- Relieve ulcer pain/symptoms

- Reduce acid secretion

- Heal the ulcer

- Prevent recurrence

- Prevent complications

- Eradicate H. pylori when present

What nonpharmacologic interventions are recommended for PUD?

- Stress reduction

- Smoking cessation

- Avoid dyspepsia-triggering foods

- Avoid spicy/acidic foods if symptomatic

- Avoid caffeine/alcohol if symptomatic

- Avoid NSAIDs if possible

- Endoscopic management for complications

What are the main components of NSAID-induced PUD treatment?

- Antisecretory therapy: PPI or H2RA

- Mucosal protection: sucralfate

- Evaluate whether NSAID should be discontinued, replaced, or continued

How is an NSAID-associated ulcer treated if the NSAID is discontinued?

PPI preferred or H2RA × 8 weeks

How is an NSAID-associated ulcer treated if the NSAID must be continued?

PPI × 12 weeks

How is an NSAID-associated ulcer treated if H. pylori is also present?

H. pylori eradication regimen

Which PPIs are available IV?

Pantoprazole and Esomeprazole.

Which H2RA is available IV?

Famotidine

How is NSAID-induced PUD monitored after treatment?

- Treatment is generally successful

- Routine follow-up is usually unnecessary

- Educate patient to monitor for side effects and PUD complications such as bleeding/dark tarry stool

How can NSAID-induced peptic ulcers be prevented?

- NSAID + PPI — preferred first line

- NSAID + H2RA• NSAID + misoprostol

- COX-2 selective NSAID• Gastroprotective agent + NSAID

What is Sucralfate's MOA?

Negatively charged sucralfate binds positively charged proteins at the ulcer site → forms a protective paste-like coating

What are the major precautions/interactions with sucralfate?

- Aluminum may accumulate when CrCl <30 mL/min

- ADRs = constipation/metallic taste

What is the MOA of Misoprostol?

Synthetic prostaglandin that replaces protective prostaglandins depleted by NSAIDs

What are the main adverse effects of Misoprostol?

- Abdominal cramping

- Diarrhea

- Nausea

What is the major contraindication for Misoprostol?

Pregnancy (abortifacient)

What medication classes/agents are used in H. pylori eradication therapy?

- Acid suppression: PPI or vonoprazan

- Antibiotics: amoxicillin, metronidazole, tetracycline, clarithromycin, levofloxacin, rifabutin

- ± Bismuth subsalicylate

What are the recommended H. pylori regimens for treatment-naïve patients?

- Optimized bismuth quadruple therapy

- PCAB dual therapy

- PCAB triple therapy

- Rifabutin triple therapy

What is optimized bismuth quadruple therapy?

- 14 days:

- PPI BID

- Bismuth subcitrate OR bismuth subsalicylate QID

- Metronidazole QID

- Tetracycline QID

What are key considerations for bismuth quadruple therapy?

- Preferred option in penicillin allergy

- QID dosing may cause poor adherence

- Frequent minor side effects

What is PCAB dual therapy for H. pylori?

14 days of Vonoprazan and Amoxicillin

What is PCAB triple therapy?

14 days of Vonoprazan, Amoxicillin, and Clarithromycin

When should clarithromycin-containing H. pylori regimens be avoided?

When macrolide susceptibility has not been demonstrated

What is Rifabutin Triple Therapy?

14 days of Omeprazole, Amoxicillin, and Rifabutin

What salvage regimens are used for persistent H. pylori infection?

- Rifabutin triple therapy

- Levofloxacin triple therapy

- Optimized bismuth quadruple therapy

- PCAB triple therapy

- High-dose dual therapy

What is levofloxacin triple therapy?

14 days of PPI, Levofloxacin, Amoxicillin OR Metronidazole

When should Levofloxacin-containing regimens be avoided?

Without demonstrated quinolone susceptibility

What is high-dose dual therapy?

14 days of Vonoprazan or PPI and Amoxicillin

What are the medication pearls for Amoxicillin?

- Beta-lactam/penicillin

- Inhibits bacterial cell wall synthesis

- ADRs: N/V/D

- Avoid in penicillin allergy

What are the medication pearls for Clarithromycin?

- Macrolide

- Binds 50S ribosome → inhibits protein synthesis

- ADRs: QT prolongation, N/V/D

- CYP3A4 inhibitor

What are the medication pearls for Metronidazole?

- Nitroimidazole

- Causes DNA strand breakage/cell death

- ADRs: CNS effects, N/V

- Avoid alcohol/propylene glycol → disulfiram reaction

- Take with food

What are the medication pearls for Levofloxacin?

- Fluoroquinolone

- Inhibits DNA gyrase

- Tendon rupture

- CNS effects

- QT prolongation

- Phototoxicity

- Hepatotoxicity

- Aortic aneurysm

What are the major counseling points for Tetracycline?

- Take on empty stomach

- 1 hour before or 2 hours after meals

- Take with adequate fluid to prevent esophageal irritation

- Separate from antacids

What is the major counseling pearl for Rifabutin?

May cause reddish-orange/brownish-orange urine; also associated with leukopenia/neutropenia

What are the major medication pearls for Vonoprazan?

• Potassium-competitive acid blocker (PCAB) • Inhibits H⁺/K⁺ ATPase • Suppresses basal and stimulated acid secretion • ADRs: nausea/diarrhea, bloating • Avoid in severe renal/hepatic impairment • If dose missed by >4 hours → skip it

What are the major medication pearls for Bismuth Subsalicylate?

- Antisecretory + antimicrobial activity

- May cause constipation

- May cause dark tongue or stool (normal and harmless)

What is the role of probiotics in H. pylori treatment?

- Limit H. pylori colonization

- Increase eradication rates

- Decrease antibiotic adverse effects

True or False: Probiotics eradicate H.pylori on their own

False

How should H. pylori eradication be monitored?

- Confirm eradication ≥4 weeks after completing antibiotics

- Withhold PPI for 1-2 weeks before testing

- Monitor symptom resolution

- Monitor for drug adverse effects

- Counsel on PUD complications such as bleeding/dark tarry stools

What can cause H. pylori treatment failure?

- Poor adherence

- Antimicrobial resistance

- NSAID use

- Cigarette smoking

- Acid hypersecretion

What should be done after H. pylori treatment failure?

- Consider GI referral/further evaluation

- Use antibiotics not used during the initial regimen

- Favor antibiotics with lower resistance concerns

How is SRMD prevented in critically ill patients?

- Restore/ensure mucosal blood flow

- Maintain intragastric pH >4 or provide mucosal protection

- PPI

- H2RA

- Sucralfate

What is the most important pharmacist intervention with SRMD prophylaxis?

- Reassess whether prophylaxis is still needed

- Stop prophylaxis when risk factors resolve

- Do not continue at discharge without another indication for PPI/H2RA