Peptic Ulcer Disease

Peptic ulcer

• an ulcer of the alimentary mucosa, usually in the stomach or duodenum, that has been exposed to acid gastric secretion 

• Aggressive factors: gastric acid from parietal cells; pepsinogen converted to pepsin from chief cells 

• Protective factors: mucus-bicarbonate barrier; prostaglandins epithelial cell defense; mucosal blood flow

NSAID-induced 

• NSAIDs irritate gastric epithelium

• Can happen within mins of ingestion or with chronic use

• Can result in bleeding

• NSAIDs cause systemic inhibition of prostaglandin synthesis (more inhibition of COX₁ than COX₂  [GI toxicity related to COX₁]

Helicobacter pylori (H. pylori) - gram negative 

• bacteria disrupts normal mucosal defense and healing mechanisms; resides in gastric epithelium

• Transmitted person-to-person via: fecal-oral, oral-oral, or gastro-oral

• Causes PUD, chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma

More

Other Causes 

• Zollinger-Ellison’s syndrome

  • Hypersecretion of gastric acid

• Viral infections

  • i.e. cytomegalovirus (CMV)

• Radiation

• Chemotherapy 

• Vascular insufficiency

  • i.e. cocaine use

• Inherited 

  • i.e. condition of hyperfunctioning parietal cells 

• Stress-related mucosal disease (SRMC) (also known as stress ulcers)

  • [NOT covered in this course; addressed with critical care topics)

Risk factors

• Age 65 years old

• Previous PUD or upper GI complications

• Chronic illness

• Smoking

• NSAID-related dyspepsia

• Alcohol use

• Previous H. pylori infection

• Rheumatoid arthritis 

• Corticosteroid+ NSAID use

• ASA + NSAID use

• NSAID use > I month

• High-dose NSAID use

• Anticoagulant use or coagulopathy 

• Antiplatelet agent use

• Oral bisphosphonate use

• SSRI use

Exacerbating factors 

• Stress – may alter inflammatory response

• Spices/spicy foods – causes dyspepsia 

• Caffeine – stimulates gastric acid 

• Food may bring on pain with gastric ulcers; pain can be relieved by food with duodenal ulcers

GI Bleeds

• Causes

  • Peptic Ulcer Disease – NSAID-induced or H. pylori 

  • Esophagitis

  • Mallory-Weiss tear (causes: vomiting, coughing, alcoholism)

  • Cancer

  • Stress ulcers/SRMD (in ICU population)

  • Varices 

Determine whether a patient’s symptoms of PUD are eligible for self-treatment or medical referral is needed

Self Treatment

• NSAID alternatives

• Reducing alcohol

• Reducing stress

• Reduce spicy food, caffeine

Medicare referral

• H. pylori

• Indications of endoscopy

  • Presence of alarm symptoms 

  • NSAID etiology has been ruled out

  • Suspicion for complications

  • Need for accurate diagnosis

  • History of previous H. pylori infection

• Alarm symptoms

  • GI bleeding

  • weight loss 

  • early satiety

  • dysphagia or odynophagia

  • family history of upper GI malignancy

  • Iron deficiency anemia

  • New upper GI symptoms when > 55 years of age (risk for cancer)

NSAID-induced ulcers treatment: PPIs

• PPIs are best at:

  • Inhibiting acid secretion 

  • Relieving ulcer symptoms

  • Healing ulcers 

  • Maintaining ulcer-healing 

• Higher PPI dosing should be divided throughout the day for good pH control 

• MOA: suppresses gastric acid secretion by inhibiting parietal cells H+/K+ ATP pump

• Onset: about 4 days for full effect (some acid suppression in 1-3 hours)

• Agents:

  • Omeprazole (Prilosec OTC) - OTC

  • Esomeprazole (Nexium 24HR) - OTC

  • Lansoprazole (Prevacid 24HR) - OTC

  • Omeprazole + sodium bicarb (Zegerid) - OTC

    • Start with once daily dosing
      

• Dexlansoprazole (Dexilant) - Rx

• Rabeprazole (Aciphex) - Rx

• Pantaprazole (Prontonix) - Rx

• Counseling: take 30 - 60 mins before AM meal

• AEs: HA, dizziness, somnolence, diarrhea/constipation, nausea; long-term: B₁₂ deficiency, C.Difficile infection, pneumonia

Prevention of NSAID-induced ulcer: Prostaglandin Analog

• Indications: prevention of NSAID-induced gastric ulcers 

• MOA: replaced the protective prostaglandin consumed with prostaglandin inhibiting therapies 

• Agent

  • Misoprostol: synthetic prostaglandin E1 analog 

    • Induced uterine contraction

      • Used for that purpose/indication, but do not admin to women of childbearing potential for ulcer prevention 

• Counseling: take 4 times daily 

Treatment of H. pylori ulcers ACG guidelines

1st case or H. pyrlori

• Preferred: Optimized Bismuth Quadruple Therapy (BQT)

  • Treatment choice in penicillin allergy 

  • Treatment choice when antibiotic resistance rates are unknown 

• 2nd line options

  • Rifabutin Triple

  • Vonoprazan Dual

ACG CPG initial treatment

Recurrence/salvage

• Empiric Options

  • Optimized Bismuth Quadruple Therapy (BQT) 

  • Rifabutin Triple

• Know antibiotic sensitivity

  • Optimized Bismuth Quadruple Therapy (BQT) 

  • Rifabutin Triple

  • Vonoprazan Triple

  • Levofloxacin Triple

ACG CPG salvage regimens 

Vonoprazan

Potassium-competitive acid inhibitor (PCAB) 

• 20 mg twice daily

• Administered with antibiotics for treatment regimen

• Indication: H. pylori infection; erosive esophagitis

• MOA: results in rapid and reversible inhibition of pumps and acid secretion

• Rapid onset of action and full effect with 1^st dose

Rifabutin

• Antitubercular agent

• Varied frequencies based on regimen

• Administered with PPI and amoxicillin

• Indication: H. pylori infection

• MOA: inhibits bacterial RNA synthesis leading to cell death of H. pylori

Steps for GI bleed

• Stabilize patient

  • Give blood, fluids 

  • Possibly admit to ICU

  • Patient may need NG tube if patient aspirates 

• Manage underlying condition 

  • Stop NSAIDs if applicable

  • Treat H. pylori if applicable 

• Endoscopic repair

  • Sclerotherapy, clips, etc. 

GI bleed treatment

• IV PPI therapy (esomeprazole or pantoprazole are only IV PPIs)

  • Dose: 80 mg IV bolus + 72 hour continuous drip

    • This dose raises gastric pH to enhance coagulation 

• Continue once daily PPI until patient considered low-risk to decrease mortality and decrease re-bleeding

• Use PPI early in management of condition (even if no endoscopy available for evaluation)

Treatment of NSAID-induced ulcers

1. Discontinue the NSAIDs

2. Administer antisecretory therapy if symptoms are still present after discontinuing NSAIDS 

   1. PPI for 4-6 weeks for ulcer <1cm; 6-8 weeks for >1cm 

   2. If NSAIDs need to be continued, continue PPI for maintenance/prevention 

3. Endoscopy if still having symptoms 

4. If H. pylori positive, follow that treatment path 

Gastric Protection for long-term NSAID use 

Adding Protection 

• Ex. someone taking low-dose aspirin for cardiac indication, add on PPI or misoprostol if they have GI risk factors 

• Someone taking low-dose aspirin for cardiac indication and ibuprofen for chronic back pain, which to naproxen, and add on PPI or misoprostol 

• Or switch to acetaminophen if possible (if don’t need anti-inflammatory action); or decrease to lowest effective dose of NSAIDs

GI risk factors 

• Advanced age

• Previous GI event

• High dose of NSAID

• Concomitant anticoagulant or corticosteroid

• Cardiovascular disease

• Pts would benefit from extra protection 

  • PPI or misoprostol

  • Naproxen or COX2 NSAID if NSAID recommended 

H. pylori Treatment 

• Choose regimen based on patient-specific/area-specific factors 

  • Penicillin allergy

  • Resistance rates

• Duration = 14-days

• Choose PPI that is cost-effective and/or preferred by patient 

Treatment of non-NSAID and non-H. Pylori ulcers

• Ulcers not caused by NSAIDs or H. pylori

  • Treat gastric ulcer with PPI for 8 weeks

  • Treat duodenal ulcers with PPI for 8 weeks