Peptic Ulcer Disease (PUD)

• Eric Ocheretyaner, PharmD, BCPS, BCIDP, is an Associate Professor of Pharmacy Practice at Fairleigh Dickinson University.
• This presentation will cover the pathophysiology and pharmacotherapy of peptic ulcer disease (PUD).

Lecture Objectives

• Identify common causes of peptic ulcer disease (PUD).
• Describe the pathophysiology of PUD.
• Determine treatment goals for managing PUD.
• Suggest prescription and nonprescription treatments for PUD.
• Develop a monitoring plan to assess treatment results in PUD patients.
• Educate patients about PUD.

Peptic Ulcer Disease (PUD)

• Ulcers are erosions that extend deep into the gastric or duodenal mucosa caused by acid.
• The three common types are NSAID-induced, Helicobacter pylori-induced, and Stress-related mucosal damage (SRMD), that is seen in critically ill patients.
• Chronic PUD involves frequent, recurrent ulcers.
• Risk factors for ulcer recurrence include untreated H. pylori, NSAID use, cigarette smoking, alcohol use, gastric acid hypersecretion, and PUD treatment nonadherence.

Characteristics of Peptic Ulcers Comparison

• H. pylori-induced ulcers typically lead to epigastric pain, and have less severe GI bleeding.
• NSAID-induced ulcers are often asymptomatic and lead to more severe GI bleeding.
• SRMD ulcers are usually asymptomatic, more superficial, and have severe superficial GI bleeding.
• H. pylori ulcers occur more in the duodenum, while NSAID and SRMD ulcers occur more in the stomach.

General Pathophysiology

• Ulcer development stems from an imbalance between gastric acid and pepsin secretion, and the body's normal mucosal defenses.
• Hypersecretion of gastric acid and pepsin leads to ulcer bleeding, perforation, penetration, or obstruction.

Clinical Presentation of PUD

• General mild epigastric pain worsens after eating or presents as life-threatening GI complications.
• PUD symptoms include burning epigastric pain, vague discomfort, abdominal fullness, cramping, heartburn, belching, and bloating.
• Nocturnal pain awakens patients from sleep, especially between 12-3 AM.
• Pain varies and frequently occurs in spring or fall.
• Discomfort presents in clusters and lasts weeks, followed by pain-free spells or remission lasting weeks to years.
• Signs include weight loss with N/V, anorexia, ulcer bleeding, perforation, penetration, or obstruction.
• Gastric acid secretory studies, low hemoglobin/hematocrit, and positive stool hemoccult tests can be seen.
• The test for H. pylori should be performed in the lab.
• Fiber-optic upper endoscopy detects >90% of ulcers, and is used for inspection, biopsy, visualization, and active bleeding sites.

Alarm Symptoms Requiring Endoscopy

• Anemia
• GI bleeding
• Vomiting
• Anorexia
• Weight loss
• Palpable mass

Goals of Therapy

• For H. pylori-induced ulcers, the goals are to eradicate the infection, heal the ulcer, cure the disease, and prevent recurrence and complications.
• For NSAID-induced ulcers, the goals are to heal the ulcer rapidly and prevent recurrence or complications.
• Patients at high risk for developing NSAID-induced ulcers should receive prophylactic co-therapy or switch to a COX-2 selective NSAID.

Nonpharmacologic Interventions

• Stress reduction
• Smoking cessation
• Avoiding alcohol
• Discontinuing NSAIDs, even "baby" aspirin 81 mg
• Avoiding foods and beverages that cause dyspepsia (spicy foods, caffeine, alcohol)
• Surgery for patients with complications such as bleeding, perforation, or obstruction

H. pylori-Induced PUD

• Helicobacter pylori is a pH-sensitive, gram-negative, flagellated bacterium.
• Gastric acid will not destroy the bacteria.
• H. pylori produces urease, converting gastric juices to ammonia and CO2.
• The ammonia protects from gastric acid breakdown.
• H. pylori causes cytotoxins, resulting in cell death and cancer.
• Associated with chronic gastritis, PUD, mucosa-associated lymphoid tissue (MALT) lymphoma.

Transmission and Risk Factors for H. pylori

• Transmission occurs via oral-oral or fecal-oral routes.
• Those with young age, are in childhood, and have low socioeconomic status are at a high risk.
• In addition, those with exposure to unsanitary conditions and health care are at a high risk.

Diagnosis of H. pylori

• Urea breath test checks for CO2 produced.
• False negatives can occur with PPIs, H2RAs, antibiotics, or bismuth; withhold PPIs or H2RAs for 1-2 weeks, and bismuth or antibiotics for 4 weeks.
• Fecal antigen tests assess for H. pylori antigens in stools.
• False negatives also occur with PPIs, H2RAs, antibiotics, or bismuth, but to a lesser extent.
• Fecal antigen tests can confirm infection eradication after therapy.
• Blood tests check for H. pylori antibodies, which can be from active or cured infections.
• Endoscopic biopsy is the preferred test if a patient is undergoing endoscopy, testing for active infection.

Drug Regimens to Eradicate H. Pylori

• Triple Therapy includes Prevpac® with lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 g PO BID for 14 days.
• Be cautious in those with macrolide-resistant antibiotic resistance.
• Bismuth Quadruple Therapy involves Pylera® for 10 days.
• Bismuth Quadruple Therapy involves Helidac® for 14 days.
• These are a good option if patient has penicillin allergies.
• Potassium-competitive acid blocker (PCAB) dual includes Voquezna DualPak, and triple includes TriplePak.
• Rifabutin triple includes Talicia.

Probiotics and H. pylori

• Probiotics may limit H. pylori colonization.
• Concomitant probiotic therapy with antibiotics may increase eradication rates and reduce antibiotic-related adverse effects.
• Probiotic monotherapy does not eradicate H. pylori infection, requiring strains of Lactobacillus and Bifidobacterium.
• Optimal probiotic strains, dose, timing, and duration are unclear; need more randomized, controlled trials.

After Treatment

• An increasing number of H. pylori strains are resistant.
• About 20% will fail their first treatment.
• Must be retested for H. pylori after treatment to confirm eradication.
• A retest is usually done 4 weeks after treatment.
• A recheck can be performed with urea breath, fecal antigen, or biopsy-based tests.

Eradication of H. pylori After Initial Treatment Failure

• Should assess patient history and antimicrobial history
• Prior macrolide exposure increases risk for clarithromycin resistance.
• Use antibiotics that have not been previously used during initial therapy, and those that are not associated with resistance.
• Use a drug that has a topical effect such as bismuth.
• Extend the duration of treatment to 14 days if the original treatment lasted 10 days.

NSAID-Induced PUD

• NSAIDs are weak acids and cause direct topical irritation of gastric mucosa.
• This leads to inhibition of the enzyme COX, reduced prostaglandin synthesis, reduced blood flow to the mucosa, decreased secretion of mucus and bicarbonate, and lack of GI mucosa protection.

NSAID-Induced PUD Drugs

• Aspirin is acetylated.
• Saltsalate and trolsalicylate are nonacetylated.
• NSAID is a Nonselective COX inhibitor, including ibuprofen and naproxen.

Risk Factors Associated with NSAID-Induced Ulcers

• Risk factors include age >65, previous peptic ulcer, prior ulcer-related GI complication, high-dose NSAIDs, multiple NSAID use, and selection of NSAID (COX-1 vs. COX-2 inhibition).
• Other risk factors are NSAID-related dyspepsia, aspirin use, using bisphosphonates, using corticosteroids, a H. pylori infection, cigarette smoking, and alcohol consumption.

Approach to PUD

• First check H. pylori status, and if negative discontinue NSAID, starting PPI for 8 weeks, and if positive discontinue NSAID and start H.pylori therapy.
• Maintenance therapy with a PPI or H₂RA is recommended for high risk patients.

NSAID-Induced PUD Treatment Notes

• When managing NSAID-induced PUD, active ulcers require PPI treatment after discontinuing NSAIDs.
• It is OK to Initiate another analgesic after ulcer heals.
• But when NSAIDs are needed it's OK to hold the NSAID, treating the PUD.
• Reinitiate NSAID at a lower dose or choose another analgesic like selective COX-2 inhibitor such as celecoxib.
• Those with moderate to high GI bleeding should take PPI for long term.
• There must be a PPI or misoprostol long-term , co-therapy with NSAID for ulcer prevention

Common drugs that can caused Drug-Induced PUD

• Can occur even with Aspirin and Clopidogrel(antiplatelet).
• Corticosteroids(prednisone).
• Erythromycin (antibiotic).
• NSAID.
• Selective serotonin reuptake inhibitors (SSRI) (ex. sertraline).

PPIs

• All PPI drugs are used in treatment for PUD
• Taking PPIs can lead to a wide range of side effects

Patient Counseling

• Take medicine with meals to reduce Gl issues
• Take PPIs 30 to 60 minutes before morning and evening
• Adverse effect counseling for medications used to treat H. pylori:
• Bismuth- dark stool and tongue
• Clarithromycin- metal taste, QT prolongation
• Metronidazole- refrain from alcohol use, neuropathy, altered taste
• Tetracycline- tooth discoloration (pediatrics yr8 years), sun sensitivity
• Levofloxacin- tendon rupture, sun sensitivity, QT prolongation

Pharmacist Role

• Noncompliance is a problem when treating those with H.pylori
• Check for drug-drug interactions as anti-biotics will interfere with other medications
• Check renal and liver function and dose appropriately

Current Guidelines

• H. pylori infection(2017): http://gi.org/guideline/treatment-of-helicobacter- pylori-infection/
• H. pylori infection(2024): https://journals.lww.com/ajg/fulltext/2024/09000/acg clinical guideline tr eatment of helicobacter.13.aspx?context=featuredarticles&collectionid=2