Peptic Ulcer Disease (PUD)

• Peptic Ulcer Disease (PUD) involves pharmacotherapy and understanding the pathophysiology
• PUD is given as a lecture in Spring 2025 at Fairleigh Dickinson University
• Common causes of peptic ulcer disease (PUD) are identified in this lecture
• Creates treatment goals for the management of PUD.
• Recommended prescription and nonprescription treatment regimens for PUD will be discussed
• Outlines a plan to monitor and evaluate treatment outcomes in patients receiving treatment for PUD.

Peptic Ulcer Disease (PUD)

• Ulcers extend deep into the gastric or duodenal mucosa, caused by acid erosion
• There are 3 main types of PUD:
  • NSAID-induced
  • Helicobacter pylori-induced
  • Stress-related mucosal damage (SRMD) is seen in critically ill patients
• Frequent, recurrent ulcers are characterized as chronic PUD
• Risk factors for ulcers include:
  • Untreated H. pylori
  • NSAID use
  • Cigarette smoking
  • Alcohol consumption
  • Gastric acid hypersecretion
  • PUD treatment nonadherence

Common Forms of Peptic Ulcer Comparison

• H. pylori-induced ulcers are chronic
• NSAID-induced ulcers are chronic
• SRMD ulcers are acute
• H. pylori affects the duodenum to a greater extent than the stomach
• NSAID affects the stomach to a greater extent than the duodenal
• SRMD affects the stomach to a greater extent than the duodenal
• Intragastric pH is more dependent in H. pylori
• Ulcer pain is usually epigastric with H. pylori
• Ulcers are often superficial with H. Pylori
• GI bleeding is less severe, with a single vessel
• NSAID ulcers are often asymptomatic
• NSAID ulcers are deep
• GI bleeding is more severe, single vessel
• SRMD ulcers are asymptomatic
• SRMD ulcers are superficial
• GI bleeding is more severe with superficial mucosal capillaries

General Pathophysiology

• Ulcer caused by an imbalance between gastric acid & pepsin secretion & the normal mucosal defense & healing
• Hypersecretion of gastric acid & pepsin
• Complications include: ulcer bleeding, perforation, penetration, obstruction

Clinical Presentation of PUD

• Mild epigastric pain worsens when eating, may progress to life-threatening GI complications
• Epigastric pain described as burning, may manifest: vague discomfort, abdominal fullness, or cramping
• The pain presents heartburn, belching, bloating
• Nocturnal pain may awaken patients from sleep, especially between 12-3 AM
• Episodes of discomfort occur in clusters lasting up to a few weeks, followed by a pain-free remission
• Signs of PUD include weight loss associated with nausea/vomiting, anorexia
• Ulcer complications: bleeding, perforation, penetration, obstruction
• Laboratory findings:
  • Gastric acid secretory studies
  • Low hemoglobin/hematocrit
  • Positive stool hemoccult studies with bleeding
  • Test for H. pylori
• Diagnostic test:
  • Fiber-optic upper endoscopy detects >90% of ulcers
  • Endoscopy allows visualization of erosions and active bleeding

Alarm Symptoms that necessitate Endoscopy

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

PUD treatment goals

• H. pylori-induced
  • Eradicate H. pylori infection
  • Heal ulcer
  • Cure disease
  • Prevent recurrence & complications
• NSAID-induced
  • Heal ulcer quickly
  • High-risk of ulcers should receive prophylactic co-therapy OR switch to a COX-2 selective NSAID
  • Prevent recurrence & complications

Nonpharmacologic Interventions

• Stress reduction
• Stop smoking
• Avoid alcohol
• Discontinue NSAIDs including "baby" aspirin 81 mg
• Avoid foods that cause dyspepsia or exacerbate symptoms: spicy foods, caffeine, alcohol
• Surgery is reserved for patients with complications: bleeding, perforation, obstruction

Treatment Algorithm for Suspected Peptic Ulcer

• Assess the patient with ulcer-like symptoms, determine if there are alarm symptoms present
• Perform endoscopy to asses the ulcer status, if alarm symptoms are present
• Test for H.pylori is ulcer appears present
• If no alarm symptoms present, determine if the patient is taking NSAIDs
• If not, discontinue NSAIDs, or decrease dose to manage discomfort
• Evaluate if patient has H. Pylori; check if previously treated.
• Treat with PPI, if serology shows positive signs.
• If serology is negative, being either H2RA or PPI
  • Initiate H.pylori based eradication, if test is positive
  • Discontinue NSAID. If it isn't possible to do so, continue and switch COX-2, if possible
  • Check following PPI, for signs and symptoms.
    • Check etiologies such as GERD/NUD if test appear negative

Helicobacter pylori (H. pylori)-Induced PUD Pathophysiology

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

Transmission and Risk Factors for H. pylori-Induced PUD

• H. pylori is transmitted either orally or fecally
• Typically acquired during childhood
• Associated with low socioeconomic status
• Living in crowded or unsanitary conditions
• Exposure to unsanitary food or water.
• Healthcare exposure involving gastric content

Diagnosing H. pylori

• The urea breath test checks for CO2 produced by the bacteria, indicates an active infection
  • False-negative results can occur with PPIs/H2RAs/antibiotics/bismuth, so these medications should be held before testing
• The fecal antigen test checks for H. pylori antigen in stools, also indicates an active infection
  • False-negatives can occur with PPIs/H2RAs/antibiotics/bismuth
  • This test can confirm infection eradication post-treatment
• A blood test for H. pylori antibodies
• Endoscopic biopsy is the preferred test if a patient requires endoscopy.

Medications to Eradicate H. Pylori

• Triple Therapy include clarithromycin 500 mg + amoxicillin 1 g PO BID
  • Avoid use in patients at risk of macrolide antibiotic resistance
• Bismuth quadruple therapy contains bismuth subsalicylate 525 mg + tetracycline 500 mg + metronidazole 250 mg QID and is a first-line, good option for patients with penicillin allergies. Talicia
• PCAB triple consist of: Vonoprazan 20 mg BID, Amoxicillin 1000 mg BID, Clarithromycin 500 mg BID is a first-line empiric treatment for clarithromycin-sensitive strains of H. pylori
• A potassium-competitive acid blocker (PCAB) dual therapy is Voquezna DualPak. It contains Vonoprazan 20 mg BID & Amoxicillin 1000 mg TID

H. Pylori Treatment

• 1st line regiments are given for treatment-Naïve patients with H.pylori infection and without Antibiotic Susceptibility Testing
• Optimized BQT, and Rifabutin is given for patients with No Penicillin Allergy
• For those with penicillin allergy, Optimized BQT is given

Table 5: Recommended regimens for treatment-naïve patients with H. pylori infection

    - Optimized bismuth quadruple therapy include PPI, bismuth, nitroimidazole, and tetracycline.
    - **Talicia** contains omeprazole 10 mg, amoxicillin 250 mg, and rifabutin 12.5 mg. Approved dosing schedule is 4 capsules TID for 14 days.
    - **PCAB dual** (Voquezna DualPak) contains *Vonoprazan* 20 mg , Amoxicillin 1,000 mg
    - PCAB triple (Voquezna TriplePak) *Vonoprazan* 20 mg. Amoxicillin 1000 mg, Clarithromycin 500 mg 

H. pylori Antibiotic Resistance Rates in the US

• Clarithromycin resistance is at 31.5%
• Levofloxacin resistance is at 37.6%
• Metronidazole resistance is at 42.1%
• Tetracycline resistance is at 0.9%
• Amoxicillin resistance is at 2.6%
• Rifabutin resistance is at 0.2%
• Dual Metronidazole/Clarithromycin resistance is at 11.7%

Salvage Regimens for Experienced Patients with Persistent H. pylori Infections.

• Lists are present for treatment
• Lists of treatments are meant to present appropriate options but are not meant to present a treatment hierarchy
• Previous Nonoptimized treatments are prescribed instead of those new to treatment

Probiotics

• They limit H. pylori colonization
• Therapy with probiotic aid may improve eradication rates
• DO NOT eradicate the H. pylori when applied with monotherapy
• The strains Lactobacillus and Bifidobacterium help treat
• Controlled trials are needed for recommendations

What to do After Treatment

• With the increasing number of resistant H. pylori strains: around 20% of patients with H. pylori infection will fail first
• Retest for H. pylori after treatment in 4 weeks to confirm eradication
• Recheck with urea breath, fecal antigen, or biopsy-based test if required

Eradication After Initial Treatment Failure

• Patient hx to assess antimicrobial history is a must before initial treatment
• Prior exposure to macrolide is likely for clarithromycin resistance
• The treatment is to use antibiotics never used during initial therapy
• Use antibiotics not associated with resistance and topical effect

Nonsteroidal anti-inflammatory drugs (NSAIDs-Induced PUD Pathophysiology

• NSAIDs are weak acids that disrupt gastric secretions
• It causes direct topical irritation of gastric mucosa

NSAID Induced PUD Info

• Nonsalicylates: indomethacin, piroxicam, ibuprofen, naproxen, diclofenac, sulindac, ketoprofen, ketorolac, flurbiprofen
• Selective COX-2 inhibitors: etodolac, nabumetone, meloxicam, celecoxib
• Salicylates
  • Acetylated: aspirin
  • Nonacetylated: salsalate/trisalicylate

NSAID Associated Risk Factors

• Age
• History
• GI complication
• NSAID dosage

Approach to PUD.

• Evaluation of H. pylori is a must If test is negative, discontinue NSAID and start 8 weeks of PPI

NSAID-Induced PUD (Treatment Guidelines)

• For Active ulcer
  • Discontinue NSAIDs and treat with PPI
  • Initiate another analgesic after ulceration heals
• For Active ulcer that is unable to discontinue NSAIDs
  • Hold NSAIDs, and use PPI
• If NSAID is continued, a risk assessment must take place (bleeding )
  • Use of PPI is highly recommended and must be a long term
  • Moderate/High risk : depends on the number of risk factors present

Serious Risk effects of Proton-pump inhibitors (PPIs)

• Gastric cancer
• Ingested nitrates
• Osteoporosis
• Kidney issues

Drug Induced PUD

• Check patients baseline and perform CBC electrolyte check
• Use mucosal protectants for constipation and renal function
• Use labeled indication ( active PUD)
• Rarely practice in treatments
• It’s important to administer correctly

What drugs can cause GI Ulcer

• Aspirin
• Clindamycin
• Selective serotonin
• Antibiotics

How to prevent GI Ulcers ( Drug Induced)

• Have a drug/approach management
• Lower Dosage
• 8 ounce of water when taking medication
• Avoid anything that can cause ulcerations
• Use appropriate formulation
• Use microencapsulated

Management of Drug-Induced PUD

• Confirm through endoscopy
• Reassess if that agent is needed
• Use lowest possible dose if needed
• Treat patient