• Naproxen = Non-selective NSAID
  → Inhibits both COX-1 and COX-2 enzymes
  → Especially blocks COX-1, which is important for stomach protection

• COX-1 normally helps produce prostaglandins
  → Prostaglandins maintain mucus, bicarbonate, and blood flow in stomach lining
  → These protect the stomach from acid damage

• Inhibition of COX-1
  → ↓ Mucus and bicarbonate secretion
  → ↓ Mucosal blood flow
  → ↑ Gastric acid damage
  → Gastric mucosa becomes vulnerable
  → Ulcer formation, bleeding, delayed healing

• In RB’s case:
  → Long-term use of naproxen 500 mg BID
  → Developed severe epigastric pain and black tarry stools
  → Diagnosed with NSAID-induced PUD

• H. pylori enters the stomach
  → Lives in the mucus layer of the stomach lining

• Produces enzyme urease
  → Urease breaks down urea → ammonia
  → Ammonia neutralizes stomach acid around the bacteria
  → Allows H. pylori to survive harsh acidic environment

• But ammonia and bacterial toxins
  → Damage the mucosal lining
  → Trigger chronic inflammation (gastritis)

• Inflammation and mucosal damage
  → Weaken protective barrier of the stomach
  → Makes the stomach lining more vulnerable to acid attack
  → Leads to ulcer formation

• Gastric ulcer –>occurs in the stomach.

• Duodenal ulcer –> occurs in the first part of the small intestine (called the duodenum).

2. Based on Cause:

• H. pylori-associated ulcer –>caused by infection with Helicobacter pylori bacteria.

• NSAID-induced ulcer –> caused by frequent use of painkillers like ibuprofen or aspirin.

• Stress ulcer –> due to severe physical stress, like after major surgery or serious illness.

• Zollinger-Ellison syndrome –> caused by a rare tumor that increases acid production.

Herbal Product & Potential Effect/Risk:

• Willow bark: Contains salicin (aspirin-like compound).

• Turmeric (high doses): May irritate stomach lining or interact with medications.

• Ginger (in large doses): Can thin blood or increase bleeding risk.

• Ginseng: May increase risk of GI bleeding with NSAIDs.

• Symptom Relief: Monitor for relief of epigastric pain, heartburn, and nausea.

• Melena: Check for dark stools and monitor hemoglobin levels if anemia is present.

• H. pylori Eradication: Evaluate effectiveness 4 weeks after therapy.

  • Urea Breath Test (Gold Standard) and Stool Antigen Test (Alternative).

  • Avoid PPIs before testing to prevent false negatives.

Managing Side Effects of Therapy:

• H. pylori Eradication Regimen (e.g., PPI + 2 antibiotics):

  • Diarrhea/Nausea: Common with antibiotics like clarithromycin and amoxicillin; consider probiotics for relief.

  • Metallic Taste: Associated with bismuth subsalicylate; typically temporary.

  • Drug Interactions:

    • Clarithromycin + Statins: Increases myopathy risk.

  • Long-Term PPI Use: Risk of hypomagnesemia, osteoporosis, and Clostridium difficile infection (C. diff).

  • PPI -> Reduce absorption of atorvastatin (monitor LDL), iron, B12, magnesium (long-term risk

• Celecoxib (COX-2 inhibitor):

  • Lower ulcer risk compared to naproxen but increases cardiovascular risk; monitor blood pressure.

• Mechanism:

  • Suppresses prostaglandin synthesis (via inhibition of phospholipase A2)

  • May delay epithelial cell turnover and healing

  • Potentiates NSAID-induced damage
    

• RB's Case: On Prednisolone 5 mg OD—low dose, but when combined with NSAIDs, there's synergistic risk for mucosal injury and ulceration.
  

📌 Combination of NSAIDs + corticosteroids is strongly associated with increased risk of GI bleeding and PUD (Ref: NCBI, PMID: 28824092).

1. Smoking (12-pack-year history)

• Delays ulcer healing

• Reduces bicarbonate secretion

• Increases gastric acid secretion

• Enhances H. pylori virulence
  

• RB's Case: Long-standing smoker. Smoking is a cofactor for duodenal ulcer formation and impairs mucosal defense.

3. Alcohol Use

• Ethanol disrupts the mucosal barrier

• Increases gastric acid secretion

• Causes direct mucosal injury
  

• RB's Case: Drinks alcohol with dinner regularly. Alcohol, especially spirits, is known to aggravate gastritis and promote ulcer symptoms like burning pain and dyspepsia.
  

4. Other Medications

• Bisphosphonates (e.g., alendronate): Cause direct mucosal irritation

• Potassium chloride: Causes esophageal and gastric ulcers

• Fluorouracil: Chemotherapeutic that may cause mucosal damage

5. Hypersecretory States

• Zollinger Ellison syndrome

• Systemic mastocytosis

• Cystic fibrosis

• Hyperparathyroidism

• Antral G cell hyperplasia

https://www.ncbi.nlm.nih.gov/books/NBK534792/

1. Creates Favorable pH Environment

PPIs raise gastric pH → enhances stability and effectiveness of antibiotics (clarithromycin, amoxicillin)

2. Improves Antibiotic Penetration

Higher pH allows better penetration into gastric mucosa, where H. pylori resides

3. Supports Mucosal Healing

While antibiotics eliminate the bacteria, PPI promotes healing of the gastric lining

1. Proton Pump Inhibitor (PPI) – e.g. Pantoprazole 40 mg BID

2. Clarithromycin – 500 mg BID

3. Amoxicillin – 1 g BID
   🔁 OR Metronidazole – 500 mg BID (if penicillin allergy)

• Pain from gastric ulcers usually starts 15–30 minutes after eating and may lead to weight loss.

• Pain from duodenal ulcers often gets better after eating and may lead to weight gain.

If a patient has anemia, black stools (melena), vomiting blood (hematemesis), or weight loss, doctors will check for serious problems like bleeding, a hole in the stomach or intestine (perforation), or cancer. On physical exam, there may be tenderness in the upper stomach and signs of anemia.

Investigations for Peptic Ulcer Disease (PUD)

1. Esophagogastroduodenoscopy (EGD)

• Most accurate test (90% sensitivity/specificity)

• Recommended for:
  • Patients over 50 with new symptoms
  • Anyone with alarm signs

2. Barium Swallow

• Used if EGD isn’t possible

3. Blood Tests

• Includes:
  • Complete Blood Count (CBC)
  • Liver Function Tests (LFTs)
  • Amylase and Lipase

4. Serum Gastrin

• Ordered if Zollinger-Ellison syndrome is suspected

5. H. pylori Testing

• Urea Breath Test – accurate, used to confirm eradication

• Rapid Urease Test – typically done during endoscopy

• Stool Antigen Test

• Serology, Urine, and Antibody Tests

6. Endoscopic Biopsy

• Used when:
  • Treatment fails
  • Resistance is suspected

• Taking samples from 4–6 sites improves accuracy

7. CT Scan (with Contrast)

• Not used to directly diagnose ulcers

• Helpful for detecting complications like:
  • Perforation
  • Obstruction

8. Fecal Occult Blood Test (FOBT)

• Detects hidden (occult) blood in the stool

• Used to screen for:
  • Colorectal cancer
  • Other sources of GI bleeding

• Two main types:
  • Guaiac-based FOBT (gFOBT)
  • Fecal Immunochemical Test (FIT)

References:

https://www.ncbi.nlm.nih.gov/books/NBK534792/#:~:text=Evaluation,be%20evaluated%20by%20an%20EGD.

https://medlineplus.gov/lab-tests/fecal-occult-blood-test-fobt/#:~:text=What%20is%20a%20fecal%20occult,cancer%20before%20you%20have%20symptoms.

• Bismuth-based quadruple therapy:

  • PPI (Omprazole 20 mg OD) / H2RA+ Bismuth subsalicylate 120 mg QID + metronidazole 400mg TDS + tetracycline 500mg TDS

RB was diagnosed with NSAID-induced peptic ulcer:

• Long-term use of naproxen (500 mg BID)

• Also on prednisolone (another ulcer risk factor)

• Symptoms: epigastric pain, melena, rebound tenderness

• Initiated on Pantoprazole for suspected NSAID-induced ulcer

After Test Results (Trigger 2):

Confirmed H. pylori-positive via:

• Urea breath test

• Rapid urease test (biopsy sample)

➡️ Final diagnosis: Mixed etiology peptic ulcer
✔ NSAID-induced
✔ H. pylori-associated

1. NSAID-Induced Ulcer

   • Caused by long-term use of NSAIDs (e.g. naproxen, ibuprofen)

   • Often asymptomatic until complications arise

   • Occurs in stomach or duodenum

   • More common in older adults or those on steroids

2. H. pylori-Associated Ulcer

   • Caused by Helicobacter pylori infection

   • Chronic inflammation weakens mucosal lining → ulceration

   • Typically affects duodenum > stomach

3. Stress-Related Ulcer

   • Seen in critically ill patients (e.g. ICU, severe trauma)

   • Due to hypoperfusion and acid hypersecretion

4. Zollinger-Ellison Syndrome

   • Rare — due to gastrin-secreting tumor → excessive acid

   • Leads to recurrent or multiple ulcers

• Metallic taste

• Black tongue or black stools (harmless but may alarm patients)

• Nausea or constipation

• Avoid in patients allergic to aspirin (contains salicylate component)

💊 Important Drug Interactions

Clarithromycin + Atorvastatin:

• Clarithromycin inhibits CYP3A4 → increases atorvastatin levels

• Risk of myopathy or rhabdomyolysis

• Recommendation: Temporarily stop statin or switch to pravastatin/rosuvastatin

Pantoprazole + Atorvastatin:

• PPI may reduce atorvastatin absorption

• Monitor LDL cholesterol levels during/after PPI therapy

🔎 Long-Term Monitoring Considerations for PPI Use

• Hypomagnesemia → Monitor for muscle cramps, arrhythmia if PPI is prolonged

• Vitamin B12 deficiency → Monitor if used >1 year or in elderly

• Osteoporosis/fractures → Consider bone health assessment in high-risk patients

• Clostridium difficile infection → Watch for persistent diarrhea

• Renal effects (CKD) → Monitor serum creatinine for long-term users

• Discontinue NSAIDs (e.g., naproxen) – switched to celecoxib with lower GI risk

• Complete H. pylori eradication therapy (e.g., PPI + amoxicillin + clarithromycin for 14 days)

• Confirm eradication with urea breath test 4 weeks after treatment

• 2. Pharmacological Strategy

• Avoid long-term PPI use once ulcer is healed and H. pylori is eradicated

• If NSAID is still needed, consider PPI co-therapy as gastroprotection

3. Lifestyle Modifications

• Stop smoking – RB has a 12-pack-year history; smoking delays ulcer healing

• Limit alcohol intake – alcohol irritates gastric mucosa

• Avoid trigger foods (e.g., spicy, acidic, fatty foods)

4. Patient Education

• Stress the importance of adherence to full H. pylori treatment

• Educate on symptoms of recurrence (e.g., melena, epigastric pain)

• Advise to avoid self-medicating with NSAIDs

5. Regular Follow-Up

• Monitor for symptom recurrence and check healing progress

• Reassess ongoing need for celecoxib or any NSAIDs

• Encourage reporting of any new GI symptoms promptly

• Mechanism: Gaviscon works by forming a protective "raft" (via alginate) that floats on top of stomach contents to reduce reflux into the esophagus, and by neutralizing acid with antacids giving a quick, short-term relief from symptoms like heartburn and acid reflux
  
  

• Limitation: It does not suppress acid production, heal ulcers, or reverse mucosal damage caused by NSAIDs or H. pylori
  
  

🔬 Source: NCBI – Gaviscon’s raft-forming mechanism is effective in GERD but not for ulcer healing (PMID: 27195314).

2. Gaviscon has no antibacterial activity against H. pylori

• Helicobacter pylori is a spiral-shaped, gram-negative bacterium that colonizes the gastric mucosa, leading to:

  • Chronic inflammation

  • Mucosal injury

  • Ulcer formation

• This infection requires antibiotic therapy + acid suppression to eradicate.

• Gaviscon does not have antibacterial activity → it cannot eliminate H. pylori or halt its inflammatory effects.
  
  

📚 Source: NIH MedlinePlus – H. pylori Infection
📚 MOH Malaysia CPG 2020 – “Antacids do not eradicate H. pylori.”

3. NSAID-Induced Mucosal Injury – The Accelerating Factor

• RB was taking naproxen (a non-selective NSAID), which:

  • Inhibits COX-1 → ↓ prostaglandins

  • Prostaglandins normally help maintain the gastric mucosal barrier by:

    • Increasing mucus and bicarbonate secretion

    • Promoting mucosal blood flow

    • Supporting cell repair

Without prostaglandins:

• The mucosa becomes vulnerable to acid and pepsin, leading to erosions and ulcers

• Alleviate epigastric pain, heartburn, nausea, and dysphagia

• Improve quality of life and reduce discomfort

• These symptoms directly affect quality of life and may worsen if untreated. Pain relief is often the first thing patients look for in PUD.

  
  

Outcome: Improved comfort, reduced episodes of pain, and better sleep quality, which all contribute to recovery.

MOH Malaysia Dyspepsia CPG (2020): Symptom relief is one of the primary endpoints in PUD therapy.

2. Eradicate Helicobacter pylori Infection

• A important goal to cure H. pylori-induced ulcers and prevent recurrence and reducing the risk of gastric cancer.

• H. pylori is responsible for most peptic ulcers, and if not eradicated, ulcers are likely to recur.

Outcome: Successful eradication of H. pylori within 14 days, leading to reduced ulcer recurrence and decreased gastric cancer risk.

NCBI – “H. pylori eradication promotes ulcer healing and prevents recurrence.” [PMID: 35405147]
NIH – “Without eradication, recurrence rates are as high as 70–90% within one year.”

3. Promote Healing of Gastric Mucosa

• Facilitate the repair of the gastric or duodenal mucosa affected by the ulcer.

• Reduce acid secretion using proton pump inhibitors (PPIs) to allow mucosa to regenerate.

Outcome: Complete healing of the ulcer over 4-8 weeks, depending on severity.

4. Prevent Recurrence and Complications

• Minimize the risk of future ulcer formation in the patient.

• Even after treatment, ulcers can recur if contributing factors (like NSAID use or ongoing H. pylori infection) are not addressed.
  

• Prevent complications such as:

  • Upper GI bleeding

  • Gastric perforation

  • Gastric outlet obstruction

Outcome: Lower risk of future ulcers and improved long-term gastric health and minimise life-threatening complications, particularly bleeding or perforation.

5. Address Modifiable Risk Factors

• Eliminate or reduce lifestyle factors that worsen ulcer healing and increase the risk of ulcer recurrence. Such as:

  
  

• Stopping NSAIDs (or substitute with celecoxib + PPI)

• Discontinue alcohol

• Encourage smoking cessation

• Manage stress, weight, and diet
  

Outcome: Improved healing rates, reduced risk of ulcer recurrence, and better overall gastric health.

• Upper gastrointestinal bleeding

• Gastric outlet obstruction

• Perforation

• Penetration

• Gastric cancer

• Naproxen is a non-selective NSAID, which means it inhibits both COX-1 and COX-2 enzymes.

  • COX-1 protects the stomach lining, so blocking it can lead to stomach ulcers, bleeding, or gastritis.

• Celecoxib is a COX-2 selective inhibitor, so it's gentler on the stomach and often preferred in patients with a history of GI issues.

2. Cardiovascular Risk

• In some cases, celecoxib might be preferred if naproxen worsens blood pressure control or interacts with cardiovascular meds.

3. Chronic Pain Management

• Celecoxib is often prescribed for chronic conditions like osteoarthritis or rheumatoid arthritis where long-term NSAID use is needed — again, due to its better GI tolerability.

• It also has a longer half-life, so can be taken once daily in some cases.

Dose for celecoxib for osteoarthritis:

200 mg OD or 100 mg BD or PRN

References:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11160842/#:~:text=Results:,inhibition%20(p%3C0.05).

https://www.mims.com/malaysia/drug/info/celebrex/dosage

In peptic ulcer disease, the aggravating factor is more than the mucosal defensive factor. This results the mucosal layer being destroyed and the damage is extended to the inner layer. On prolonged exposure of stomach lining to gastric acid, perforation and gastric bleeding occurs.

RB likely has severe peptic ulcer (evidenced by bleeding, melena, and positive FOBT).

Antacids like Gaviscon are typically effective for mild or occasional heartburn, not for active ulcers or severe gastric inflammation.

2. NSAID-Induced Mucosal Damage:

RB was taking Naproxen (an NSAID), which inhibits COX-1 enzyme.

This leads to reduced prostaglandin synthesis, which is essential for:

Mucosal protection (stimulating mucus and bicarbonate secretion).

Maintaining mucosal blood flow and healing.

Antacids do not repair mucosal injury or reverse prostaglandin inhibition caused by NSAIDs.

3. Rebound Acid Hypersecretion:

Frequent use of antacids may lead to rebound acid hypersecretion.

This occurs when the stomach increases acid production in response to temporary neutralization.

Can potentially worsen symptoms once the effect of the antacid wears off.

Retesting may be needed if symptoms persist or based on initial findings.

Medication interference: Antibiotics, PPIs, bismuth, and possibly H2 blockers can affect test accuracy.

Stop antibiotics ≥4 weeks and PPIs/bismuth ≥2 weeks before testing if possible.

Post-treatment confirmation of eradication should be done ≥4 weeks after antibiotics using the same diagnostic tests (e.g., urea breath test, stool antigen test).

https://www.racgp.org.au/afp/2014/may/helicobacter-pylori-eradication

Frequent or persistent heartburn can be a sign of gastroesophageal reflux disease (GERD), a more serious condition. 

• Blood clotting:

  COX-1 in platelets helps produce thromboxane, which is involved in blood clotting. 

• Stomach lining protection:

  COX-1 helps maintain the integrity of the stomach lining by producing prostaglandins that protect against ulcers and other damage. 

• Kidney function:

  COX-1 contributes to renal blood flow regulation.