Peptic Ulcer Disease

Andrea M. Wilkins-Daly

BSc.,PharmD October 2009

Peptic Ulcer Disease

• Peptic Ulcer - an imbalance between aggressive factors (gastric acid and pepsin) +protective factors (gastric mucus, bicarbonate, prostaglandins).

• Peptic ulcers are chronic most often solitary, lesions that occur in any portion of gastrointestinal tract exposed to the aggressive action of acid-peptic juices.

Pathophysiology

Duodenal Ulcer – H.pyloric (95%)

- NSAIDS

Gastric Ulcer – NSAIDS

H.pyloric

ROLE OF H. Pylori INFECTION

H. pylori infection is present in almost all patients with duodenal ulcers and 70% cases with gastric ulcers.

Duodenal ulcers - Usually associated with gastritis confined to the antrum.

Gastric ulcers - Usually associated with pangastritis (inflammation of the entire stomach)

.

Other factors causing PUD -high gastrin level and excess acid production. Gastrinoma may

cause multiple peptic ulceration as in Zollinger Ellison syndrome. There is increased parietal cell mass.

- impaired mucosal defense . The gastric acid and pepsin levels are normal and no H.pylori are present.

- Chronic use of NSAIDs (aspirin) causes suppression of mucosal prostaglandin and direct irritative topical effect.

• Repeated use of corticosteroid and Chemotherapy in high dose.

• Cigarette smoking impair healing and favour recurrences.

• Alcoholic cirrhosis.• Psychological stress, ischemia.

Sites of Peptic Ulcer

• Duodenum: First portion ( few cms from the pyloric ring). Anterior wall is more often affected.

• Stomach: Usually antrum. Lesser curvature (common) . Anterior and posterior wall and greater curvature (less common).

• In the margins of a gastroenterostomy (stomal ulcer)• In the duodenum, stomach or jejunum of patients with

Zollinger-Ellison syndrome.

Mechanism of H pyloric

• Mechanism – H pylori secretes urease (generates ammonia), protease (breaks down glycoprotein in the gastric mucus)

• - breakdown of mucosal defense

****Show H plyoric Slide**treatment options

H

Mechanism Of H pyloric

• Damage of the protective mucosal layer. The epithelial cells are exposed to the damaging effect of acid-peptic digestion.

• Inflammation of the gastric mucosa.

• Chronically inflamed mucosa more susceptible to acid- peptic injury and prone to peptic ulceration.

• Ulcers occur at sites of chronic inflammation Eg - Antrum

PEPTIC ULCER DISEASE

Duodenal Ulcer

Duodenal Ulcer

DU in 65yo male

DU in 35 yo female

Duodenal ulcer

Pathophysiology

Case Presentation

• Mr. Sloley is a 45 year old male who

presents to your clinic with epigastric

abdominal pain x 2 weeks.

• What is your initial differential diagnosis at this point given the limited information?

Case Presentation

Mr Sloley History • PMH: HTN stable, Osteoarthritis in knees,

treated for an ulcer 3 years ago • Meds: Hydrochlorothiazide, ibuprofen prn • Soc HX: Married, employed as bank manager,

smokes 1ppd x 20years, drinks 2 beers per day, and 2-4 cups coffee per day

• What risk factors can you identify for PUD?

Diagnosis of H pyloric

• Breath Tests & Stool antigen tests

- Urea Breath Test ( 95-100% specificity)

-In office test (breath)

• Urea Blood test – Less Specific

• Endoscopy – culture of organism to determine antibiotic therapy

• Serologic test – not reliable (persisting antibiodies)

PUD Diagnosis

Initial Differential Diagnosis More Common: • Gastroesophageal reflux disease • Nonulcer dyspepsia/ Gastritis • Ulcer disease • Gastroenteritis • Biliary colic or cholecystitis • Pancreatitis • Irritable bowel disease

Case Study

• Mr. Sloley is a 45 year old male who presents to your clinic with epigastric abdominal pain x 2 weeks. He describes it as a burning pain which is non-radiating and is worse after he eats. He has frequent belching with bloating sensation but denies nausea, vomiting, diarrhea, constipation, or weight loss. He has tried Maalox which do help a little.

• Which symptoms support the possible diagnosis of PUD?

Case Presentation

Signs and Symptoms of PUD • Epigastric pain is most common symptom • Pain described as gnawing, burning or annoying• May radiate to the back (consider penetration) • Pain occurs when stomach is empty• Relieved by food, antacids (duodenal),

Dyspepsia including belching/ bloating • Hematemesis or melena with GI bleeding

Gastric Ulcers

• Pts with Gastric or Duodenal ulcers have similar symptoms

• Lacks pattern

• Pain occurs at anytime of day: frequently immediately or within 1-3 hrs after a meal

• Mortality rate is higher in these patients

• 10% of pts with PUD present with complications and have no prior Hx of pain

Treatment Goals

• Relieve symptoms

• Healing of ulcer

• Eliminating cause of ulcer

Treatment

• No single medication works to get rid of H pylori infection.

• 2 combinations are available Triple or Dual Therapy

• Ideal treatment regimen for H pyloric has not been identified

Treatment Options

• PPI* + clarithromycin (500 mg bid) + amoxicillin (1 gm bid ) x 10-14 days

• Eradication rate 70-85%

• PPI* + clarithromycin (500 mg bid) + metronidazole (500 mg bid) x 10-14 days Eradication rate 70-85%, use with penicillin allergy

Treatment Options

• Bismuth subsalicylate 525 mg qid + metronidazole 250 mg qid), tetracycline (500 mg bid), ranitidine 150 mg bid or PPI* x 10-14 days

• Eradication rate 75-90%, use with penicillin allergy

Treatment Options

• PPI* + amoxicillin (1 gm bid) x 5 days, then PPI + clarithromycin 500 mg bid + tinidazole 500 mg bid x 5 days

• Eradication rates > 90%, efficacy shown only in European studies

Treatment Options

FDA approved regimens

Bismuth 525 mg qid + metronidazole 250 qid, tetracycline 500 mg qid x 2 weeks + H2RA x 4 weeks

Lansoprazole* 30 mg bid + clari 500 mg bid + amoxicillin 1 gm bid x 10 days

*Substitute omeprazole 20 mg bid x 10 d or esomeprazole 40 mg qd x 10d or rabeprazole 20 mg bid x 7 days

Treatment

H. Pylori Triple Therapy Treatment • Triple therapy for 14 days is treatment of choice • Two forms of triple therapy: PPI–based and

bismuth-based • PPI based = PPI + 2 antibiotics for 2 wk, cont

PPI for additional 2 weeks. • Bismuth-based = bismuth subsalicylate and 2

antibiotics, for 2 weeks with addition of H2- blocker to optimize ulcer healing.

Treatment

For NDAID-related PUD – removal of offending agent

- Use of an anti-secretory agent therapy for relieve of symptoms

- If H pyloric present- eradication therapy

- Prevention of PUD – H2RA or PPI or misprostol with pt with chronic NSAID use at risk for developing PUD

Treatment

• Patient Counseling – adherence to therapy, proper dosing, side-effects

• Surgery –reserved pts with refractory ulcers or hemorrhage

NEW DEVOLPMENTS

• Supplementation with vitamin C enhances the success of Helicobacter pylori eradication efforts, researchers from Iran report.

• **PLEASE REMEMBER TO READ CPT MANUAL ON DRUGS AND S/E