1. Lecture 11 Gastrointestinal Disorders Peptic Ulcer
University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY II
PHCY 410
Lecture 11 Gastrointestinal Disorders Peptic Ulcer
Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

2. Course Outcomes
Upon completion of this lecture the students will be able to
Describe etiology, clinical manifestations and diagnosis of peptic ulcer.
Develop skills for monitoring drug therapy and patient education in patients with peptic ulcer.
Explain drug related problems and develop pharmaceutical care plan in patients with peptic ulcer.

3. Peptic ulcer disease (PUD) refers to a group of ulcerative disorders of the upper GI tract that require acid and pepsin for their formation.
The three common forms of peptic ulcers include
Helicobacter pylori (HP)– associated ulcers,
nonsteroidal antiinflammatory drug (NSAID)–induced ulcers,
and stress-related mucosal damage (also called stress ulcers).

4. PATHOPHYSIOLOGY
The pathogenesis of duodenal ulcers (DU) and gastric ulcers (GU) is multifactorial.
Most peptic ulcers occur in the presence of acid and pepsin when HP, NSAIDs, or other factors disrupt normal mucosal defense and healing mechanisms.
HP infection causes gastritis in all infected individuals and is causally linked to PUD.
Most non-NSAID ulcers are infected with HP, and HP eradication markedly decreases ulcer recurrence.

5. HP may cause ulcers by direct mucosal damage, altering the immune/inflammatory response, and by hypergastrinemia leading to increased acid secretion.
Nonselective NSAIDs (including aspirin) cause gastric mucosal damage by two mechanisms:
(1) a direct or topical irritation of the gastric epithelium,
(2) systemic inhibition of the cyclooxygenase-1 (COX-1) enzyme, which results in decreased synthesis of protective prostaglandins.
Use of corticosteroids alone does not increase the risk of ulcer or complications, but ulcer risk is doubled in corticosteroid users taking NSAIDs concurrently.

6. Cigarette smoking to PUD, impaired ulcer healing, and ulcer-related GI complications. The risk is proportional to the amount smoked per day.
Ulcer patients are adversely affected by stressful life events.
Coffee, tea, cola beverages, beer, milk, and spices may cause dyspepsia but do not increase PUD risk.
Ethanol ingestion in high concentrations is associated with acute gastric mucosal damage and upper GI bleeding

8. Helicobacter Pylori Infection
HP is transmitted person-to-person by three different pathways; fecal-oral, oral-oral, and iatrogenic (Physician Induced).
Helicobacter pylori is a spiral-shaped, pH-sensitive, gram-negative, micro aerophilic bacterium that resides between the mucus layer and surface epithelial cells in the stomach.
The combination of its spiral shape and flagellum permits it to move from the lumen of the stomach, where the pH is low, to the mucus layer, where the local pH is neutral.

9. HP produces large amounts of urease, which hydrolyzes urea in the gastric juice and converts it to ammonia and carbon dioxide.
The local buffering effect of ammonia creates a neutral microenvironment within and surrounding the bacterium, which protects it from the lethal effect of acid.
The diagnosis of HP infection can be made using endoscopic or non-endoscopic tests including serologic antibody detection tests, the urea breath test (UBT), and the stool antigen.

10. CLINICAL PRESENTATION
Abdominal pain is the most frequent symptom of PUD.
The pain is often epigastric and described as burning but can present as vague discomfort, abdominal fullness, or cramping.
A typical nocturnal pain may awaken patients from sleep, especially between 12 AM and 3 AM.
Pain from DU often occurs 1 to 3 hours after meals and is usually relieved by food, whereas food may precipitate or highlight ulcer pain in GU.

11. Antacids provide rapid pain relief in most ulcer patients.
Heartburn, belching, and bloating often accompany the pain. Nausea, vomiting, and anorexia are more common in GU than DU.
Complications of ulcers caused by HP and NSAIDs include upper GI bleeding, perforation into the peritoneal cavity, penetration into an adjacent structure (e.g., pancreas, biliary tract, or liver), and gastric outlet obstruction.
Bleeding may be occult or present as melena or hematemesis.

12. DIAGNOSIS
The physical examination may reveal epigastric tenderness between the umbilicus and the xiphoid process that less commonly radiates to the back.
The hematocrit, hemoglobin, and stool hemoccult tests are used to detect bleeding.
The diagnosis of HP infection can be made using endoscopic or nonendoscopic tests.
The nonendoscopic tests include serologic antibody detection tests, the urea breath test (UBT), and the stool antigen test.
Serologic tests detect circulating immunoglobulin G directed against HP.
The diagnosis of PUD depends on visualizing the ulcer crater either by upper GI radiography or endoscopy.

13. TREATMENT
The goals of treatment are relieving ulcer pain, healing the ulcer, preventing ulcer recurrence, and reducing ulcer-related complications.
NONPHARMACOLOGIC TREATMENT
Patients with PUD should eliminate or reduce psychological stress, cigarette smoking, and the use of nonselective NSAIDs (including aspirin). If possible, alternative agents such as acetaminophen, a nonacetylated salicylate (e.g., salsalate), or a COX-2 selective inhibitor should be used for pain relief.
patients should avoid foods and beverages that cause dyspepsia or exacerbate ulcer symptoms (e.g., spicy foods, caffeine, alcohol).

14. PHARMACOLOGIC TREATMENT
Eradication of HP is recommended for HP-infected patients with GU, DU, ulcer-related complications.
First-line eradication therapy is a proton pump inhibitor (PPI)–based, three-drug regimen containing two antibiotics, usually clarithromycin (500mg BID)and amoxicillin(1gm BID) or metronidazole 500 mg BID (for back-up therapy in penicillin-allergic patients) for 10 to 14 days.
The PPI should be taken 30 to 60 minutes before a meal along with the two antibiotics.
Omeprazole 20 mg twice daily or
lansoprazole 30 mg twice daily or
pantoprazole 40 mg twice daily or
esomeprazole 40 mg daily or
rabeprazole 20 mg daily or

15. bismuth based quadruple therapy using a PPI (with bismuth, metronidazole, and tetracycline) is recommended as alternative as second-line treatment.
All medications except the PPI should be taken with meals and at bedtime.
If the initial treatment fails to eradicate HP, second-line empiric treatment should:
(1) use antibiotics that were not included in the initial regimen;
(2) include antibiotics that do not have resistance problems;
(3) use a drug that has a topical effect (e.g., bismuth); and (4) be extended to 14 days.
Thus, if a PPI–amoxicillin–clarithromycin regimen fails, therapy should be instituted with a PPI, bismuth subsalicylate, metronidazole, and tetracycline for 14 days.

16. Treatment with a conventional antiulcer drug (e. g
Treatment with a conventional antiulcer drug (e.g., PPI, histamine-2 receptor antagonist [H2 RA], or sucralfate alone.
Maintenance therapy with a PPI or H2RA is recommended for high-risk patients with ulcer complications, patients who fail HP eradication, and those with HP-negative ulcers.
Patients with ulcers refractory to treatment should undergo upper endoscopy to confirm a nonhealing ulcer, exclude malignancy, and assess HP status.
HP-positive patients should receive eradication therapy.
In Hpnegative patients, higher PPI doses (e.g., omeprazole 40 mg/day) heal the majority of ulcers.

17. Treatment of NSAID-induced ulcers
Nonselective NSAIDs should be discontinued (when possible) if an active ulcer is confirmed.
Most uncomplicated NSAID-induced ulcers heal with standard regimens of an H2RA, PPI, or sucralfate.
If the NSAID must be continued reduce the NSAID dose or switching to acetaminophen, a non acetylated salicylate, a partially selective COX-2 inhibitor, or a selective COX-2 inhibitor.

18. PPIs are the drugs of choice when NSAIDs must be continued because potent acid suppression is required to accelerate ulcer healing.
If HP is present, treatment should be initiated with an eradication regimen that contains a PPI.
Patients at risk of developing serious ulcer-related complications while on NSAIDs should receive prophylactic cotherapy with misoprostol or a PPI.
In Hp negative patients, higher PPI doses (e.g., omeprazole 40 mg/day) heal the majority of ulcers.