PUD) Peptic ulcer disease (PUD) refers to a group of ulcerative disorders of the upper gastrointestinal (GI) tract that

require acid and pepsin for their formation. Ulcers differ from gastritis and erosions in that they extend deeper into the muscularis mucosa.

Helicobacter pylori (HP)-associated ulcers, nonsteroidal anti-inflammatory drug (NSAID)induced ulcers, and stress-related mucosal damage (also called stress ulcers).

Factors that Increase Acidity

Factors that Protect Against Acidity

Factors Increasing
H. pylori NSAIDs Acidic agents Pepsin Smoking

Factors Decreasing
Mucus production Buffers Blood flow Prostaglandins

Most peptic ulcers occur in the presence of acid and pepsin when H. pylori, NSAIDs, or other factors disrupt normal mucosal defense and healing mechanisms. Acid is an independent factor that contributes to disruption of mucosal integrity. Alterations in mucosal defense induced by H.Pylori or NSAIDs are the most important cofactors in peptic ulcer formation.

Mucosal defense mechanisms include mucus

and bicarbonate secretion, intrinsic epithelial cell defense, and mucosal blood flow. Maintenance of mucosal integrity and repair is mediated by endogenous prostaglandin production.

H. pylori 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. H. pylori may cause ulcers by:
direct mucosal damage, impairing mucosal defense via elaboration of toxins and enzymes( urase), altering the immune/inflammatory response, and increasing antral gastrin release, which leads to increased acid secretion.

Nonselective NSAIDs (including aspirin) cause gastric mucosal damage. Use of corticosteroids alone does not increase the risk of ulcer or complications, but ulcer risk is doubled in corticosteroid users taking NSAIDs concurrently.

Epidemiologic evidence links cigarette smoking to PUD, impaired ulcer healing, and ulcer-related GI complications. Although clinical observation suggests that ulcer patients are adversely affected by stressful life events, controlled studies have failed to document a cause-and-effect relationship.

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 but is not clearly the cause of ulcers.

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. Pain from Duodenal Ulcer often occurs 1 to 3 hours after meals and is usually relieved by food, whereas food may precipitate or accentuate ulcer pain in Gastric Ulcer. 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. 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.

Physical examination may reveal epigastric tenderness between the umbilicus and the xiphoid process that less commonly radiates to the back. Hct, Hb, and stool hemoccult tests are used to detect bleeding. The diagnosis of HP infection can be made using endoscopic or non-endoscopic tests.

Non-endoscopic

tests

include

serologic

antibody

detection tests, the urea breath test (UBT), and the stool antigen test. The diagnosis of PUD depends on visualizing the ulcer crater either by upper GI radiography or endoscopy.

Radiography may be the preferred initial diagnostic

procedure in patients with suspected uncomplicated PUD.

If complications are thought to exist or if an accurate diagnosis is warranted upper

endoscopy should be performed. If a gastric ulcer is found on radiography, malignancy should be excluded by direct endoscopic visualization and histology.

The goals of treatment are:

Relieving ulcer pain, healing the ulcer, preventing ulcer recurrence, and reducing ulcer-related complications. In HP-positive patients, the goals are to eradicate the organism, heal the ulcer, and cure the disease with a cost-effective drug regimen.

Nonpharmacologic Treatment Patients with PUD should eliminate or reduce psychological stress, cigarette smoking, and the use of NSAIDs. Patients should avoid foods and beverages that cause dyspepsia or exacerbate ulcer symptoms (e.g., spicy foods, caffeine, and alcohol).

Eradication of HP is recommended for HPinfected patients with GU, DU, ulcer-related complications, and in some other situations.

Treatment should be effective, well tolerated, easy to comply with, and cost-effective.
First-line eradication therapy is
o a proton pump inhibitor (PPI)-based three-drug regimen containing two antibiotics.

The PPI should be taken 15 to 30 minutes before meals along with the two antibiotics. Although an initial 7-day course provides minimally acceptable eradication rates, longer treatment periods (10 to 14 days) are associated higher eradication rates and less with antimicrobial resistance. First-line treatment with quadruple therapy using a PPI (with bismuth, metronidazole, and tetracycline) achieves similar eradication rates as PPI-based triple therapy and permits a shorter treatment duration (7 days).

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); (4) be extended to 10 to 14 days.

Conventional treatment with standard dosages of H2RA or sucralfate alone (without antibiotics) relieves ulcer symptoms and heals most gastric and duodenal ulcers in 6 to 8 weeks. PPIs provide comparable healing rates over 4 weeks.

Maintenance therapy with a PPI, low-dose H2RA, or sucralfate may be indicated for :
patients who have a history of ulcer-related complications, a healed refractory ulcer, failed HP eradication therapy, or who are heavy smokers or NSAID users.

Most uncomplicated NSAID-induced ulcers heal with standard regimens of an H2RA, PPI, or sucralfate if the NSAID is discontinued.
If the NSAID must be continued, consideration should be given to:
reducing the NSAID dose or switching to acetaminophen, a nonacetylated salicylate, a partially selective COX-2 inhibitor, or a selective COX-2 inhibitor.

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 ulcerrelated complications while on NSAIDs should receive prophylactic cotherapy with misoprostol or a PPI.

Patients with ulcers refractory to treatment should undergo upper endoscopy to confirm a nonhealing ulcer, exclude malignancy, and assess HP status.
HP-positive therapy. patients should receive eradication

In HP-negative patients, higher PPI doses (e.g., omeprazole 40 mg/day) heal the majority of ulcers. Continuous PPI treatment is often necessary to maintain healing.

Patients should be monitored for symptomatic relief of ulcer pain as well as potential adverse effects and drug interactions related to drug therapy. Ulcer pain typically resolves in a few days when NSAIDs are discontinued and within 7 days upon initiation of antiulcer therapy. Most patients with uncomplicated PUD will be symptom-free after treatment with any one of the recommended antiulcer regimens.

High-risk patients on NSAIDs should be closely monitored for signs and symptoms of bleeding,

obstruction, penetration, and perforation.

Follow-up endoscopy is justified in patients with frequent disease, symptomatic recurrence, or refractory suspected

complications,

hypersecretory states.