Download Peptic Ulcer Disease (PUD)

Peptic Ulcer Disease
(PUD)
Pharm.D Balsam Alhasan
DEFINITION:
• Peptic ulcer disease (PUD) refers to a group of ulcerative
disorders of the upper 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.
• The three common forms of peptic ulcers include:
1. Helicobacter pylori (HP)– associated ulcers,
2. Nonsteroidal antiinflammatory drug (NSAID)–induced ulcers,
3. And stress-related mucosal damage (also called stress
ulcers).
PATHOPHYSIOLOGY
• The pathogenesis of duodenal ulcers (DU) and gastric ulcers
(GU) is multifactorial and most likely reflects a combination of
pathophysiologic abnormalities and environmental and genetic
factors.
• Most peptic ulcers occur in the presence of acid and pepsin
when HP, NSAIDs, or other factors disrupt normal mucosal
defense and healing mechanisms.
• Acid is an independent factor that contributes to disruption of
mucosal integrity. Increased acid secretion has been observed
in patients with DU and may result from HP infection. Patients
with GU usually have normal or reduced rates of acid
secretion.
PATHOPHYSIOLOGY (Cont.)
• Alterations in mucosal defense induced by HP or NSAIDs are
the most important cofactors in peptic ulcer formation.
Mucosal defense and repair 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.
PATHOPHYSIOLOGY (Cont.)
• HP infection causes gastritis in all infected individuals and is
causally linked to PUD. However, only about 20% of infected
persons develop symptomatic PUD. Most non-NSAID ulcers
are infected with HP, and HP eradication markedly decreases
ulcer recurrence. HP may cause ulcers by direct mucosal
damage, altering the immune/inflammatory response, and by
hypergastrinemia leading to increased acid secretion.
PATHOPHYSIOLOGY (Cont.)
• Nonselective NSAIDs (including aspirin) cause gastric mucosal
damage by two mechanisms:
• (1) A direct or topical irritation of the gastric epithelium, and
• (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.
Other Factors:
• Epidemiologic evidence links cigarette smoking to PUD,
impaired ulcer healing, and ulcer-related GI complications.
• The risk is proportional to the amount smoked per day.
• 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.
Other Factors:
• 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.
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
accentuate ulcer pain in GU.
CLINICAL PRESENTATION
• 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.
• The severity of symptoms varies from patient to patient and
may be seasonal, occurring more frequently in the spring or
fall.
CLINICAL PRESENTATION
• Pain does not always correlate with the presence of an ulcer.
• Asymptomatic patients may have an ulcer at endoscopy, and
patients may have persistent symptoms even with
endoscopically proven healed ulcers. Many patients
(especially older adults) with NSAID-induced, ulcer-related
complications have no prior abdominal symptoms.
Complications:
• Complications of ulcers caused by HP and NSAIDs include:
1.
Upper GI bleeding,
2. Perforation into the peritoneal cavity,
3. Penetration into an adjacent structure (e.G., Pancreas,
biliary tract, or liver),
4. And gastric outlet obstruction.
• Bleeding may be occult or present as melena or hematemesis.
Complications:
• Perforation is associated with sudden, sharp, severe pain,
beginning first in the epigastrium but quickly spreading over
the entire abdomen.
• Symptoms of gastric outlet obstruction typically occur over
several months and include early satiety, bloating, anorexia,
nausea, vomiting, and weight loss.
DIAGNOSIS
• The physical examination may reveal epigastric tenderness
between the umbilicus and the xiphoid process that less
commonly radiates to the back.
• Routine laboratory tests are not helpful in establishing a
diagnosis of uncomplicated PUD. The hematocrit, hemoglobin,
and stool hemoccult tests are used to detect bleeding.
Diagnostic Procedures:
• The diagnosis of HP infection can be made using endoscopic
or nonendoscopic tests. The tests that require upper
endoscopy are invasive, more expensive, uncomfortable, and
usually require a mucosal biopsy for histology, culture, or
detection of urease activity.
• The nonendoscopic tests include serologic antibody detection
tests, the urea breath test (UBT), and the stool antigen test.
Diagnostic Procedures:
• Serologic tests detect circulating immunoglobulin G directed
against HP but are of limited value in evaluating posttreatment eradication.
• The UBT is based on urease production by HP.
• Testing for HP is only recommended if eradication therapy is
considered.
Diagnostic Procedures:
• If endoscopy is not planned, serologic antibody testing is
reasonable to determine HP status. The UBT is the preferred
nonendoscopic method to verify HP eradication after
treatment.
• 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.
Diagnostic Procedures:
• Upper endoscopy should be performed if complications
are thought to exist or if an accurate diagnosis is
warranted. If a GU is found on radiography, malignancy
should be excluded by direct endoscopic visualization
and histology.
DESIRED OUTCOME
• The goals of treatment are relieving ulcer pain, healing
the ulcer, preventing ulcer recurrence, and reducing
ulcer-related complications.
• In HP positive patients with an active ulcer, a previously
documented ulcer, or a history of an ulcer-related
complication, the goals are to eradicate the organism,
heal the ulcer, and cure the disease with a cost-effective
drug regimen.
TREATMENT
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.
• Although there is no need for a special diet, patients should
avoid foods and beverages that cause dyspepsia or
exacerbate ulcer symptoms (e.g., spicy foods, caffeine,
alcohol).
PHARMACOLOGIC
TREATMENT
• Eradication of HP is recommended for HP-infected
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
(Table 29-1).
Therapeutic Options:
• First-line eradication therapy is a proton pump inhibitor
(PPI)–based, three-drug regimen containing two antibiotics,
usually clarithromycin and amoxicillin, reserving
metronidazole for back-up therapy (e.g., clarithromycin–
metronidazole in penicillin-allergic patients). The PPI should
be taken 30 to 60 minutes before a meal along with the two
antibiotics.
Therapeutic Options:
• Although an initial 7-day course provides minimally
acceptable eradication rates, longer treatment periods (10 to
14 days) are associated with higher eradication rates and less
antimicrobial resistance.
• First-line treatment with quadruple therapy using a PPI (with
bismuth, metronidazole, and tetracycline) achieves similar
eradication rates as PPIbased triple therapy and permits a
shorter treatment duration (7 days).
• However, this regimen is often recommended as secondline treatment when a clarithromycin–amoxicillin
regimen is used initially. All medications except the PPI
should be taken with meals and at bedtime.
Failed Eradication:
• 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.
Conventional Protocols:
• Treatment with a conventional antiulcer drug (e.g., PPI,
histamine-2 receptor antagonist [H2RA], or sucralfate alone is
an alternative to HP eradication but is discouraged because of
the high rate of ulcer recurrence and ulcer-related
complications.
• Dual therapy (e.g., H2 RA plus sucralfate, H2RA plus PPI) is not
recommended because it increases cost without enhancing
efficacy.
Maintenance therapy:
• Maintenance therapy with a PPI or H2RA (Table 29-2) is
recommended for high-risk patients with ulcer complications,
patients who fail HP eradication, and those with HP-negative
ulcers.
• For 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 (see Table 29-2) if the
NSAID is discontinued.
Patients on NSAIDs:
• 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.
Special Cases:
• Patients at risk of developing serious ulcer-related
complications while on NSAIDs should receive prophylactic
therapy 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 patients should receive eradication therapy. 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.
Evaluation Of Therapeutic
Outcomes:
• 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.
Evaluation Of Therapeutic
Outcomes:
• The persistence or recurrence of symptoms within 14
days after the end of treatment suggests failure of ulcer
healing or HP eradication, or an alternative diagnosis
such as gastroesophageal reflux disease.
• Most patients with uncomplicated HP-positive ulcers do
not require confirmation of ulcer healing or HP
eradication.
Evaluation Of Therapeutic
Outcomes:
• 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 symptomatic recurrence, refractory disease,
complications, or suspected hypersecretory states.
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