Transcript Slide 1

Clinical Pharmacy
Chapter Eight
Peptic ulcer disease
Rowa’ Al-Ramahi
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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.
•
1.
2.
3.
The three common forms of peptic ulcers include:
Helicobacter pylori (HP)– associated ulcers.
NSAID–induced ulcers.
Stress-related mucosal damage (also called stress
ulcers).
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PATHOPHYSIOLOGY
• 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.
• 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.
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• 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.
• 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.
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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. 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.
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DIAGNOSIS
• The hematocrit, hemoglobin, and stool hemoccult tests are
used to detect bleeding.
• 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.
• Serologic tests detect circulating immunoglobulin G
directed against HP but are of limited value in evaluating
posttreatment eradication.
• The urea breath test UBT is based on urease production
by HP. Testing for HP is only recommended if eradication
therapy is considered.
• Radiography may be the preferred initial diagnostic
procedure in patients with suspected uncomplicated PUD.
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 and6
histology.
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).
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PHARMACOLOGIC TREATMENT
• First-line eradication therapy for HP 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. 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 PPI based triple
therapy and permits a shorter treatment duration (7
days). However, this regimen is often recommended as
second-line treatment when a clarithromycin–amoxicillin
regimen is used initially. All medications except the PPI
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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.
• Treatment with a conventional antiulcer drug (e.g., PPI,
histamine-2 receptor antagonist [H 2 RA], or sucralfate
alone is an alternative to HP eradication but is discouraged
because of the high rate of ulcer recurrence and ulcerrelated complications. Dual therapy (e.g., H 2 RA plus
sucralfate, H 2 RA plus PPI) is not recommended because
it increases cost without enhancing efficacy.
• Maintenance therapy with a PPI or H 2 RA is
recommended for high-risk patients with
ulcer
complications, patients who fail HP eradication, and those
with HP-negative ulcers.
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• 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 H 2 RA, PPI, or
sucralfate if the NSAID is discontinued. If the NSAID must be
continued, consideration should be given to reducing the
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
ulcer-related complications while on NSAIDs should receive
prophylactic cotherapy with misoprostol or a PPI.
• Patients with ulcers refractory to treatment should undergo
upper endoscopy. 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 10to
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.
• 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.
• 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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