Peptic Ulcer Disease

1
 Definition

• 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.
• The three common forms of peptic ulcers include
Helicobacter pylori (HP)-associated ulcers, nonsteroidal
anti-inflammatory drug (NSAID)-induced ulcers, and
stress-related mucosal damage (also called stress ulcers).2
 Pathophysiology

• 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 HP or

NSAIDs are the most important cofactors in peptic ulcer

formation. 3
Gastric parietal cell undergoing transformation after
secretagogue-mediated stimulation

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 Gastric Mucosa & Secretions
• The inside of the stomach is bathed in about 2 liters of
gastric juice every day

• Gastric juice
– is composed of digestive enzymes & concentrated
hydrochloric acid, which can readily tear apart the
toughest food or microorganism

• The gastroduodenal mucosal integrity is determined by

protective (defensive) & damaging (aggressive) factors
 Pathophysiology
Defensive factors:
-Mucus: continually secreted, protective effect
-Bicarbonate: secreted from endothelial cells
-Blood flow: good blood flow maintains
mucosal integrity
-Prostaglandins: stimulate secretion of
bicarbonate and mucus, promote blood flow,
suppress secretion of gastric acid
Components involved in providing gastroduodenal
mucosal defense and repair

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H.pylori as a cause of
PUD

85 95% DU
%
GU
 Pathophysiology….

• H. pylori may cause ulcers by direct

mucosal damage, impairing mucosal
defense via elaboration of toxins and
enzymes, altering the immune/inflammatory
response, and by increasing antral gastrin

release, which leads to increased acid

secretion. 10
1 . Etiology – Helicobacter pylori
Outline of the bacterial and host factors important in
determining H. pylori–induced gastrointestinal disease.

MALT- mucosal-
associated lymphoid
tissue.
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Etiology -Non-Steroidal Anti-inflammator
Drugs (NSAIDS)
 Pathophysiology….
• 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.

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Mechanisms by which NSAIDs may induce
mucosal injury

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Risk Factors Associated with Nonsteroidal Anti-
inflammatory
Drug (NSAID)–Induced Ulcers and Upper
Complicatio
Gastrointestinal ns
 Pathophysiology….
• 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. 17
 Peptic Ulcer Disease…..Classification
• Two types………duodenal and gastric ulcer
• Duodenal Ulcer……….Common causes:
– H. pylori infection (95%)
– NSAIDs
• Other causes……
– Infection (CMV /Cytomegalovirus/, Herpes simplex, TB)
• Clinical sings/Symptoms
– Epigastric pain…………..pain at night when stomach is
empty
– Pain occurs 1-3 hrs after a meal
– relieved by eating ………..b/s the acid stays in the
stomach
 PUD…..
Gastric ulcer

• Common causes…………………NSAIDs, H. pylori

• Clinical sings/symptoms:
– Epigastric pain worsen by eating
• Risk factors……………..Age >60………and…..
• History of previous ulcer
• Medications
– Concurrent use of
corticosteroids/anticoagulants/NSAIDs
 Clinical Presentation of Peptic Ulcer Disease
Symptoms in general :

• Mild epigastric pain that may be described as burning, or aching in

character.

• Abdominal pain may be described as burning or a feeling of

discomfort.

• Some patients report nocturnal pain.

• The severity of pain often fluctuates.

• Pain often occurs 1 to 3 hours after meals.

• Patients may also complain of heartburn, belching, bloating, nausea,

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or vomiting.
 Presentation of Peptic Ulcer Disease

Signs:
• Weight loss may be associated with
nausea and vomiting.
• Complications such as bleeding,
perforation, or obstruction may occur.
• Alarm signs and symptoms include:
bleeding, anemia, tarry stools or “coffee-
grounds” emesis, and weight loss.
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 PUD: Complication
• Acute perforation
– Severe abdominal pain
– Shock
– Abdominal boardlike rigidity (and rebound and other signs of
peritoneal irritation)
– Free intraperitoneal air
• Hemorrheage
– Hematemesis and/or melena
– Hemodynamic changes, anemia
• Gastric outlet obstruction
– Satiation(being full), inability to ingest food, belching
– Nausea, vomiting (and related disturbances)
– Weight loss
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Diagnostic Paths And Tools In Ulcer Disease

• Path 1 Morphologic Diagnosis

– Gastroduodenoscopy
– Endoscopic ultrasound (selected cases only)
– Computed tomography (useful in selected cases)
• Path 2 Etiologic Diagnosis
• HELICOBACTER PYLORI TESTING
– Histologic examination of gastric mucosa
– Stool antigen test
– Carbon-13–urea breath test
– Serum antibodies 23
 Type of H. pylori testing

• Invasive……………use endoscopic
• Rapid urase tests ……
– detects the presence of NH3
– False negative – GI bleeding, Use of PPIs,
H2RAs
• Culture –time consuming but 100% specific
 Urea breath tests
Radioactive CO2 after the ingestion of 13C labeled urea
False negative – recent use of antibiotic or PPI (up to 40%)
 Type of H. pylori testing
• Serologic – detects antibody to H. pylori …
– 85% sensitive
– Detects both active infection vs. past exposure
– Not a good monitoring test for eradication
– Discontinue PPI 2 wks prior and 4 weeks after testing
• Stool antigen Test
– Antibody test to detect the presence of H.
pylori in the stool (88-92%) sensitive
– Bismuth, PPI, antibiotics….interfere with the test
 Diagnosis

• 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.

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Endoscopy demonstrating: A. a benign duodenal
ulcer; B. a benign gastric ulcer.

A B

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Endoscopic view of uncomplicated erosive
gastritis

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Endoscopic view of an ulcer at the anterior wall
of the duodenal bulb

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 TREATMENT

• The treatment selected for PUD

depends on the following factors:
I. the etiology of the ulcer;
II. whether the ulcer is new or
recurrent; and
III. the presence of any ulcer-related
complications.

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 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, the goals are to
eradicate the organism, heal the ulcer, and cure
the disease with a cost-effective drug regimen.
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 PUD Treatment
• Therapy is directed at enhancing host defense &
eliminating aggressive /damaging factors;
Aggressive Factors Defensive Factors

H. pylori 
Mucus

NSAIDs 
bicarbonate layer

Acid 
Blood flow
 
cell renewal

Prostaglandins

Phospholipid
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Non pharmacological recommendations

◦Elevate head @ bed

◦Weight loss
◦Smoking cessation
◦reduce psychological stress
◦Avoid trigger foods:
 Fatty
 Spicy
 Chocolate
 Citrus
 EtOH
 Caffeine
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 Drugs
Therapy
 H2-Receptors antagonists
 Proton pump inhibitors
 Cyto-protective agents
 Prostaglandin agonists
 Antacids
Antimicrobials for H. pylori

eradication
Such as clarithromycin,
metronidazole, amoxicillin
 PPIs
• Most potent suppressors of acid secretion
– 24-48 hr effects on acid suppression

• Irreversible inhibitor of proton pump

(H+/K+ATPase); blocks 98% of acid secretion in all
forms

• The drug is given in gelatin coated capsule to

resist breakdown in stomach acid.

• It reaches the intestine, well absorbed, enters

blood stream,reaches the parietal cell.
 Histamine H2 Receptor Blockers
• Inhibit secretion of gastric acid through competitive
inhibition of Histamine H2 receptors

• These drugs are less potent than proton pump inhibitors

but still suppress 24-hour gastric acid secretion by ~70%.

• Prevention & tx of PUD, Esophagitis, GI bleeding, and stress

ulcers

Cimetidine Famotidine Ranitidine Nizatidine

 Pharmacokinetics of H2 Receptor Blockers

 Rapidly absorbed after oral administration, which

may be enhanced by food or decreased by
antacids.
 Excretion: renal filtration and tubular secretion of
the parent and metabolites, metabolism in liver.
 Dose adjustment may be required in patients with
decreased creatinine clearance.
Adverse effects H2 Receptor Blockers
 Generally well tolerated and very few side effects
(except for cimetidine)
 Include diarrhea, headache, drowsiness, fatigue,
muscular pain, and constipation.
 Less common: confusion, delirium, hallucinations,
slurred speech (with IV administration)
 Galactorrhea in women(inhibit estrogen metabolism)
and gynecomastia in men , reduced sperm count, and
impotence in men (with larger dose and/or prolonged
use of Cimetidine)
 Prostaglandins (PGE2 & PGI2 )
• Produced by the gastric mucosa, inhibit
secretion of gastric acid and stimulate
secretion of mucus and bicarbonate
Stimulates:
Inhibits: – Mucus secretion
– Acid secretion – Bicarbonate secretion
– Gastrin release – Mucosal blood flow
– Pepsin secretion
These compounds act by both inhibition of acid
production and by increasing defense mechanisms

• These compounds are also effective against direct

damage produced by alcohol, aspirin and NSAIDs,
and are therefore termed “cytoprotective”
 Misoprostol: a stable analog of PGE2
• Inhibits secretion of gastric acid and stimulate
secretion of mucus and bicarbonate.
• Dilate blood vessel of mucous membrane.
• less effective than H2-receptor antagonists for
acute treatment of peptic ulcers.
 Previously for prevention of gastric ulcers
induced by NSAIDs.
• Produces uterine contractions and is
contraindicated during pregnancy.
 Sucralfate (Carafate)
• Stimulates local prostaglandin synthesis, adsorbs pepsin
- protects the gastric and duodenal mucosa from acid/pepsin attack
(cytoprotective).
• - It has no acid-buffering capacity.

 Use: frequently used for prophylaxis of stress-induced gastritis in

patients in intensive care units.
Side effects:
• The compound is not really absorbed and, therefore,
side-effects are minimal:
– constipation
– diarrhea
– nausea
 Antacids
• Have been used for centuries in the
treatment of patients with acid-peptic
disorders.
• Were the mainstay of treatment for
acid-peptic disorders until the advent
of H2-receptor antagonists and proton
pump inhibitors.
 Antacids….
• Antacids are weak bases that neutralize HCl in
the stomach.

• They do not decrease the secretion of acid.

• They do not suppress nocturnal acid secretion

1. Neutralize acid
2. Decrease acid load to duodenum
3. Diminish pepsin activity
 Antacids

• Magnesium hydroxide

• Magnesium trisilicate

• Magnesium-aluminum mixtures

• Calcium carbonate

• Sodium bicarbonate
 Antacids….
• Given orally 1-3 hrs after meals

• Impair absorption of some drugs

 Al3+ and Mg2+ antacids chelate other drugs forming

insoluble complexes that pass through the GI tract
without absorption.

– Take 2 hrs before or after other drugs

• Mg+2 based preparations increase gastric motility….

– Diarrhea

• Al+3 based preparations relax gastric smooth muscle

producing delayed gastric emptying and constipation.
 Combinations of Mg2+ and Al3+
hydroxides provide a relatively
balanced and sustained neutralizing
capacity.
 Maalox is a hydroxymagnesium
aluminate complex that is converted
rapidly in gastric acid to Mg(OH)2 and

Al(OH)3
H. pylori eradication
– If H. pylori detected, eradication of
the bacteria, along with inhibition
of acid.
– Eradication of H. pylori is a cure as
reinfection rates in Western
countries is less than 1%.
 Treatment – H. Pylori

• PPI + Amoxicillin + Clarithromycin – known as

Triple therapy
– 90% cure rate
• PPI + Metronidazole + Clarithromycin
– for PCN allergy patients but metronidazole
resistant occurs 10-20%)
• Standard treatment regimen for peptic ulcer:
• Omeprazole 20mg BID+ Amoxicillin 1gm BID+
Clarithromycin 500mg BID for 10 -14 days
and continue PPI for the next 2 wks
• PPI + Bismuth + Mtronidazole +TTC – known as
Quadruple therapy

– good for patients who failed Triple therapy

 Pharmacologic Treatment…

• The PPI should be taken 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 with higher eradication
rates and less antimicrobial
resistance. 51
 Pharmacologic Treatment…
• If the initial treatment fails to
eradicate HP, second-line
empiric treatment should:
–use antibiotics that were not
included in the initial regimen;
–include antibiotics that do not
have resistance problems;
–use a drug that has a topical
effect (e.g., bismuth); 52
 Pharmacologic Treatment…
Alternative ( second lines)…..
• Quadruple-based therapy …….if triple therapy
fails
– bismuth, metronidazole, TTC, and PPI
• Sequential therapy
– PPI and amoxicillin x 5 days;
– followed by a PPI, clarithromycin, and tinidazole
x 5 days
• Levofloxacin-based triple therapy for ………..
– resistant patients
 Pharmacologic Treatment
NSAID-induced
• Most uncomplicated NSAID-induced
ulcers heal with standard regimens
of an H2RA, PPI, or sucralfate if the
NSAID is discontinued.

• PPIs are the drugs of choice when

NSAIDs must be continued
because potent acid suppression is
required to accelerate ulcer healing
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 Pharmacologic Treatment
NSAID-induced…
• Patients at risk of developing serious ulcer-related
complications while on NSAIDs should receive
prophylactic co-therapy with misoprostol or a
PPI.
• Misoprostol + NSAID
– poorly tolerated – diarrhea (40%), abdominal pain,
frequent dosing
– H2 antagonists ……..not effective
• 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
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 Pharmacologic Treatment
Summary

• In HP-negative patients,
higher PPI doses (e.g.,
omeprazole 40 mg/day)
heal the majority of
ulcers.

• Continuous PPI treatment 57

 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.
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Evaluation of Therapeutic Outcomes

• 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, and perforation.
• Follow-up endoscopy is justified in patients
with frequent symptomatic recurrence,
refractory disease, complications, or
suspected hypersecretory states.

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The End!

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