In the name of God
Peptic Ulcer Disease
By: E. Salehifar
(Clinical Pharmacist)
Peptic Ulcer Disease (PUD)
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PUD: 10% of the people in their lifetime
Prevalence of active disease: 1-2%
Duodenal ulcers
Gastric ulcers
Others: Ulcers of esophagus
Zollinger-Ellison
(gastrin-producing tumor)
Upper Gastrointestinal Disorders
Dyspepsia
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25-55% of the people in
their lifetime
Abdominal pain or
discomfort
Symptoms of early
satiety, bloating,
nausea & vomiting
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Nonulcer Dyspepsia: 60%
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PUD: 20%
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GERD: 20%
GERD
Backflow of GI contents into the esophagus
resulting in esophagitis
 Classic symptom: Heartburn or burping up
of stomach contents into the mouth
 Major concern: Barrett’s esophagus
(a predisposing factor for esophagus cancer)
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Mucus secreting cells
Antrum:
G cells (Gastrin)
Body:
Parietal cells (H+, IF),
chief cells (Pepsinogen)
Stomach physiology
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Fundus (mucus-secreting cells)
Body (80-90%)
Parietal cells (acid, intrinsic factor)
Chief cells (pepsinigen)
Antrum (10-20%)
G cells (gastrin)
Regulation of acid secretion
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Increase
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Decrease
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ACH
Histamine
Gastrin
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PGE
Cholecystokinin
Glucagon
VIP
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What is the cause of PUD?
 No
acid, No Ulcer! (PH)
 Helicobacter
pylori (HP)
 NSAIDs
 Cigarette
Smoking
HP: A Gram negative spiral bacteria
HP
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Was isolated in 1983 (Campylobacter pylori)
Infection is more common in older
individual
Person to person transmission
Is found most consistently in gastric
antrum
pathogenesis: Urease (↑NH3), cytotoxin,
inflammation, breakdown of mucosal
defense
Why HP is implicated in PUD?
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90% of PUD, in the absent of NSAIDs exposure,
are associated with HP
Is found in 90% of DU & 70% of GU patients
Eradication of HP accelerates the ulcer healing
and decreases the recurrence rate
PUD in HP negatives is rare
HP: Is not a single cause of PUD!
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HP positive: 50-90% of general population
15-30%: PUD
20-40%: Nonulcer dyspepsia
30-65%: Asymptomatic
HP infection is not associated with acute
perforated DU
When PUD occurs?
Aggressive factors
Defensive factors
HP
 H+
 Pepsin
 NSAIDs (Direct, ↓PGE)
 Smoking
(↑H+ & bile salt reflux,
↓PGE & mucosal
blood flow)
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PGE
Somatostatin
Mucus
HCO3¯
Mucosal blood flow
Rapid regeneration
Resitution
Clinical presentation
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The most common symptom: epigastric
pain
Pain is not well localized
DU pain commonly occurs with empty
stomach and relieves by food and antacid
GU pain occurs at any time frequently
immediately or 1-3 hours after a meal
Clinical presentation (continue)
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Pain dose not always correlate with ulcer
especially in elderly taking analgesics and
in patients with high pain tolerance
Other symptoms: nausea, vomiting,
belching, bloating & anorexia
endoscopy is needed for definitive
diagnosis
PUD: Is there any role for foods?
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Caffeine, milk, alcohol, spicy foods
increase acid secretion and cause
dyspepsia, but they can not increase risk
of PUD
Acute alcohol ingestion can damage the
gastric mucosa, leading to GI bleeding,
however alcohol has not been proven to
cause PUD
PUD: Genetic association
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20-50% of patients with DU have a
positive family history of PUD
PUD: Association with Stressful life
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Stressful life events thought by some to
exacerbate PUD
Epidemiology (incidence & prevalence)
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Increase in PUD during the beginning of
the 20th century with a peak in 1950s
Over the past 2 decade, DU have declined
(both outpatient & inpatient episodes)
GU has remained stable perhaps due to
aging & use of ulcerogenic drugs
PUD (Geographic variation)
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In Japan, GU is 5-10 times more common
In the US & European countries, DU is 2
times more common
PUD (gender)
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In 1968, rate of PUD in men was twice, but
now is similar for men & women
Hospitalization of women with GU have
increased markedly for patients older
than 65
PUD (age)
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GU is rare before age 40, and the peak
incidence occurs from ages 55-65
The incidence of DU increase with age
until the age of 60 years
PUD (morbidity & mortality)
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Mortality of PUD has declined during the
past 20 years
Less than 2% of patients receiving
therapy are expected to have a
complication
One of the most common GI diseases that
results in loss of work and high-cost
service
Comparison of DU & GU
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DU
Increases with age
Common in US
Hyperacidity
Hypergastrinemia
↑ parietal cell mass
Genetic influence
Incidence ↓
↑ frequency in cirrhosis
More common in blood O
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GU
Rare before 40
Common in Japan
Normal or low acid
Normal or sl. ↑ gastrin
Normal parietal cell mass
No genetic influence
No ↓ in incidence
No ↑frequency in cirrhosis
More common in blood A
Treatment
Goals
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Relief of symptoms
Promotion of ulcer healing
Prevention of ulcer recurrence and
complications
Treatment
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Eradication of HP (seropositive DU & GU)
Acid suppression (DU)
PPIs
H2-blockers
Antiacids
Enhancing mucosal defenses (GU, DU)
Sucralfate
Treatment
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In HP (+) patients:
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Eradication of HP
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In HP (–) patients:
H2 blockers, Sucralfate & antacid are equally
effective, but H2 blockers are much easier to
use with less drug interactions
PPIs may be slightly more effective than H2
blocker and should be reserved for refractory
cases
H2 Blockers
Cimetidine (Tagamet)
Tab: 200mg, Inj: 200 mg/2ml
 Ranitidine (Zantac)
Tab: 150 mg, Inj: 50 mg/2ml
 Famotidine
Tab: 20 mg, 40 mg
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B
B
B
H2 Blockers (indications)
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DU
GU
GERD
ZE
have equal efficacy (70-95% healing rate after 4-8 weeks of
therapy)
Potency & duration of action of famotidine (& nizatidine) is
greater, but all can be used once daily
In GERD, all H-2 blockers should be used before meals
H2 Blocker dosage for DU & GU
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Cimetidine: 300 mg QID, 400 mg BD, 800
mg HS
Ranitidine: 150 mg BD, 300 mg HS
Famotidine: 20 mg BD, 40 mg HS
-Dosage adjustment in moderate to
severe renal insufficiency
-Sr Cr may increase with cimetidine
H2 Blockers (Adverse Effects)
Are remarkably safe
 Common: GI (diarrhea, constipation),
CNS (confusion, headache, dizziness,
drowsiness), Rash
 Gynecomastia & Impotence: Cimetidine
 Heptotoxicity: Ranitidine
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Drug interactions
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Cimetidine: Phenytoin, Warfarine,
theophylline
Cimetidine & Ranitidine: Procainamide &
NAPA (↓tubular secretion)
All H2-Blockers: Ketokonazole, Fe
Proton pump inhibitors (PPIs)
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Omeprazole (Prilosec®) Cap: 10, 20 mg
Lansoprazole (Prevacid®) Cap: 15, 30 mg
Rabeprazole (Aciphex®) Tab: 20 mg
Pantoprazole (Protonix®) Tab: 20, 40 mg
- PPIs relieve symptoms and heal
ulcer more quickly than H2 Blockers (2-4
W compared to 4-8 W)
PPIs (Pharmacokinetic)
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Enteric-coated granules within capsule
Bioavailability: 30-80%
Omeprazole & lansoprazole are prodrugs
for O. sulfonamide, L. sulfone, hydroxy
lansoprazole
Despite the short t1/2, antisecretory
effects is present 72 hr
No dosage adjustment in renal disease
PPIs (ADRs)
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ADRs are relatively negligible
Include GI (nausea, diarrhea, abdominal
pain), CNS (dizziness, headache), rash,
gynecomastia, ↑ SGOT, SGPT
No risk of hyperplasia and carcinoid
tumor in spite of hypergastrinemia
PPIs (Drug Interactions)
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Omeprazole decreases metabolism of
diazepam, phenytoin, warfarin (2C9)
Less interaction with Lansoprazole
Pantoprazole also is metabolized by
sulfotransferase, it appears to interact
less with cyp450
Rabeprazole can modestly increase Dig
Sucralfate (Carafate®)
Protects ulcerated tissue from aggressive
factors (pepsin, acid, bile salts)
 PH 2-2.5 → forms a physical barrier to injury
 Not absorbed systemically
 Other protective actions on the mucosa
(PG, bicarbonate)
 Duodenal ulcer (active, maintenance) & Gu
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Sucralfate (ADR)
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Constipation
Dry mouth
Nausea
Rash
Eradication of H.Pylori
Monotherapy not recommended
 PPI or bismuth + two antibiotics
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Amoxicillin
Clarithromycin
Metronidazole
Tetracycline
OCA (10 days)
Omeprazole: 20 mg BD
 Clarithromycin: 500 mg BD
 Amoxicillin: 1000 mg BD
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LAC (14 days)
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Lansoprazole 30mg bid before meals
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Amoxicillin 1000mg bid with meals
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Clarithromycin 500mg bid with meals
OC
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Omeprazole 20mg BID, 30days
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Clarithromycin 500mg TID, 14days
LCM, OCM (14 days)
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PPI: (Lansoprazole 30 mg BD or Omeprazole
20 mg BD), 2 weeks
Clarithromycin: 500 mg BD, 2 weeks
Metronidazole: 500 mg BD, 2 weeks
Summary
 Importance
of HP in development
of PUD
 Clinical symptoms of DU & GU
 Treatment principles