Acid Peptic Disease Smoot
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Transcript of Acid Peptic Disease Smoot
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Acid-Peptic DiseasePUD/GERD/NSAIDs
Duane T. Smoot, M.D., FACP,
FACG
Associate Professor and Chief
Gastroenterology Division
Howard University
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Lifestyle measures
Raise the head of the bed, or lie on left side
Decrease fat intake
Avoid certain foods
Avoid lying down for 3 hours after eating
Stop smoking Lose weight if appropriate
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Role of lifestyle measures
Role in GERD debatable
Many physicians feel that lifestyle advice is
worthwhile
Lifestyle measures are generally insufficient
by themselves
Lifestyle measures may have a negative
impact on patient lifestyle
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Evolution of pharmacological
therapy Antacids
Prokinetics
H2-receptor antagonists
Proton pump inhibitors
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Tytgat and Nio. Baillires Clin Gastroenterol 1987; Klinkenberg-Knol et al. Drugs 1995;Furman et al. Gastroenterology 1982; Wolfe and Sachs. Gastroenterology 2000
Pharmacological therapy
antacids, prokinetics and H2RAs Antacids
Prompt but temporary relief
No objective proof of superiority to placebo
Prokinetics
Improvement of symptoms in mild GERD
Effective for healing only mild erosive esophagitis
Can be useful in a select patient population
H2RAs
Relief of symptoms in ~50% of patients
Effective for healing only mild erosive esophagitis
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Koelz et al. Gastroenterology 1986
23
38
78
0 20 40 60 80 100
6-week healing rate (%)
p < 0.001
Isolated erosions
Longitudinally confluenterosions
Circumferential erosions
H2RAs are effective only in mild
erosive esophagitis
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Kahrilas et al. Am J Gastroenterol 1999
0
10
20
30
40
50
Week 4 Week 8
%
patie
ntswi t
h
m
ildor
nohe
artburn
Standard dose
Double dose
Doubling the dose is ineffective
in patients refractory to H2RAs
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Klinkenberg-Knol et al. Drugs 1995
Pharmacological therapy
PPIs
Significantly more effective than H2RAs for
both symptom resolution and healing of
erosive esophagitis Also effective in more severe cases of GERD
Most patients respond well to standard
therapy, but some require prolonged and/orhigh-dose treatment
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DeVault et al. Am J Gastroenterol 1999
PPIs are the most effective drugs
for the initial treatment of GERD
PPIs provide rapid symptomatic relief and
healing of erosive esophagitis in the highest
percentage of patients
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Chiba et al. Gastroenterology 1997
%
esophagiti s
ca
se
shealed
0
20
40
60
80
100
2 4 6 8 10
Weeks of treatment
12
PPIs
H2RAs
Placebo
p < 0.0005
PPIs are the most effective drugs for
the initial treatment of GERD
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H. pylori: Clinical Manifestations in
Children Compared to Adults
q Chronic-active/chronic gastritis - different
histopathology; neutrophils much less frequentq Duodenal ulceration - less frequent than adults
q Gastric ulceration - occurs but uncommon
q MALT lymphoma - 6 case reports in literature
q Gastric cancer - one case reported
q Controversial: recurrent abdominal pain (RAP),
non-ulcer dyspepsia; others?
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Age, HP & Acid secretion
Subjects with a mean age of 57 when
compared to subjects with a mean age of 33
higher mean basal
higher meal-stimulated
higher pepsinogen I & II levels
Age positively effected acid secretion
H. pylori negatively effected acid secretion
Goldschmiedt, et al., Gastro, 1991
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Age, HP & Acid secretion
The decline in acid output in the elderly was
primarily due to atrophic gastritis and
partially to tobacco smoking After adjusting for histology,H. pylori and
other variables, age had no independent
effect on acid secretion. Age is associated with reduced pepsin
output.
Feldman, et al., Gastro, 1996
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Pathogenesis of Ulcers
Aggressive Factors Acid, pepsin
Bile salts
Drugs (NSAIDs)
H. pylori
Defensive Factors Mucus, bicarbonate layer
Blood flow, cell renewal
Prostaglandins
Phospholipid
Free radical scavengers
Therapy is directed at enhancing host defense oreliminating aggressive factors; i.e., H. pylori.
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Helicobacter pyloriin GERD
Infection withH. pylori
may cause a variety of
gastric diseases In the context of GERD,
however,H. pylori may
have some beneficial
effects
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%
patie
ntsw
i th
erosiveesoph a
gitis
Patients remaining infected (n =
216)
12.9%
p < 0.001between groups0
10
15
20
25
30
5
62 1812 3024 36
Months
Patients cured ofH. pyloriinfection (n =
244)
25.8%
Labenz et al. Gastroenterology 1997
H. pyloriprotection against
reflux esophagitis?
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Van Herwaarden et al. Aliment Pharmacol Ther 1999
Median24-ho
ur
intraga
stricpHwith
PPI10
8
6
4
2
0
5.51
Hp
Rx
Hp
Rx
Placebo Placebo
5.3
3.53
5.07
PreHp Rx PostHp Rx
p = 0.002
H. pylori improvement of the
efficacy of PPIs?
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NSAIDs andH. pylori
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Prevention of ulcers in NSAID Users
32
1013 12
10
3
0
10
20
30
40
50
UlcerRecurrence(%)
Gastric U lcer Duodenal U lcer
Placebo n = 155
Misoprostol 200 ug bin = 296
Omeprazole 20 mg qdn = 274
Hawkey et al, 1998
**
**
P
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Prevention of ulcers in NSAID Users
16.3
5.2 5.7
0.5
0
10
20
30
Ulc
erRecurrence(%)
Gastric U lcer Duodena l U lcer
Ranitidine 150 mgn = 215
Omeprazole 20 mgn = 210
Yeomans et al, 1998
*
** p< 0.05
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H. pylori& NSAID Ulcers
Ulcers Naproxen
HP+ (n=43)
Naproxen
HP- (n=38)
P value
Gastric 9 2 0.04
Duodenal 2 0
Both 1 0
Total 12 (28%) 2 (5%) 0.007
Chan et al, 1997
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H. pyloriand ulcer relapse in
patients with healed duodenal
ulcer: 6 month double-blind trial
0
20
40
60
80
100
UlcerRelapse(%)
Placebo Omeprazole
20mg qd
Misoprostol
200mg bid
H. pylori-negati
H. pylori-positiv
Hawkey et al, Gut 1996
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NSAID Use in the Arthritis
Patient with a History ofBleeding Ulcer
TreatingH. pylori is likely to be of benefit
if there was a duodenal ulcer; test and treat
forH. pylori is recommended.
Use COX2 Inhibitor
Add a PPI or Misoprostol
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Tests For Initial Diagnosis
of Infection Urea Breath Test and Stool Assay
Non-invasive, sensitive and specific Serology
O.K. for initial diagnosis
Fair sensitivity and specificity Endoscopy Not necessary for
diagnosis
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Diagnostic Tests to Evaluate
Treatment Success
Urea Breath Test and Stool Assay Can be done 4 weeks post treatment
PPIs can interfere with the Breath Test, not with Stool
Assay
Endoscopy (antral and fundal biopsies)
Also allows for bacterial Culture and Sensitivity
Rapid Urease Assays Also influenced by PPIs, biopsy from antrum and fundus
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What Diseases Have Evidence-Based
Justification For TreatingH. pylori
Peptic ulcer disease: duodenal (67%) and gastric ulcers
(59%) recur if no eradication
Bleeding duodenal ulcer: rebleeding in 30% if no eradication
with 1 year follow up MALT lymphoma: justified based on best-available
evidence to treat in low-grade MALT lymphoma
Gastric cancer: justified in early gastric cancer; 9%
recurrence incidence in untreated controls Non-ulcer dyspepsia: evidence not yet definitive; up to 40%
with abdominal pain recurrence with . H. pylori eradication
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H. pyloriInfection and
Ulcer Recurrence
Twelve-month rates of
duodenal ulcer recurrence
in patients whomH. pylori
was eradicated and those
in whom it was not.
(Walsh JH. N.E.J.M.1995;333:984)
0
20
40
60
80
100
R
ecur r
ence(%
)
Not
Eradicated Eradicated
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Known Factors Which Determine
Success ofH. pyloriTherapy
Patient compliance or non-compliance
Medicine complications or side effects Antimicrobial resistance of infectingH. pylori strains
Duration of Therapy
Correct dosing
Clearance of H. pylori infection is not equivalent to
eradication.
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Who Should Be Treated For
H. pyloriInfection?
Patients who have documentedH. pylori infection and: Definitely had or has a duodenal or stomach ulcer
Have had stomach lymphoma or family hx of stomach cancer
Consider treatment if: Presence of severe histologic gastritis and H. pylori infection
Ulcer-like dyspepsia in the absence of an ulcer or prior to endoscopy
in a young patient
Source: 1997 Digestive Health Initiative International Update Conference, 1997 Canadian Consensus
Conference
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H. pylori: Treatment
Agents Which InhibitH. pylori In Vivo
Antibiotic Resistance No Antibiotic Resistance
- metronidazole - colloidal bismuth subcitrate
- tinidazole - bismuth subsalicylate
- erythromycin base - tetracycline
- clarithromycin - nitrofurantoin
- ciprofloxacin - furazolidone
- ofloxacin
- norfloxacin
- amoxicillin (rare)
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.Infection
Azithromycin 5
Doxycycline 5
Metronidazole 5
Tinidazole 5
Tetracycline 5
Bismuth subsalicylate 5-10Quinolones 10
Erythromycin 15
Amoxicillin 15
Nitrofurantoin 20
Furazolidone 20-40Colloidal bismuth subcitrate 30-40
Clarithromycin 40-60
(Blecker U, Gold B. Pediatr Infect Dis J 1997;16:391)
Drug Cure Rate (%)
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H. pyloriTreatment:
Resistance in Pediatric Strains
No of Strains
State Tested
Georgia 15
Alabama 4
Florida 12
South Carolina 3
Ohio 10
Resistance
(mean %) Antibiotic
5 Clarithromycin
20 Metronidazole
25 Metronidazole
25 Clarithromycin,
60 Metronidazole
1 Amoxicillin15 Metronidazole
10 Metronidazole
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FDA-Approved Treatment
Regimes
forH. pyloriInfection
Omeprazole 20 mg BID + Clarithromycin 500
mg BID + Amoxicillin 1 g BID for 10 days
Lansoprazole 30 mg BID +Clarithromycin 500
mg BID + Amoxicillin 1 g BID for 10 days
Bismuth subsalicylate (Pepto Bismol) 525 mg
QID + Metronidazole 250 mg QID + Tetracycline500 mg QID X 14 days + H
2receptor antagonist x
4 wks
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H. pylori: Pediatric Treatment
Pediatric Treatment Recommendationsx 2 wks omeprazole (1 - 3 mg/kg/D bid) + clarithromycin (15
mg/kg/D bid) + metronidazole (15 mg/kg/D tid)x followed by 2 wks ofomeprazole (2 mg/kg/D qd)
x 2 wks omeprazole (1 - 3 mg/kg/D bid) + clarithromycin (15
mg/kg/D bid) + amoxicillin (50 mg/kg/D tid)x followed by 2 wks ofomeprazole (2 mg/kg/D qd)
x 2 wks amoxicillin (50 mg/kg/D tid) + metronidazole (15
mg/kg/D tid) +bismuth subsalicylate (qid) + H2 receptorantagonist (e.g., ranitidine 5 mg/kg/D bid)
x possible to substitute lansoprazole foromeprazole