Acid Peptic Disease Smoot

8/8/2019 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

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