Acid peptic disease nsaids

Acid-Peptic DiseasePUD/GERD/NSAIDs

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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


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


Evolution of pharmacological therapy

• Antacids

• Prokinetics

• H2-receptor antagonists

• Proton pump inhibitors


Tytgat and Nio. Baillière’s 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


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


Kahrilas et al. Am J Gastroenterol 1999

0

10

20

30

40

50

Week 4 Week 8

% p

atie

nts

with

mild

or

no h

ea

rtbu

rn

Standard dose

Double dose

Doubling the dose is ineffective in patients refractory to H2RAs


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/or high-dose treatment


Chiba et al. Gastroenterology 1997

% e

sop

hag

itis

case

s h

eal

ed

0

20

40

60

80

100

2 4 6 8 10Weeks of treatment

12

PPIs

H2RAs

Placebo

p < 0.0005

PPIs are the most effective drugs for the initial treatment of GERD


H. pylori: Clinical Manifestations in Children Compared to Adults

Chronic-active/chronic gastritis - different histopathology; neutrophils much less frequent

Duodenal ulceration - less frequent than adults Gastric ulceration - occurs but uncommon MALT lymphoma - 6 case reports in literature Gastric cancer - one case reported Controversial: recurrent abdominal pain (RAP),

non-ulcer dyspepsia; others?www.freelivedoctor.com

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, 1991www.freelivedoctor.com

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, 1996www.freelivedoctor.com

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 or eliminating aggressive factors; i.e., H. pylori.


Helicobacter pylori in GERD

• Infection with H. pylori may cause a variety of gastric diseases

• In the context of GERD, however, H. pylori may have some beneficial effects


% p

atie

nts

with

ero

sive

eso

pha

giti

s

Patients remaining infected (n = 216)12.9%

p < 0.001between groups0

10

15

20

25

30

5

62 1812 3024 36

Months

Patients cured of H. pylori infection (n = 244)

25.8%

Labenz et al. Gastroenterology 1997

H. pylori –protection against reflux esophagitis?


Van Herwaarden et al. Aliment Pharmacol Ther 1999

Me

dia

n 2

4-h

our

intr

ag

astr

ic p

H w

ith P

PI

10

8

6

4

2

0

5.51

HpRx

HpRx

Placebo Placebo

5.3

3.53

5.07

Pre–Hp Rx Post–Hp Rx

p = 0.002

H. pylori – improvement of the efficacy of PPIs?


NSAIDs and H. pylori


Prevention of ulcers in NSAID Users

32

1013 12 10

3

0

10

20

30

40

50

Ulc

er R

ecur

renc

e (%

)

Gastric Ulcer Duodenal Ulcer

Placebo n = 155

Misoprostol 200 ug bid n = 296

Omeprazole 20 mg qd n = 274

Hawkey et al, 1998

**

**

P<0.001 omeprazole & misoprostol vs placeboP<0.001 omeprazole vs placebo & misoprostolwww.freelivedoctor.com

Prevention of ulcers in NSAID Users

16.3

5.2 5.7

0.5

0

10

20

30

Ulc

er R

ecur

renc

e (%

)

Gastric Ulcer Duodenal Ulcer

Ranitidine 150 mg bidn = 215Omeprazole 20 mg qdn = 210

Yeomans et al, 1998

*

** p< 0.05


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 www.freelivedoctor.com

H. pylori and ulcer relapse in patients with healed duodenal

ulcer: 6 month double-blind trial

0

20

40

60

80

100

Ulc

er R

elap

se (%

)

Placebo Omeprazole20mg qd

Misoprostol200mg bid

H. pylori-negativeH. pylori-positive

Hawkey et al, Gut 1996 www.freelivedoctor.com

NSAID Use in the Arthritis Patient with a History of

Bleeding Ulcer

• Treating H. pylori is likely to be of benefit if there was a duodenal ulcer; test and treat for H. pylori is recommended.

• Use COX2 Inhibitor

• Add a PPI or Misoprostol


Tests For Initial Diagnosisof 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


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 www.freelivedoctor.com

What Diseases Have Evidence-Based Justification For Treating H. 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


H. pylori Infection and Ulcer Recurrence

Twelve-month rates of duodenal ulcer recurrence in patients whom H. 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

Rec

urre

nce

(%)

NotEradicated

Eradicatedwww.freelivedoctor.com

Known Factors Which Determine Success of H. pylori Therapy

Patient compliance or non-compliance Medicine complications or side effects

Antimicrobial resistance of infecting H. pylori strains Duration of Therapy Correct dosing

Clearance of H. pylori infection is not equivalent to eradication.


Who Should Be Treated For H. pylori Infection?

Patients who have documented H. 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


H. pylori: Treatment

Agents Which Inhibit H. pylori In VivoAntibiotic Resistance No Antibiotic

Resistance- metronidazole - colloidal bismuth

subcitrate

- tinidazole - bismuth subsalicylate

- erythromycin base - tetracycline

- clarithromycin - nitrofurantoin

- ciprofloxacin - furazolidone

- ofloxacin

- norfloxacin

- amoxicillin (rare)


Monotherapy for H. pylori Infection

Azithromycin 5

Doxycycline 5

Metronidazole 5

Tinidazole 5

Tetracycline 5

Bismuth subsalicylate 5-10

Quinolones 10

Erythromycin 15

Amoxicillin 15

Nitrofurantoin 20

Furazolidone 20-40

Colloidal bismuth subcitrate 30-40

Clarithromycin 40-60(Blecker U, Gold B. Pediatr Infect Dis J 1997;16:391)

Drug Cure Rate (%)


H. pylori Treatment: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

25Clarithromycin,

60 Metronidazole

1 Amoxicillin

15 Metronidazole

10 Metronidazolewww.freelivedoctor.com

FDA-Approved Treatment Regimes

for H. pylori Infection

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 + Tetracycline 500 mg QID X 14 days + H2 receptor antagonist x 4 wks


H. pylori: Pediatric Treatment

Pediatric Treatment Recommendations 2 wks omeprazole (1 - 3 mg/kg/D bid) +

clarithromycin (15 mg/kg/D bid) + metronidazole (15 mg/kg/D tid)

followed by 2 wks of omeprazole (2 mg/kg/D qd) 2 wks omeprazole (1 - 3 mg/kg/D bid) + clarithromycin

(15 mg/kg/D bid) + amoxicillin (50 mg/kg/D tid) followed by 2 wks of omeprazole (2 mg/kg/D qd)

2 wks amoxicillin (50 mg/kg/D tid) + metronidazole (15 mg/kg/D tid) + bismuth subsalicylate (qid) + H2 receptor antagonist (e.g., ranitidine 5 mg/kg/D bid)

possible to substitute lansoprazole for omeprazole www.freelivedoctor.com

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Acid peptic disease nsaids