Acid peptic diseases pharmacological approach to treatment.pdf
Acid peptic disease nsaids
Transcript of 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
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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. 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
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Koelz et al. Gastroenterology 1986
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38
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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
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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/or high-dose treatment
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Chiba et al. Gastroenterology 1997
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PPIs
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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
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.
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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
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% p
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Patients remaining infected (n = 216)12.9%
p < 0.001between groups0
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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?
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Van Herwaarden et al. Aliment Pharmacol Ther 1999
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p = 0.002
H. pylori – improvement of the efficacy of PPIs?
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NSAIDs and H. pylori
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Prevention of ulcers in NSAID Users
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Ulc
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Gastric Ulcer Duodenal Ulcer
Placebo n = 155
Misoprostol 200 ug bid n = 296
Omeprazole 20 mg qd n = 274
Hawkey et al, 1998
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P<0.001 omeprazole & misoprostol vs placeboP<0.001 omeprazole vs placebo & misoprostolwww.freelivedoctor.com
Prevention of ulcers in NSAID Users
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Gastric Ulcer Duodenal Ulcer
Ranitidine 150 mg bidn = 215Omeprazole 20 mg qdn = 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 www.freelivedoctor.com
H. pylori and ulcer relapse in patients with healed duodenal
ulcer: 6 month double-blind trial
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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
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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
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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 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
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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)
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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.
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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
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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)
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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 (%)
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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
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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