Acid Peptic Disease

Acid-Peptic Disease PUD/GERD/NSAIDs Duane T. Smoot, M.D., FACP, FACG Associate Professor and Chief Gastroenterology Division Howard University 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 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 Tytgat and Nio. Baillière’s Clin Gastroenterol 1987; Klinkenberg-Knol et al. Drugs 1995; Furman et al. Gastroenterology 1982; Wolfe and Sachs. Gastroenterology 2000 H2RAs are effective only in mild erosive esophagitis Isolated erosions Longitudinally confluent erosions Circumferential erosions 0 20 23 40 60 80 100 78 38 p < 0.001 6-week healing rate (%) Koelz et al. Gastroenterology 1986 Doubling the dose is ineffective in patients refractory to H2RAs 50 % patients with mild or no heartburn 40 30 20 Standard dose Double dose 10 0 Week 4 Week 8 Kahrilas et al. Am J Gastroenterol 1999 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 Klinkenberg-Knol et al. Drugs 1995 PPIs are the most effective drugs for the initial treatment of GERD 100 % esophagitis cases healed PPIs 80 60 40 Placebo 20 0 H2RAs p < 0.0005 2 4 6 8 Weeks of treatment 10 12 Chiba et al. Gastroenterology 1997 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? 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 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 Pathogenesis of Ulcers Therapy is directed at enhancing host defense or eliminating aggressive factors; i.e., H. pylori. Aggressive Factors     Defensive Factors      Acid, pepsin Bile salts Drugs (NSAIDs) H. pylori Mucus, bicarbonate layer Blood flow, cell renewal Prostaglandins Phospholipid Free radical scavengers 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 H. pylori –protection against reflux esophagitis? 30 % patients with erosive esophagitis 25 20 15 10 5 0 2 6 12 18 24 30 36 p < 0.001between groups Patients remaining infected (n = 216) 12.9% Patients cured of H. pylori infection (n = 244) 25.8% Months Labenz et al. Gastroenterology 1997 H. pylori – improvement of the efficacy of PPIs? p = 0.002 10 Median 24-hour intragastric pH with PPI 8 6 4 2 0 Hp Placebo Rx Pre–Hp Rx Hp Placebo Rx Post–Hp Rx 5.51 5.3 3.53 5.07 Van Herwaarden et al. Aliment Pharmacol Ther 1999 NSAIDs and H. pylori Prevention of ulcers in NSAID Users 50 Ulcer Recurrence (%) Placebo n = 155 40 30 20 10 0 32 10 * 13 * 12 Misoprostol 200 ug bid n = 296 Omeprazole 20 mg qd n = 274 10 ** 3 Gastric Ulcer Duodenal Ulcer P<0.001 omeprazole & misoprostol vs placebo P<0.001 omeprazole vs placebo & misoprostol Hawkey et al, 1998 Prevention of ulcers in NSAID Users 30 Ulcer Recurrence (%) 20 16.3 Ranitidine 150 mg bid n = 215 Omeprazole 20 mg qd n = 210 5.2 * 10 5.7 0.5 * * p< 0.05 0 Gastric Ulcer Yeomans et al, 1998 Duodenal Ulcer H. pylori & NSAID Ulcers Ulcers Gastric Naproxen 9 Naproxen 2 0 0 2 (5%) 0.007 P value 0.04 HP+ (n=43) HP- (n=38) Duodenal 2 Both Total Chan et al, 1997 1 12 (28%) H. pylori and ulcer relapse in patients with healed duodenal ulcer: 6 month double-blind trial 100 Ulcer Relapse (%) 80 60 40 20 0 H. pylori-negative H. pylori-positive Placebo Omeprazole Misoprostol 20mg qd 200mg bid Hawkey et al, Gut 1996 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 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 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 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 100 80 Recurrence (%) 60 40 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) 20 0 Not Eradicated Eradicated 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 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  Consider treatment if:   Source: 1997 Digestive Health Initiative International Update Conference, 1997 H. pylori: Treatment Agents Which Inhibit H. pylori In Vivo Antibiotic Resistance Resistance - metronidazole subcitrate - tinidazole subsalicylate - erythromycin base - clarithromycin - ciprofloxacin - ofloxacin No Antibiotic - colloidal bismuth - bismuth - tetracycline - nitrofurantoin - furazolidone Monotherapy for H. pylori Infection Drug Azithromycin Doxycycline Metronidazole Tinidazole Tetracycline Bismuth subsalicylate Quinolones Erythromycin Amoxicillin Nitrofurantoin Furazolidone Colloidal bismuth subcitrate Clarithromycin (Blecker U, Gold B. Pediatr Infect Dis J 1997;16:391) Cure Rate (%) 5 5 5 5 5 5-10 10 15 15 20 20-40 30-40 40-60 H. pylori Treatment: Resistance in Pediatric Strains State Georgia No of Strains Tested 15 Resistance (mean %) 5 20 25 25 60 1 15 10 Antibiotic Clarithromycin Metronidazole Metronidazole Clarithromycin, Metronidazole Amoxicillin Metronidazole Metronidazole Alabama Florida 4 12 South Carolina Ohio 3 10 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