Acid Peptic Diseases

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Acid Peptic Diseases

• Clinical Management Course
• February 4, 2005
• Walter Smalley, MD MPH

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Acid - Peptic Diseases

• Conditions Covered
• Heartburn
• Gastroesophageal Reflux (GERD)
• Peptic Ulcer Disease
• H. Pylori
• NSAIDs
• Drugs
• Antacids
• H2RAs (H-2 blockers)
• Proton Pump Inhibitors (PPIs)
• Selective COX-II inhibitors

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Antacids

• Immediate effect on gastric pH
• Effect is short-lived
• Typical dose 30-60 cc
• Frequent use may cause diarrhea

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H-2 Receptor Antagonists

• Inhibit H-2 receptors (competitive inhibition)
• Partially inhibit acid production
• Relatively safe drugs
• Less effective than PPIs
• Less expensive than PPIs
• Available over the counter at prices more
  expensive than prescription costs

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Cimetidine Safety Considerations

• Brand name Tagamet
• Induces cytochrome p450 system
• Drug interactions with coumadin, theophylline,
  dilantin and others
• Rarely clinically relevant
• But why not use ranitidine
• Confusion in the elderly
• Thrombocytopenia

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H2 blockers No difference in efficacy
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Proton Pump Inhibitors

• Raise gastric pH to gt 5 for several hours
• Binds covalently to H/K pump
• Prodrugs bioavailable at acid pH
• Maximal effectiveness
• After several doses
• When taken before meals
• After a long fast
• (Prior to breakfast)

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Proton Pump Inhibitors

• Omeprazole
• (generic cost about 80 of prescription costs )
• Lansoprazole
• Rabeprazole
• Pantoprozole oral and IV form
• Esomeprazole
• Very effective, no important predictable
  differences in efficacy
• Very expensive (2-4/day)
• 1 per day generic

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Case 1

• 35 year old healthy man
• Occasional heartburn
• Occurs only with large meals, EtOH ingestion
• No dysphagia

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Heartburn Summary

• How soon does the patient want relief ?
• How long does it need to last ?
• How much are they willing to pay ?

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Heartburn Summary

• Prevention
• Antacids are effective immediately in reducing
  acid - work for 1-2 hours
• H2-blockers are effective in 1-2 hours - they
  work for gt 6-8 hours
• Available over the counter

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Case 1

• Consider not eating large meals
• Consider PRN antacids
• Consider OTC H2 blockers

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Case 2

• 50 yo with frequent nocturnal heartburn
• No dysphagia
• Trial of lifestyle modification only minimally
  effective
• Antacids ineffective
• EGD - distal esophageal erosions

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Gastroesophageal Reflux

• Reflux of gastroduodenal contents
• Acid ( gastric)
• Alkaline (biliary, pancreatic)
• Decreased lower esophageal sphincter (LES) tone
• Decreased rate of gastric emptying
• Increased intra-abdominal pressure
• Decreased salivary clearance

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GERD Lifestyle Modification

• weight loss, avoid tight-fitting clothes
• NPO 3-4 hours before bedtime
• elevate head of bed 8''
• avoid foods and drugs that decrease LES pressure
  or gastric emptying rate
• fat, EtOH, tobacco , peppermint, garlic, onions,
  chocolate, Cachannel blockers, nitrates,
  theophylline, antidepressants
• No strong RCT evidence to support important
  effect of lifestyle modification

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GERD Overview

• Antacids temporary relief
• H2-antagonists
• high (double) doses, frequent dosing
• Prokinetics no more effective than HRAs
• Proton pump inhibitors most effective, most
  expensive

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GERD H2-antagonists

• NO BETWEEN - DRUG DIFFERENCES IN EFFICACY
• symptomatic relief lt 60 - 70 cases
• endoscopic improvement lt symptomatic relief
• higher doses (gt2X ulcer doses) improve efficacy
  slightly

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GERD Prokinetic Agents

• Adverse reactions
• Metoclopramide fatigue, lethargy,
  extrapyramidal symptoms occur in 10 - 30.

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Case 2

• Continue lifestyle modification
• Trial of H2 blockers at high doses

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Case 3

• Patient 2 returns after 8 week trial of H2
  blockers
• Therapy only minimally effective

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GERD Proton Pump Inhibitors

• Causes healing and resolution of symptoms in 80
  of patients with disease resistant to H2-blockers
• Expensive, single source drugs ( 2 - 4 / day)

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GERD When to perform diagnostic tests

• Endoscopy
• Dysphagia
• Weight loss
• Age gt 50
• Failure of medical therapy
• Motility prior to fundoplication
• pH monitoring might resolve diagnostic
  uncertainty in absence of esophagitis

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Case 3

• Proton pump inhibitor

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Case 4

• Patient from Case 3 returns
• Symptoms well controlled on omeprazole
• Symptoms recur immediately after stopping drug
• Hates taking meds

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GERD Anti - Reflux Surgery

• Indications
• patient preference over drug treatment
• young patients with severe esophagitis
• difficult to dilate strictures
• recurrent esophageal ulcers
• GER-respiratory/ENT syndromes
• 80 - 90 of cases have some improvement

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GERD Anti - Reflux Surgery

• Side effects about 10 cases
• "gas bloat"
• dysphagia
• strictures
• other
• Usually wont work if PPIs dont work

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Endoscopic therapies for GERD

• Stretta radiofrequency destruction of GEJ
  myenteric plexus
• Endoscopic Plication sewing gastric cardia
  mucosa to augment GEJ
• Injection of GEJ with plastic
• All should be considered experimental at this
  point

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Utilization of GERD pharmaceuticals in patients
treated medically and surgically
Khaitan et al, Arch Surgery 2003
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Case 4

• Consider anti reflux procedure
• Weighing potential benefits of not taking
  medication vs. risk of side effects from surgery
  (probably 1- 3 in experienced hands)

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Case 5

• 40 yo with epigastric pain
• EGD duodenal ulcer
• H pylori positive
• no NSAIDs

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Ulcer Disease Basic Concepts

• H. pylori is associated with GU and DU
• NSAID use is associated with GU and DU
• Most ulcers are not the result of excess acid
• Acid suppression aids in healing ulcers
• Prior to the H pylori era most of the cost of
  ulcer disease had been in maintenance therapy

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H pylori Concepts

• H pylori infection is chronic
• Prevalence in US adults 50 - 80
• Lifetime risk of ulcer disease 10
• Associated with chronic gastritis - a
  histological diagnosis
• H pylori is a risk factor for gastric
  adenocarcinoma

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H pylori - Diagnosis

• EGD - Biopsy for histology and CLO
• Breath Tests - commercially available, big hassle
• Serology widely available, followup is
  problematic

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H pylori. treatment - Efficacy

• For treatment of duodenal ulcer
• Eradication of H.pylori alone treatment with
  H2-blockers alone
• For preventing recurrent duodenal ulcer
• Eradication of H.pylori gtgt continuous H2-blocker
  therapy

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H pylori. treatment - Efficacy

• Eradication of H.pylori is also of use in
  treating gastric ulcers
• Eradication of H.pylori
• NO PROVEN BENEFIT IN NON-ULCER DYSPEPSIA in about
  50 of studies
• Positive articles demonstrate modest effects

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H pylori. treatment - Options

• Many different regimens
• No "standard of care"
• Best therapy yet to be determined
• Big problems
• compliance
• resistance
• Current (2/05) favorite combination
• Amoxicillin, PPI, Clarithromycin

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Peptic Ulcer Treatment Outcomes
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Case 5

• Treatment with acid suppression
• QD H2 blockers, or
• proton pump inhibitor
• Treat H pylori
• Amoxicillin 1000 BID
• Clarithromycin 500 BID
• Omeprazole 20 BID

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Case 6

• 65 yo male with osteoarthritis with recent ulcer
• On ibuprofen 1800 mg per day
• Ulcer has healed
• H pylori negative

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NSAIDs and Ulcers - Concepts

• Higher doses ---gt greater risk
• Long time users still have increased risk after
  12 months
• Absolute risk is high
• about one ulcer hospitalization per 100 person
  years in the elderly
• About 2/3 of ulcers in NSAID users are due to the
  NSAID use

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NSAIDs and PUD Treatment

• Stop NSAIDs
• Acid suppression
• Drug Healing at 6 - 8 weeks
• Omeprazole gt 90
• H2-Blockers 70-90
• Misoprostol 70-90
• Sucralfate not effective

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NSAIDs and Ulcers - Prevention

• Does the patient really need NSAIDs ?
• objective pain control
• NSAIDs do not prevent progression in
  osteoarthritis
• little evidence demonstrating superiority of
  NSAIDs over acetaminophen in osteoarthritis
  patients.
• No NSAID is "safe".

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NSAIDs and Ulcers - Prevention

• Misoprostol - a synthetic PGE analog
• Prevents GU and DU
• Expensive therapy - for prevention.
• Debate on cost effectiveness continues.
• Side effects diarrhea (10), abdominal pain (10
  - 20)
• Causes spontaneous abortions - do not use in
  potentially fertile women

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NSAIDs and Ulcers - Prevention

• H-2 blockers at high doses may be reliable
  preventive agents for DU prevention
• Misoprostol is very effective in preventing
  ulcers in clinical trials.
• PPIs are as probably as effective as misoprostol
  and better tolerated

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Selective COX-II Inhibitors COXIBs

• Celecoxib, Rofecoxib,Valdecoxib
• NO more effective than traditional NSAIDs
• Potential benefit is GI safety
• Still have renal toxicity, other toxicities ?
• Large trials demonstrate decreased ulcer rate
• Decrease of about 50
• Do high-risk patients still need acid suppression
  ?
• Risk of cardiac events has led to the removal of
  rofecoxib (VIOXX) and celecoxib (CELEBREX)

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Case 6

• Consider alternatives to NSAIDs
• narcotics
• non-narcotics
• physical therapy
• topical therapy
• Consider misoprostol
• Consider acid suppression with PPI
• For now would not consider any COXIB drugs left
  on the market

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Peptic Ulcer Disease

• Stop NSAIDs.
• Acid suppression acutely
• Test for H pylori and treat if present.

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Uncomplicated DU and GU

• Acid suppression - omeprazole or H2 blockers,
  sucralfate
• If H pylori present and treated
• no need for long term maintenance H2 blocker
• ? test for eradication (breath tests)
• If GU repeat endoscopy after 8-12 weeks to
  confirm healing and rule out cancer

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Complicated DU and GU

• Bleeding or comorbid conditions
• Acid suppression - omeprazole or H2 blockers
• test and treat for H pylori
• F/U EGD to ensure healing - test for eradication
• long term maintenance therapy (H2 blocker or PPIs)

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Case 7

• 75 yo admitted with hematemesis, shock
• Intubated for airway protection (NPO)
• EGD reveals gastric ulcer with visible vessel
• Treatment with heater probe controls bleeding

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Acid Suppression

• There is evidence that acid suppression may
  decrease rebleeding rates, surgical rates, and
  hospital days
• There is no evidence that it saves lives
• (studies would have to be huge)
• IV PPI data is based on trials using IV
  OMEPRAZOLE which is not available in the US
• Most studies involved bleeding ulcers requiring
  endoscopic therapeutic interventions (injection
  therapy or heater probe)

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A COMPARISON OF OMEPRAZOLE AND PLACEBO FOR
BLEEDING PEPTIC ULCER. M KHUROO et al N Engl J
Med 19973361054-8.

• Design Placebo controlled RCT
• Population Bleeding peptic ulcers - not treated
  endoscopically
• InterventionOmeprazole 40 mg BID or placebo
• Primary outcome Recurrent bleeding, surgery or
  death

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• Continued bleeding
• ARR 0.36-.11.25
• NNT 4
• Surgery
• ARR 0.23-0.06 0.17
• NNT6

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Effect of Intravenous Omeprazole on Recurrent
Bleeding after Endoscopic Treatment of Bleeding
Peptic Ulcers James Y.W. Lau, M.B., B.S., et
al NEJM 343(5)310-316. 2000

• Design Placebo controlled RCT
• Population Patients with bleeding ulcers who
  received endoscopic therapy (N240)
• Intervention IV OMEPRAZOLE or Placebo
• Outcome rebleeding within 30 days

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After adjustment for the covariates of the size
and location of ulcers, the presence or absence
of coexisting illnesses and a history of ulcer
disease, and the American Society of
Anesthesiology grade in the Cox
proportional-hazards model, the hazard ratio was
3.9 (95 percent confidence interval, 1.7 to
9.1).
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Effect of Intravenous Omeprazole on Recurrent
Bleeding after Endoscopic Treatment of Bleeding
Peptic Ulcers James Y.W. Lau, M.B., B.S., et
al NEJM 343(5)310-316. 2000
ARR(.225-0.067)0.158 NNT 6
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PPIs Summary

• In the select group of patients who require
  endoscopic therapy the few published studies
  demonstrated potential advantage for IV
  Omeprazole
• In our settings most endoscopies will be done
  quite early - there is little advantage in
  starting IV PPIs prior to EGD in most cases
• Oral PPIs may have some protective effect
  compared to placebo

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Case 7

• Start IV Pantoprazole (80 mg bolus folllowed by 8
  mg per hour)
• Start PPI of choice after patient is taking oral
  meds