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Acid Peptic Diseases Clinical Management Course February 2007 Walter Smalley, MD MPH.

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Presentation on theme: "Acid Peptic Diseases Clinical Management Course February 2007 Walter Smalley, MD MPH."— Presentation transcript:

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2 Acid Peptic Diseases Clinical Management Course February 2007 Walter Smalley, MD MPH

3 Acid - Peptic Diseases Drugs Antacids H2RAs (“H-2 blockers”) Proton Pump Inhibitors (PPI’s) Selective COX-II inhibitors Conditions Covered Heartburn Gastroesophageal Reflux (GERD) Peptic Ulcer Disease H. Pylori NSAIDs

4 Antacids Immediate effect on gastric pH Effect is short-lived Typical dose cc Frequent use may cause diarrhea

5 H-2 Receptor Antagonists Inhibit H-2 receptors (competitive inhibition) Partially inhibit acid production Relatively safe drugs Less effective than PPI’s Less expensive than PPI’s Available over the counter: at prices more expensive than prescription costs

6 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

7 H2 blockers : No difference in efficacy within group

8 Proton Pump Inhibitors Raise gastric pH to > 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)

9 Proton Pump Inhibitors Omeprazole (generic cost about 80% of prescription costs ) Immediate release omeprazole 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

10 Case 1 35 year old healthy man Occasional heartburn Occurs only with large meals, EtOH ingestion No dysphagia

11 Heartburn : Summary How soon does the patient want relief ? How long does it need to last ? How much are they willing to pay ?

12 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 > 6-8 hours Available over the counter

13 Case 1 Consider not eating large meals Consider PRN antacids Consider OTC H2 blockers On the horizon ? Immediate release omeprazole – Direct to consumer marketing Marginal benefit vs other PPIs

14 Case 2 50 yo with frequent nocturnal heartburn No dysphagia Trial of lifestyle modification only minimally effective Antacids ineffective

15 GERD: When to perform diagnostic tests Endoscopy Dysphagia Weight loss Age > 50 Failure of medical therapy Motility : prior to fundoplication pH monitoring: might resolve diagnostic uncertainty in absence of esophagitis

16 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

17 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, Ca++channel blockers, nitrates, theophylline, antidepressants No strong RCT evidence to support important effect of lifestyle modification

18 Case 2 50 yo with frequent nocturnal heartburn No dysphagia Trial of lifestyle modification only minimally effective Antacids ineffective EGD - distal esophageal erosions

19 GERD : Overview Antacids: temporary relief H2-antagonists: high (“double”) doses, frequent dosing Prokinetics: as effective as H2RA’s Metoclopramide Proton pump inhibitors: most effective most expensive

20 GERD: H2-antagonists NO BETWEEN - DRUG DIFFERENCES IN EFFICACY symptomatic relief < % cases endoscopic improvement < symptomatic relief higher doses (>2X ulcer doses) improve efficacy slightly

21 GERD : Prokinetic Agents Metoclopramide As effective as H2RAs Adverse reactions: –fatigue, lethargy, extrapyramidal symptoms occur in 10% - 30%.

22 Case 2 Continue lifestyle modification Trial of H2 blockers at high doses

23 Case 3 Patient #2 returns after 8 week trial of H2 blockers Therapy only minimally effective

24 GERD : Proton Pump Inhibitors Causes healing and resolution of symptoms in 80% of patients with disease resistant to H2-blockers Expensive, single source drugs ($ / day) Over the counter more expensive than prescription Not on Wal-mart list Generic omeprazole still > $1 per day

25 Case 3 Proton pump inhibitor

26 Case 4 Patient from Case 3 returns Symptoms well controlled on omeprazole Symptoms recur immediately after stopping drug “Hates taking meds”

27 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 % of cases have some improvement

28 GERD: Anti - Reflux Surgery Side effects: about 10 % cases "gas bloat" dysphagia strictures other Usually won’t work if PPI’s don’t work

29 Utilization of GERD pharmaceuticals in patients treated medically and surgically Khaitan et al, Arch Surgery 2003 Acid suppression days per quarter Most fundoplication patients end up taking some acid meds after operation

30 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 (removed from market) All should be considered experimental at this point

31 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)

32 Case 5 40 yo with epigastric pain

33 “ALARM FEATURES” unexplained weight loss anorexia early satiety vomiting progressive dysphagia odynophagia bleeding anemia jaundice abdominal mass lymphadenopathy family history of upper GI cancer history of peptic ulcer, previous gastric surgery or malignancy. ACG dyspepsia management guidelines

34 Case 5 40 yo with epigastric pain Relieved with meals No clinical signs of bleeding No vomiting Reasonable approaches Empiric trial of acid suppression “Test and treat” for H pylori Refer for endoscopy

35 Case 5 40 yo with epigastric pain 8 week trials of PPI fails EGD : duodenal ulcer H pylori positive no NSAIDs confirmed

36 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

37 H pylori : Concepts H pylori infection is chronic Prevalence in US adults = % Lifetime risk of ulcer disease = 10% Associated with chronic gastritis - a histological diagnosis H pylori is a risk factor for gastric adenocarcinoma

38 H pylori - Diagnosis EGD – Biopsy for histology and CLO Breath Tests – commercially available big hassle Serology – widely available, followup is problematic (positivity persists months after eradication) Stool antigen test: problem = it’s stool.

39 H pylori. treatment - Efficacy For treatment of duodenal ulcer > gastric ulcer Eradication of H.pylori alone = treatment with H2- blockers alone For preventing recurrent duodenal ulcer: Eradication of H.pylori >> continuous H2-blocker therapy Marginal (if any) benefit in treating non ulcer dyspepsia

40 H pylori. treatment - Options Many different regimens No "standard of care" Best therapy yet to be determined Big problems compliance resistance Current (2/07) favorite combination Amoxicillin, PPI, Clarithromycin Metrondazole, PPI, Clarithromycin

41 Peptic Ulcer: Treatment Outcomes

42 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

43 Case 6 65 yo male with osteoarthritis with recent ulcer On ibuprofen 1800 mg per day Ulcer has healed H pylori negative

44 NSAIDs and Ulcers - Concepts Higher doses ---> 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 By far our most important complication of pharmaceutical use

45 NSAIDs and PUD : Treatment Stop NSAIDs Acid suppression DrugHealing at weeks Omeprazole > 90% H2-Blockers70-90% Misoprostol70-90% Sucralfatenot effective

46 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".

47 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 ( %) Causes spontaneous abortions - do not use in potentially fertile women

48 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. PPI’s are as probably as effective as misoprostol and better tolerated Eradicating H pylori is helpful in preventing recurrence (RCT evidence)

49 Selective COX-II Inhibitors: COXIBs Celecoxib, rofecoxib, valdecoxib, etoricoxib and lumiracoxib 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 and valdecoxib

50 Results from a polyp prevention trial

51 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

52 Peptic Ulcer Disease Stop NSAIDs. Acid suppression acutely Test for H pylori and treat if present.

53 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

54 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) Most 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)

55 Lancet 2005 Proton pump inhibitor (IV or PO) Moderate effects on: reduced rebleeding (table left) OR 0.46, 95%CI 0.33 to 0.64 NNT =12 surgery OR %CI 0.46 to 0.76 NNT = 20 treatment had no significant effect on mortality OR 1.11, 95%CI 0.79 to 1.57 NNT = incalculable

56 PPI’s 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 PPI’s prior to EGD in most cases Oral PPIs may have some protective effect compared to placebo

57 Case 7 Start IV Pantoprazole (80 mg bolus followed by 8 mg per hour) Start PPI of choice after patient is taking oral meds


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