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Dyspepsi IRF 26. januar 2010

Dyspepsi IRF 26. januar 2010. Læge, ph.d, Christina Reimer. Behandling og behandlingsvarighed. Ulcus Profylakse Funktionel Dyspepsi Gastroesophageal Reflux Sygdom . A02 Midler mod syrerelaterede forstyrrelser. Antacida H2-receptor antagonister Prostaglandiner Protonpumpehæmmere

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Dyspepsi IRF 26. januar 2010

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  1. DyspepsiIRF 26. januar 2010 Læge, ph.d, Christina Reimer

  2. Behandling og behandlingsvarighed Ulcus Profylakse Funktionel Dyspepsi GastroesophagealReflux Sygdom

  3. A02Midler mod syrerelaterede forstyrrelser • Antacida • H2-receptor antagonister • Prostaglandiner • Protonpumpehæmmere • Andre midler (sucralfat, alginsyre)

  4. Ulcussygdom H. pylori ASA/NSAIDs

  5. Ulcus ætiologi Reimer et al, Scand J Gastroenterology 2008

  6. Behandling og behandlingsvarighed ved H. pylori positivt ulcus • PPI i standarddosis x 2 dagligt • Clarithromycin 500 mg x 2 dagligt • Amoxicillin 1 g x 2 dagligt • Behandlingsvarighed: 7 dage • Ved større ulcera suppleres med • PPI behandling i 2-4 uger • H.Pylori test 4-6 uger efter kur Positiv H. pylori test

  7. Behandling og behandlingsvarighed ved NSAID/ASA associeret ulcus Seponer ASA/NSAID PPI i standard dosis i 4-8 uger Negativ H. pylori test Oplysninger om forbrug af ASA/NSAID

  8. Hvornår er vedligeholdelsesbehandlingmed syrepumpehæmmer (PPI) efter ulcusheling indiceret? • Ved recidiverende ulcera, trods Helicobacterpylori-negativ test (idiopatiskulcus) • Ved gentagne mislykkede forsøg på Helicobacterpylori-eradikation • Ved fortsat indikation for ASA/NSAID-behandling. Klinisk vejledning: Udredning og behandling af dyspepsi. DSAM 2009

  9. Hvordan forebygges ASA/NSAID-relateredeulcuskomplikationer? Genovervej indikationen for ASA/NSAID-behandling Vurder patientens risiko for ulcus-komplikation: • Alder (risiko er stigende med alder, specielt > 60 år) • Tidligere ulcus • Tidligere ulcusblødning/perforation • Dyspepsi • Anden sygdom (diabetes, hjerte-kar-sygdom eller svær kronisk leddegigt) • Samtidig behandling med steroid, SSRI eller AK-behandling

  10. Ofte er risikoen åbenlys

  11. Gastroskopien var normal……. Behandling af funktionel dyspepsi Detkommeraf græsk Hva´ kommerdyspepsiaf?

  12. Medikamentelbehandlingaffunktioneldyspepsi • Stort placebo respons • H2RA og PPI hjælper kun få (10-15%) • Ingenindikation for antacida • Ringesymptomatiskeffektaferadikation (NNT = 15) • Beroligelseog information omtilstandensgodartedenaturhjælper

  13. Reflukspyramiden Adenocarcinom Barrett ogkomplikationer Sværerosiv Mild erosiv NERD

  14. Non-Erosiv Reflukssygdom ErosivOesophagitis Barrett’sOesophagus Forskellige former for GERD ≥60% ~35% <5% Non-progressiv Normal endoskopi StrikturUlcusGI blødning Adenocarcinomi oesophagus

  15. Virker livsstilmodifikationer ved GERD? • Vægttab Effektivt • Ligge højt med hovedet Effektivt • Rygeophør Ingen evidens • Ophør med alkohol Ingen evidens • Kostændring Ingen evidens Kaltenbach et al. Arch Intern Med 166: 965-71 (2006)

  16. Medicinsk behandling? • Patienter med komplikationer til GERD (erosioner, ulceration, striktur, Barrettsøsofagus) og patienter som oplever nedsat livskvalitet som følge af symptomerne bør tilbydes medicinsk behandling • Patienter med milde og sporadiske symptomer kan behandles med antacida og H2-blokker • Ved svære og hyppige symptomer behandles med syrepumpehæmmer i standarddosis

  17. Almost all GERD patients relapse after treatment discontinuation Relapsed% 100 80 60 Severe (Grade C) 40 Moderate (Grade B) Mild (Grade A) 20 No esophagitis 0 0 1 2 3 4 5 6 Time (months) Lundell et al. Gut 45:172–80 (1999)

  18. Continuous maintenance (months–years) Intermittent courses (weeks) On-demand (days) S S S S S S S Treatment options in GERD S = symptom recurrence

  19. PPI (4)–8 weeks Success: continuous PPI Endoscopy Normal endoscopy NERD Mild reflux esophagitis Severe refluxesophagitis Bytzer P, Blum AL. Aliment Pharmacol Ther 20:389–98 (2004)

  20. PPI (2)–4 weeks Success:continuous/on-demand PPI Endoscopy Normal endoscopy NERD Mild reflux esophagitis Severe refluxesophagitis Bytzer & Blum, Aliment Pharmacol Ther 20:389–98 (2004)

  21. PPI 4 weeks Success: Consider on demand or continuous PPI Endoscopy Mild reflux esophagitis Severe refluxesophagitis NERD Bytzer & Blum, Aliment Pharmacol Ther 20:389–98 (2004)

  22. Heling proportional med syrehæmning Heling af øsofagit(%) 100 PPI 80 H2-receptorantagonister 60 40 placebo 20 0 0 2 4 6 8 10 12 Tid (uger) Chiba et al 1997

  23. Opsamling • Behandling af ulcussygdommen er i størstedelen af tilfældene kortvarig (4-8 uger) • Længerevarende fast behandling med PPI er indiceret ved erosiv reflukssygdom og som profylakse mod ASA/NSAID-relaterede ulcuskomplikationer

  24. Opsamling • Langtids-PPI-behandling af NERD kan ofte være symptomstyret efter on-demand principperne • Ved behandling af funktionel dyspepsi er der kun evidens for en beskeden effekt af syrehæmmende behandling i kortere tid • P.g.a højt placeborespons og stort symptomoverlap må langtids-PPI-behandling baseret på symptomer evalueres kritisk og følges af regelmæssige seponeringsforsøg

  25. PPIs on prescriptionUse in DDD/1000 inhabitants per day Danish Medicines Agency. Medicinal Product Statistics 2008

  26. Long-termuse of PPIs in primarycare in Denmark • 22 GP’s with a total of 42.634 registered pts. • Standardized search for prescription of PPIs in each practice prescribing register • Patients who had prescriptions of ≥120 tablets in previous year defined as long-term users • Indications for long-term therapy ascertained by reviewing records for results of endoscopy, H. pylori testing, pH-monitoring and clincal assesment by the GP

  27. Reasons for PPI therapy Verifiedindications Treatmentbasedon symptoms • Investigatedwithoutfindings • Non-erosiverefluxdisease (NERD) • Functionaldyspepsia • Endoscopically • documented GERD • Unexplainedor • NSAID/ASA induced • pepticulceror GI • bleed • Uninvestigated • Empiricaltherapy of upper GI sxs

  28. Prevalence of long-term PPI therapy 5.3% (2.275/42.634) had at leastone PPI prescription 2.1% (901/42.634) were long-term treated (≥120 tablets/previous year) Verifiedindication 27% (247/901) Treatedbasedon symptoms 73% (654/901) Reimer et al. Aliment pharm and ther. 2009

  29. Indications and reasons for long-term PPI therapy (N=901) Reimer et al. Aliment pharm and ther. 2009

  30. Self-reported characteristics of patients long-term treated based on symptoms (n=194)

  31. Maximal acid output in 12 H.pylori-negative subjects before, during and after 8 weeks treatment with a PPI mmol/h Gillen, Gastroenterology 2004;126: 980-988

  32. Treatmentwith a PPI for at least 8 weeksinducesreboundacidhypersecretion (RAHS) aftertherapy has beendiscontinued in H.pylori negative individuals • It sets off 1-2 weeksaftertherapy is withdrawn and is a temporaryphenomenon • Is it clinically relevant? • Couldthisphenomenonprovokeacid-related symptoms and thuslead to PPI dependency?

  33. Placebo 120 healthyvolunteers Esomeprazole 40 mg od Placebo Week 0 4 8 12 Week 0,1,2,3,4,5,6,7,8,9,10,11,12: GSRS (Gastrointestinal Symptom Rating Scale) Week 0, 4, 8, 12: Gastrin, Chromogranin A (CgA)

  34. Placebo Randomisation Esomeprazole 40 mg x 1 placebo • Outcomemeasures • 1. Have youbeenbothered by stomachacheorpain in the upper abdomen during the pastweek? • 2. Have youbeenbothered by heartburnduring the pastweek? • 3. Have youbeenbothered by acidrefluxduring the pastweek? • (1) Nodiscomfort at all • (2) Slightdiscomfort • (3) Mild discomfort • (4) Moderate discomfort • (5) Moderatelyseverediscomfort • (6) Severediscomfort • (7) Veryseverediscomfort 0 4 8 12

  35. Mean GSRS score for dyspepsia, heartburn and regurgitation p< 0.05 Reimer et al. Gastroenterology 2009

  36. Proportion with score >2 for dyspepsia, heartburn or regurgitation p< 0.05 Reimer et al. Gastroenterology 2009

  37. Conclusions • Acid inhibition with a PPI for 8 weeks induces acid-related symptoms in a significant proportion (44%) of previously asymptomatic subjects when therapy is withdrawn • The most likely underlying explanation is RAHS • PPI dependency as one of the explanations for the prevalent and increasing long-term use of PPIs is supported by this study

  38. Implications • Rationalisation of PPI prescribing can be obtained in subgroups of patients treated long-term based on symptoms only • In patients who are treated based on unspecific symptoms that are not likely to be acid-related, a short course of empirical therapy is important in order to avoid inducing true acid-related symptoms caused by RAHS • Otherwise induction of a true need for PPIs in patients with a questionable indication for therapy in the first place is risked

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