Gastroenterology: Gastroesophageal Reflux Disease - PowerPoint Presentation

1. Gastroenterology:Gastroesophageal Reflux Disease Courses in Therapeutics and Disease State Management

2. Learning ObjectivesDefine GERD and describe the various stages of disease severityDescribe the etiology of GERD and risk factors associated with the diseaseDiscuss typical symptoms, atypical symptoms, alarm symptoms, aggravating factors and complications associated with GERDDescribe how GERD is diagnosed and the role of endoscopyDiscuss the various pharmacologic approaches for the treatment of GERD

3. Learning ObjectivesReview the roles of the H2-antagonists and proton pump inhibitors in the treatment of GERD and prevention of its recurrenceDescribe non-pharmacologic and lifestyle measures that may be beneficial in the reduction of symptoms of reflux diseaseGiven a GERD patient history, be able to recommend appropriate pharmacologic and nonpharmacologic therapies and explain the rationale behind your decisionDiscuss drug adverse effects and monitoring parameters for drugs and GERD

4. Required and Recommended ReadingMay D, Thiman M, Rao SC. Gastroesophageal Reflux Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; 2017.

5. GERD DefinitionsGERD (Gastroesophageal Reflux Disease)A condition that occurs when refluxed stomach contents lead to troublesome symptoms and/or complicationsEpisodic pyrosis (heartburn) that is not frequent enough or painful enough to be considered bothersome by the patient is not included in the above consensus GERD definitionPyrosis frequency of more than 2 times per week is sometimes used as a criteria for GERDChronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. Symptoms of GERD vary in severity, duration, and frequency.When the esophagus is repeatedly exposed to refluxed material for prolonged periods of time, inflammation of the esophagus (esophagitis) occurs, and in some cases it can progress to erosion of the squamous epithelium of the esophagus (erosive esophagitis) and may lead to other complications.

6. EpidemiologyHeartburn is the most frequent clinical complaint Reported to occur at least once daily in 10% 20% weekly; 44% monthly of U.S. adults $5 billion for OTC/Rx per yearMost frequently occurs in adults over 40 years of ageIncidence in similar between men and women

7. EpidemiologyAbout 50% of pregnant women will experience GERDCan also occur in infantsPrevalence depends on geographic region but is highest in Western countries

8. Risk FactorsObesity (BMI ≥ 30)Alcohol use SmokingExcessive caffeine intakeRespiratory diseases

9. Key Factors in the Development of GERDA decrease in lower esophageal sphincter (LES) pressureDecreased clearance of gastric contents from the esophagusDecreased mucosal resistance in the esophagus

10. Key Factors in the Development of GERDComposition of reflux contents “extra acidic” Gastric fluid that has a pH < 4 is extremely caustic to the esophageal mucosa.Decreased gastric emptying (increased gastric emptying time) Certain anatomic features Most commonly a hiatal hernia

11. Pathophysiology of GERD (Role of the Lower Esophageal Sphincter) Link: Figure of comparison of esophageal high-resolution manometryLink: Figure of pathophysiology of esophageal reflux disease (LES, lower esophageal sphincter)

12. Hiatal HerniaA hiatal hernia occurs when a portion of the stomach protrudes through the diaphragm into the chest Causes a disruption in the normal anatomic barriers between the stomach and the esophagusLink: Figure of radiographic anatomy of the gastroesophageal junction

13. GERD SymptomsGERD symptoms are often grouped in 3 categoriesTypical or “classic” esophageal symptomsAlarm or complicated symptomsMay be indicative of GERD complicationsAtypical or extraesophageal symptoms

14. Typical or “Classic” SymptomsPyrosis (heartburn)Hallmark symptomA substernal feeling of warmth or burning rising up from the abdomen that may radiate to the neckRegurgitation/Belching Acid brash/HypersalivationChest pain (non cardiac in nature)

15. Alarm (Complicated) SymptomsAny of these symptoms warrant immediate referral for testingDysphagiaOdynophagiaBleeding Unexplained weight lossChokingChest pain (if could be cardiac in nature)

16. Extraesophageal Symptoms/Manifestations (Atypical Symptoms)These symptoms have an association with GERD but causality should only be considered if a concomitant esophageal symptoms are presentChronic coughAsthma-like symptomsAbout 50% of those with asthma have GERDLaryngitis/HoarsenessRecurrent sore throatDental enamel erosion

17. GERDGERD is often described on either esophageal symptoms or esophageal tissue injurySymptom-based GERD syndromes (with or without esophageal tissue injury)Tissue injury-based GERD syndromes (with or without esophageal symptoms)Extraesophageal GERD syndromes may also occurGERD is also sometimes described in terms of the absence or presence of esophageal erosionsNon-erosive reflux disease (NERD)Erosive reflux disease (ERD)

18. Symptom-Based GERD SyndromesMay or may not have esophageal tissue injuryHave typical or “classic” esophageal symptomsMay have alarm symptoms particularly if GERD complications (see next section) are present

19. Tissue-Injury Based GERD SyndromesExamples of esophageal tissue injury include the presence of any of the following:Esophagitis (inflammation of the esophagus)Erosions (erosion of the squamous epithelium of the esophagus)StricturesBarrett’s esophagusEsophageal adenocarcinomaMay present with alarm symptoms particularly if have GERD complicationsMay or may not have typical or classic symptoms

20. Extraesophageal GERD SyndromesPresent with extraesophageal or atypical symptomsMay or may not have typical esophageal symptomsExtraesophageal symptoms have an association with GERD, but causality should only be considered if a concomitant esophageal GERD syndrome is also presentExtraesophageal manifestations of GERD are being recognized with increasing frequency. GERD may be either a causative or exacerbating factor in up to 50% of patients who experience these symptoms.

21. Aggravating FactorsRecumbencyIncreased intra-abdominal pressureReduced gastric motilityDecreased LES tone or pressureDirect mucosal irritation

22. Decrease in LES PressureExamples of foods that decrease LES pressureFatty foods, peppermint, spearmint, chocolate, coffee, cola, tea, garlic, onions, chili peppersExamples of medications that decrease LES pressureAnticholinergics, barbiturates, benzodiazepines, caffeine, dihydropyridine calcium channel blockers, dopamine, estrogen, ethanol, narcotics, nicotine, nitrates, progesterone, theophylline

23. Direct Mucosal IrritationExamples of foods that are direct irritants to the esophageal mucosaSpicy foods, orange juice, tomato juice, coffeeExamples of medications that are direct irritants to the esophageal mucosaOral bisphosphonates, aspirin, iron, NSAIDs, quinidine, potassium

24. Foods and Medications that May Worsen GERD SymptomsFoods/BeveragesMedicationsDecreased Lower Esophageal Sphincter PressureFatty mealAnticholinergicsCarminatives (peppermint, spearmint)BarbituratesChocolateCaffeineCoffee, cola, teaDihydropyridine calcium channel blockersGarlicDopamineOnionszEstrogenChili peppersNicotineAlcohol (wine)NitratesProgesteroneTetracyclineTheophyllineDirect Irritants to the Esophageal MucosaSpicy foodsAspirinOrange juiceBisphosphonatesTomato juiceNonsteroidal antiinflammatory drugs (NSAIDs)CoffeeIronTobaccoQuinidinePotassium chloride

25. Complications of GERDEsophagitisLink: Figure of EGD demonstrating linear red streaks with a central white streak extended up the esophagus in peptic regurgitant esophagitisErosions and ulceration of the esophageal mucosaStrictures of the esophagusSecondary to fibrous tissue deposition after long standing erosionBarrett’s esophagusPresent in about 10% of those with GERDMost prevalent in white males in Western countriesEsophageal adenocarcinoma

26. Barrett’s EsophagusBarrett’s esophagus occurs when the normal squamous cell epithelium in the esophagus converts to a columnar cell epithelium (intestinal-type epithelium)More common in men than womenBarrett’s esophagus does not cause specific symptoms but the reflux does

27. Barrett’s EsophagusThose with Barrett’s esophagus develop adenocarcinoma of the esophagus at a rate of 0.12% per yearGender ratio for esophageal adenocarcinoma is 8:1 (male:female)Patients must be monitored via endoscopy to evaluate changes in cell type and conversion to adenocarcinoma

28. Complications of GERDLink: Photos of endoscopic appearance of peptic esophagitis, a peptic stricture, Barrett’s metaplasia, and adenocarcinoma

29. GERD Diagnosis/Diagnostic TestsClinical HistoryPatient’s description of typical or classic GERD symptoms such as pyrosis, is often enough to consider GERD as an initial diagnosis (uncomplicated GERD)Empiric trial of proton pump inhibitor (PPI) therapyACG (American College of Gastroenterology) guidelines state that it is reasonable to assume a GERD diagnosis in patients who respond to appropriate therapy

30. GERD Diagnosis/Diagnostic TestsEndoscopyEndoscopy is the technique of choice to identify complications of GERD such as ulcerations, erosions, Barrett’s esophagus, etc.Biopsy of the esophageal tissue is needed to identify and diagnose Barrett’s esophagus and esophageal adenocarcinoma Many patients with GERD (presenting with typical or atypical symptoms) will have normal appearing esophageal mucosa on endoscopyUsually not part of the work-up except in certain subsets of patients (alarm symptoms, those refractory to treatment, etc.)

31. GERD Diagnosis/Diagnostic TestsAmbulatory pH MonitoringIdentifies patients with excessive esophageal acid exposure and helps determine if symptoms are acid relatedUseful in patients not responding to acid-suppression therapyBarium RadiographyNot routinely used to diagnose GERD due to a lack of sensitivity and specificityCan detect hiatal hernia

32. GERD Diagnosis/Diagnostic TestsPatients presenting with extraesophageal or atypical symptoms should be reviewed on a case-by-case basis to be considered for testingAlarm symptoms always warrant further testing

33. Therapeutic Approach to GERDThe initial treatment used is determined by the patient’s condition:Frequency of symptomsDegree of symptomsPresence and/or degree of esophagitisPresence of complications

34. Goals of TreatmentAlleviate or eliminate acute symptomsDecrease frequency of recurrencePromote healing if esophageal tissue injury is presentPrevent complications

35. General Treatment ApproachInitial therapy in patients who present with typical GERD symptoms should include patient-directed (self-care) therapy (antacids, OTC H2-antagonist, or OTC PPIs) and lifestyle modificationsThose who do not respond to patient-directed therapy and lifestyle modifications after 2 weeks should seek medical attention and are usually started on empiric therapy consisting of an acid suppression agent such as a proton pump inhibitor (PPI)Those who do not respond to empiric acid suppression therapy or have alarm symptoms should undergo testing such as an endoscopy

36. Nonpharmacologic TherapiesLifestyle modifications Should be incorporated into the management of GERD regardless of the severity of diseaseLifestyle modifications should be tailored to an each individual patient’s needsAnti-reflux surgeryUsed as a last resort option in select patientsWhen long-term pharmacologic therapy is undesirableWho have refractory GERDHave complicationsEndoscopic therapies Results have been disappointing and hence are not usually recommended

37. Lifestyle ModificationsWeight loss (if the patient is overweight or obese)Elevation of the head of the bed 6 to 8 inchesEat smaller, more frequent meals (as opposed to larger meals less frequently)Include protein-rich meals in diet (increases LES pressure)

38. Lifestyle ModificationsAvoid eating 3 hours prior to sleeping or lying downAvoid foods or medications that exacerbate GERD Avoid alcoholTobacco cessation

39. Endoscopic InterventionsStretta Procedure Stretta is an endoscopically guided radiofrequency (RF) energy delivery system. The device is guided down the esophagus and RF energy is delivered to tissues via catheters/needles. RF energy is thought to improve GERD symptoms by increasing collagen deposition at the LES, increasing muscle wall thickness and reconstituting the barrier to the reflux of gastric contents.  LINX Reflux Management System (FDA approved March 2012)A series of titanium beads each with a magnetic core connected together with a wire to form a ring shape.Implanted in the LESThe force of the magnetic beads provides additional strength to a keep a weak LES closed.

40. Therapeutic Interventions in the Management of GERDLink: Figure of therapeutic interventions in the management of gastroesophageal reflux disease

41. Pharmacologic Agents Used in the Treatment of GERDAntacids and alginic acid productsH2-receptor antagonists (HRA) Proton pump inhibitors (PPIs)Promotility agents

42. AntacidsMOANeutralize hydrochloric acid in the stomach, which results in an increase in gastric pHAgentsMagnesium hydroxideAluminum hydroxideCalcium carbonateAdverse effectsDiarrhea (magnesium hydroxide)Constipation (aluminum hydroxide and calcium carbonate)Alterations in mineral metabolismAcid-base disturbances

43. AntacidsMonitoringPeriodic calcium and phosphate levels if on chronic antacid therapyPatient counselingAntacids can decrease the levels of numerous other drugs including tetracyclines, digoxin, iron supplements, fluroquinolones, and ketoconazole. Patients should separate antacids and other medications by at least 2 hoursPatients with renal impairment should not use aluminum or magnesium containing antacids unless directed by their physicianOnset of relief is less than 5 minutes and duration of relief is 20 to 30 minutes

44. Composition and Acid Neutralizing Capacities of Popular Antacid PreparationsPRODUCTAl(OH)3aMg(OH)2aCaCO3aSIMETHICONEaACID NEUTRALIZING CAPACITYbTabletsGelusil20020002510.5Maalox Quick Dissolve00600012Mylanta Double Strength40040004023Riopan Plus Double StrengthMagaldrate, 10802030Calcium Rich Rolaids80412011Tums EX00750015LiquidsMaalox TC6003000028Milk of Magnesia04000014Mylanta Maximum Strength40040004025RiopanMagaldrate, 540015aContents, milligrams per tablet or per 5 ml.bAcid neutralizing capacity, milliequivalents per tablet or per 5 ml.The U.S. marketplace for antacids is fluid. The current trend of "reusing" well-known brand names to introduce new products that contain an active ingredient different from expected is a source of confusion that can present a danger to patients. Medication safety experts encourage clinical practitioners to refer to the active ingredient(s) in conjunction with the proprietary (brand) name when selecting OTC products.

45. Antacid-Alginic Acid CombinationMOAThe antacid neutralizes stomach acid and the alginic acid is a foaming agent that creates a viscous solution that floats on top of the stomach contents and may be protect the esophagus from refluxed stomach acidAgentsAluminum hydroxide/Magnesium carbonate/Alginic acid (Gaviscon)

46. H2-Receptor AntagonistsMOACompetitive inhibition of histamine at H2 receptors of gastric parietal cells which inhibits gastric acid secretionAgentsCimetidine (Tagamet)Famotidine (Pepcid)Nizatidine (Axid)Ranitidine (Zantac)

47. H2-Receptor AntagonistsAdverse effectsHeadache, somnolence, fatigue, dizziness, constipation, diarrheaMonitoringMonitor for CNS effects (rare) in those over 50 years old or in those with renal or hepatic impairmentPatient counselingIf taking once a day, it is preferable to take the dose at bedtimeOnset of relief is 30 to 45 minutes and duration of relief is 4 to 10 hours

48. Proton Pump Inhibitors (PPIs)MOABlocks acid secretion by inhibiting gastric H+/K+ adenosine triphosphatase found on the secretory surface of gastric parietal cellsResults in a long-lasting anti-secretory effect that can maintain gastric pH levels above 4AgentsDexlansoprazole (Dexilant)Esomeprazole (Nexium)Lansoprazole (Prevacid)Omeprazole (Prilosec)Omeprazole/sodium bicarbonate (Zegerid)Pantoprazole (Protonix)Rabeprazole (Aciphex)

49. Proton Pump Inhibitors (PPIs)Common adverse effectsHeadache, dizziness, somnolence, diarrhea, constipation, flatulence, abdominal pain, nauseaSerious adverse effectsIncreased risk of Clostridium difficile infectionsIncrease risk of community-acquired pneumoniaLong-term adverse effects (> 1 year)HypomagnesemiaBone fracturesVitamin B12 deficiency

50. Proton Pump Inhibitors (PPIs)MonitoringAppearance of diarrhea (frequency and type of diarrhea episodes)Periodic magnesium levels (if long-term therapy)Routine bone density studies (DXA scans) If other risk factors for osteoporosis or bone fractures presentPatient counselingPreferable to take a PPI 30 to 60 minutes before a meal (mainly breakfast)If a second dose is needed, take prior to the evening mealOnset of relief is 2 to 3 hours and the duration of relief is 12 to 24 hours

51. Evaluate the Risks versus Benefits of Long-Term PPI UseLong-term PPI use has been associated with increased risk of:FracturesInfections such as C. Diff and pneumonia (expand)HypomagnesemiaVitamin B12 deficiency

52. Evaluate the Risks versus Benefits of Long-Term PPI UseLong-term PPI use MAY BE associated with increased risk of:DementiaRenal diseaseCardiovascular disease

53. Promotility AgentsPromotility agents, such as metoclopramide and bethanechol, have been used as adjunct therapy to acid suppression agents such as PPIs in patients who have a known motility defectHowever, they are not generally recommended to be used for GERD treatment due to their limited effectiveness and undesirable adverse effect profiles

54. Pharmacologic TherapyPatient directed therapy (Self-care) is appropriate for intermittent, mild pyrosis and is managed using over-the-counter products such as antacids, OTC H2-receptor antagonists, and OTC proton pump inhibitors (PPIs)Link: Table on Therapeutic Approach to GERD in Adults

55. Pharmacologic TherapySymptomatic relief of uncomplicated GERD is treated with prescription H2-receptor antagonists or prescription PPIs at the following doses and durations:Refer to Link: Table on Therapeutic Approach to GERD in Adults

56. Pharmacologic TreatmentHealing of erosive esophagitis or treatment of patients presenting with moderate to severe symptoms or complicationsRefer to Link: Table on Therapeutic Approach to GERD in Adults

57. PPIs v. H2-Receptor AntagonistsSymptomatic improvement as well as endoscopic healing rates are higher for the PPIs compared to the H2-receptor antagonistsPPIs are therefore preferred over H2-receptor antagonists in patients with erosive disease, moderate to severe symptoms, or with complications

58. Maintenance TherapyWhat patients should receive maintenance therapy?Those with symptomatic relapse following discontinuation of the drug or a decrease in dose.If NERD/uncomplicated GERD, try to manage with on-demand or intermittent PPI therapy or H2-receptor antagonists

59. Maintenance TherapyWhat patients should receive maintenance therapy?Those with a history of complications (e.g. Barrett’s esophagus, strictures, hemorrhage, ulcerations, etc.)Long-term maintenance therapy with PPIs at the lowest possible dose Can consider intermittent or on demand PPI therapy in some circumstances

60. PPIs and Rebound Acid SecretionThere have been reports of rebound acid secretion when PPIs are abruptly discontinued.This can happen when PPIs are used for as little as 2 months (and of course when they are used longer)These hyperacidity symptoms include dyspepsia and heartburnOften attributed to a relapse of the disorder (e.g. GERD), but it can even happen in patients who didn’t have these symptoms to start with

61. PPIs and Rebound Acid SecretionTapering strategies for patients experiencing rebound acid secretion(1) Taper PPI over 4 to 6 weeksFirst lower the dose of the PPIThen extend the PPI dosing interval to every other day then every 3rd dayAn H2-antagonist or antacid can be used for symptoms on “off days” as needed(2) Suggest a switch to an H2-antagonist with antacids used as needed for several weeks then discontinue

62. Patients with Extraesophageal (Atypical) GERDGERD can be considered as a potential co-factor in patients with asthma, chronic cough, or laryngitisCareful evaluation of non-GERD causes should be undertaken in all of these patients Patients with atypical symptoms may need higher doses of acid suppression therapy with longer treatment duration compared to those patients with typical symptoms

63. Patients with Extraesophageal (Atypical) GERDA PPI trial is recommended to treat extraesophageal symptoms in patients who have typical GERD symptoms as wellReflux monitoring should be considered before a PPI trial in patients with extraesophageal symptoms who do not have typical GERD symptoms

64. Pediatric PatientsA suspected cause of reflux in infants is a developmentally immature LESMany infants have reflux with little or no clinical consequenceThis uncomplicated reflux usually manifests as regurgitation or spitting upUsually responds to supportive therapyChronic vomiting associated with GERD must be carefully evaluated and distinguished from other causes

65. Pediatric PatientsCareful consideration should be given before a medication is recommendedWhen a medication is deemed necessary, ranitidine dosed at 2 to 4mg/kg twice a day is often usedPPIs are increasing being used in children older than 1 yearLansoprazole, esomeprazole, and omeprazole are indicated for treating symptomatic and erosive GERD in children > 1 year oldSee next slide for dosing rangesOmeprazole has been used off-label in children less than 1 year old at a dose of 1mg/kg/day

66. PPIs in Children > 1 year of ageLansoprazole 15mg per day is recommended for children weighing < 30kg30mg per day is recommended for children weighing > 30kgEsomeprazoleDosed 10 to 20mg a day for children 1 to 11 years oldDosed at 20 to 40mg a day for children 12 to 17 years oldOmeprazole5mg daily in children weighing between 5 and 10kg10mg daily in children weighing between 10 and 20kg20mg daily in children weighing ≥ 20kg

67. Elderly PatientsMany elderly patients have decreased defense mechanisms such as decreased saliva productionPPI therapy may be warranted for those > 60 years of age with symptomatic GERDThey have superior efficacy and have once a day dosingLong-term risk of bone fractures is a concern and elderly patients should be monitored appropriatelyElderly are at higher risk of being sensitive to possible CNS effects of H2-receptor antagonists

68. Patients with Refractory GERDRefractory GERD should be considered in patients who have not responded to a standard course of twice a day PPI therapyThe majority of patients with refractory symptoms experience nocturnal acid breakthroughSwitching to a different PPI may be effective in some patientsAdding an H2-receptor antagonist at bedtime for nocturnal symptoms is reasonable but the effect may decrease over time due to tachyphylaxis with H2-receptor antagonists

69. ReferencesMay D, Thiman M, Rao SC. Gastroesophageal Reflux Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; 2017.Mills JC, Stappenbeck TS. Gastrointestinal Disease. In: Hammer GD, McPhee SJ. eds. Pathophysiology of Disease: An Introduction to Clinical Medicine, Seventh Edition. New York, NY: McGraw-Hill; 2013.Kahrilas PJ, Hirano I. Diseases of the Esophagus. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015.

70. ReferencesWallace JL, Sharkey KA. Pharmacotherapy of Gastric Acidity, Peptic Ulcers, and Gastroesophageal Reflux Disease. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e. New York, NY: McGraw-Hill; 2011.Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013; 108: 308-328.Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Internal Medicine 2016; 176(2): 172-174.

71. References Micromedex Solutions.  Truven Health Analytics, Inc. Ann Arbor, MI.  Accessed October 15, 2016.Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc. Accessed October 15, 2016.