GERD讲解胃食管反流英文培训课件

1、OverviewIntroductionSymptomsCausesPeptic Ulcer DiseaseH. pyloriNSAIDsGERDTreatments1GERD讲解胃食管反流英文10/3/2022OverviewIntroduction1GERD讲解胃食管Who is Affected?Gastric acidity and GERD affects people of all ages, races, and gender 2GERD讲解胃食管反流英文10/3/2022Who is Affected?Gastric aciditSymptomsHeartburnAcid In

2、digestionRegurgitationNausea 3GERD讲解胃食管反流英文10/3/2022SymptomsHeartburnRegurgitationSymptoms ContinuedHoarsenessSore ThroatChest PainBad BreathDry CoughAsthma*4GERD讲解胃食管反流英文10/3/2022Symptoms ContinuedHoarseness4GSymptoms in ChildrenVomiting CoughingBreathing Problems5GERD讲解胃食管反流英文10/3/2022Symptoms in

3、ChildrenVomiting 5Acid-Peptic DisordersPeptic Ulcer DiseaseOccurs when there is an imbalance between the mucosal defense factors and the acid and pepsin.6GERD讲解胃食管反流英文10/3/2022Acid-Peptic DisordersPeptic UlHelicobacter pylori InfectionCauses 80% of peptic ulcersSurvives the acid environment by attac

4、hing to the sugar molecules that line the stomach wallUses the mucus layer as protection7GERD讲解胃食管反流英文10/3/2022Helicobacter pylori InfectionCH. pyloriProduce large amounts of urease UreaseH203 NH3 + CO2Urea8GERD讲解胃食管反流英文10/3/2022H. pyloriProduce large amountsH. pyloriSecret proteins and toxins that

5、interact with the stomachs epithelial cellsLeads to inflammation and damage9GERD讲解胃食管反流英文10/3/2022H. pyloriSecret proteins and tNSAIDsAspirin, Ibuprofen, NaproxenCan have an affect at very low dosesSuppresses cylooxygenase-1 Decrease production of prostaglandins 10GERD讲解胃食管反流英文10/3/2022NSAIDsAspirin

6、, Ibuprofen, NaprWhat is GERD?Condition where the stomach acid/content is pushed back or “refluxed” into the esophagusAffects 10 million AmericansApproximately 7% have daily symptomsLink11GERD讲解胃食管反流英文10/3/2022What is GERD?Condition where tGERD vs. NERDPatients suffering symptoms are placed in two g

7、roups Non-erosive reflux disease, or NERDErosive esophagitisErosive esophagitis is characterized by swelling and InflammationBarretts EsophagusPrecursor to Esophageal Cancer12GERD讲解胃食管反流英文10/3/2022GERD vs. NERDPatients sufferinCauses of GERDAbnormalities with the Lower Esophageal Sphincter, or LESSt

8、omach AbnormalitiesHiatal herniaLink13GERD讲解胃食管反流英文10/3/2022Causes of GERDAbnormalities wiCauses MedicationsNSAIDsCalcium Channel Blockers (high blood pressure, angina)14GERD讲解胃食管反流英文10/3/2022Causes Medications14GERD讲解胃食管反MedicationsAnticholinergics (urinary tract disorders)Beta Adrenergic Agonists

9、(asthma)Dopamine (Parkinsons disease)15GERD讲解胃食管反流英文10/3/2022MedicationsAnticholinergics (uCausesFood and DrinksCarbonated beveragesChocolate AlcoholCitrus FruitsCoffee or TeaFatty foodsContaining tomatoesMintSpicy Food 16GERD讲解胃食管反流英文10/3/2022CausesFood and Drinks16GERD讲解胃CausesSmokingDamages mucus

10、 membranesImpairs muscle reflexes in the throatIncreases acid secretionReduces LES function and salivation 17GERD讲解胃食管反流英文10/3/2022CausesSmoking17GERD讲解胃食管反流英文10CausesObesityLaying down after a large mealEating close to bed timeExercise 18GERD讲解胃食管反流英文10/3/2022CausesObesity18GERD讲解胃食管反流英文10Release o

11、f Gastric Acid19GERD讲解胃食管反流英文10/3/2022Release of Gastric Acid19GERD讲Release of Gastric acidHistamine stimulates acid release by interacting with the histamine receptor, H2Acetylcholine activates the cholinergic receptorsGastrin is released when food is present in the stomach20GERD讲解胃食管反流英文10/3/2022R

12、elease of Gastric acidHistamiTreatmentsAntacidsAlginatesSucralfateProton Pump InhibitorsHistamine H2-Recptor AntagonistsProkineticsNew Treatments21GERD讲解胃食管反流英文10/3/2022TreatmentsAntacids21GERD讲解胃食管AntacidsQuick but short termBuffer gastric acid, increasing the pHNeutralize acid by the following rea

13、ctionAl(OH)3 + 3 HCl AlCl3 + 3 H2O22GERD讲解胃食管反流英文10/3/2022AntacidsQuick but short term22AntacidsMaalox Al(OH)3 (aluminum hydroxide), Mg(OH)2 (magnesium hydroxide)23GERD讲解胃食管反流英文10/3/2022AntacidsMaalox 23GERD讲解胃食管反流英文AntacidsTums CaCO3 (calcium carbonate)24GERD讲解胃食管反流英文10/3/2022AntacidsTums 24GERD讲解胃

14、食管反流英文10AntacidsPepto-BismolC7H5BiO4 (bismuth subsalicylate)25GERD讲解胃食管反流英文10/3/2022AntacidsPepto-Bismol25GERD讲解胃食AntacidsAlka-SeltzerNaHCO3 (sodium bicarbonate)26GERD讲解胃食管反流英文10/3/2022AntacidsAlka-Seltzer26GERD讲解胃食AlginatesAlginatesUsually combined with an antacidForms protective barrier on top of

15、gastric contentsGavisconSodium Alginate, Sodium Bicarbonate, and Calcium CarbonateLink27GERD讲解胃食管反流英文10/3/2022AlginatesAlginates27GERD讲解胃食管反AlginatesPolysaccharide found in the cell walls of brown algaeSodium alginate is the sodium salt of alginic acid28GERD讲解胃食管反流英文10/3/2022AlginatesPolysaccharide

16、found Alginic Acid29GERD讲解胃食管反流英文10/3/2022Alginic Acid29GERD讲解胃食管反流英文10/SucralfateReacts with stomach acid to from a cross linked viscous polymer that acts as an acid bufferCan bind to proteins on the surface of an ulcer to prevent further acid damageHas been shown to aid in healing by promoting epi

17、dermal growth factors and prostaglandins30GERD讲解胃食管反流英文10/3/2022SucralfateReacts with stomach Sucralfate (Carafate)31GERD讲解胃食管反流英文10/3/2022Sucralfate (Carafate)31GERD讲解胃Proton Pump InhibitorsProton pump inhibitors (PPIs) Inhibits the gastric acid pump, H+/K+ ATPase Are prodrugs32GERD讲解胃食管反流英文10/3/20

18、22Proton Pump InhibitorsProton pPPIs Diffuse into the parietal cells of the stomach and accumulatesActivated by proton-catalyzed formation of sulfenic acidThis prevents the drug from diffusing outActivated form then irreversibly binds at the sulfhydryl groups of the cysteins of the H+/K+ ATPaseLink3

19、3GERD讲解胃食管反流英文10/3/2022PPIs Diffuse into the parietalCysteine34GERD讲解胃食管反流英文10/3/2022Cysteine34GERD讲解胃食管反流英文10/1/2035GERD讲解胃食管反流英文10/3/202235GERD讲解胃食管反流英文10/1/2022PPIsRabeprazol (Acipex)36GERD讲解胃食管反流英文10/3/2022PPIsRabeprazol (Acipex)36GERD讲PPIsLansoprazole (Prevacid)37GERD讲解胃食管反流英文10/3/2022PPIsLanso

20、prazole (Prevacid)37GPPIsEsomeprazole (Nexium)38GERD讲解胃食管反流英文10/3/2022PPIsEsomeprazole (Nexium)38GERPPIsOmeprazole (Prilosec)Omeprazole/sodium bicarbonate (Zegerid)39GERD讲解胃食管反流英文10/3/2022PPIsOmeprazole (Prilosec)OmeprPPIs Pantoprazole (Protonix)40GERD讲解胃食管反流英文10/3/2022PPIs Pantoprazole (Protonix)40

21、TreatmentsHistamine H2-recptor antagonists (H2RAs)The hormone, histamine stimulates the release of acid by interacting with the histamine receptor, or H2 receptor.Inhibit acid secretion by competitively and reversibly blocking parietal cell H2-receptorsLess potent then PPIs41GERD讲解胃食管反流英文10/3/2022Tr

22、eatmentsHistamine H2-recptorAgonist vs. AntagonistAn agonist is a drug that produces the same response at a receptor as the natural messengerAn antagonist is a drug which binds to a receptor without activating it, prevent an agonist or natural messenger from binding42GERD讲解胃食管反流英文10/3/2022Agonist vs

23、. AntagonistAn agoniHistamine43GERD讲解胃食管反流英文10/3/2022Histamine43GERD讲解胃食管反流英文10/1/244GERD讲解胃食管反流英文10/3/202244GERD讲解胃食管反流英文10/1/2022H2RAsCimetidine (Tagamet) 45GERD讲解胃食管反流英文10/3/2022H2RAsCimetidine (Tagamet) 45GEH2RAsNizatidine (Axid)46GERD讲解胃食管反流英文10/3/2022H2RAsNizatidine (Axid)46GERD讲解Other H2RAsRa

24、nitidine HCl (Zantac)Famotidine (Pepcid) 47GERD讲解胃食管反流英文10/3/2022Other H2RAsRanitidine HCl (ZanTreatmentsProkineticsIncrease LES function Release stomach contents by Activating serotonin receptorsActing on dopaminergic receptors48GERD讲解胃食管反流英文10/3/2022TreatmentsProkinetics48GERD讲解胃ProkineticsMetoclo

25、pramide (Reglan, Degan)49GERD讲解胃食管反流英文10/3/2022ProkineticsMetoclopramide (RegProkineticsDomperidone (Motilium, Costi)50GERD讲解胃食管反流英文10/3/2022ProkineticsDomperidone (MotiliProkineticsCisapride (Prepulsid, Propulsid)51GERD讲解胃食管反流英文10/3/2022ProkineticsCisapride (PrepulsiProkineticsRarely used because o

26、f severe side effects FatigueTremorsParkinsonismTardive DyskinesiaSevere cardiac events52GERD讲解胃食管反流英文10/3/2022ProkineticsRarely used becausNew TreatmentsCholecystokinin2 receptor antagonists (CCK2)Potassium competitive acid blockers (P-CABs)53GERD讲解胃食管反流英文10/3/2022New TreatmentsCholecystokinin2Trea

27、tmentsCholecystokinin2 receptor antagonists (CCK2)Block the CCK2 receptors inhibiting acid secretionStill in clinical trialsBest use in combination with PPIs54GERD讲解胃食管反流英文10/3/2022TreatmentsCholecystokinin2 recCCK2Itriglumide55GERD讲解胃食管反流英文10/3/2022CCK2Itriglumide55GERD讲解胃食管反流英文CCK2Z-36056GERD讲解胃食管

28、反流英文10/3/2022CCK2Z-36056GERD讲解胃食管反流英文10/1/2TreatmentsPotassium competitive acid blockers (P-CABs)Target H+/K+ ATPaseIonically binds to the proton pumpSpecific for the K+ binding region and prevents acid secretionBinds reversiblyStill in clinical trials57GERD讲解胃食管反流英文10/3/2022TreatmentsPotassium comp

29、etitivP-CABsRevaprazan58GERD讲解胃食管反流英文10/3/2022P-CABsRevaprazan58GERD讲解胃食管反流英P-CABsSoraprazan59GERD讲解胃食管反流英文10/3/2022P-CABsSoraprazan59GERD讲解胃食管反流英Treatment for H. pyloriAmoxicillin + clarithromycin + proton pump inhibitorMetronidazole + clarithromycin + proton pump inhibitorBismuth subsalicylate + m

30、etronidazole + tetracycline + proton pump inhibitor60GERD讲解胃食管反流英文10/3/2022Treatment for H. pyloriAmoxiciAssigned ReadingVesper, J.B. et all, Gastroesophageal Reflux Diesease, Is there More to the Story?, ChemMedChem (2008), 3, 552-559.61GERD讲解胃食管反流英文10/3/2022Assigned ReadingVesper, J.B. eHomework QuestionsWhat is an antagonist and how do the H2RAs (histamine receptor antagonists) act as one?Explain the precise biological mechanism whereby prokinetics achieve their effect, in