GERD-胃食管反流英文版課件

1、Agents to Treat Gastric Acidity and Gastroesophageal Reflux Disease(GERD)Presented byAbby RothOverviewIntroductionSymptomsCausesPeptic Ulcer DiseaseH. pyloriNSAIDsGERDTreatmentsWho is Affected?Gastric acidity and GERD affects people of all ages, races, and gender SymptomsHeartburnAcid IndigestionReg

2、urgitationNausea Symptoms ContinuedHoarsenessSore ThroatChest PainBad BreathDry CoughAsthma*Acid-Peptic DisordersPeptic Ulcer DiseaseOccurs when there is an imbalance between the mucosal defense factors and the acid and pepsin.Helicobacter pylori InfectionCauses 80% of peptic ulcersSurvives the acid

3、 environment by attaching to the sugar molecules that line the stomach wallUses the mucus layer as protectionH. pyloriSecret proteins and toxins that interact with the stomachs epithelial cellsLeads to inflammation and damageNSAIDsAspirin, Ibuprofen, NaproxenCan have an affect at very low dosesSuppr

4、esses cylooxygenase-1 Decrease production of prostaglandins What is GERD?Condition where the stomach acid/content is pushed back or “refluxed” into the esophagusAffects 10 million AmericansApproximately 7% have daily symptomsLinkCauses of GERDAbnormalities with the Lower Esophageal Sphincter, or LES

5、Stomach AbnormalitiesHiatal herniaLinkCauses MedicationsNSAIDsCalcium Channel Blockers (high blood pressure, angina)CausesFood and DrinksCarbonated beveragesChocolate AlcoholCitrus FruitsCoffee or TeaFatty foodsContaining tomatoesMintSpicy Food CausesSmokingDamages mucus membranesImpairs muscle refl

6、exes in the throatIncreases acid secretionReduces LES function and salivation CausesObesityLaying down after a large mealEating close to bed timeExercise Release of Gastric AcidRelease of Gastric acidHistamine stimulates acid release by interacting with the histamine receptor, H2Acetylcholine activa

7、tes the cholinergic receptorsGastrin is released when food is present in the stomachTreatmentsAntacidsAlginatesSucralfateProton Pump InhibitorsHistamine H2-Recptor AntagonistsProkineticsNew TreatmentsAntacidsMaalox Al(OH)3 (aluminum hydroxide), Mg(OH)2 (magnesium hydroxide)AntacidsTums CaCO3 (calciu

8、m carbonate)AntacidsAlka-SeltzerNaHCO3 (sodium bicarbonate)AlginatesAlginatesUsually combined with an antacidForms protective barrier on top of gastric contentsGavisconSodium Alginate, Sodium Bicarbonate, and Calcium CarbonateLinkAlginatesPolysaccharide found in the cell walls of brown algaeSodium a

9、lginate is the sodium salt of alginic acidAlginic AcidSucralfateReacts 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 epidermal growth fact

10、ors and prostaglandinsSucralfate (Carafate)Proton Pump InhibitorsProton pump inhibitors (PPIs) Inhibits the gastric acid pump, H+/K+ ATPase Are prodrugsPPIs Diffuse into the parietal cells of the stomach and accumulatesActivated by proton-catalyzed formation of sulfenic acidThis prevents the drug fr

11、om diffusing outActivated form then irreversibly binds at the sulfhydryl groups of the cysteins of the H+/K+ ATPaseLinkCysteinePPIsRabeprazol (Acipex)PPIsLansoprazole (Prevacid)PPIsEsomeprazole (Nexium)PPIsOmeprazole (Prilosec)Omeprazole/sodium bicarbonate (Zegerid)PPIs Pantoprazole (Protonix)Treatm

12、entsHistamine 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 PPIsAgonist vs. AntagonistAn agonist

13、 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 bindingHistamineH2RAsCimetidine (Tagamet) H2RAsNizatidine (Axid)Other H2RAsRanitidine HCl (Zantac)Fam

14、otidine (Pepcid) TreatmentsProkineticsIncrease LES function Release stomach contents by Activating serotonin receptorsActing on dopaminergic receptorsProkineticsMetoclopramide (Reglan, Degan)ProkineticsDomperidone (Motilium, Costi)ProkineticsCisapride (Prepulsid, Propulsid)ProkineticsRarely used bec

15、ause of severe side effects FatigueTremorsParkinsonismTardive DyskinesiaSevere cardiac eventsNew TreatmentsCholecystokinin2 receptor antagonists (CCK2)Potassium competitive acid blockers (P-CABs)TreatmentsCholecystokinin2 receptor antagonists (CCK2)Block the CCK2 receptors inhibiting acid secretionS

16、till in clinical trialsBest use in combination with PPIsCCK2ItriglumideCCK2Z-360TreatmentsPotassium 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 trialsP-CABsRevap

17、razanP-CABsSoraprazanTreatment for H. pyloriAmoxicillin + clarithromycin + proton pump inhibitorMetronidazole + clarithromycin + proton pump inhibitorBismuth subsalicylate + metronidazole + tetracycline + proton pump inhibitorAssigned ReadingVesper, J.B. et all, Gastroesophageal Reflux Diesease, Is

18、there More to the Story?, ChemMedChem (2008), 3, 552-559.Homework 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, including the receptors they act upon. Are they agonists or antagonists? Of which chemical messenger?What is a prodrug? What causes the PPIs to become an active drug?Bacteria in the upper GI tract may play a role in GERD. Explain.ReferencesBak, Young-Tae. Management Strategies for Gastroe