GERD胃食管反流英文版

Agents to Treat Gastric Acidity and Gastroesophageal Reflux Disease(GERD),Presented byAbby Roth,Overview,IntroductionSymptomsCausesPeptic Ulcer DiseaseH. pyloriNSAIDsGERDTreatments,Who is Affected?,Gastric acidity and GERD affects people of all ages, races, and gender,Symptoms,HeartburnAcid Indigestion,RegurgitationNausea,Symptoms Continued,HoarsenessSore ThroatChest PainBad BreathDry CoughAsthma*,Symptoms in Children,Vomiting CoughingBreathing Problems,Acid-Peptic Disorders,Peptic Ulcer DiseaseOccurs when there is an imbalance between the mucosal defense factors and the acid and pepsin.,Helicobacter pylori Infection,Causes 80% of peptic ulcersSurvives the acid environment by attaching to the sugar molecules that line the stomach wallUses the mucus layer as protection,H. pylori,Produce large amounts of urease,Urease,H20,3 NH3 + CO2,Urea,H. pylori,Secret proteins and toxins that interact with the stomachs epithelial cellsLeads to inflammation and damage,NSAIDs,Aspirin, Ibuprofen, NaproxenCan have an affect at very low dosesSuppresses 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 symptomsLink,GERD vs. NERD,Patients suffering symptoms are placed in two groups Non-erosive reflux disease, or NERDErosive esophagitisErosive esophagitis is characterized by swelling and InflammationBarretts EsophagusPrecursor to Esophageal Cancer,Causes of GERD,Abnormalities with the Lower Esophageal Sphincter, or LESStomach AbnormalitiesHiatal herniaLink,Causes,MedicationsNSAIDsCalcium Channel Blockers (high blood pressure, angina),Medications,Anticholinergics (urinary tract disorders)Beta Adrenergic Agonists (asthma)Dopamine (Parkinsons disease),Causes,Food and DrinksCarbonated beveragesChocolate AlcoholCitrus FruitsCoffee or TeaFatty foodsContaining tomatoesMintSpicy Food,Causes,SmokingDamages mucus membranesImpairs muscle reflexes in the throatIncreases acid secretionReduces LES function and salivation,Causes,ObesityLaying down after a large mealEating close to bed timeExercise,Release of Gastric Acid,Release of Gastric acid,Histamine stimulates acid release by interacting with the histamine receptor, H2Acetylcholine activates the cholinergic receptorsGastrin is released when food is present in the stomach,Treatments,AntacidsAlginatesSucralfateProton Pump InhibitorsHistamine H2-Recptor AntagonistsProkineticsNew Treatments,Antacids,Quick but short termBuffer gastric acid, increasing the pHNeutralize acid by the following reactionAl(OH)3 + 3 HCl AlCl3 + 3 H2O,Antacids,Maalox Al(OH)3 (aluminum hydroxide), Mg(OH)2 (magnesium hydroxide),Antacids,Tums CaCO3 (calcium carbonate),Antacids,Pepto-BismolC7H5BiO4 (bismuth subsalicylate),Antacids,Alka-SeltzerNaHCO3 (sodium bicarbonate),Alginates,AlginatesUsually combined with an antacidForms protective barrier on top of gastric contentsGavisconSodium Alginate, Sodium Bicarbonate, and Calcium CarbonateLink,Alginates,Polysaccharide found in the cell walls of brown algaeSodium alginate is the sodium salt of alginic acid,Alginic Acid,Sucralfate,Reacts 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 factors and prostaglandins,Sucralfate (Carafate),Proton Pump Inhibitors,Proton pump inhibitors (PPIs) Inhibits the gastric acid pump, H+/K+ ATPase Are prodrugs,PPIs,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+ ATPaseLink,Cysteine,PPIs,Rabeprazol (Acipex),PPIs,Lansoprazole (Prevacid),PPIs,Esomeprazole (Nexium),PPIs,Omeprazole (Prilosec),Omeprazole/sodium bicarbonate (Zegerid),PPIs,Pantoprazole (Protonix),Treatments,Histamine 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 PPIs,Agonist vs. Antagonist,An 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 binding,Histamine,H2RAs,Cimetidine (Tagamet),H2RAs,Nizatidine (Axid),Other H2RAs,Ranitidine HCl (Zantac),Famotidine (Pepcid),Treatments,ProkineticsIncrease LES function Release stomach contents by Activating serotonin receptorsActing on dopaminergic receptors,Prokinetics,Metoclopramide (Reglan, Degan),Prokinetics,Domperidone (Motilium, Costi),Prokinetics,Cisapride (Prepulsid, Propulsid),Prokinetics,Rarely used because of severe side effects FatigueTremorsParkinsonismTardive DyskinesiaSevere cardiac events,New Treatments,Cholecystokinin2 receptor antagonists (CCK2)Potassium competitive acid blockers (P-CABs),Treatments,Cholecystokinin2 receptor antagonists (CCK2)Block the CCK2 receptors inhibiting acid secretionStill in clinical trialsBest use in combination with PPIs,CCK2,Itriglumide,CCK2,Z-360,Treatments,Potassium 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 trials,P-CABs,Revaprazan,P-CABs,Soraprazan,Treatment for H. pylori,Amoxicillin + clarithromycin + proton pump inhibitorMetronidazole + clarithromycin + proton pump inhibitorBismuth subsalicylate + metronidazole + tetracycline + proton pump inhibitor,Assigned Reading,Vesper, J.B. et all, Gastroesophageal Reflux Diesease, Is there More to the Story?, ChemMedChem (2008), 3, 552-559.,Homework Questions,What 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