GERD-PPT胃食管反流英文版.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,GERD_PPT胃食管反流英文版,Overview,Introduction,Symptoms,Causes,Peptic Ulcer Disease,H.pylori,NSAIDs,GERD,Treatments,Who is Affected?,Gastric acidity and GERD affects people of all ages,races,and gender,Symptoms,Heartburn,Acid Indigestion,Regurgitation,Nausea,Symptoms Continued,Hoarseness,Sore Throat,Chest Pain,Bad Breath,Dry Cough,Asthma*,Symptoms in Children,Vomiting,Coughing,Breathing Problems,Acid-Peptic Disorders,Peptic Ulcer Disease,Occurs when there is an imbalance between the mucosal defense factors and the acid and pepsin.,Helicobacter pylori Infection,Causes 80%of peptic ulcers,Survives the acid environment by attaching to the sugar molecules that line the stomach wall,Uses the mucus,layer as protection,H.pylori,Produce large amounts of urease,Urease,H,2,0,3 NH,3,+CO,2,Urea,H.pylori,Secret proteins and toxins that interact with the stomachs epithelial cells,Leads to inflammation and damage,NSAIDs,Aspirin,Ibuprofen,Naproxen,Can have an affect at very low doses,Suppresses cylooxygenase-1,Decrease production of prostaglandins,What is GERD?,Condition where the stomach acid/content is pushed back or“refluxed”into the esophagus,Affects 10 million Americans,Approximately 7%have daily symptoms,Link,GERD vs.NERD,Patients suffering symptoms are placed in two groups,Non-erosive reflux disease,or NERD,Erosive esophagitis,Erosive esophagitis is characterized by swelling and Inflammation,Barretts Esophagus,Precursor to Esophageal Cancer,Causes of GERD,Abnormalities with the Lower Esophageal Sphincter,or LES,Stomach Abnormalities,Hiatal hernia,Link,Causes,Medications,NSAIDs,Calcium Channel Blockers(high blood pressure,angina),Medications,Anticholinergics(urinary tract disorders),Beta Adrenergic Agonists(asthma),Dopamine(Parkinsons disease),Causes,Food and Drinks,Carbonated beverages,Chocolate,Alcohol,Citrus Fruits,Coffee or Tea,Fatty foods,Containing tomatoes,Mint,Spicy Food,Causes,Smoking,Damages mucus membranes,Impairs muscle reflexes in the throat,Increases acid secretion,Reduces LES function and salivation,Causes,Obesity,Laying down after a large meal,Eating close to bed time,Exercise,Release of Gastric Acid,Release of Gastric acid,Histamine stimulates acid release by interacting with the histamine receptor,H,2,Acetylcholine activates the cholinergic receptors,Gastrin is released when food is present in the stomach,Treatments,Antacids,Alginates,Sucralfate,Proton Pump Inhibitors,Histamine H,2,-Recptor Antagonists,Prokinetics,New Treatments,Antacids,Quick but short term,Buffer gastric acid,increasing the pH,Neutralize acid by the following reaction,Al(OH),3,+3 HCl AlCl,3,+3 H,2,O,Antacids,Maalox,Al(OH),3,(aluminum hydroxide),Mg(OH),2,(magnesium hydroxide),Antacids,Tums,CaCO,3,(calcium carbonate),Antacids,Pepto-Bismol,C,7,H,5,BiO,4,(bismuth subsalicylate),Antacids,Alka-Seltzer,NaHCO,3,(sodium bicarbonate),Alginates,Alginates,Usually combined with an antacid,Forms protective barrier on top of gastric contents,Gaviscon,Sodium Alginate,Sodium Bicarbonate,and Calcium Carbonate,Link,Alginates,Polysaccharide found in the cell walls of brown algae,Sodium 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 buffer,Can bind to proteins on the surface of an ulcer to prevent further acid damage,Has 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 accumulates,Activated by proton-catalyzed formation of sulfenic acid,This prevents the drug from diffusing out,Activated form then irreversibly binds at the sulfhydryl groups of the cysteins of the H,+,/K,+,ATPase,Link,Cysteine,PPIs,Rabeprazol(Acipex),PPIs,Lansoprazole(Prevacid),PPIs,Esomeprazole(Nexium),PPIs,Omeprazole(Prilosec),Omeprazole/sodium bicarbonate(Zegerid),PPIs,Pantoprazole(Protonix),Treatments,Histamine H,2,-recptor antagonists(H,2,RAs),The hormone,histamine stimulates the release of acid by interacting with the histamine receptor,or H,2,receptor.,Inhibit acid secretion by competitively and reversibly blocking parietal cell H,2,-receptors,Less potent then PPIs,Agonist vs.Antagonist,An agonist is a drug that produces the same response at a receptor as the natural messenger,An antagonist is a drug which binds to a receptor without activating it,prevent an agonist or natural messenger from binding,Histamine,H,2,RAs,Cimetidine(Tagamet),H,2,RAs,Nizatidine(Axid),Other H,2,RAs,Ranitidine HCl(Zantac),Famotidine(Pepcid),Treatments,Prokinetics,Increase LES function,Release stomach contents by,Activating serotonin receptors,Acting on dopaminergic receptors,Prokinetics,Metoclopramide(Reglan,Degan),Prokinetics,Domperidone(Motilium,Costi),Prokinetics,Cisapride(Prepulsid,Propulsid),Prokinetics,Rarely used because of severe side effects,Fatigue,Tremors,Parkinsonism,Tardive Dyskinesia,Severe cardiac events,New Treatments,Cholecystokinin,2,receptor antagonists(CCK,2,),Potassium competitive acid blockers(P-CABs),Treatments,Cholecystokinin,2,receptor antagonists (CCK,2,),Block the CCK,2,receptors inhibiting acid secretion,Still in clinical trials,Best use in combination with PPIs,CCK,2,Itriglumide,CCK,2,Z-360,Treatments,Potassium competitive acid blockers(P-CABs),Target H,+,/K,+,ATPase,Ionically binds to the proton pump,Specific for the K,+,binding region and prevents acid secretion,Binds reversibly,Still in clinical trials,P-CABs,Revaprazan,P-CABs,Soraprazan,Treatment for H.pylori,Amoxicillin+clarithromycin+proton pump inhibitor,Metronidazole+clarithromycin+proton pump inhibitor,Bismuth 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 H,2,RAs(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.,References,Bak,Young-Tae.,Management Strategies for Gastroesophageal Reflux Disease,.Journal of Gastroenterology and Hepatology(2004),19,S49-S53.,Horn,J.,Understanding the Pharmacodynamic and Pharmacokinetic Differences between proton pump inhibitors-focus on pKa and metabolism.,AP&T(2006),2,340-350.,Pettit,M.,Treatment of Gastroesophageal Reflux Disease.,Pharm World Sci(2005),27,432-435.,Vakil,N.,New Pharmacological Agents for the Treatment of Gastroesophageal Reflux Disease.,AP&T(2006),19,1041-1049.,Vesper,J.B.et all,Gastroesophageal Reflux Diesease,Is there More to the Story?,ChemMedChem(2008),3,552-559.,Goodman and Gilman pg 967-980.,Patrick pg 643-671.,