Learning Outcomes (Week 10)

Asal Ardalan Learning Outcomes - Week 10 March 26, 2024 PHAR 744 – GI/Nutrition Farris Diseases of the Upper Alimentary Canal 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Describe the etiology and primary symptoms of GERD.?? Symptoms are caused by backflow of gastric acid an other gastric contents into the esophagus due to incompetent barriers at the gastroesophageal junction. Lower esophageal sphincter, anatomic factors, esophageal clearnce,mucosal resistance and gastric emptying Describe the three mechanisms most responsible for failure of LES. List six medications that are direct irritants to the esophageal mucosa. Describe how the size of Hiatal Hernia changes with frequency of transient LES relaxations. The size of a hiatal hernia is proportional (Direct relationship) the frequency of transient LES relaxations. More relaxations occur, the larger the hernia is. List factors other than incompetent LES that can lead to GERD. Gastric volume increased, lying down, pregnancy, obisty Define the abbreviations “GERD”, “NERD”, and “ENRD”. Distinguish between Mild Esophagitis, Erosive Esophagitis, and Barrett’s Esophagus. Barrett’s esophagus: Serious complications of GERD, Replacement of the stratified squamous epithelium of the normal esophagus with simple columnar epithelium and goblet cells, both of which are found in lower regions of the GI tract, A strong association with the development of esophageal adenocarcinoma, most prevalent in white adult males in Western countirs,an example of epithelial to mesenchymal transformation Define “Peptic Ulcer Disease” Break or ulceration in the protective mucosal lining of the lower esophagus, stomach or duodenum List the three primary risk factors for development of Peptic Ulcer Disease H. pylori induced, NSAID-induced, SRMD Differentiate between superficial (mucosal layer) and deep peptic ulcer (mucosal and submucosal).degree of involvement Compare the ulcer depth, and preferred site of damage for H. pylori, NSAID induced, and SRMD ulcers. H. polyri induced: Chronic, superficial, duodenum>stomach NSAID-induced: Chronic, deep, stomach>duodenum SRMD: Acute, most superficial, stomach>duodenum Identify where H. pylori typically resides in the gut. Outer surface of stomach cell, beneath the mucus layer Name the enzyme produced by H. pylori that is key to protecting itself against the acid environment. Urease List the three mechanisms by which H pylori damages the stomach lining. 1.direct mucosal damage(release virulence factors , damage stomach cell directly) 2.Alternations in the host immune/inflammatory response( damage epithelial cells by cell Asal Ardalan 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. mediated immune mechanism or by activated neutrophils or macrophages attemptin to phagocytose bacteria DNA bacterial products) 3.Hypergastrinermia leading to increased acid secretion List two important mechanisms by which NSAIDs damage the stomach lining.?? 1.Direct of topical irritation of the gastric epithelium 2. systemic inhibition of endogenous mucosal prostaglandin synthesis (predominant role in generation of gastric ulcer ) Differentiate between the functions of the two forms of cyclooxygenase. Describe Barrett’s Esophagus and explain its origin. Explain the concept of Epithelial-to-Mesenchymal Transformation(previously reviewed ?) Recognize the three acid neutralizing agents most commonly used in antacids and any significant advantages and/or disadvantages they may have. Aluminum hydroxide, Magnesium hydroxide, calcium carbonate Name the four H2-receptor antagonists we discussed in class, how they differ from one another, and the duration of action and percentage of acid inhibition. Need to know PPI(Nexium,Prilosec,pantoprazole-protonix,rabeprazole-Aciphex,Lansoprazoleprevacid) H2-recepter antagonist(cimetidine-tagamet,famotidine-pepcid,ranitinine,Niatidine-Axid) Define “basal” acid secretion and describe its role in duodenal ulcer. How much acid is being secreted at night or at times when we are not ingesting food. Primary factor in duodenal ulcer Describe the metabolism of the H2-receptor antagonists. State which of the four H2-receptor antagonists has the largest inhibitory effect on CYPs. Cimetidine and it can also increase levels of the drugs that ae substrate for these enzymes Identify the class of drugs that is the most potent suppressor of gastric acid secretion(PPI) List the two structural features shared by all proton-pump inhibitors.Know the structures Pyridine ring and benzimidazole ring and the s double bound O that connects them Describe the mechanism of action of the proton-pump inhibitors and explain why their duration of action may approach 48 hours despite the fact that their plasma half-life is about 1 hour.?? - Parent drug is ingested, enters the parietal cell, excreted into the lumen (acidic), undergoes protonatation to rearrangement from pro drug to sulfenic acid (under acid presence), converted to cyclic sulfonamide which can attach directly to cystine on the proton pump by a covalent disulfide bind which is an irreversible bond - Drugs binds and blocks protein pump inhibitor Irreversibly bound, 27. Explain why PPIs are commonly administered orally as enteric coated granules. Activated by acid so drug can be absorbed and isn’t broken down too soon Asal Ardalan 28. Shown the structure of a molecule be able to identify it as an H2 Receptor Antagonist or as a Proton Pump Inhibitor. 29. Name the pro-drug and active forms of PPIs. Prodrugs: lansoprazole, rabeprazole, pantoprazole Active forms: Sulfenic acid and cyclic sulfonamide