Peptic Ulcer Disease (PUD) PDF

Peptic Ulcer Disease (PUD) Dr. Simón Q. Rodríguez Lara MD, PHD WE MAKE DOCTORS Learning Objectives 1. Define peptic ulcer disease 2. Identify the clinical hallmarks of PUD 3. Outline the pathophysiology of PUD 4. Distinguish the structure, p...

Peptic Ulcer Disease (PUD) Dr. Simón Q. Rodríguez Lara MD, PHD WE MAKE DOCTORS Learning Objectives 1. Define peptic ulcer disease 2. Identify the clinical hallmarks of PUD 3. Outline the pathophysiology of PUD 4. Distinguish the structure, pharmacokinetic & pharmacodynamic properties of medications used in the treatment of PUD A. Antacids B. H2R antagonist C. PPIs D. Prostaglandin analogues E. Cholinomimetics F. Dopamine antagonist 5. Apply the therapeutic algorithms provided by American guidelines for the treatment of H. pylori. Definition Peptic ulcer disease refers to acid peptic injury of the digestive tract, resulting in a mucosal break reaching the submucosa. Usually located in the stomach or proximal duodenum, but also found in the esophagus or Meckel’s diverticulum. Peptic ulcer is a mucosal lesion extending beyond the muscularis mucosa coat of the gastrointestinal tract that are exposed to hydrochloric acid and pepsin. Gastritis describes any inflammation of the gastric mucosal. The imbalance between mucosal defense and aggressive factors results in varying degrees of gastritis and/or frank ulceration. Lanas A, Chan FK. Peptic ulcer disease. The Lancet. 2017;390(10094):613-24. Urs AN, Narula P, Thomson M. Peptic ulcer disease. Paediatrics and Child Health. 2014;24(11):485-90. 3 Epidemiology Life time prevalence of peptic ulcer disease in the general population has been estimated to be about 5-10%. Incidence 79 cases per 100,000 people per year. Complications in peptic ulcers are less than 30 cases per 100,000 people per year. The causes of peptic ulcer disease in adult is helicobacter pylori associated , NSAID- associated and idiopathic. The commonest cause of peptic ulcer disease in childhood is Helicobacter pylori infections. Primary ulcers often tend to be chronic and are located in duodenal portion. Secondary ulcers tend to be acute. 4 H. Pylori pathophysiology The genome of the H.pylori includes several putative virulence factors. VacA (Vacuolating cytotoxin A); IceA, OipA, HrgA, LPS (lipopolysaccharide), NAP (Neutrophil Activating Protein). The CagPAI are a major virulence factors 1. Enters to the gastric lumen (surviving is determinate by the actions of urease that produce ammonia molecules that works as buffer for the acid gastric pH). 2. The flagella propel allow to reach the apical domain and get anchored by adhesins. 3. Injection of CagA (alteration of the cytoskeleton, pedestal formation and induce the expression of proinflamatory cytokines) VacA (induce alterations of the tight junctions, formation of large vacuoles and induction of release of CytoC) and NAP (recruits neutrophil and monocytes). 4. Over expression od FAS and FASL, induction of epithelial-mesenchymal-transdifferentiation. 5 6 Pathophysiology 7 8 Process of mucus coat production. PGE PGE PGE 9 2 2 2 NSAIDs  Sucralfate Sucralfate Exposed proteins with positive charge. 10 Treatment Dietary H. Pillory Lifestyle treatment Therap Antacids (sodium bicarbonate, calcium carbonate, magnesium y hydroxide, aluminum hydroxide). H2R antagonist (cimetidine, Drugs Inhibitors of ranitidine, nizatidine, famotidine). stimulating PPIs (omeprazole, esomeprazole, gastric acid gastrointestina l motility secretion lansoprazole, dexlanzoprazole, Cholinemimetics (neostigmine). pantoprazole, rabeprazole). Dopamine antagonist (metoclopramide, domperidone, cisapride). Mucosal protective Mucosal coat (sucralfate, bismuth subsalicylate, bismuth subcitrate potassium). Prostaglandin analogs (misoprostol). 11 Omeprazole Indications: Active duodenal ulcer in adults Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults Active benign gastric ulcer in adults Symptomatic gastroesophageal reflux disease (GERD) in patients 1 year of age and older Erosive esophagitis (EE) due to acid-mediated GERD in patients 1 month of age and older Maintenance of healing of EE due to acid-mediated GERD in patients 1 year of age and older Pathologic hypersecretory conditions in adults 12 Omeprazole Mechanism of action: Translocated & Target Phosphorylate d Potassium-transporting ATPase alpha chain 1 antagonist Aryl hydrocarbon receptor agonist Omeprazol e 13 Omeprazole Pharmacological effect Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of the H+/K+ ATPase pump, inhibiting gastric acid secretion for up to 36 hours Omeprazole, raises gastric pH, discouraging the growth of H.pylori. Proton pump inhibitors inhibit the urease enzyme. 14 Omeprazole Metabolism: Hepatic, by the cytochrome P450 (CYP) enzyme system. Half life: 0.5-1 hour (healthy subjects, delayed-release capsule). Adverse effects: In 24-month studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was seen in male and female animals. Carcinoid tumors have also been found in rats treated with a fundectomy or long-term treatment with other proton pump inhibitors, or high doses of H2-receptor antagonists. Overdose Symptoms of overdose include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, and dry mouth. 15 Bismuth subsalicylate Indications: nausea, heartburn, indigestion, upset stomach, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract. Mechanism of action: As an antacid, bismuth has weak antacid properties. Bismuth subsalicylate is largely hydrolyzed in the stomach to bismuth oxychloride and salicylic acid. Inhibiting synthesis of a prostaglandin responsible for Salicylic acid intestinal inflammation and hypermotility. Bismuth Binds bacterial toxins & Bismuth bactericidal action subsalicylate oxychloride 16 Misoprostol Indications: Ulceration (duodenal, gastric and NSAID induced) and prophylaxis for NSAID induced ulceration. Termination of an intrauterine pregnancy used alone or in combination with methotrexate. Induction of labour in a selected population of pregnant women with unfavourable cervices. Serious postpartum hemorrhage. 17 Misoprostol Mechanism of action: Target Prostaglandin E2 receptor EP2, EP3 and EP4 subtype agonist. Pharmacological effects Inhibit gastric acid secretion by a direct action on the parietal cells through binding to the prostaglandin receptor. 18  Misoprost ol Epithelial cells: Parietal cells: Increase Decrease secretion of production, HCO3- and translocation and mucus activation of Proton pumps 19 20  Replacement Increased of secretion of prostaglandins bicarbonate Improvement of mucosal Decrease in the regeneration volume and capacity pepsin content Misoprostol Pharmacological effects “Cytoprotective actions” Stabilization of Prevents disrupting tissue the tight junctions lysozymes/vascul between the ar endothelium epithelial cells. Enhanced mucosal blood Increased flow as a result thickness of of direct mucus layer vasodilatation 21 22 Treatment for H. Pylori. 23 Treatment for H. Pylori. 24 Lanas A, Chan FK. Peptic ulcer disease. The Lancet. 2017;390(10094):613-24.  25 Lanas A, Chan FK. Peptic ulcer disease. The Lancet. 2017;390(10094):613-24. 1. 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