Top Banner

Click here to load reader

Peptic ulcer (defination, cause, tratment)

Jul 16, 2015

ReportDownload

Education

mohd-mohd

  • Presented by:Mohd akhtarM.Pharm. (Pharmacology)

  • Anatomy of StomachAcid Peptic DisordersPeptic ulcer diseaseComparison of Gastric & Duodenal ulcersRisk factors SymptomsPhysiology of Acid secretionTreatment of peptic ulcerSummary

  • MuscularisSerosaMucosaSubmucosaFundic regionEsophagusDuodenumAntrumLayersParietalcellsBodyPyloricsphincterChief cellsGastric pit

  • Peptic UlcersGastric ulcerDuodenal UlcerGastro Esophageal Reflux Disease (GERD)DyspepsiaStress UlcersGastric Cancers

  • Peptic ulcer refers to an erosion of the mucosal layer anywhere in the GI tract; however, it usually refers to erosions in the stomach or duodenum. Over 80% of peptic ulcers are caused by Infection with the bacterium Helicobacter pylori.

  • Pathophysiology of Peptic Ulcer Disease (PUD)Mucosal Defenses Bicarbonate Mucus Prostaglandin Growth factor Mucosal regeneration Luminal Aggressors H. pylori NSAIDs Acid Pepsin

  • DUODENALGASTRICINCIDENCEMore commonLess commonANATOMY First part of duodenum anterior wallLesser curvature of stomachDURATIONAcute or chronicChronicMALIGNANCYRareBenign or malignant

  • HELICOBACTER PYLORI InfectionNon Steroidal Anti-inflammatory DrugsSteroid therapy SmokingExcess alcohol intake Genetic factorsZollinger Ellison syndrome rare syndrome caused by gastrin-secreting tumour Blood group OHyperparathyroidism

  • Nausea Vomiting Anorexia Epigastric pain after meal and during mealIntolerance of fatty food Heartburn Loss of weightOral flatulence, bloatingPain radiating to the back

  • Feldman: Sleisenger & Fortrans Gastrointestinal and Liver Disease, 7th ed.

  • Gastrointestinal hemorrhageChronic iron deficiency anemia Pyloric stenosisPerforationperitonitis

  • BacteriaGram Negative spiral bacterium40% of patients >60 years are +ve for H.pyloriTransmitted: possibly person to personMost common cause of antral gastritisMechanism of gastric injuryAdherence to epithelial cellsInfects mucosa of stomach > inflammatory response > gastritis > increased gastrin secretion > gastric metaplasia > damage to mucosa > ulceration Cytotoxin

  • Inhibits prostaglandin synthesis (COX inhibition) Disrupts functional mucosal integrity mucosal blood flow cell regenerationDirect GI irritationAntiplatelet effect (causing bleeding) acid (basal and maximal stimulation) secretion

  • ProglumideAChPGE2HistamineGastrinAdenyl cyclaseATPcAMPProtein Kinase (Activated) Ca++Ca++Proton pumpK+H+ Gastric acid Parietal cellLumen of stomachH2M3PGE receptorGastrin receptorCl-K+

  • Promotion of ulcer healing.Symptomatic relief of pain.Prevention of recurrence (relapse).Prevention of complications

  • I. Gastric hyposecretory drugsProton pump inhibitorsH2 receptor blockersMuscarinic receptor blockers II. Eradication of H. pylori infections To prevent relapseIII. Mucosal cytoprotective agentsSucralfateColloidal bismuthProstaglandin analoguesIV. Neutralizing agents (antacids)

  • Proton pump inhibitorsH2 receptor blockersMuscarinic receptor blockers

  • Mechanism of actionIrreversible inhibition of proton pump (H+/ K+ ATPase) that is responsible for final step in gastric acid secretion from the parietal cell.

    PP inhibitors include: Omperazole Lansoprazole PantoprazoleRabeprazole

  • They are prodrugs taken orally.Are given as enteric coated capsules They are activated in the acidic medium of the secretory parietal cell canaliculus.They are inactivated if (combined with H2 receptor blockers).Have long duration of action (> 18 -24 hr).Bioavailability is reduced by food.Given 1 hr before meal.

  • PPIs are quite safe but may occur:GIT disturbances: nausea, vomiting, diarrhoea Achlorhydria: increase the risk of enteric infections due to Shigella, salmonella Hypergastrinaemia Gastric hyperplasia

  • Mechanism of actionThey competitively and reversibly block to H2 receptors on the parietal cells thus reduce gastric secretion. They include:H2 Receptor inhibitors include:Cimetidine RanitidineFamotidine Nizatidine

  • Good oral absorptionPlasma half life (1-3 h).Duration (4-12 h).First pass metabolism (50% Except Nizatidine 100 % bioavailability).Given before meals.Metabolized by liver.Excreted mainly in urine.Cross placenta & excreted in milk

  • These are extremely safe drugs but may occur:nausea, vomiting, bradycardia and hypotension (rapid I.V.)Gynecomasteia, impotence in maleGalactorrhea in female on long term use of cimitidine Decrease metabolism of oral anticoagulant, phenytoin, benzodiazepines.

  • Acid (control)H2 BlockPPI

  • Mechanism of actionBlocks M3 receptors on the parietal cells.Selectively inhibit gastric acid secretionDecreased gastric motility Delayed gastric emptying Muscarinic blockers:OxyphenoniumDicyclomine PirenzepineTelenzepine

  • TreatmentCombined therapy is usually used.Clarithromycin, tetracycline, amoxicillinProton pump inhibitors or H2 receptor blockersBismuth compoundsMetronidazoleResistance may develop to antibiotics so the better eradication is obtained using proton pump inhibitors, clarithromycin & Amoxicillin.

  • The BEST among all the Triple therapy regimen is

    Omeprazole/Lansoprazole- 20/30 mg bdClarithromycin- 500 mg bdAmoxycillin/Metronidazole-1gm/500 mg bdGiven for 14 days followed by P.P.I for 4 6 weeks.Short regimens for 7 10 days not very effective.

  • SucralfateProstaglandin analogsColloidal bismuthBismuth subcitrateTripotassium dicitrato bismuthate

  • Sucralfate (aluminum hydroxide + sucrose)Form a sticky like gel over ulcer crater to protect gastrointestinal mucosa and stimulates prostaglandin synthesisIt promote mucosal repair and ulcer healingIt has no acid neutralising action and delay gastric emptyingDose: 1 g QID

  • Misoprostol is a prostaglandin E1 analog that stimulates the secretion of mucus and bicarbonates and inhibits acid secretion to a minor degree. The drug has significant side effects, primarily mild to moderate diarrhoeaIs too costly to be used by most patients.

  • Drugs used to relief gastric pain associated with hypersecretion of HCL and neutralize the gastric acid.Mechanism of ActionNeutralization of HCLInhibition of pepsin (inactive at PH 5)1. Systemic AntacidsSodium bicarbonate Calcium Carbonate2. Non Systemic AntacidsAluminum Hydroxide GelMagnesium Trisilicate

  • Sodium bicarbonateCalcium CarbonateNaHCO3 + HCL NaCL + CO2Disadvantages Rebound hyperacidityStomach distension due to CO2 liberation pain sensationSodium load salt and water retention ( # in cardiac patients)Systemic alkalosis

  • Aluminum Hydroxide GelMagnesium Trisilicate Al (OH)3 + HCL HCL3 + H2OAdvantagesLonger duration of action.Gradual neutralization of HCL No rebound hyperacidity.Adsorbs pepsin.No stomach distention

  • Due to the benign nature of duodenal ulcersWhen patients with duodenal ulcers require surgery, it is usually one of three procedures:Vagotomy,Vagotomy with antrectomy,Pyloroplasty

  • A peptic ulcer is a break in superficial epithelial cells penetrating down to muscularis mucosa Duodenal > gastric ulcers H pylori is a predominant risk factorH pylori diagnosed by c urea breath test, stool antigen or if validated serology, treated with PAC500 or PMC250 regimenComplications of PUD can lead to acute emergency of upper GI bleed

  • *****

    *****