Peptic Ulcer Disease

Vanessa Ting Ching Ching


Heterogeneous group of disorders involving upper GI tract Caused by imbalance between aggressive factors and defensive factors Acute: specific patient population and clinical situation (eg stress ulcers) Chronic: usually H.Pylori or NSAID ulcers with risk factors. Has remission and recurrence episodes

nih.nlm.Physiology of upper GI tract     Stomach consists of: Cardia Body – contains parietal cells (secrete acid and intrinsic factor) and chief cells (secrete pepsinogen) Antrum – contains G cells (secrete gastrin) Adapted from .

Secreted by parietal cells Pepsinogen  forms pepsin in pH<3.Aggressive factors   K+-H+-ATPase pump secretes acid and is stimulated by:  Acetylcholine – neurologic impulses of sight. smell and taste of food or due to food distension or food protein.  Gastrin .released by stimulation of Ach on antral G cells  Histamine .5  combines with acid to form proteolytic complex .

Defensive factors  Prostaglandin E and somatostatin  inhibit gastric acid secretion. maintain mucosal blood flow. and acts as a lubricant neutralises H ions transport oxygen and substrates to the mucosa and remove acids  epithelial cells and mucous cells   Gastric mucus   Bicarbonate secretion   Network of vascular capillaries  . and stimulate production of mucus and bicarbonate secrete mucus traps microorganisms. prevents back difussion of H ions from the mucosa.

Risk factors Established  Age >60 years  H. multiple NSAID use  Concomitant anticoagulant use / coagulopathy  Chronic major organ impairment Possible  NSAID-related dyspepsia  Duration of NSAID use  Cigarette smoking  Rheumatoid arthritis Questionable  Alcohol consumption  Psychological stress  Dietary factors * Combinations of risk factors are additive .pylori infection  Previous PUD and UGIB  Concomitant corticosteroid therapy  High dose.

perforation.Signs and Symptoms     Epigastric pain (burning. obstruction . fullness) Nocturnal pain that awakes patient Heartburn. vomiting. anorexia   Weight loss Complications eg ulcer bleeding. bloating Nausea. belching. penetration. cramping.

pylori Other diagnostic tests  Fibreoptic upper endoscopy  routine single-barium contrast techniques .Diagnosis Laboratory Tests  Gastric acid secretory studies  Fasting serum gastrin concentrations  FBC – low haematocrit and haemoglobin  Tests for H.

pylori Antibiotics. misoprostol) Gastric ulcers associated with normal/↓acid secretion   Eliminate H. H2-antagonists) Neutralise gastric acid (antacids) Duodenal ulcers associated with ↑acid secretion    Increase mucosal defences Protect GI mucosa (sucralfate. bismuth .Treatment Aims     Decrease gastric acidity Inhibit gastric secretion (PPIs.

Proton Pump Inhibitors      Potency: esomeprazole=rabeprazole> pantoprazole=lansoprazole=omeprazole Inhibit K+H+ATPase covalently Up to 72 hours antisecretory effect Faster onset compared to H2-antagonists. warfarin. but similar rate of healing Metabolised by CYP450 system therefore drug interactions with diazepam. tolbutamide  Except pantoprazole – metabolised by cytosolic sulfotransferase . phenytoin.

H2-Receptor Antagonists      Potency: famotidine > nizatidine=ranitidine >cimetidine Block histamine receptors – decrease acid secretion Cimetidine metabolised by CYP450 – decrease theophylline elimination by 20-30% Cimetidine. ranitidine excreted by renal tubular secretion – decrease procainamide elimination Alter gastric pH – decrease ketoconazole absorption .

binds to damaged and ulcerated tissue thus creates physical barrier  Take with an empty stomach to prevent binding to phosphate and protein in food Efficacy same as H2-antagonists. but requires complicated dosage regimens  Multiple daily doses.5.Sucralfate    At pH 2-2. large size Affect bioavailability of other drugs  Space out 2 hours before sucralfate  Consider other antiulcer therapy if giving fluoroquinolones .

inhibits gastric acid production dose-dependent – 50-200mcg  cytoprotective – >200mcg   Causes dose-dependent diarrhoea  take with meals or at bedtime  Uterotropic – contraindicated in pregnant women .Misoprostol  Synthetic PGE1 analogue.

Bismuth  Antidiarrhoeal agent with ulcer-healing effects    Antibacterial effect Local gastroprotective effect Stimulates endogenous PGs   Used in combination regimens for eradication of H.pylori Safe but may cause salicylate sensitivity .

Antacids     Neutralize acids. stimulate restitution of gastric mucosa Effective at low doses. alter profile of e/c drugs. CaCO3 – ↑gastric acid production at ↑doses. form complex with fluoroquinolones and tetracyclins . NaCO3 – systemic alkalosis at prolonged periods ↑ gastric pH: ↓bioavailability of ketoconazole. AlOH – constipation. as effective as H2antagonists but short duration of action (~2hrs) MgOH – diarrhoea. cytoprotective (stimulates PG production).

fecal-oral. bacterial enzymes and adherence to stomach wall Altered inflammatory response  Cell-mediated immune mechanisms or phagocytosis Increased gastric acid secretion  HP products eg ammonia . Pylori infection      Spiral Gram negative bacilli that colonizes the body of the stomach Transmission: oral-oral. iatrogenic Direct mucosal damage  By cytotoxins.H.

rapid results Quantitative. results are not immediate. easily performed. as effective as urea breath test Adapted from Pharmacotherapy: A pathophysiologic approach .Detection of H. tests for active infection >90% sensitive and specific. >95% sensitive and specific. results are not immediate Sensitivity testing. 95% sensitive and specific. results take about 2 days Stool antigen  Identifies HP antigen in stool Tests for active HP infection. labeled CO2 exhaled Comments Gold standard.pylori Test Histology Culture Biopsy urease Antibody detection Urea breath test Description Microbiologic examination Culture of biopsy Detects ammonia released by HP urease Detects antibodies to HP in serum HP urease breaks down ingested labeled Curea. unable to determine if antibody is caused by active or cured infection Tests for active HP infection.

Treatment of H.pylori     Eradication of H.pylori with combination therapy = ↓ulcer recurrence 7-day treatment is minimally effective but 14day treatment is recommended Use of single antibiotic has variable and marginal eradication rates and ↑antibiotic resistance Clarithromycin is single most effective antibiotic .

5g/day Marginal and variable eradication rates Similar to PPI-based tripletherapy.Pylori Eradication Regimens Regimen Omeprazole 20mg bd + clarithromycin 500mg bd + metronidazole 400mg bd or amoxycillin 500mg bd Duration Comments 1 week All combos of 3 antibiotics similarly effective. tetracycline more effective than amoxycillin Better eradication rate using PPI Omeprazole 20mg bd + amoxycillin 2 weeks 500mg tds or clarithromycin 500mg tds Bismuth salicylate 120 mg qid + metronidazole 400mg tds + amoxycillin 500mg tds or tetracycline 500mg tds Ranitidine 300mg + amoxycillin 500mg tds + metronidazole 400mg tds  2 weeks 2 weeks Adapted from Pharmacotherapy: A pathophysiologic approach . usually clarith + amoxy. ↑eradication rates with clarith1.H.

medscape. 2 mechanisms: Direct irritant effect – acidic properties COX-1 inhibition – inhibition of PG release causing decrease in GI mucosal integrity and platelet homeostasis Leukotrienes stimulate neutrophil adherence which damages endothelium  Taken from www. 2.NSAID use  .

Treatment of NSAID Ulcers  Withdrawal/reduction of NSAID  Replace with paracetamol/selective COX-2 inhibitors  Duodenal ulcers/smaller gastric ulcers – full dose H2-antagonist for min 8 weeks  Ranitidine 150mg bd  Gastric ulcers/continued NSAID use – PPI for 8 weeks  Omeprazole 20mg/day  Misoprostol 800mcg/day in divided doses .

up to 360mg/day Octreotide (synthetic somatostatin) inhibits gastric acid secretion  s/c 100-250mcg tds . fasting serum gastrin >1000 pg/mL Treat with high dose PPIs in divided bd/tds doses  Eg omeprazole 60-80mg/day.Zollinger-Ellison Syndrome      Non-β-islet cell tumours (gastrinoma) secrete additional gastrin –hyperstimulation of gastric acid secretion Characterised by severe recurrent PUD Basal acid output >15mEq/h.

exposed visible vessel or clot-covered ulcer  Adrenaline injection up to 15 mL  Concomitant high-dose continuous IV infusion of PPI    Omeprazole 80mg load.Acute Upper GI Bleeding  Endoscopic therapy if active bleeding. then 8mg/h for 3 days Less severe bleeders: IV 40mg bd Continue PPI for 4-6 weeks then H2antagonist for another 4-6 weeks .

sepsis.Stress Ulcers      Acute in nature. occur in critically-ill patients ↓ gastric mucosal blood flow in haemorrhagic. coagulopathy  Others: shock. multiple organ failure. burns. high-dose CCS therapy. trauma. CNS injury . cardiogenic and septic shock ↓ rate of proliferation and cellular turnover of gastric mucosa No prostaglandin and mucous formation Risk factors: mechanical ventilation >48 hrs.

↓frequency of bleeding.Stress Ulcer Prophylaxis Improve physiological conditions  Inotropic drugs  Vasodilators  Intravascular volume replacement  Prevention of infection  Analgesia and sedation  Enteral nutrition Adequate neutralisation of gastric acid  At pH 3.5-4. at pH<7.2512mg/h)  IV omeprazole 40mg od has ↑antisecretory effects but also ↑nosocomial pneumonia . impaired clot stability  Sucralfate 1g qid via nasogastric tube  IV ranitidine (bolus 50mg tds or infusion 6.

8th edition. New York: McGraw-Hill. Moore. Yee GC. Pharmacotherapy: A pathophysiologic approach. Tan SS et al. 6th edition. 2005. Applied therapeutics: the clinical use of drugs. 2006 Koda-Kimble MA. Talbert RL. et al. Malaysian Clinical Practice Guidelines. Ritter. Consensus of Management of Peptic Ulcer Disease. Kew ST. Pharmacology. USA: Lippincott Williams & Wilkins. Dale. Rang. Elsevier Science Limited. 2003 .References     Dipiro JT.

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