Gastric Acid Secretion 1. Acid synthesis – regulated by 3 transporters

1. Gastric Acid Secretion 1. Acid synthesis – regulated by 3 transporters Plasma Lumen Parietal cell

2. 2. Action of secretagogues Cholinergic nerve Mast-like cell Blood vessel Acetylcholine Histamine Gastrin Parietal cell

3. Gastric Mucosa & Secretions • The defensive forces • Bicarbonate • Mucus layer • Mucosal blood flow • Prostaglandins • Growth factors • The aggressive forces • Helicobacter pylori • HCl acid • Pepsins • NSAIDs • Bile acids • Ischemia and hypoxia. • Smoking and alcohol • When the aggressive factors increase or the defensive factors decrease, mucosal damage will result, leading to erosions and ulcerations.

4. Structural Considerations Mechanisms that maintain mucosal integrity

5. Etiology • The two most common causes of PUD are: • Helicobacter pylori infection • Non-steroidal anti-inflammatory drugs (NSAIDS) • Other uncommon causes include: • Gastrinoma (Gastrin secreting tumor) • Stress ulceration (trauma, burns, critical illness) • Viral infections • Vascular insufficiency

6. Etiology – Helicobacter pylori Helicobacter pylori

7. Etiology – Helicobacter pylori Helicobacter pylori as a cause of PUD • The majority of PUD patients are H. pylori infected. • Studies show that about 95% of patients with DU and 85% with GU are infected with H. pylori • Cure of H. pylori infection reduces ulcer recurrence.

8. Etiology – Helicobacter pylori Helicobacter pylori as a cause of PUD • Over a 10 year period 1 out of 133 (0.75%) individuals without H. pylori developed a peptic ulcer, compared with 35 out of 321 (11%) with H. pylori infection. • The incidence of peptic ulcers in H.pylori infected people is about 1% per year.

9. Etiology – NSAIDs Non-steroidal anti-inflammatory drugs (NSAIDs) • Symptomatic GI ulceration occurs in 2% to 4% of patients treated with NSAIDs for 1 year. • In view of the million of people who take NSAIDs annually, these small percentages translate into a large number of symptomatic ulcers. • The effects of aspirin and NSAIDs on the gastric mucosa ranges from mucosal hemorrhages to erosions and acute ulcers.

10. Etiology – NSAIDS Effect of NSAIDS • All NSAIDs reduce the mucosal production of prostaglandins from precursor membrane fatty acids. • The drugs also generate oxygen-free radicals and products of the lipoxygenase pathway that may contribute to ulceration.

11. Etiology – NSAIDS • Users of NSAIDs are at approximately 3 times greater relative risk of serious adverse gastrointestinal events than nonusers. • Additional risk factors include: • Age greater than 60 years • Smoking • Previous history of GI events • Concomitant corticosteroid use. In terms of serious complications, the combination of steroids and NSAIDs leads to a 10-fold increase in GI bleeding and a 20-fold increase in GI-related death.

12. Etiology – NSAIDS Type of NSAID and Risk of Ulcer Risk Group Drug Relative Risk Low Ibuprofen 2.0 Diclofenac 4.2 Medium Naproxen 9.1 Indomethacin 11.3 Piroxicam 13.7 High Ketoprofen 23.7 Azapropazone 31.5

13. Diagnosis of H. pylori Tests for Helicobacter pylori Non-invasive • C13 or C14 Urea Breath Test • Stool antigen test • H. pylori IgG titer (serology) Invasive • Gastric mucosal biopsy • Rapid Urease test

14. Peptic Ulcer Disease - Diagnosis • Gastric Ulcer on Endoscopy Chronic Gastric Ulcers

15. PUD – Complications Complications of PUD • Bleeding • Perforation • Gastric outlet or duodenal obstruction • Chronic anemia

16. Peptic Ulcer Disease - Complications • Complications of PUD on Endoscopy Bleeding DU Perforated GU Duodenal stricture

17. Peptic Ulcer Disease - Treatment Sites of Drug Action in PUD

18. Neutralise secreted acid – Antacids • Bases that raise GI tract pH • Primarily salts of calcium, magnesium and aluminium • • Aluminium hydroxide • • Calcium carbonate • • Magnesium hydroxide or trisilicate

19. 2. Drugs that inhibit acid secretion Cholinergic nerve Mast-like cell Blood vessel 1. H2R antagonists [Ranitadine] Acetylcholine Histamine Gastrin Parietal cell 3. Arachidonic acid agonists [Misoprostol] 2. Proton pump inhibitors [Pantoprazole

20. 3. Protect mucosa from damage Agents that coat the mucosa and protect from acid irritation - Bismuth subcitrate (colloidal suspension) - Sucralfate (complex of aluminium hydroxide and sucrose) Peptic Ulcer + sucralfate After 5 days of treatment

21. 4. Eradicate causative agent (H. pylori) • Most common cause of gastric ulcers. • Infects ~ 30% population. • Readily detected with ‘urea breath test’, blood test (for antibodies). H. Pylori invades the stomach and duodenal lining, weakens the resistance of the lining to acid and stimulates acid secretion. Local inflammation can also be observed.

22. Treatment of NSAID-induced gastric ulcers 1. Stop NSAID, if possible. 2. If NSAID required, use lowest effective dose, for shortest period. 3. Effective treatment with proton pump inhibitor (Pantoprazole). Guide to minimising NSAID gastric ulcer risk: [Always check for H. pylori involvement]

23. Regimen for eradication of H pylori: TRIPLE THERAPY X 14 DAYS: [PPI + Clarithromycin 500 mg + ( Metronidazole 500 mg or amoxicillin 1 g)] twice a day. (Tetracycline 500 mg can be substituted for amoxicillin or metronidazole.) QUADRUPLE THERAPY x 14 DAYS: PPI twice daily + Metronidazole 500 mg three times daily + (Bismuth subsalicylate 525 mg + tetracycline 500 mg four times daily) OR H2 receptor antagonist twice a day + ( Bismuth subsalicylate 525 mg + Metronidazole 250 mg + tetracyclione 500 mg) four times daily