1. Block 1 Pharm Cameron Blair & Josh Solomon

2. Learning outcomes Mechanisms of action, S/E & examples of: O Drugs that protect the stomach O Anti-diarrhoeal drugs O Laxatives

3. Physiological regulation of gastric acid secretion Increase gastric acid secretion: Histamine Ach Gastrin Inhibition of gastric acid secretion Somatostatin Prostaglandins Enteric hormones

4. Antacids How do they work? O E.g. CaCO 3 + HCl  CaCl 2 + H 2 O + CO 2 O E.g. magnesium hydroxide, calcium carbonate

5. Alginates Mechanism of action: O Upon mixing with water they form a viscous “raft” layer that sits on top of the gastric content, protecting the oesophagus from reflux O E.g. sodium alginate (Gaviscon)

6. Drugs that protect the mucosa Bismuth Chelate O Coats the mucosa O Enhances prostaglandin synthesis O Stimulates HCO3 Misoprostol (PGE 1 agonist) O Binds the PGE 1 R on parietal cells O Inhibits HCl secretion O Increases mucosal blood flow O Augments mucus secretion Misoprostol causes uterine contraction – contraindicated in women of child bearing age

7. Proton Pump Inhibitors How do they work? O Antagonise the H + /K + ATPase pump preventing acid secretion into the stomach lumen O E.g. omeprazole, lansoprazole

8. H 2 receptor antagonists How do they work? O Prevent histamine binding at H 2 receptors, causing a knock on decrease in acid secretion O Eg cimetidine, ranitidine Cimetidine is a liver enzyme inhibitor (important in polypharmacy)

9. Functions of the colon O Na+ and H20 reabsorption O Make and store faeces O Movement of faeces O Haustral contractions mix O Mass movements propel

10. Laxatives TypeMode of actionSide effectsExample Bulk FormingIncrease the bulk of the stool n/aFibre Methylcellulose Fybogel OsmoticCreate an osmotic gradient across the gut wall, retain water in lumen dehydrationMagnesium hydroxide (Given before bowel procedures) StimulantsIncrease colonic contraction (mass movements) and motility Cathartic colon (with chronic use) Senna Bisacodyl SoftenersAct as a surfactant to coat stool in lubricant n/aDocusate BOSS (to remember the classes of laxatives)

11. Diarrhoea O Oral Rehydration Therapy Replace important electrolytes and H2O O Antibiotics Treat the underlying cause of the diarrhoea O Anti-diarrhoeals (loperamide) Loperamide is u-opioid receptor agonists. Increases haustral contractions but decreases mass movements reducing motility of the gut