Drugs for GORD Flashcards
What are lifestyle treatment options for peptic disease
- Increase exercise
- Stop smoking
- Reduce alcohol intake
- Do not sleep or lie down after eating
- Using extra pillows when sleeping
- Stop NSAIDs
What are drug therapy options for peptic disease
- Proton pump inhibitors
- H2 receptor antagonists
- Antacids
What are surgical options for peptic disease
- Highly selective vagotomy - denervation of vagus nerve supplying lower oesophagus and stomach, thus reducing acid secretion
- Anti-reflux surgery - wrap fundus of stomach about lower oesophagus to act as a sphincter
What are the defences within the gastric mucosa
- Epithelial integrity
- Small epithelial junctions
- Cell replication and restitution when injury occurs
- Stem cells found in crypts and mobilized when needed
- Mucous membrane barrier
- Vascular supply
- Extensive network of arterioles and venules running within the mucosa and submucosa
What are the aggressive factors which can cause damange to the gastric mucosa
- Acid
- Helicobacter pylori
- Drugs - NSAIDs
Describe the physiology of acid secretion by parietal cells
- Proton pump located on the canalicular membrane which exchanges H out for K in
- Basolateral membrane receptors control rate of action of proton pump
- Acetylcholine (parasympathetics), CCK receptor (gastrin), H2 receptor (histamine)
Describe the mechanism of proton pump inhibitors
- Eg. Omeprazole, lansoprazole
- Block all H+ secretion by destroying proton pumps
- Only bind to active pumps - activated after eating
- Delayed action as not all pumps active all of the time - cannot destroy all pumps immediately
- Max efficacy after 2-3 days - complete acid inhibition
- Restoration of acid secretion requires de novo synthesis after stopping PPI
- Delayed restoration - 2-3 days
- Would have to be given for life to prevent development of Barrett’s oesophagus or cancers - increased ADR risk
Describe the ADRs of proton pump inhibitors
- When proton pump stopped, gastrin levels increase in an attempt to produce acid leading to gastrinomas
- Might change calcium reuptake in small intestine - pH changes to calcium absorption decreases
- Can lead to osteoporosis
- Diarrhoea - increased C. difficile risk
Explain the mechanism of H2 receptor antagonists
- Eg. Cimetidine, ranitidine, nizatidine, famotidine
- Do not block all H+ secretion as other 2 stimulatory pathways still functional
- Have a short half life - 2 doses a day needed
List ADRs of H2 receptor antagonists
- Safe drugs with minimal interactions and ADRs
- Loose stools
- Cimetidine metabolized by CYP450
- Dizziness, confusion, constipation
Describe what antacids and alginates are
- Antacids
- Alkaline buffers - offer temporary relief
- Eg. Aluminium hydroxide (Maalox), gaviscon
- Alkaline buffers - offer temporary relief
- Alginates
- Viscous substance which adheres to gastric/duodenal mucosa to prevent damage
Describe step up regimes in treating GORD/peptic disease
- Step up regimes are usually implemented by primary care
- Lifestyle -> antacids/alginates -> H2 receptor antagonists -> PPI
- Treatment is intensified if previous treatment does not work
Describe step down regimes in treating GORD/peptic disease
- Step down regimes are usually implemented by secondary care
- PPI -> H2 receptor antagonists -> antacids/alginates -> lifestyle
- Treatment is downgraded as patient gets better
Describe how H. pylori can cause peptic ulcer disease
- Gram negative bacteria which can cause gastric and duodenal inflammation/ulceration
- Toxic to epithelial cells and degrade mucous lining by secreting urease
- Ulcers form as stomach acid and pepsin overwhelm the protective mechanism within the stomach
How can you test for H. pylori
Urease breath test, endoscopy, stool antigen test
