GI Pharmacology Flashcards
Medications that exacerbate GORD
Alpha blockers, anticholinergics, benzodiazepines, beta blockers, bisphosphates, calcium channel blockers, corticosteroids, NSAIDs, nitrates, tricyclic antidepressants
Management of GORD
Lifestyle: weight loss, avoid triggers, eat smaller meals earlier, reduce alcohol/ caffeine, stop smoking
Proton pump inhibitors (rapid relief & healing in >80%) 8 weeks trial (often continue)
If incomplete response to PPIs: + H2 RA, surgery (fundoplication- wrap fundus around LOS)
Give some examples of PPIs
Omeprazole
Esomeprazole
Lansoprazole
Gastritis management
Avoid: NSAIDs, alcohol,bile
Triple therapy: PPI + 2X antibiotics* (eradication of H pylori in 70-80%)
Quadruple therapy (if previously taken macrolide/ metronidazole) as above + bismuth
Autoimmune: cyanocobalamin treatment (probs long term) - increases absorption B12, secretes IF
- amoxicillin + clarithromycin (lots resistance) OR metronidazole (lots side effects)
Peptic ulcer disease management
Goal: eliminate underlying cause, relive symptoms, heal ulcers, treat complications
- Stop NSAIDs - if needed consider misoprostol (prostaglandin analogue)
- cOX-2 inhibitor could be considered e.g. celecoxib
- PPI (H2 RA considered if unresponsive)
Test for H pylori using carbon-13 urea breath test/ stool antigen/ lab serology if needed: H pylori eradication regime e.g. PPI + amoxicillin + clarithromycin or metronidazole
How do NSAIDS work? Include the two isoforms they can work against.
They inhibit cyclooxygenase (COX) enzymes which catalyse prostaglandin synthesis from arachidonic acid
COX-1: high conc platelets, vascular endothelium, stomach, kidney - production prostaglandins for: maintenance normal endocrine & renal function/ gastric mucosal integrity/ haemostasis
COX-1: normal conditions v low (brain, kidney, bone) increases sites tissue damage
COX- 2 inhibitors: gastric protection, not so good for CVS long term
Role of prostaglandins in GI system
PGE2 & PGI2
Potent vasodilators,
decrease acid secretion at high concentrations,
stimulate mucus/ bicarbonate secretion,
reduced permeability epithelium to back flow of acid,
reduce release inflammatory mediators,
promote ulcer healing (increasing blood flow)
How do gastric parietal cells transform form their resting phase to their stimulated phase?
Non secreting phase - proton pumps (H,K ATPase) in membrane bound tubovesicles (lack K permeability), apical membrane has involutions (canaliculi) with microvilli ->
When stimulated ->
Tubovesicles fuse with canalicular membrane (movement of membrane & elongation microvilli) - proton pump now in a position it can exchange H+ for K+
How do proton pump inhibitors work?
Pro drugs - acidic conditions of parietal cell canaliculus activates* - PPIs weak bases, accumulate in acidic space - bind covalently to gastric H,K ATPase irreversibly & blocks
Prolonged/ nearly complete suppression of acid secretion
E.g. omeprazole
*oral forms need enteric coating prevent premature activation in stomach
Proton pump inhibitors interactions & side effects
Metabolised by cytochrome P450 enzymes, metabolites excreted by kidneys
- liver failure smaller doses
- headaches
- nausea
- GI tract issues
- abdo pain
- cause increase levels gastrin -> parietal cell/ ECL hyperplasia -> could increase risk gastric carcinoid tumours
- May decrease effectiveness clopidogrel (antiplatelets) as same enzyme
- increased risk hip fractures (more alkaline stomach reduce gastric absorption of Ca2+)
- increased risk infections
How do histamine (H2) receptor antagonists work?
Competitive/ reversible inhibit binding of histamine - indirectly block effects gastrin & Ach on parietal cell - stops activation PKA which creates canaliculi
Gastrin causes ECL cell to produce histamine binds H2 R -> activation PKA -> conformational change parietal cells
Excreted liver/ kidney
E.g. Ranitidine, cimetidine
Side effects and interactions of H2 receptor antagonists
Diarrhoea
Constipation
Muscle ache
Fatigue
Reduced ketoconazole absorption (needs acidic environment)
Cimetidine Inhibits several cytochrome P450 enzymes -
Decreases metabolism: lidocaine, phenytoin, theophylline, warfarin
Potentially -> toxic levels
Used much less now
What’s the main treatment for NSAID induced ulcers? How do they work?
Prostaglandin analogues
Act on PGE2, affects similar pathways to H2 RAs (inhibits PKA so don’t get conformation change parietal cells)
E.g. Misoprostol
Side effects and contraindications for prostaglandin analogues
❌ diarrhoea, abdo pain
Can’t use in pregnant women as can induce uterine contractions (abortion drug & used post partum haemorrhage to stop bleeding)
What’s the main use of antacids? How do they work? Give 4 examples
Seton relief for dyspepsia
Neutralise HCL - forms water and salt
Al(OH)3 - constipation, Lowe phosphate levels (weakness, malaise), renal failure can cause neurotoxicity
Mg(OH)2 - diarrhoea, avoid in renal failure
NAHCO3 - reacts HCl -> H2O, CO2, salt - avoid hypertension & fluid overload
CaCO3 - recast HcL -> Cacl + CO2
