Treatment of Peptic Ulcers Flashcards
Explain the underlying pathology of peptic ulcers
Identify the drugs used in the treatment of peptic ulcers and their mechanisms of action
Explain why combination treatment is the current best practice
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Descirbe the pathophysiology of H.Pylori positive peptic ulcer
- H Pylori dissolves mucus layer (via Urease enzyme)
- -> less protection for epithelial layer
- Causes epithelial cell death (due to acidic environment)
- -> by endotoxins + Inflammation
- Increased acidity –> peptic ulcer
How would you treat H.Pylori positive peptic ulcer ?
Complicated vs Uncomplicated
Uncomplicated
a) Antibiotics = Amoxicillin + Clarithromycin/Metronidazole
b) Proton Pump Inhibitor (PPI) – reduces acid production ( 1week)
Complicated
a) Antibiotics = Amoxicillin + Clarithromycin/Metronidazole
b) Proton Pump Inhibitor (PPI) – reduces acid production (4-12 weeks)
c) Consider quinolone, tetracycline
What is H.Pylori?
- Gram negative,
- motile
- microaerophilic bacterium
- Resides in human GI tract – exclusively colonising gastric-type epithelium
How does H pylori cause ulcer formation?
1) causes Increased gastric acid formation – increases gastrin or decreases somatostatin
- -> increase acid production
2) causes Gastric metaplasia – cell transformation due to excessive acid exposure
3) causes Downregulation of defence factors - decreases epidermal growth factor & decreases bicarbonate production
Describe the onset of virulence of H.Pylori
a) Urease – catalyses urea into ammonium chloride & monochloramine –> damages epithelial cells
b) Urease = antigenic –> evokes immune response
c) Certain virulent strains produce CagA (antigenic) or VacA (cytotoxic) genes – increases virulence of H.Pylori –> cause more intense tissue inflammation
What are proton pumps
proton pump = H+ K+ ATPase
- -> expressed on secretory vesicles in parietal cells
- -> increase in intracellular calcium levels - causes increase in cAMP levels
- -> causes translocation of secretory vesicles to parietal cell apical surface
- -> causes H+ Secretion
ulcer formation = via increased activity of proton pump –> increases H+ secretion
–> reduces gastric PH
Describe the pathophysiology behind peptic ulcer due to NSAID USE
NSAID = Directly cytotoxic
- Reduces mucus production
- Increases likelihood of bleeding
- Increased acidity –> causes peptic ulcer
How would you treat peptic ulcer due to NSAID USE
- Removal of NSAID
- Proton Pump Inhibitor or histamine H2 receptor antagonist (Ranitidine) – 4-8 weeks
- H2 receptor increases acid secretion
Describe how gastric acid is regulated
- Acetylcholine (ACh) released from neurones (vagus / enteric) acts on muscarinic (M3) receptors - increases [Ca2+] intracellularly
- Prostaglandins (PGs) released from local cells act on EP3 receptors - Increase [cAMP]
- Histamine released from enterochromaffin-like cells (ECL) act on H2 receptors - increase [cAMP]
- Gastrin released from blood stream acts on cholecystokinin B receptors - increases [Ca2+] intracellularly
What the difference between pathophysiology of uncomplicated and complicated peptid ulcer due to H.Pylori ?
UNCOMPLICATED
H Pylori –> causes increased gastrin production
–> gastric metaplasia–> reduced defence
COMPLICATED
H Pylori –> causes increased gastrin production –> which increases activity of proton pump –> which increases acid production
How do you get gastric acid secretion?
increase in intracellular [Ca2+] & [cAMP] –> causes translocation of secretory vesicles to parietal cell apical surface –> which then causes H+ secretion
How do proton pump inhibitors act as treatment for peptic ulcers?
Proton pump inhibitors: e.g. omeprazole – reduce acid production from parietal cells
How do Histamine H2 Antagonists act as treatment for peptic ulcers?
Histamine H2 antagonists: reduce acid production from parietal cells
Why is combination treatment the best practice
- combination –> targets multiple targets simultaneously
