Anti-Ulcer Drugs Flashcards
What are the two types of peptic ulcer?
Gastric ulcer
Duodenal ulcer
Which cells produce stomach acid?
Parietal cells
What is a simple way of testing for the presence of helicobacter in a subject?
Carbon-urea breath test
Stool antigen test
What treatment strategy is used against H Pylori positive peptic ulcers?
Triple therapy
2 Antibiotics (to treat underlying cause) e.g. Amoxicillin + Clarithromycin
PPI (to reduce acid production)
How does H Pylori cause ulceration?
Epithelial cells produce mucous layer, protective against acidic environment of stomach
H Pylori dissolves the mucous layer in patches
Exposes epithelial cells to acidity- causing peptic ulceration
Why is ulceration a major problem in the stomach?
Stomach receives high blood flow
Thus, ulceration can lead to severe bleeding
Describe 2 characteristics of H Pylori
Gram negative
Motile (can cause multiple sites of ulceration)
How does H Pylori cause ulcer formation?
Increases gastric acid formation (increases gastrin or decreases somatostatin- increasing activity of proton pump + thus acidity)
Exposes epithelial cells to excess acid, causing gastric metaplasia
Downregulates defence factors (epidermal growth factor + bicarbonate production)
How does the Urease breath test detect H Pylori?
H Pylori produces Urease enzyme which can directly damage epithelial cells or produce substances e.g. NH4 which damage the epithelial cells
How can a stool test detect H Pylori? What is the consequence of this characteristic?
H Pylori is antigenic
Evokes immune response, causing more inflammation + damage
How can H Pylori cause more intense tissue inflammation?
Virulent strains can produce:
CagA (antigenic- increases inflammation)
VacA (cytotoxic- directly damages cells)
How does treatment of chronic H pylori infection differ from acute?
Modify the triple therapy e.g. Quinolone antibiotic instead of penicillin
Use other drugs e.g. Bismuth or Surcalfate (reduce acidity + inflammation)
What type of ion transporter is the proton pump found in parietal cells?
H+/K+ ATPase
What signals cause translocation of proton pumps to the apical membrane of parietal cells?
Increase in Ca2+ levels
Increase in cAMP (due to Gs protein activation)
How does increased proton pump expression and activity cause ulcer formation?
Increases H+ secretion
Reduces pH
Increases acidity
What is the mechanism of action of PPIs? What are the effects of PPIs? Give an example of a PPI
Irreversible inhibitors of H+/K+ ATPase
Reduces acid production from parietal cells
e.g. Omeprazole
If the H Pylori test is negative, what may be the cause of the peptic ulcers?
NSAID use
Especially if used long term
How does stimulation of histamine H2 receptors influence pH?
Increase acid secretion (decrease pH)
What are the effects of histamine receptor antagonists? Give 2 examples
Inhibit gastric acid secretion from parietal cells
Ranitidine
Cimetidine
Why is it important to treat GERD?
Chronic GERD can progress to pre-malignant mucosal cells that can potentially lead to oesophageal adenocarcinoma
How do NSAIDs cause peptic ulcers?
Directly cytotoxic
Inhibit COX enzymes- decreases prostaglandin production, which usually have protective effect of decreasing cAMP
Reduce mucous production
Increase likelihood of bleeding
Why are patients with NSAID induced peptic ulcers at higher risk of serious outcomes?
High blood flow to stomach
NSAIDs are blood thinners, thus increase bleeding
How are NSAID induced peptic ulcers treated?
If possible: removal of NSAID (NSAID may be essential for other disease e.g. CVS dysfunction) Use PPIs (reduce production of acid) Use Histamine H2 receptor antagonists (reduce production of acid)
Which external factors increase intracellular Calcium in parietal cells, consequently increasing expression of proton pumps?
PNS stimulation of M3 muscarinic receptors
Gastrin release from G cells + its action on CCK B receptors
Which external factor increases intracellular cAMP in parietal cells, consequently increasing expression of proton pumps?
Histamine released from enterochromaffin like cells, acts on H2 receptors
Which external factor decreases intracellular cAMP in parietal cells, consequently decreasing expression of proton pumps? Thus which class of drug precipitates peptic ulcer formation?
Prostaglandins released from local cells, act on EP3 receptors
NSAIDs precipitate ulcer formation as inhibit the protective effect of prostaglandins
What is the effect of somatostatin in the stomach?
Binds to GPCR, antagonistically inhibits stimulatory effect of histamine, thus decreases acid secretion
Why is combination treatment the current best practice?
Because it eliminates the bacterial infection whilst decreasing the H+ ions produced from the parietal cells in the stomach.
i.e. Treats underlying cause and disease itself.
