Gastrointestinal ulcers Flashcards
Example of a systemic antacid
Sodium Bicarbonate NaHCO3
MOA of NaHCO3
- dissociates in the stomach
- the bicarbonate ion is absorbed into the blood and slightly increases pH
- increases the pH of the stomach
- quick, easy and effective SHORT TERM Tx
Problems with NaHCO3
- alkalotic urine can increase the deposition of Ca+ and P to form a kidney stone
- this increases blood Na levels, thus exacerbating HTN
- acid rebound due to feedback regulation (aka stomach’s response to rising pH is to make more acid)
List 3 examples of non-systemic antacids. How do they differ from NaHCO3 (bicarbonate)?
- CaCO3, Al(OH)3, Mg(OH)2
- they do NOT effect extracellular or blood pH; however, they have the same problem with rebound acidity as bicarbonate
How can you counteract the constipation often seen with Al and Ca antacids?
Combine them with magnesium
MOA of anticholinergic drugs to treat ulcers
- Muscarininc ACh receptors in parietal cells stimulate HCl secretion from these cells
- inhibition of these receptors reduces acid secretion (but not by much)
List an example of a muscarinic type 1 receptor blocker
Pirenzipine
Side effects of anti-cholinergic drugs
dry mouth, vision problems, sedation, etc.
Anticholinergics are very non-selective
- thus, lots of side effects and limited acid reduction
What are cytoprotectives?
Drugs which protect cells from acidic damage, either directly or through stimulation of mucus
List the two major cytoprotective drugs
- Sucralfate
- Misoprostol (taken if patient is on long-term NSAIDs)
Describe sucralfate and its MOA
- Aluminum base salt
- binds to H+ ions to increase pH
- also binds to degenerating cells, forming a protective layer of ‘artificial’ mucus
- works for 8-12h and specifically protects damaged tissue as well as reduces acidity
Problem with sucralfate
Can inhibit absorption of other drugs
Misoprostol MOA
- Cytoprotectant (recall)
- given w/ NSAIDs because COX inhibition causes PGE inhibition. PGE is critical for mucus production to protect the stomach.
- Misoprostol stimulates production of the mucosal barrier
How do H2 blockers work?
- stimulation of H2 receptors in parietal cells increases HCl production
- inhibition of H2 is highly effective in a number of acid-related disorders
List 3 H2 blockers
- Cimetidine
- Ranitidine
- Famotidine
Describe Cimetidine
- 50-60% reduction in acidity
- binds to CYP 450 so can cause drug interactions
- can cause SE’s due to binding to androgen receptors (reduced libido, impotence, etc)
Describe Ranitidine
- More effective than Cimitidine (reduces acid by 65-70%)
- less drug interaction
- does NOT bind androgen receptors
Describe Famotidine
- H2 blocker that is most effective (best at reducing acid secretion)
- very few adverse effects (does not bind P450 at all)
MOA of PPIs
- Inhibits the gastric H+/K+ ATPase (proton pump)
- especially good for rapid reduction of acid
- bind to H+ extrusiion sites and block the release of H+ and Cl-
Pathway:
- PPIs go to the small intestine and enter the parietal cell after absorption
- the prodrug is converted to the active drug by the acidity
- active drug binds very tightly to the pump
- long half life
List two PPI drug examples
- omeprazole
- esomeprazole
What additional benefit does the PPI Rabeprazole have?
also increases mucus secretion
H. Pylori is present in what % of ulcers?
- 95% of duodenal ulcers
- 80% of gastric ulcers
Pathogenesis of H. Pylori
- H. Pylori burrows into the gastric mucosa to escape the stomach acid
- It then produces urease, the enzyme that converts urea to ammonia and CO2
- this kills mucosal epithelial cells, leaving the gut unprotected
Testing for H. pylori infection
- breath test for urea
- serological
- culture
- histology
