Pharmacotherapy of GERD and PUD Flashcards
What are the classic symptoms of GERD?
Heartburn and regurgitation
What are other symptoms of GERD?
Dyspepsia,
Chest pain,
Belching,
Chronic cough
What are the standard treatments for GERD?
Medications that suppress gastric acid
What is the most common cause of PUD?
H. pylori
What are other causes for PUD?
Use of NSAIDs, including aspirin
Bile reflux
What is the treatment for healing the ulcers themselves?
PPI for ulcer healing
What is the function of parietal cells?
They are the “factory of H+”
What is the direct way of regulating acid secretion?
Acetylcholine, gastrin, and histamine stimulate the parietal cells, triggering the secretion of H+ into the lumen
What is the indirect way of regulation acid secretion?
Acetylcholine and gastrin also stimulate the ECL cell, resulting in the secretion of histamine which then acts on the parietal cells
What is the etiopathogenesis of peptic ulcer?
PUD: chronic mucosal ulceration affecting mostly the duodenum or stomach
It can occur in any part of the GIT
What is the function of the tubulovesicular structures?
Increase the apical surface, for instance allowing more space for the cell to produce HCl
What are the aggressive factors of peptic ulcers?
H. pylori
NSAIDs
Gastric acid
Pepsin
Smoking
What are the defensive factors of peptic ulcers?
Mucus
Bicarbonate
Blood flow
Prostaglandins
What is mucus and how is it a defensive factor?
It is a barrier that protects underlying cells from acid and pepsin, mucus is also an alkaline
What is bicarbonate and how is it a defensive factor?
Mostly remain trapped in the mucus where it neutralises the H+ (in duodenum, neutralises stomach acid)
What is blood flow and how is it a defensive factor?
Ischemia leads to injury, increasing vulnerability to acid and pepsin
What are prostaglandins and how is it a defensive factor?
They stimulate to secretion of mucus and bicarbonate and promote vasodilation, also suppresses acid secretion
What is H. pylori and why is it an aggressive factor?
It is a gram (-) bacteria which resides between epithelial cells and the mucus barrier
What are NSAIDs and why are they an aggressive factor?
They inhibit synthesis of prostaglandins
What is gastric acid and how is it an aggressive factor?
An absolute requirement for ulcer generation, however, not sufficient by itself to cause ulcers
What is pepsin and why is it an aggressive factor?
Can injure unprotected cells
What is smoking and how is it an aggressive factor?
Delays ulcer healing and increase the risk of recurrence
What is the classes of anti-ulcer dugs?
Antibiotics
Anti-secretory agents
Mucosal protectants
Antacids
Antisecretory agents that enhance mucosal defence
What are the examples of antibiotics?
Clarithromycin, Amoxicillin, Metronidazole, Bismuth
What receptor does acetylcholine bind to?
M3 muscarinic receptors
What receptors does CCK bind to?
CCK2
What receptors does histamine bind to?
H2 receptors
What is the effect of acetylcholine, CCK and H2?
Through a Ca2+ or cAMP (histamine) pathway they increase the function of the proton pump (H+/K+ ATPase)
What receptor do prostaglandins bind to? How do they work?
EP3 and the inhibit the cAMP pathway and thus inhibit the proton pump, less HCl production
Which is the most efficient treatment for blocking the H+/K+ ATPase?
PPIs
What is the function of Clarythromycin?
Inhibits protein synthesis of H. pylori
What are the side effects of Clarythromycin?
Nausea, diarrhoea, and distortion of taste
What is FDA update for clarithromycin?
Increased risk of CV events and death in patients with CAD
What is the function of Amoxicillin?
Disrupts cell wall
When is the activity of Amoxicillin ideal?
When the pH is neutral; thus reducing gastric acidity will enhance its activity
What can be used to reduce the gastric acidity in combination with Amoxicillin?
Omeprazole
What are the side effects of Amoxicillin?
Diarrhea
What is the function of Metronidazole?
Degradation of biological macromolecules and DNA chains
Which is the antibiotic which 40% of H. pylori has become resistant to?
Metronidazole
What are the adverse effects of Metronidazole?
Nausea and headaches
Metallic taste and some neurology effects (seizures)
What are the contraindications of Metronidazole?
Avoid alcohol consumption
What has caused the resistance of H. pylori to Metronidazole?
The misuse and the overuse
What is the function of Bismuth?
Acts topically to disrupt cell wall –> lysis of H. pylori