Cytoprotective prostaglandin synthesis.
Inhibition of COX-1 may lead to ulcers and bleeding.
Inflammatory prostaglandin synthesis.
Inhibition of COX-2 leads to reduced inflammation, pain, and fever.
Topic Effects of NSAIDs
Most NSAIDs are weak organic acids. They are non-ionized and lipid-soluble in the stomach. They diffuse across the mucosal cell membranes into the cytoplasm (which is a neutral pH), become ionized and lipid-insoluble. They then become trapped and accumulate within the cells, causing cellular injury.
NSAIDs and PPIs
NSAIDs can be combined with PPIs to lower the risk of gastric ulcer disease (GUD). Lowering the pH of the stomach reduces injury to the mucosa.
Are weak bases which neutralize gastric acid. They also inhibit the formation of pepsin (as pepsinogen is converted to pepsin at a low pH).
Used to relieve occasional heartburn and/or acid indigestion.
Potential Adverse Effects of Antacids
- Sodium overload, alkalosis
- Distension, discomfort, belching (CO2-producing agents)
- Kidney stones (rare)
- Osteoporosis in aluminum-containing agents (rare)
Include H2As and PPIs
These agents reduce gastric acid secretion.
H2A Drug Interactions
H2As inhibit CYP-P450 which inhibits the metabolism of many drugs.
Types of PPIs
There are currently six of them...
All of them work extremely similarly. They are the most effective drugs in anti-ulcer therapy.
PPI Mechanism of Action
The drugs are inactive at a neutral pH, but when the pH drops below 5, they rearrange to their activated form and irreversibly bind to and inactivates H+/K+ ATPase proton pumps which inhibits acid secretion by parietal cells. Acid secretion only resumes with the synthesis of new enzymes.
Frequency of Prescribed PPIs
PPIs are one of the most frequently prescribed drugs in the world because of...
1. High level of efficacy
2. Low toxicity
3. Reduced cost
4. Lack of alternative therapies
Threshold for Gastric Pepsin Activity
After you cross the pH of 4 threshold, gastric pepsin activity drops from around 90% down to about 40%. This is important in the healing of ulcers, as you do not want pepsin (a protease) digesting the clotting factors or the blood clot.