Drugs Affecting Acid Secretion Flashcards
Why is anti-reflux surgery rarely used nowadays?
Because drugs have taken over their function
What happens in anti-reflux surgery?
The gastric fundus gets wrapped around the LOS and supports it
What defensive factors does the gastric mucosa have?
- Epithelial integrity
- Cell replication and restitution
- Mucous membrane barrier
- Vascular supply
What factors can damage the gastric mucosa?
- Acid
- Helicobacter pylori
How deep is the gastric mucous barrier?
2-3mm
How much does the pH change in the gastric mucosa?
From pH 2 to pH 7
Why do cuts to gastric mucosa heal very quickly?
Because they have extra cells at the bottom of pits that can quickly migrate to the surface if needed
What drug targets are found in the parietal (oxyntic) cell?
- Stimulatory receptors
- Proton pumps
Where in the parietal cells are the stimulatory receptors found?
Those in the baso-lateral membrane
What stimulatory receptors are found in the parietal cell?
- Gastrin receptors
- Histamine receptors
- ACh receptors
What does the proton pump do?
Exchanges protons for potassium
Blocking which parietal cell stimulatory receptor has the most effect?
H2 receptor antagonists
How does the parietal cell proton pump work?
It uses ATP to provide energy to swap H+ for K+
How long does the onset of action of proton pump inhibitors take?
2-3 days
Why is the onset of action of proton pump inhibitors delayed?
Because not all pumps are active all the time
What does restoration of acid secretion after giving a proton pump inhibitor require?
De novo synthesis, as PPI destroys the pumps in an irreversible process
What hormones are involved in the neuro-endocrine regulation of acid secretion?
- Cholecystokinin B
- Gastrin and gastrin releasing protein
- Somatostatin
What cells are involved in the neuro-endocrine regulation of acid secretion?
Enterochromaffine like cells
How are PPI prodrugs activated?
With acid
How do PPIs exert their action on the K/H-ATPases?
They bind covalently to cysteines of ATPases
Do H2 receptor antagonists have a long or short half life?
Short
What is the result of the short half life of H2 receptor antagonists?
- Faster onset of action
- Requires twice a day dosing
What % of duodenal ulcers are associated with H pylori?
96%
What % of gastric ulcers are associated with H pylori?
75%
What categories of drugs can be used for peptic disorders?
- Antacids
- Alginates
- H2 receptor antagonists
- PPIs
Give two examples of antacids
- Rennies
- Gaviscon
How do antacids work?
They act as buffers
What happens once the buffering effect of antacids is exhausted?
You get symptoms
Give an example of an alginate
Sucralfate
What are alginates?
Complex molecules that adhere to exposed mucosa, and form a barrier
What is good about alginates?
- Can take several times a day to achieve good symptomatic relief
- Last a bit longer than antacids
Why are alginates not used more clinically?
Because there is no money in them, and so no one will pay for clinical trials
Give four examples of H2 receptor antagonists
- Cimetidine
- Ranitidine
- Nizatidine
- Famotidine
What is the clinical advantage of H2 receptor antagonists?
They are safe, with minimal side effects
What is the problem with the use of cimetidine?
It metabolises with P450, so causes side effects, particular gynacomastia
Give 5 examples of PPIs
- Omeprazole
- Lansoprazole
- Rabeprazole
- Pantoprazole
- Esomeprazole
What are the principles of GORD treatment?
- Symptom control
- Healing of oesophagitis
What steps are taken in GORD symptom control?
- Lifestyle changes
- Antacids or alginates
- H2 receptor antagonists
- PPIs
How should peptic ulceration be managed?
- Stop NSAIDs if at all possible
- H2 receptor antagonists and PPI for 6 weeks
- H pylori eradication
How is H pylori eradication achieved?
- 2 antibiotics and full acid blockade with PPI
What is the side effect of H pylori eradication treatment?
Get bad diarrhoea
How long is H pylori eradication treatment?
At least 7 days
Why is it important to complete H pylori eradication treatment?
Because if you get treatment failure the first time, you are at a much greater risk of non-eradication in subsequent attempts
