Pharmacology of upper and lower GI tract drug treatments Flashcards
What cell secretes Gastric acid and is responsible for ulceration and inflammation?
Parietal cell
What are the four controls of acid secretion?
1) ACH (Vagal nerve control)
2) H2 receptor (Histamine)
3) Gastrin (triggered by diet)
4) PGE2 (prostaglandin)
- only prostaglandin decreases acid release rest increase
- Each affect H+/K+ ATPase proton pump
What is a peptic ulcer?
Defect in the gastric or duodenal mucosa caused by an increase in acid secretion
What are the three things that need to be done when treating peptic ulcer?
1) pain relief
2) Heal Ulcer
3) Prevent relapse or complications
4) Ensure not gastric carcinoma
What are the five treatments types for peptic ulcers?
1) Remove irritants (drugs or dietary)
2) Antacids
3) Proton Pump inhibitors
4) H2 receptor antagonists
5) Antibiotics (if H Pylori present)
How can NSAIDs cause ulceration?
- NSAIDs act on COX1 and COX2
- COX1 responsible for prostaglandin synthesis
- when inhibited by NSAIDs Prostaglandin can’t decrease acid secretion
What are the other major causes of Ulceration?
1) Aspirin
2) Corticosteroids
3) Bisphosphonates (mucosal toxic)
4) Nicotine
5) Alcohol
6) Caffeine
7) Severe stress (increases acid sec)
8) Hypersecretory states (uncommon)
What bacteria can cause Ulcers?
Helicobacter Pylori
What are the most common antacids?
Magnesium and aluminium salts often combination
What are the disadvantages of antacid use?
1) only symptomatic relief won’t actually decrease acid over production so only effective briefly
2) Antacids which are too well absorbed can metabolic alkalosis in blood
What are the main Proton Pump Inhibitors?
- Omeprazole (irreversible)
- Lansoprazole
- Pantoprazole
- Esomeprazole
What is the MOA of Proton pump Inhibitors?
Inhibit H+/K+ Proton pump in parietal cells to prevent acid secretion
What are the adverse reactions of omeprazole?
Common: GI disturbance (vomiting, diarrhoea or constipation) and headaches
Important: Inc risk of C Diff and pneumonia, hyponatraemia, hypomagnesaemia, CKD, liver problems and blood disorders e.g. dec platelets or WBCs
What drugs does omeprazole interact with
1) Warfarin = increases anticoagulant effects as CYP450 enzyme inhibited so warfarin not metabolised
2) Clopidogrel = less activated as hepatic pro-drug, reduce anti platelet effects
Why might PPIs be contraindicated?
1) reduction in efficacy of clopidogrel but lansoprazole can be used instead (less CYP450 inhibition) usually necessary in post NSTEMI patients
2) Can get rebound effect where cells secrete more cells in response to drugs but shorter treatment times decrease likelihood