S11) Drugs Affecting Acid Secretion Flashcards
What are the defensive factors for gastric mucosa?
- Epithelial integrity
- Cell replication and restitution
- Mucous membrane barrier
- Vascular supply
Which factors aggravate gastric mucosa?
- Acid
- Drugs
- Helicobacter pylori
What are the stimulatory receptors on the basolateral membrane of a parietal cell?
- Acetylcholine
- Cholecystokinine B (CCK-B)
- Histamine 2 receptor (H2)
The proton pump is found on the canicular membrane of the parietal cell.
How does this pump work?
HK ATPase exchanges H+ for K+
Briefly, describe some key features of proton pump inhibitor action
- Delayed action – not all pumps active at a time
- Max efficacy after 2-3 days
- Restoration of acid secretion requires de novo synthesis
Briefly, illustrate the relationship between Helicobacter pylori and the following peptic ulcer disease:
- Gastric ulcer
- Duodenal ulcer
Identify some common drugs which can be used to treat peptic disorders
- Antacids
- Alginates
- H2RA
- PPI
What medical advice is given to the patient in ‘step one’ for treating GORD?
- Weight loss
- Decrease alcohol
- Stop smoking
- Smaller meals / less acidic foods
- Antacids e.g. Gaviscon
What treatment is given to the patient in ‘step two’ for treating GORD?
H2 receptor antagonist e.g. ranitidine
What treatment is given to the patient in ‘step three’ for treating GORD?
Proton pump inhibitors e.g. omeprazole, lansoprazole, esomeprazole
What are the side effects of proton pump inhibitors?
- Diarrhoea
- Osteoporosis (with long term use)
What investigation should one perform if a patient presents with any red flags for GORD?
Urgent upper GI endoscopy – ulcers, malignancy, hiatus hernia
What is Helicobacter pylori?
- H.pylori is a gram negative bacteria found in the GI tract, which can cause gastric and duodenal inflammation / ulceration
- It is toxic to epithelial cells / degrades mucosal lining
→ gastritis, peptic ulcer and potentially gastric cancer
How do we test for H.pylori?
- Carbon-13 urea breath test
- Stool antigen test
How do we eradicate H.pylori?
Triple therapy for 1 week:
- Clarithromycin 500mg BD
- Amoxycillin 1g BD
- Lansoprazole 30mg BD
describe some features of gastric and duodenal ulcers
→ epigastric pain so not accurate location
→ chronic ulcers can be asymptomatic
→ bleeding, perforation and scarring
→ early gastric emptying
→ after Heliobacter pylori, NSAIDS are most common cause
what things are involved with acid secretion
→ actetylcholine activates protein kinase, releasing acid
→ histamine → increases Camp → PK activated
→ gastrin
→ inhibition of prostaglandins by NSAIDS (these can inhibit blood supply)
Gaviscon
CLASS: Alginates and antacids
ROLE: buffers stomach acid
MOA: increase stomach acid viscosity and reduce acid reflux, foamy protective layer around stomach
TAKEN: alginic acid (sodium alginate and aluminium hydroxide)
ADVERSE EFFECTS: mg = diarrhoea, al = constipation
WARNING: renal failure, hyperglycemia
DRUG-DRUG: reduce absorption of drugs (alginate), increase urine alkalinity → aspirin excretion
give two examples of PPI
→ lansoprazole
→ omeprazole
PPIs MOA
MECHANISM: Inhibit H/K ATPase in gastric parietal cells in final stage of pathway so reduce acid secretion significantly
PPIs adverse effects
GI disturbance, headache
contradictions of PPIs
→ can mask gastro-oesophageal cancer
→ osteoporosis → risk of fractures
drug reactions of PPIs
omeprazole is a CYP inhibitor
reduce effects of clopidogrel and increase effects of warfarin and phenytoin
what other meds are PPIs often prescribed with
shortest effective duration at lowest dose
long NSAID or steroid
