17. Upper GI Pharmacology Flashcards
Which cells release pepsinogen?
Chief cells
What is mucous production stimulated by?
Prostaglandins
What cells produce gastrin?
G cells
What stimulates the production of gastrin?
AAs and peptides
What is the function of gastrin?
Binds to CCK-B receptors on parietal cells
Increase pepsinogen and gastric motility
What receptors does ACh work on in the stomach?
M3 on parietal cells
What cells secrete histamine?
Mast cells or enterochromaffin cells
What factors increase the secretion of histamine?
Gastrin and ACh
What factors decrease acid secretion?
Prostaglandins E2 and I2
Somatostatin
What is the treatment for peptic ulcers if a patient is not taking NSAIDs?
Test for h.pylori
+ 1 week eradication
- PPI 4-8 weeks
What is the treatment for peptic ulcers if a patient is taking NSAIDs?
Stop NSAID if possible
Test for h.pylori
+ 8 weeks PPI then 1 week eradication
- PPI 8 weeks
How is H. pylori eradicated?
Triple therapy:
Amoxicillin and clarithromycin/metronidazole
plus a PPI
for 1 week
Name a PPI
Omeprazole
prodrug which is metabolically active at a low pH
How does omeprazole work?
Blocks H+/K+ ATPase, ie no H+ for HCl acid
What method of dosing is used for PPIs?
‘Step down’ start with a high dose and reduce it
What are the side effects of PPIs?
C.diff
Low magnesium
B12 deficiency
What are the indications for PPIs?
PUD, GORD
Prophylaxis if taking NSAIDs
Zollinger Ellison Syndrome
Name 2 H2 receptor antagonists
Cimetidine
Ranitidine
How does cimetidine work?
Blocks the effects of histamine, ACh and gastrin on parietal cells
> reduced pepsin secretion
What are the side effects of cimetidine?
Interact with CYP450
Antiandrogenic
Ranitidine doesn’t have these effects
Both cause drowsiness
Name 3 cytoprotective agents
Misoprostol
Sucralfate
Bismuth
What is the MOA of misoprostol?
Synthetic prostaglandins: increase mucous production, decrease secretion by acting on parietal cells
Which group is misoprostol used for?
High-risk groups taking NSAIDs
What are the side effects of misoprostol?
Diarrhoea and uterine contractions (contraindicated in pregnancy)
What is the MOA of sucralfate?
Binds to base of ulcer and increases prostaglandins and bicarb
What side effect is associated with sucralfate?
Bezoar formation which can cause gastric blockage
Avoid by making sure well hydrated
What is the MOA of bismuth?
Increase prostaglandin synthesis and bicarb and inhibits h.pylori
Used in triple therapy if allergy or resistance
What are antacids?
Weak bases used to neutralise gastric acid
Used for symptom relief
Eg. sodium bicarb, calcium carbonate, magnesium, aluminium
What is the MOA of Gaviscon?
Rafting agent: floats on top of acid so it doesn’t enter the oesophagus
Alginate
What is the treatment for GORD?
Lifestyle modification
PPIs first line
H2 antagonist if needed
Antacids/alginates for mild symptoms
Name 2 D2 antagonists used as anti-emetics
Metoclopramide
Domperidone
What is the MOA of metoclopramide?
Dopamine receptor antagonist
Reduce smooth muscle relaxation at D2 receptor and inhibits ACh which increases gastric emptying
What side effects are associated with metoclopramide?
Extrapyramidal: tremors, seizures
What side effects are associated with domperidone?
Doesn’t cross BBB so no extrapyramidal
Ventricular arrhythmia and sudden cardiac death
What regulatory mechanisms are associated with vomiting?
Cholinergic Histamine Dopamine Serotonin Cannabinoid
What are anticholinergics and antihistamines used for?
Motion sickness
What side effect is associated with anti-histamines?
Sedation
What are dopamine receptor antagonists, serotonin receptor antagonists and cannabinoids used for?
Reduce vomiting caused by chemo
Name 2 dopamine receptor antagonists
Phenothiazides
Butyrophenones
Name a serotonin receptor antagonist
Ondansetron
What are the side effects associated with serotonin receptor antagonists?
Constipation and headache
Name a cannabinoid
Nabilone
What side effects are associated with cannabinoids
Drowsiness, psychotic reactions
