week 4- Pharmacology overview of Drugs Used in Upper GI diseases Flashcards
what are the 2 major disease in the upper GI TRACT?
Peptic ulcers
GORD
what is the pharmacology of the drugs?
- Inhibit or neutralise gastric acid secretion
- Treat H pylori infection
- Protect the mucosa
how is acid secreted into the stomach?
- the parietal cells produce water which is then metabolised into H+ TO OH-
- the H+ are secreted into the lumen through H+ K+ ATPase pump
- then the OH- combine with CO2 from cellular metabolism to form bicarbonate which is then exported out of the cell through secondary active transport bringing in CL-and combining with H= in the lumen to form HCL
what mediators inhibit secretion?
- PgE2 and PgI2 – from epithelial cells
- Somatostatin – from D cells
how does histamine lead to secretion of acid from parietal cells?
-G cells in the gastric pits secreting gastrin which then goes onto bind to CCK2 receptors on enterochromaffin-like cells (ECL cell)
-ECL cells produce histamine and histamine binds to histamine 2 receptors on parietal cell leading to acid secretion .
-gastrin also affects CCK receptors on parietal cells to produce acid too
-
how does acetylcholine binding lead to acid secretion?
acetylcholine binds to muscarinic receptors to secrete acid in parietal cells
how does somatostatin binding prevent to acid production?
somatostatin binds to somatostatin 2 receptors on the G cells on ECL cells and parietal cells and prevent secretion
how does prostaglandin (PGE2) binding prevent to acid production?
prostaglandin binds to receptors on ECL cells
where do proton pump inhibitors target in the cell to prevent acid secretion/production?
H+ K+ ATPase pump on the parietal cells
where do H2 receptor antagonists target in the cell to prevent acid secretion/production?
-act on H2 receptor beofre entering parietal cell
where do proglumide target in the cell to prevent acid secretion/production?
-act on CCK receptor on ECL cells switching off secretion
how do NSAIDS affect acid secretion?
- they inhibit prostaglandins production
- can cause damage to stomach
- COX 2 better
how do misoprostol affect acid secretion?
-affects ECL
how do atropine affect acid secretion?
inhibits muscarinic receptors reducing secretion
which mediators encourage secretion of acid
- Histamine – from enterochromaffin-like cells
- Gastrin – from G cells
- Acetyl choline – from postganglionic cholinergic neurons
what does Histamine H2 receptor
antagonists do?
Inhibit histamine and gastrin induced acid secretion and
inhibit pepsin secretion as gastric juice volume decreases
Reduce basal and food-stimulated acid secretion by
>90%
Promote healing of peptic ulcers
-can get relapses
Cimetidine, ranitidine, nizatidine, famotidine
what does PPI do?
Irreversibly inhibit the H+-K+-ATPase (proton pump)
Basal and stimulated gastric acid secretion is reduced
Omeprazole, lansoprazole (pantoprazole, rabeprazol)
what is omeprazole made from?
Omeprazole first PPI – specific for parietal cells Racemic mixture of 2 enantiomers Weak acid that accumulates in the canaliculi of the parietal cell where con
what are antacids and how do they work?
Simple traditional treatment to neutralise acid
Results in pepsin (and rennin) inhibition
Promote healing of duodenal (not gastric) ulcers
Most are magnesium or aluminium salts or combination
Converted to chlorides in the stomach
Magnesium salts – Mg hydroxide, Mg carbonate
Aluminium hydroxide gels – chloridde forms in stomach
and reabsorbed in the intestine
Alginates or simeticone sometimes combined with
antacids
what is H.pylori and how does it work? risk factors
Increases gastric acid production
Risk factor for duodenal ulcers, gastroduodenitis and
gastric cancer
Eradication promotes rapid and long-term healing
Antibiotics usually combination therapy – amoxicillin
and metronidazole or clarithromycin
Often triple therapy of 2 antibiotics + PPI and possibly
bismuth prep also
Reinfection can occur even after eradication and long
term remission of ulcers
what are some Drugs that protect the mucosa ?
- Enhance endogenous protective mechanism or provide a physical
barrier - Bismuth chelate
Prevents H pylori adhering to the mucosa
Other mucosa protective actions - Sucralfate
Complex of aluminium OH and sulfated sucrose
Releases Al in presence of acid and forms complex gels with mucus to
protect
Stimulates secretion of mucus, HCO3 and prostaglandins locally - Misoprostol
Stable analogue of PgE1
Promotes healing of ulcers
Prevents gastric damage from NSAIDs
Direct effect on ECL cell to inhibit basal and food-induced gastric secretion
Enhances mucus and HCO3 secretion
