week 4- Pharmacology overview of Drugs Used in Upper GI diseases

Question 1

what are the 2 major disease in the upper GI TRACT?

Answer 1

Peptic ulcers

GORD

Question 2

what is the pharmacology of the drugs?

Answer 2

• Inhibit or neutralise gastric acid secretion
• Treat H pylori infection
• Protect the mucosa

Question 3

how is acid secreted into the stomach?

Answer 3

• 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

Question 4

what mediators inhibit secretion?

Answer 4

• PgE2 and PgI2 – from epithelial cells

- Somatostatin – from D cells

Question 5

how does histamine lead to secretion of acid from parietal cells?

Answer 5

-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
-

Question 6

how does acetylcholine binding lead to acid secretion?

Answer 6

acetylcholine binds to muscarinic receptors to secrete acid in parietal cells

Question 7

how does somatostatin binding prevent to acid production?

Answer 7

somatostatin binds to somatostatin 2 receptors on the G cells on ECL cells and parietal cells and prevent secretion

Question 8

how does prostaglandin (PGE2) binding prevent to acid production?

Answer 8

prostaglandin binds to receptors on ECL cells

Question 9

where do proton pump inhibitors target in the cell to prevent acid secretion/production?

Answer 9

H+ K+ ATPase pump on the parietal cells

Question 10

where do H2 receptor antagonists target in the cell to prevent acid secretion/production?

Answer 10

-act on H2 receptor beofre entering parietal cell

Question 11

where do proglumide target in the cell to prevent acid secretion/production?

Answer 11

-act on CCK receptor on ECL cells switching off secretion

Question 12

how do NSAIDS affect acid secretion?

Answer 12

• they inhibit prostaglandins production
• can cause damage to stomach
• COX 2 better

Question 13

how do misoprostol affect acid secretion?

Answer 13

-affects ECL

Question 14

how do atropine affect acid secretion?

Answer 14

inhibits muscarinic receptors reducing secretion

Question 15

which mediators encourage secretion of acid

Answer 15

• Histamine – from enterochromaffin-like cells
• Gastrin – from G cells
• Acetyl choline – from postganglionic cholinergic neurons

Question 16

what does Histamine H2 receptor

antagonists do?

Answer 16

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

Question 17

what does PPI do?

Answer 17

Irreversibly inhibit the H+-K+-ATPase (proton pump)
Basal and stimulated gastric acid secretion is reduced
Omeprazole, lansoprazole (pantoprazole, rabeprazol)

Question 18

what is omeprazole made from?

Answer 18

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

Question 19

what are antacids and how do they work?

Answer 19

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

Question 20

what is H.pylori and how does it work? risk factors

Answer 20

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

Question 21

what are some Drugs that protect the mucosa ?

Answer 21

• 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