20) Anti-Ulcer Drugs

Question 1

What are the protective factors that protect the stomach lining from damage?

Answer 1

Mucous lining the stomach
Bicarbonate produced by cells in the stomach
Prostaglandins facilitate a good blood flow in the stomach, increasemucous and bicarbonate production and inhibit acid secretion

Question 2

Parietal cells 
Gastric chief cells
H cells 
G cells
D cells
Superficial Epithelial Cells 
Surface Mucous / Foveolar Cell

Answer 2

Parietal cells –> HCl
Gastric chief cells –> pepsinogens
H cells –> Histamine
G cells –> Gastrin
D cells –> Somatostatin
Superficial Epithelial Cells –> bicarbonate
Surface Mucous / Foveolar Cell –> mucous

Question 3

What triggers Gastrin secretion

What activates parietal cells

Gastrin function

Somatostatin

Vagus Nerve

Where are parietal cells in the stomach?
Where are G cells?

Answer 3

Breakdown of food in stomach+ aa liberation

Histamine activates parietal cells

Gastrin triggers Histamine (H cells) and HCl (parietal cells) release

Ss inhibits H cells and G cells

Vagus N –> H cells –> Histamine –> Parietal Cells –> Gastric Acid

Parietal cells are in the fundus
G cells are in the Antrum

Question 4

State some factors that could contribute to the pathogenesis of ulcers.

Answer 4

Increase in acid production  
Decrease in bicarbonate production  
Decreased thickness of mucosal layer  
Increase in pepsin  
Decreased mucosal blood flow  
Increase in H. pylori

Question 5

What is the aim of antibiotics treatment with regards to ulcers?

Answer 5

90% eradication of H. pylori within 7-14 days

Question 6

What is a simple way of testing for the presence of helicobacter in a subject?

Answer 6

Give a urate mixture that contains a distinctive isotope of carbon
H. pylori has enzymes that can break down the urate mixture and liberate the carbon isotope
This carbon isotope is then incorporated into carbon dioxide and is breathed out – this can then be detected to confirm high levels of H. pylori

Question 7

PEPTIC ULCER TREATMENT METHOD

Answer 7

TRIPLE THERAPY
Antibiotics
Drugs that reduce HCl secretion
Drugs that promote healing

Question 8

Omeprazole and its MOA and its effects

Answer 8

proton pump inhibitor
Irreversible inhibitors of H+/K+ ATPase in Parietal Cells

Inhibits basal and stimulated gastric acid secretion from the parietal cells by >90%

Question 9

Drugs involved in Ulcer Treatment

Answer 9

PPI -proton pump inhibitor - irreversible
Histamine Receptor Antagonist
Antacids
Cytoprotective Drugs

Question 10

What features of PPIs limits its action on other proton pumps around the body?

Answer 10

Inactive at neutral pH
It is a WEAK BASE so it accumulates in the cannaliculi of the parietal cells – this concentrates its actions in the cannaliculi

Question 11

What are some uses of PPIs?

Answer 11

Peptic ulcers
GERD
Prophylaxis of ulcers in the intensive care setting, and among high-risk patients being prescribed aspirin, NSAIDs, anti-platelets and anticoagulants

Question 12

Cimetidine

Ranitidine

Answer 12

Histamine receptor antagonists.

Question 13

What are the effects of histamine receptor antagonists?

Answer 13

Inhibits gastric acid secretion from the parietal cells by about 60%

Question 14

Sucralfate
Bismuth Chelate
Misoprostol
.

Answer 14

cytoprotective drugs

Question 15

Sucralfate + Bismuch Chelate MOA

Answer 15

It acquires a strong negative charge when in an acidic environment

It binds to positively charged groups in large molecules (proteins, glycoproteins) resulting in gel-like complexes

The gel-like complexes coat and protect the ulcer, limit H+ diffusion and pepsin degradation of mucus

It also increases prostaglandin synthesis and reduces H. pylori

Question 16

What is misoprostol?

Answer 16

It is a prostaglandin analogue (PGE1)
Prostaglandins inhibit acid secretion, stimulate mucus and bicarbonate secretion, alter mucosal blood flow, and provide dramatic protection against a wide variety of agents which cause acute mucosal damage.

Question 17

What are the uses of misoprostol?

Answer 17

May be co-prescribed with oral NSAIDs when used chronically

Question 18

Give three examples of antacids and their speed of onset.

Answer 18

Sodium bicarbonate (FAST) 
Aluminium hydroxide (slow) 
Magnesium trisilicate (slow)

Question 19

What is the drug of choice for gastroesophageal reflux disease?

Answer 19

Proton pump inhibitors e.g. omeprazole

Question 20

What other type of drug could be given with PPIs to reduce the risk of reflux?

Answer 20

Drugs that increase gastric motility and gastric emptying e.g. dopamine receptor antagonists

Question 21

Why is it important to treat GERD?

Answer 21

Chronic GERD can progress to pre-malignant mucosal cells that can potentially lead to oesophageal adenocarcinoma