Anti-Ulcer Drugs

Question 1

What are the two types of peptic ulcer?

Answer 1

Gastric ulcer

Duodenal ulcer

Question 2

Which cells produce stomach acid?

Answer 2

Parietal cells

Question 3

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

Answer 3

Carbon-urea breath test

Stool antigen test

Question 4

What treatment strategy is used against H Pylori positive peptic ulcers?

Answer 4

Triple therapy
2 Antibiotics (to treat underlying cause) e.g. Amoxicillin + Clarithromycin
PPI (to reduce acid production)

Question 5

How does H Pylori cause ulceration?

Answer 5

Epithelial cells produce mucous layer, protective against acidic environment of stomach
H Pylori dissolves the mucous layer in patches
Exposes epithelial cells to acidity- causing peptic ulceration

Question 6

Why is ulceration a major problem in the stomach?

Answer 6

Stomach receives high blood flow

Thus, ulceration can lead to severe bleeding

Question 7

Describe 2 characteristics of H Pylori

Answer 7

Gram negative

Motile (can cause multiple sites of ulceration)

Question 8

How does H Pylori cause ulcer formation?

Answer 8

Increases gastric acid formation (increases gastrin or decreases somatostatin- increasing activity of proton pump + thus acidity)
Exposes epithelial cells to excess acid, causing gastric metaplasia
Downregulates defence factors (epidermal growth factor + bicarbonate production)

Question 9

How does the Urease breath test detect H Pylori?

Answer 9

H Pylori produces Urease enzyme which can directly damage epithelial cells or produce substances e.g. NH4 which damage the epithelial cells

Question 10

How can a stool test detect H Pylori? What is the consequence of this characteristic?

Answer 10

H Pylori is antigenic

Evokes immune response, causing more inflammation + damage

Question 11

How can H Pylori cause more intense tissue inflammation?

Answer 11

Virulent strains can produce:
CagA (antigenic- increases inflammation)
VacA (cytotoxic- directly damages cells)

Question 12

How does treatment of chronic H pylori infection differ from acute?

Answer 12

Modify the triple therapy e.g. Quinolone antibiotic instead of penicillin
Use other drugs e.g. Bismuth or Surcalfate (reduce acidity + inflammation)

Question 13

What type of ion transporter is the proton pump found in parietal cells?

Answer 13

H+/K+ ATPase

Question 14

What signals cause translocation of proton pumps to the apical membrane of parietal cells?

Answer 14

Increase in Ca2+ levels

Increase in cAMP (due to Gs protein activation)

Question 15

How does increased proton pump expression and activity cause ulcer formation?

Answer 15

Increases H+ secretion
Reduces pH
Increases acidity

Question 16

What is the mechanism of action of PPIs? What are the effects of PPIs? Give an example of a PPI

Answer 16

Irreversible inhibitors of H+/K+ ATPase
Reduces acid production from parietal cells
e.g. Omeprazole

Question 17

If the H Pylori test is negative, what may be the cause of the peptic ulcers?

Answer 17

NSAID use

Especially if used long term

Question 18

How does stimulation of histamine H2 receptors influence pH?

Answer 18

Increase acid secretion (decrease pH)

Question 19

What are the effects of histamine receptor antagonists? Give 2 examples

Answer 19

Inhibit gastric acid secretion from parietal cells
Ranitidine
Cimetidine

Question 20

Why is it important to treat GERD?

Answer 20

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

Question 21

How do NSAIDs cause peptic ulcers?

Answer 21

Directly cytotoxic
Inhibit COX enzymes- decreases prostaglandin production, which usually have protective effect of decreasing cAMP
Reduce mucous production
Increase likelihood of bleeding

Question 22

Why are patients with NSAID induced peptic ulcers at higher risk of serious outcomes?

Answer 22

High blood flow to stomach

NSAIDs are blood thinners, thus increase bleeding

Question 23

How are NSAID induced peptic ulcers treated?

Answer 23

If possible: removal of NSAID (NSAID may be essential for other disease e.g. CVS dysfunction)
Use PPIs (reduce production of acid)
Use Histamine H2 receptor antagonists (reduce production of acid)

Question 24

Which external factors increase intracellular Calcium in parietal cells, consequently increasing expression of proton pumps?

Answer 24

PNS stimulation of M3 muscarinic receptors

Gastrin release from G cells + its action on CCK B receptors

Question 25

Which external factor increases intracellular cAMP in parietal cells, consequently increasing expression of proton pumps?

Answer 25

Histamine released from enterochromaffin like cells, acts on H2 receptors

Question 26

Which external factor decreases intracellular cAMP in parietal cells, consequently decreasing expression of proton pumps? Thus which class of drug precipitates peptic ulcer formation?

Answer 26

Prostaglandins released from local cells, act on EP3 receptors
NSAIDs precipitate ulcer formation as inhibit the protective effect of prostaglandins

Question 27

What is the effect of somatostatin in the stomach?

Answer 27

Binds to GPCR, antagonistically inhibits stimulatory effect of histamine, thus decreases acid secretion

Question 28

Why is combination treatment the current best practice?

Answer 28

Because it eliminates the bacterial infection whilst decreasing the H+ ions produced from the parietal cells in the stomach.
i.e. Treats underlying cause and disease itself.