Anti-Ulcer Drugs

Question 1

What are the two types of peptic ulcer?

Answer 1

• Gastric ulcer
• Duodenal ulcer

Question 2

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

Answer 2

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

Question 3

Which cells produce stomach acid?

Answer 3

Parietal cells

Question 4

Which cells produce pepsinogens?

Answer 4

Gastric chief cells

Question 5

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

Answer 5

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 6

Explain the ways of testing for H pylori

Answer 6

1. Carbon urate breath test 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 2. Stool antigen test Test for antigens of H. Pylori and urease

Question 7

What treatments can be put together to form the best practice ‘Triple Therapy’?

Answer 7

Antibiotics Drugs that reduce gastric acid secretion Drugs that promote healing

Question 8

Where are parietal cells found in the stomach?

Answer 8

Fundus

Question 9

Which cells in the stomach produce histamine?

Answer 9

H cells

Question 10

Which cells in the stomach produce gastrin and where are these cells found?

Answer 10

G cells Located in the antrum

Question 11

What triggers gastrin release from G cells?

Answer 11

The breakdown of food in the stomach and the liberation of amino acids stimulate gastrin release

Question 12

What do D cells release?

Answer 12

Somatostatin

Question 13

What are the effects of somatostatin?

Answer 13

It is inhibitory – it decreases the release of histamine and gastrin

Question 14

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

Answer 14

H+/K+ ATPase

Question 15

Which cells produce bicarbonate?

Answer 15

Superficial epithelial cells

Question 16

Give an example of a proton pump inhibitor.

Answer 16

Omeprazole

Question 17

What is the mechanism of action of PPIs?

Answer 17

Irreversible inhibitors of H+/K+ ATPase

Question 18

What are the effects of PPIs?

Answer 18

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

Question 19

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

Answer 19

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 20

Describe the pharmacokinetics of omeprazole.

Answer 20

Orally active Enteric-coated slow release formulation

Question 21

Give an example of a histamine receptor antagonist.

Answer 21

Ranitidine

Question 22

What are the effects of histamine receptor antagonists?

Answer 22

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

Question 23

What is the drug of choice for gastroesophageal reflux disease?

Answer 23

Proton pump inhibitors e.g. omeprazole

Question 24

What is the presentation of a H. Pylori infections causing peptic ulcers?

Answer 24

Uncomplicated infection: Epigastric pain and a burining sensation that occurs after eating a meal Complicated infection: Constant epigastric pain and burning sensation

Question 25

What is the treatment for H. Pylori infection?

Answer 25

1. Antibiotics: * Amoxicillin * & Clarithromycin/Metronidazole 2. Proton Pump Inhibitor (PPI) : * Omeprazole * Reduces acid production

Question 27

What is H Pylroi?

Answer 27

* Gram negative * motile * microaerophilic bacterium

Question 28

Where does H Pylori live?

Answer 28

* Normally a commensal * Resides in human GI tract – exclusively colonising gastric-type epithelium

Question 29

How does H Pylori form Peptic ulcers?

Answer 29

1. Increased gastric acid formation * increased­ gastrin or decreased somatostatin 2. Gastric metaplasia * Cell transformation due to excessive acid exposure 3. Downregulation of defence factors * Reduced epidermal growth factor (stimulates epithelial cell growth * Reduced bicarbonate production - reduced mucus layer 4. Urease enzyme * Catalyses urea into ammonium chloride & monochloramin - damage epithelial cells * It's antigenic - evokes immune response -\> inflammation and associated damage of epithelial cells

Question 30

What is the difference in treatment for a complex H Pylori infection over a simple infection?

Answer 30

1. Quinolone and Tetracycline administered 2. Omeprazole * Given for 7 days in a simple infection * Given for 4-12 weeks in a complex infection

Question 31

What are the specific virulence factors for H Pylori?

Answer 31

* CagA - antigenic * VacA - cytotoxic

Question 32

How does the H⁺-K⁺-ATPase get to the apical membrane of the parietal cell?

Answer 32

* Normally found in vesicles inside the cell * Increased Ca²⁺ -\> Increased cAMP * Causes increased translocation of secretory vesicles to the apical membrane * More ATPase in the membrane -\> more H⁺ excretion

Question 33

What are the 2 most common causes of a peptic ulcer?

Answer 33

* H Pylori. infection * NSAID use - particularly aspirin

Question 34

Why do NSAIDS cause peptic ulcers?

Answer 34

* Directly cytotoxic * Reduces mucus production * Increases likelihood of bleeding * Increased acidity à peptic ulcer

Question 35

What is the treatment for NSAID induced peptic ulcer?

Answer 35

* Removal of NSAID * Proton Pump Inhibitor or histamine H2 receptor antagonist (Ranitidine) – 4-8 weeks

Question 36

What are the 4 receptors that stimulate gastric acid production and how do they do this?

Answer 36

1. Muscarininc (M₃) receptor * ACh from vagus or enteric nerves * Increases parietal cell Ca²⁺ levels 2. EP₃ receptors * Prostaglandins from local cells * increased cAMP 3. Histamine (H₂) receptors * Released from enterochromaffin-like cells (ECL) * Increase ­cAMP 4. Cholecystokinin B (CCKB) receptors * Gastrin from the blood stream * Increased intracellular Ca²⁺

Question 37

How does asprin increase gastric acid production?

Answer 37

* Main effect is on increasing histamine release * Also increases prosta glandin release