Anti-Ulcer Drugs

Question 1

What are the two types of peptic ulcer?

Answer 1

Gastric ulcer

Duodenal ulcer

Question 2

Describe how gastric ulcers and duodenal ulcers can be distinguished based on their symptoms.

Answer 2

Gastric ulcer – pain at meal times when gastric acid is secreted

Duodenal ulcer – pain relieved by a meal as the pyloric acid closes –pain -3 hours after a meal

Question 3

Which type of peptic ulcer is more common?

Answer 3

Duodenal (4:1)

Question 4

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

Answer 4

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 5

Which cells produce stomach acid?

Answer 5

Parietal cells

Question 6

Which cells produce pepsinogens?

Answer 6

Gastric chief cells

Question 7

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

Answer 7

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 8

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

Answer 8

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

Question 9

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

Answer 9

Antibiotics

Drugs that reduce gastric acid secretion

Drugs that promote healing

Question 10

Where are parietal cells found in the stomach?

Answer 10

Fundus

Question 11

Which cells in the stomach produce histamine?

Answer 11

H cells

Question 12

Explain how the parasympathetic nervous system affects gastric acid production.

Answer 12

The parasympathetic nervous, via the vagus nerve, stimulates histamine production by H cells

Histamine then stimulates an increase in acid production by parietal cells

Question 13

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

Answer 13

G cells

Located in the antrum

Question 14

What triggers gastrin release from G cells?

Answer 14

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

Question 15

What are the effects of gastrin?

Answer 15

They trigger the release of histamine from H cells

They also directly trigger acid production by the parietal cells

Question 16

What do D cells release?

Answer 16

Somatostatin

Question 17

What are the effects of somatostatin (in stomach)?

Answer 17

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

Question 18

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

Answer 18

H+/K+ ATPase

Question 19

Which cells produce bicarbonate?

Answer 19

Superficial epithelial cells

Question 20

Give an example of a proton pump inhibitor.

Answer 20

Omeprazole

Question 21

What is the mechanism of action of PPIs?

Answer 21

Irreversible inhibitors of H+/K+ ATPase

Question 22

What are the effects of PPIs?

Answer 22

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

Question 23

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

Answer 23

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 24

What are some uses of PPIs?

Answer 24

Peptic ulcers

GORD - gastro oesophageal reflux disease

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

Question 25

Describe the pharmacokinetics of omeprazole (PPI).

Answer 25

Orally active Enteric-coated slow release formulation

Question 26

What are the unwanted effects of omeprazole (PPI)?

Answer 26

Rare with short-term use Long-term and high-dose use is associated with enteric infections, community acquired pneumonia, hip fracture

Question 27

Give two examples of histamine receptor antagonists (H2- anti ulcer ones).

Answer 27

Cimetidine Ranitidine

Question 28

What are the effects of histamine receptor antagonists? | H2- anti ulcer ones

Answer 28

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

Question 29

Describe the pharmacokinetics of histamine receptor antagonists. (H2- anti ulcer ones).

Answer 29

Orally active Ranitidine is longer acting than cimetidine

Question 30

What are the unwanted effects of histamine receptor antagonists? (H2- anti ulcer ones).

Answer 30

Rare – dizziness, headache Ranitidine has fewer side effects

Question 31

Give three examples of cytoprotective drugs.

Answer 31

Sucralfate Bismuth Chelate Misoprostol

Question 32

What is sucralfate composed of? | cytoprotective drug

Answer 32

It is a polymer containing aluminium hydroxide and sucrose octa-sulfate

Question 33

Describe the mechanism of action of sucralfate. | cytoprotective drug

Answer 33

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 34

What are the unwanted effects of sucralfate? | cytoprotective drug

Answer 34

Most of the orally administered sucralfate remains in the GI tract and this may cause constipation or reduced absorption of other drugs

Question 35

How does bismuth chelate work? (cytoprotective drug)

Answer 35

Same as sucralfate

Question 36

What is misoprostol? (cytoprotective drug)

Answer 36

It is a prostaglandin analogue (PGE1)

Question 37

What are the unwanted effects of misoprostol? (cytoprotective drug)

Answer 37

``` Diarrhoea Abdominal cramps Uterine contractions (not to be given during pregnancy) ```

Question 38

Give three examples of antacids and their speed of onset.

Answer 38

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

Question 39

What is the drug of choice for gastroesophageal reflux disease?

Answer 39

Proton pump inhibitors e.g. omeprazole

Question 40

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

Answer 40

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

Question 41

Why is it important to treat GORD?

Answer 41

Chronic GORD can progress to pre-malignant mucosal cells that can potentially lead to oesophageal adenocarcinoma- Barrett's oesophagus