Drugs Affecting Acid Secretion

Question 1

Why is anti-reflux surgery rarely used nowadays?

Answer 1

Because drugs have taken over their function

Question 2

What happens in anti-reflux surgery?

Answer 2

The gastric fundus gets wrapped around the LOS and supports it

Question 3

What defensive factors does the gastric mucosa have?

Answer 3

• Epithelial integrity
• Cell replication and restitution
• Mucous membrane barrier
• Vascular supply

Question 4

What factors can damage the gastric mucosa?

Answer 4

• Acid
• Helicobacter pylori

Question 5

How deep is the gastric mucous barrier?

Answer 5

2-3mm

Question 6

How much does the pH change in the gastric mucosa?

Answer 6

From pH 2 to pH 7

Question 7

Why do cuts to gastric mucosa heal very quickly?

Answer 7

Because they have extra cells at the bottom of pits that can quickly migrate to the surface if needed

Question 8

What drug targets are found in the parietal (oxyntic) cell?

Answer 8

• Stimulatory receptors
• Proton pumps

Question 9

Where in the parietal cells are the stimulatory receptors found?

Answer 9

Those in the baso-lateral membrane

Question 10

What stimulatory receptors are found in the parietal cell?

Answer 10

• Gastrin receptors
• Histamine receptors
• ACh receptors

Question 11

What does the proton pump do?

Answer 11

Exchanges protons for potassium

Question 12

Blocking which parietal cell stimulatory receptor has the most effect?

Answer 12

H₂ receptor antagonists

Question 13

How does the parietal cell proton pump work?

Answer 13

It uses ATP to provide energy to swap H⁺ for K⁺

Question 14

How long does the onset of action of proton pump inhibitors take?

Answer 14

2-3 days

Question 15

Why is the onset of action of proton pump inhibitors delayed?

Answer 15

Because not all pumps are active all the time

Question 16

What does restoration of acid secretion after giving a proton pump inhibitor require?

Answer 16

De novo synthesis, as PPI destroys the pumps in an irreversible process

Question 17

What hormones are involved in the neuro-endocrine regulation of acid secretion?

Answer 17

• Cholecystokinin B
• Gastrin and gastrin releasing protein
• Somatostatin

Question 18

What cells are involved in the neuro-endocrine regulation of acid secretion?

Answer 18

Enterochromaffine like cells

Question 19

How are PPI prodrugs activated?

Answer 19

With acid

Question 20

How do PPIs exert their action on the K/H-ATPases?

Answer 20

They bind covalently to cysteines of ATPases

Question 21

Do H2 receptor antagonists have a long or short half life?

Answer 21

Short

Question 22

What is the result of the short half life of H2 receptor antagonists?

Answer 22

• Faster onset of action
• Requires twice a day dosing

Question 23

What % of duodenal ulcers are associated with H pylori?

Answer 23

96%

Question 24

What % of gastric ulcers are associated with H pylori?

Answer 24

75%

Question 25

What categories of drugs can be used for peptic disorders?

Answer 25

* Antacids * Alginates * H2 receptor antagonists * PPIs

Question 26

Give two examples of antacids

Answer 26

* Rennies * Gaviscon

Question 27

How do antacids work?

Answer 27

They act as buffers

Question 28

What happens once the buffering effect of antacids is exhausted?

Answer 28

You get symptoms

Question 29

Give an example of an alginate

Answer 29

Sucralfate

Question 30

What are alginates?

Answer 30

Complex molecules that adhere to exposed mucosa, and form a barrier

Question 31

What is good about alginates?

Answer 31

* Can take several times a day to achieve good symptomatic relief * Last a bit longer than antacids

Question 32

Why are alginates not used more clinically?

Answer 32

Because there is no money in them, and so no one will pay for clinical trials

Question 33

Give four examples of H2 receptor antagonists

Answer 33

* Cimetidine * Ranitidine * Nizatidine * Famotidine

Question 34

What is the clinical advantage of H2 receptor antagonists?

Answer 34

They are safe, with minimal side effects

Question 35

What is the problem with the use of cimetidine?

Answer 35

It metabolises with P450, so causes side effects, particular gynacomastia

Question 36

Give 5 examples of PPIs

Answer 36

* Omeprazole * Lansoprazole * Rabeprazole * Pantoprazole * Esomeprazole

Question 37

What are the principles of GORD treatment?

Answer 37

* Symptom control * Healing of oesophagitis

Question 38

What steps are taken in GORD symptom control?

Answer 38

1. Lifestyle changes 2. Antacids or alginates 3. H2 receptor antagonists 4. PPIs

Question 39

How should peptic ulceration be managed?

Answer 39

* Stop NSAIDs if at all possible * H2 receptor antagonists and PPI for 6 weeks * H pylori eradication

Question 40

How is H pylori eradication achieved?

Answer 40

* 2 antibiotics and full acid blockade with PPI

Question 41

What is the side effect of H pylori eradication treatment?

Answer 41

Get bad diarrhoea

Question 42

How long is H pylori eradication treatment?

Answer 42

At least 7 days

Question 43

Why is it important to complete H pylori eradication treatment?

Answer 43

Because if you get treatment failure the first time, you are at a much greater risk of non-eradication in subsequent attempts