Dyspepsia and GORD

Question 1

Which age groups does Peptic Ulcer Disease (PUD)?

Answer 1

Occurs in children (rare)
Peak in population 55 and 65 years
Duodenal ulcers 25 and 75 years

Question 2

Which gender has a higher risk of PUD?

Answer 2

Twice as more risky for males

Question 3

What are risk factors of PUD?

Answer 3

Caffeine
Smoking
Alcohol
NSAIDs
Stress

Question 4

What are some causes of PUD?

Answer 4

H.Pylori
Long term use of NSAIDs
Stress Ulcers

Question 5

Which ulceration is associated with normal/decreased acid secretion?

Answer 5

Gastric Ulceration

Question 6

Which ulceration is associated with normal/increased acid secretion?

Answer 6

Duodenal Ulceration

Question 7

What is the development of a peptic ulcer normally assosicated with?

Answer 7

Disruption of mucosal-damaging and mucosal-protecting mechanisms

Question 8

What is an example of an NSAID which reduces prostaglanding formation (COX 1 inhibition)?

Answer 8

Aspirin

Question 9

What can COX1 inhibition trigger?

Answer 9

Gastric ulceration

Bleeding

Question 10

How can gastric damage be prevented (NSAID)?

Answer 10

Stable PGE1 analogue

Misoprostol

Question 11

What are the two ways we can treat dyspepsia and GI disorders?

Answer 11

Neutralisation

Reduction of Acid Secretion

Question 12

What are the medications used for Neutralisation?

Answer 12

Antacids
Alginates
Sucralfate (mucosal protectants)

Question 13

What are the medications used for Reduction of acid secretion?

Answer 13

PPIs
Histamine H2 Receptor Antagonists
Prokinetics

Question 14

What are antacids?

Answer 14

Weak bases which NEUTRALISE xs stomach acid

Question 15

How do antacids neutralise acid?

Answer 15

Buffer the gastric acid, neutralising gastric acid.

Question 16

What are they combined with to achieve a higher pH?

Answer 16

Alginates with anti-foaming agents, anti-foaming agents reduce surface tension of stomach acid to prevent bubbles, producing a defoaming action.

Question 17

What are the two types of antacids?

Answer 17

Systemic and Non-systemic

Question 18

What are the advantages of Systemic Antacids?

Answer 18

Useful in short-term therapy

Rapid onset

Question 19

What is the disadvantage of Systemic Antacids?

Answer 19

Prolonged use causes an overload on kidneys

Question 20

What are the advantages of Non-Systemic Antacids?

Answer 20

Remain in GI tract

Useful in long-term therapy

Question 21

What are examples of Non-systemic Antacids?

Answer 21

Calcium-based antacids
Magnesium antacids
Aluminium-based antacids
Bicarbonate based antacids

Question 22

What are the pharmacokinetic interactions and pharamacodynamic interactions?

Answer 22

Binding of other drugs to the antacid causing reduced bioavailiability
Chemical inactivation of drugs
Increased gastric pH

Question 23

What are the adverse effects of Antacids?

Answer 23

Relatively minor contraindications

Question 24

What side effects does Magnesium hydroxide have?

Answer 24

Laxative properties

Question 25

What side effects does Aluminium hydroxide have?

Answer 25

Causes constipation

Question 26

What side effects does Calcium carbonate?

Answer 26

May cause renal calculi (stones) and constipation

Question 27

What side effects can Carbonates have?

Answer 27

Generation of CO2 leading to bloating and flatulence

Question 28

What side effects can Sodium bicarbonate have?

Answer 28

Metabolic alkalosis

Question 29

What is an Alginate?

Answer 29

Polysaccharide found in cell walls of brown algae

Question 30

What is Gaviscon composed of?

Answer 30

Antacids and Alginate

Question 31

How does Gaviscon react?

Answer 31

Reacts rapidly with acid to form alginic-acid gel, near neutral pH

Question 32

How are PPIs delivered?

Answer 32

Via the systemic circulation to the secretory gastric canaliculi

Question 33

What are prodrugs?

Answer 33

They are inactive at a neutral pH, but activated at a strongly acidic environment

Question 34

What happens when a prodrug binds to a cysteine of the H+/K+pump?

Answer 34

An irreversible reaction takes place and inhibits the active proton pump, preventing movement of H+ into the stomach

Question 35

What is the result of the prodrug binding irreversibly?

Answer 35

Achlorhydria "ALL gastric acid secretion blocked"

Question 36

Give an example of a common PPI?

Answer 36

Omeprazole

Question 37

Describe Omeprazole Activation and Activity

Answer 37

Diffuses into the parietal cells of stomach and accumulates Activated by proton-catalyzed formation of sulfenic acid Active drug binds to sulfhydryl groups of cysteines of H+/K+ pump Charged drug molecule cannot diffuse out of parietal cells Irreversible activation of proton pump

Question 38

Which is the best time to take a PPI?

Answer 38

At a time when the PPIs are effective

Question 39

How does Histamine stimulate acid production?

Answer 39

Histamine binds to H2 receptors on parietal cells

Question 40

Which other hormone stimulates high levels of histamine?

Answer 40

Gastrin which is stimulated by ECL cells

Question 41

What are examples of H2 receptor blocks?

Answer 41

Cimetidine | Ranitidine

Question 42

What is the mechanism of a H2 receptor antagonist?

Answer 42

1) Acts as a competitive antagonist on basolateral membrane of parietal cells 2) Block the histamine H2 receptor and reduces secretion evoked by gastrin and ACh

Question 43

How is it usually administered and how often should it be taken?

Answer 43

OAD/BOD via oral administration

Question 44

What are the side effects of Histamine H2 anatagonists?

Answer 44

Overall, less than 3% incidence of side effects.

Question 45

What are the pharmacokinetics of Histamine H2 receptors? - absorption? - serum concentrations? - therapeutic levels?

Answer 45

Rapid absorption Serum concentrations peak in 1-3 hour Therapeutic levels maintained upto 12 hours

Question 46

What are the drug interactions of Histamine H2 receptors?

Answer 46

Cimetedine inhibits P450s | Inhibits absorption of drugs

Question 47

Which prostaglandins are synthesized by the gastric mucosa?

Answer 47

PGE2 and PGI2

Question 48

Which receptors do PGE2 and PGI2 bind to?

Answer 48

EP3 receptor

Question 49

What are the cytoprotective effects of prostaglandins?

Answer 49

Stimulate mucin and bicarbonate production

Question 50

What are the pharmacokinetics effects of Prostaglandins? - absorption? - therapeutic effects?

Answer 50

Rapidly absorbed | Effects peak at 60-90 minutes and lasts 3 hours (4x a day does)

Question 51

What are the adverse effects of Prostaglandins?

Answer 51

Diarrhoea Can excaerbate inflammatory bowel disease Contraindicated during pregnancy

Question 52

What is Sucralfate used for?

Answer 52

Treatment of Benign gastric and duodenal ulceration

Question 53

What is Sucralfate composed of?

Answer 53

Aluminium hydroxide and sucrose octasulphate

Question 54

How does Sucralfate work?

Answer 54

Dissociates in gastric acidic environment to anionic form Forms complex gel with mucus and forms cross-linked viscous polymer Acts as an acid buffer and impairs diffusion of H+

Question 55

What is the mechanism of Sucralfate?

Answer 55

Acts as acid buffer and impairs diffusion of H | Stimulates PG-sythesis and bicarbonate secretion

Question 56

What are the pharmacokinetics of Sucralfate? | -side effects

Answer 56

Only slightly absorbed in the gut Free if side effects May cause constipation

Question 57

What are prokinetics?

Answer 57

Dopamine receptor antagonist

Question 58

What do prokinetics do?

Answer 58

Enhances gastric motility Increases rate of gastric emptying Increases gastro-oesophageal tone

Question 59

What are the severe side effects of prokinetics?

Answer 59

``` Fatigue Tremors Parkinsonism Tardive Dyskinesia Severe cardiac events ```