Treatment of Dyspepsia, Peptic Ulcer Disease + GORD

Question 1

What are the 3 main treatments?

Answer 1

Neutralisation
Reduction of acid secretion
Prokinetics

Question 2

What are the treatments for neutralisation?

Answer 2

Antacids
Alginates
Sucralfate (mucosal protectants)

Question 3

What are the treatments for reduction in acid production?

Answer 3

Proton pump inhibitors
Histamine H2 receptor antagonists

Question 4

What are antacids?

Answer 4

Weak bases
Neutralise excess acid in stomach

Question 5

Describe treatment of antacids

Answer 5

Quick BUT short term
Increase pH

Question 6

What do antacids not do?

Answer 6

Prevent over-production of acid

Question 7

What is an example of antacid?

Answer 7

Gaviscon
Has foaming agent = stops acid damaging mucosa

Question 8

What are antacids normally combined with?

Answer 8

Alginates + foaming agents

Question 9

Describe systemic antacids

Answer 9

Useful in short term therapy
Rapid onset
BUT prolonged = overload to kidney

Question 10

Describe non-systemic antacids

Answer 10

Useful in long term
Most doses remain in GI tract
eg. Tums, Rennies

Question 11

What are the interactions of antacids?

Answer 11

Bind to other drugs = reduce bioavailability
Chemical inactivation of drugs
Increase gastric pH = decrease drug absorption + excretion

Question 12

What can be the adverse effects of antacids?

Answer 12

Mg(OH)2 = laxative properties
Al(OH)3 = constipation
CaCO3 = renal calculi (stones)
CO3 = bloating + flatulence

Question 13

Describe alginates

Answer 13

Forms protective barrier on top of gastric contents
Usually combined with antacid

Question 14

What do muscarinic receptor antagonists do?

Answer 14

Block competively

Question 15

What do H2 receptor antagonists do?

Answer 15

Block competively

Question 16

What do PPIs do?

Answer 16

Block by covalent modification

Question 17

What do NSAIDs do?

Answer 17

Block irreversibly

Question 18

What do PPIs do?

Answer 18

Act upon parietal cells

Question 19

What are PPIs?

Answer 19

Pro-drugs

Question 20

What are examples of PPIs?

Answer 20

Omeprazole
Lansoprazole

Question 21

What does it mean that PPIs are prodrugs?

Answer 21

Inactive at neutral pH
BUT active in acidic conditions

Question 22

What do PPIs have?

Answer 22

Enteric coating to resist gastric metabolism

Question 23

How do PPIs work?

Answer 23

Activated form binds irreversibly to cysteines of H+/K+-ATPase
= inhibits active proton pump
= prevents movement of H+

Question 24

What is achlorhydria?

Answer 24

All gastric acid secretion blocked

Question 25

Describe omeprazole activation + activity

Answer 25

Diffuse into parietal cells Activated by proton-catalysed formation of sulfenic acid Active drug irreversibly binds sulfhydryl group of cysteines of H+/K+ pump Irreversible inactivation of proton pump

Question 26

Why is timing of dosing important for PPIs?

Answer 26

Drug must be present in plasma at effective conc whilst proton pumps are active Before food (30-60mins)

Question 27

When is full effect of PPI achieved?

Answer 27

After repeated dosing

Question 28

What does histamine do?

Answer 28

Stimulate acid production by parietal cells

Question 29

What does gastrin do?

Answer 29

Stimulate ECL cells to release high levels of histamine

Question 30

What are the 2 H2 receptor blockers?

Answer 30

Cimetidine Ranitidine = fewer side effects

Question 31

How do H2 receptor antagonists work?

Answer 31

Act as competitive antagonists Block histamine-mediated component of acid secretion + reduce secretion evoked by Ach + gastrie

Question 32

When is H2 receptor antagonists effective?

Answer 32

Once/twice daily by oral administration

Question 33

What are the pharmacokinetics of H2 antagonists?

Answer 33

Rapidly absorbed after oral administration Conc peak 1-3hrs Therapeutic levels maintained up to 12hrs

Question 34

What does cimetidine inhibit?

Answer 34

Hepatic P450s = which modulate drug metabolism

Question 35

What decreases effectiveness of H2 antagonists?

Answer 35

Smoking

Question 36

What does PGE + PGI do?

Answer 36

Synthesized by gastric mucosa Bind to EP3 receptors = decrease acid production

Question 37

What are the cytoprotective effects of PGE + PGI?

Answer 37

Stimulate mucin + bicarbonate production

Question 38

What are the adverse effects of PGE + PGI?

Answer 38

Diarrhoea + abdominal cramps Exacerbate inflammatory bowel disease

Question 39

What is sucralfate?

Answer 39

Complex of aluminium hydroxide + sucrose octasulphate

Question 40

What does sucralfate do?

Answer 40

Dissociates in gastric acid environment to anionic form Forms complex gel with mucus + forms cross-linked viscous polymer

Question 41

What is the mechanism for sucralfate?

Answer 41

Acts as acid buffer + impairs diffusion of H+ Stimulates PG-synthesis + bicarbonate secretion

Question 42

What are the pharmacokinetics for sucralfate?

Answer 42

Only slightly absorbed from gut Essentially free of side effects Absorbed fraction excreted unchanged by kidney

Question 43

What is an example of prokinetic?

Answer 43

Dopamine receptor antagonist

Question 44

What does dopamine receptor antagonist do?

Answer 44

Enhance gastric motility Increase rate of gastric emptying Increase gastro-oesophageal tone

Question 45

Why are prokinetics rarely used?

Answer 45

Severe side effects eg. fatigue, tremors , cardiac events