S10 L1 GI pharmacology

Question 1

What GI pathology can arise from inappropriate acid secretion?

Answer 1

Gastric and duodenal ulcers

Question 2

What is the problem with gastric and duodenal ulcers?

Answer 2

Symptoms not reliable - guide is epigastric pain
Chronic ulcers are asymptomatic
Bleeding, perforation, scarring and possible obstruction is possible

Question 3

What are the risk factors for ulceration?

Answer 3

1. Acid is essential for ulceration- inability to switch off acid secretion is a major risk factor
2. Early gastric emptying can be a risk factor- ↓pH of contents into duodenum causes damage
3. Helicobacter pylori
4. NSAIDs - anti-inflammatory → inhibit protective mechanisms of acid secretion by inhibiting PGE2 and reducing mucosal blood supply - disrupts the hydrogen carbonate levels in the mucosa
5. Smoking and alcohol delay healing

Question 4

What medications can be used to inhibit GI pathology?

Answer 4

1. Alginates and antacids
2. Proton pump inhibitors
3. H2 receptor antagonists
4. Aminosalicylates

Question 5

What are alginates and antacids?

Answer 5

Antacids- buffer stomach acid
Alginic acid- increases stomach content viscosity and reduce reflex
Often taken as compound preparations → sodium alginate and aluminium hydroxide/magnesium carbonate

Question 6

What is an example of an alginate and antacid?

Answer 6

Gaviscon

Question 7

What are the adverse effects of alginate and antacids?

Answer 7

Magnesium salts → diarrhoea
Aluminium salts → constipation
Taken together balance each other out

Question 8

What are the contraindications of alginates and antacids?

Answer 8

Na+ and K+ containing preparation should be used with caution in renal failure
High [sucrose] in some preparations - hyperglycaemia in DM

Question 9

What are the important drug drug interactions of alginates and antacids?

Answer 9

Reduce absorption of many drugs so doses should be separated- disrupts the bioavailability of other drugs
↑urine alkalinity = ↑aspirin excretion

Question 10

What are proton pump inhibitors?

Answer 10

Irreversibly inhibit the H+/K+ ATPase in gastric parietal cells
Final stage it the pathway so very significant reduction effect
Shortest effective duration at lowest effective dose
Often prescribed alongside long term NSAID or steroid

Question 11

What are examples of proton pump inhibitors?

Answer 11

‘-prazole’
Lansoprazole
Omeprazole

Question 12

What are the adverse effects of the proton pump inhibitors?

Answer 12

GI disturbances - abdominal pain, constipation diarrhoea
Headache, dizziness
Drowsiness/confusion

Question 13

What are the contraindications of proton pump inhibitors?

Answer 13

Mask symptoms of gastro-oesophageal cancer

Osteoporosis- fracture risk

Question 14

What are the important drug-drug interactions of proton pump inhibitors?

Answer 14

Omeprazole CYP inhibitors- (specific action of omeprazole not all PPIs)- reduced clopidogrel action - prevents conversion to active metabolites
PPIs can increase effects of warfarin and phenytoin - monitor

Question 15

What are the H2 receptor antagonists?

Answer 15

Inhibition of H2 receptors- local histamine release contributes to proton pump activation (secreted from enteroendocrine cells- act on H2 receptor on parietal cells)
Only partial reduction in acid secretion (other routes to activate parietal cells)

Question 16

What are the adverse effects of H2 receptor antagonists?

Answer 16

Generally well tolerated

Diarrhoea and headaches possible

Question 17

What are the contraindications of H2 receptor antagonists?

Answer 17

Mask the symptoms of gastro-oesophageal cancers, renal impairment

Question 18

What are the important drug-drug interactions of H2 receptors antagonists?

Answer 18

Few DDI

Reduced exposure to some antivirals and protein kinase inhibitors

Question 19

What is an example of the H2 receptor antagonists?

Answer 19

Ranitidine

- Current large scale recall on most products due to possible carcinogenic contaminant

Question 20

What is helicobacter pylori?

Answer 20

Gram negative bacteria

Colonises the gastric mucosa

Question 21

When should helicobacter pylori infection be considered?

Answer 21

Patients with duodenal or gastric ulcers

Not associated with NSAIDs or unresponsive to lifestyle PPI and antacids

Question 22

How is H.Pylori infection confirmed?

Answer 22

Urea breath test

• Urea labelled with C13 isotope given to patients
• H.Pylori have own urease enzymes converts urea to CO2 with C13
• Patient breathes it out can be detected on test

Question 23

How it H.Pylori infection treated?

Answer 23

One week triple therapy
PPI and two antibacterial agents
Lansoprazole + clarithromycin + amoxicillin
Lansoprazole + clarithromycin + metronidazole (if allergic to amoxicillin, some local resistance to metronidazole in leic)
Full compliance with course important for effectiveness and minimise risk of bacterial resistance

Question 24

What are the aminosalicylates?

Answer 24

Anti-inflammatory drug
First line treatment for ulcerative colitis
Release of 5-aminosalicylic acid
Topical action at colon- enteric coated to prevent/limit breakdown within the stomach

Question 25

What is an example of the aminosalicylate?

Answer 25

‘-salazine’
Mesalazine - no role in RA
Sulfasalazine - more side effects so used infrequently for UC but sulfa group good for RA

Question 26

What are the adverse effects of aminosalicylates?

Answer 26

GI disturbances - nausea, dyspepsia

Leukopenia - rare

Question 27

What are the contraindications of aminosalicylates?

Answer 27

Salicylates like aspirin - pt with aspirin hypersensitivity show caution with prescribing of aminoalicylates

Question 28

What are the important drug drug interactions?

Answer 28

Enteric coated tablets may breakdown quicker in presence of PPI because of ↑pH - so interferes with the enteric coat