Clinical Pharmacology of Alimentary System

Question 1

3 targets for gastric acid suppression drugs?

Answer 1

H2 (histamine) receptors on gastric cell membranes (H2 antagonists)

Proton pump (PPI)

H+ in the stomach lumen (antacids)

Question 2

How do antacids suppress gastric acid?

Answer 2

Contain Mg or Al to neutralize gastric acid

taken when symptoms occur

Question 3

How do alginates work? Example drug?

Answer 3

They form a viscous gel that floats on stomach contents and prevents reflux

Eg. Gaviscon

Question 4

How do H2 receptor antagonists work? When are they indicated? Admission route?

Answer 4

Block histamine receptors in parietal cells, reduce acid secretion

Indicated in GORD/peptic ulcer disease

Oral/IV

Question 5

When are proton pump inhibitors indicated? Route of administration?
Example?

Answer 5

Indicated in GORD/peptic ulcer disease

Oral/IV

Omeprazole

Question 6

Common issues with PPI’s?

Answer 6

GI upset
c. difficile infection
Hypomagnesaemia
B12 deficiency

Question 7

What do prokinetic agents do for gut motility? When are they indicated?

Answer 7

Increase gut motility and gastric emptying

Gastroparesis (can’t empty stomach)
GORD
Anti-emetics (anti-vomiting)

Question 8

What is the mechanism by which drugs decreasing GI motility work? Drug example?

Answer 8

Act on opiate receptors in the GI tract to reduce ACh release

Loperamide (immodium)

Question 9

What effect do anti-spasmodics have on GI motility?

Answer 9

Relax the smooth muscle in the gut wall - reduces symptoms due to IBS

Question 10

How do laxatives work?

Route of administration?

Answer 10

Increase faecal bulk or draw fluid into the gut

Route of administration can depend on what’s causing the constipation - either oral or rectal

Question 11

What are aminosalicylates used to treat? What is their action?
Examples?

Answer 11

Used to treat IBD
Anti-inflammatory action

Mesalazine, olsalazine

Question 12

route of administration for aminosalicylates? Contraindications?

Answer 12

Oral or rectal

Salicylate allergy
Renal impairment

Question 13

When are corticosteroids indicated?
Route of administration?
Concerns/contraindications?

Answer 13

Indicated in IBD - anti-inflammatory effect
Orally, IV or rectally

Osteoporosis,
cushings features
May become susceptible to infection
Addisonian crisis with abrupt withdrawal

Question 14

Main immunosuppressant drug for IBD? Mechanism?

Answer 14

Azathioprine

Prevents purine formation required for DNA synthesis - reduces immune cell proliferation

Question 15

Concerns/contraindications for azathioprine?

Answer 15

Bone marrow suppression
Azathioprine hypersensitivity
Organ damage (lung, liver, pancreas)

Question 16

How do biologics treat IBD?

Examples?

Answer 16

They are largely antibodies to cytokines involved in the inflammatory response - stop inflammation

Infliximab
Certolizumab, adalimumab etc.

Question 17

Which cytokine is infliximab an antibody to? How was infliximab made?

Answer 17

The TNF alpha cytokine

Infliximab is a mouse-human chimera

Question 18

Cautions/Contraindications for infliximab?

Adverse effects?

Answer 18

Current TB/other serious infection
MS
Pregnancy/breast feeding

Adverse effects:
Infection risk, infusion reaction (fever, itch)
Anaemia
Demyelination (can cause MS)
Malignancy

Question 19

Drug classes used to treat IBD?

Answer 19

Biologics
Aminosalicylates
Immunosuppressants
Corticosteroids

Question 20

What does cholestyramine treat? Mechanism?

Answer 20

Treats pruritis from biliary cause

Binds bile salts in the gut and then excretes as an insoluble complex

Question 21

What does Ursodeoxycholic acid treat? Mechanism?

Answer 21

Gallstones and primary biliary cirrhosis (PBC)

Inhibits enzyme involved in cholesterol formation - altering the amount in bile and slowly dissolving non-calcified stones

Question 22

What drug properties can be affected by GI or liver disease?

Answer 22

Absorption
Distribution
Metabolism
Excretion

Question 23

How can liver disease affect drug distribution?

Answer 23

Low albumin results in decreased binding and higher free drug concentration

Question 24

How can liver disease affect drug metabolism?

Answer 24

Fewer liver enzymes - less detoxification

Question 25

How can liver disease affect drug excretion?

Answer 25

Less excretion if hepatobiliary disease - more toxicity

Question 26

What is the major consequence of NSAID abuse?

Answer 26

Mucosal injury and bleeding

Via prostaglandins (?)

Question 27

What can drug induced liver injury do to the gut?

Answer 27

Change the bacterial flora - reduced vitamin K absorption & overgrowth of pathogenic bacteria

Question 28

How do we classify the severity of liver disease?

Answer 28

Child - Pugh classification

< 7 - A
7-9 - B
>9 - C

Question 29

Which drugs should be prescribed with care to patients with liver disease?

Answer 29

Drugs which may become toxic due to changes in
- Liver metabolism
- Biliary excretion
&
- Drugs that are hepatotoxic
- Drugs that may worsen non-liver aspects of liver disease (encephalopathy)

Question 30

Particular drugs to be cautious of in liver diseased patients?

Answer 30

• Warfarin/anti-coagulants (clotting factors already low in liver disease)
• Aspirin/NSAIDS (can increase bleeding time/worsen ascites)
• Opiates/benzodiazepines (precipitate encephalopathy)