Inflammatory bowel disease

Question 1

What are the 2 major forms of IBD?

Answer 1

Ulcerative colitis

Crohn’s disease

Question 2

Summarise the pathology driving each form of IBD

Answer 2

Auto-immune diseases
UC = Th2 dominated
CD - Th1 (and therefore TNF-alpha) domianted

Question 3

Compare the extent of disease in UC and CD

Answer 3

Depth: UC = just mucosa + submucosa, CD = all layers
Spread: UC = begins at rectum and moves proximally, CD = patchy coverage of entire bowel length

Question 4

Compare the efficacy of surgery in UC and CD

Answer 4

In UC = usually curative

In CD = usually not so helpful

Question 5

In which form of IBD are fistulae and abscesses more likely to develop?

Answer 5

CD

Question 6

Recall 5 significant systemic effects of IBD

Answer 6

1. Weight loss
2. Arthritis
3. Anaemia
4. Skin rash
5. Ulcers

Question 7

Recall the 4 most influential risk factor for IBD

Answer 7

1. White European ethnicity
2. Diet
3. Smoking
4. Microbiota

Question 8

Recall 3 supportive therapies for IBD

Answer 8

Fluids
Blood/ oral iron
Nutritional support

Question 9

Why is symptomatic treatment so necessary in IBD

Answer 9

Symptoms nearly always recur, so want to keep patients in remission as long as possible

Question 10

Recall the 3 symptomatic treatments that may be used in IBD treatment

Answer 10

Glucocorticoids
Aminosalicylates
Immunosuppressants

Question 11

Recall the 2 examples of glucocorticoid therapy that are most commonly used, and a benefit of each over the other

Answer 11

Prednisolone: more effective at inducing remission
Budesonide: high hepatic first-pass metabolism so very little reaches systemic circulation = fewer side effects

Question 12

Recall the likelihood of GC use in each form of IBD

Answer 12

In UC: low usage as aminosalicylates are preferable

In CD: drug of choice for inducing remission

Question 13

Recall the 2 key examples of aminosalicylate drug for IBD and their structures

Answer 13

1. Mesalazine = 5-ASA analogue

2. Olsalezine = 2 x 5-ASA molecule dimerised

Question 14

Why might olsalezine be chosen over mesalazine

Answer 14

Olsalezine needs to be cleaved by colonic bacteria to produce active drug so it is only active in colon. If disease is concentrated here it will be drug of choice

Question 15

Recall the mechanism of action of aminosalicylates

Answer 15

Downregulate pro-inflammatory cytokines (eg TNF) and PGs (eg PGF2-alpha)

Question 16

Recall the likelihood of use -of amino-salicylates for each form of IBD

Answer 16

In UC: drug of choice for induction and maintenance of remission
In CD: pretty-well useless

Question 17

Name an example of an immunosuppressant drug used for IBD treatment

Answer 17

Azothioprine

Question 18

Recall the pharmacokinetics of azothioprine

Answer 18

Activated by gut flora to 6-mercaptopurine

Question 19

Summarise the mechanism of action of azothioprine

Answer 19

Once activated, antagonises purines to interfere with DNA synthesis + cell replication

Question 20

How does DNA synthesis inhibition by azothioprine benefit IBD patients? (5 ways)

Answer 20

Inhibition of:
immune responses
Lymphocyte proliferation
Mononuclear cell infiltration
Ab synthesis
Enhances:
T cell apoptosis

Question 21

Recall 3 side effects of immunosuppression with azothioprine

Answer 21

Pancreatitis
Suppression of bone marrow
Significantly increased lymphoma + skin cancer risk

Question 22

Recall the likelihood of use of azothioprine in each form of IBD

Answer 22

In UD: aminosalicylates preferred so rarely used

In CD: no benefit in active disease but often used to maintain remission

Question 23

Recall the 2 potentially curative approaches of therapy for IBD

Answer 23

1. Microbiome manipulation

2. Biologic therapies

Question 24

Recall the 3 approaches of microbiota manipulation to cure IBD

Answer 24

1. Nutrition-based (probacteria etc)
2. Faecal microbiota replacement
3. Antibiotic therapy

Question 25

Which of the approaches to microbiome manipulation is most effective so far?

Answer 25

Antibiotic therapy

Question 26

How does antibiotic manipulation of the microbiome work?

Answer 26

Bonds to RNA polymerase

Question 27

What is the most widely-used biologic therapy

Answer 27

Anti-TNF-alpha - infliximab

Question 28

Recall 2 key issues with infliximab treatment, in addition to its side effects

Answer 28

1. Only about 60% of patients respond

2. Tolerance usually develops within 3 years

Question 29

Recall the mechanism by which tolerance to infliximab is usually developed

Answer 29

1. Increased clearance

2. Production of anti-drug antibodies

Question 30

What other conditions are patients on infliximab at a greater risk of having?

Answer 30

1. The major one = TB
2. Septicaemia
3. De-myelinating disease
4. Malignancy

Question 31

Recall the key pharmacokinetic factors to take into consideration with infliximab

Answer 31

IV administration is a bit of a mare

Half life v long (9,5 days)

Question 32

Recall the mechanism of action of infliximab

Answer 32

1. Mops up all soluble TNF-alpha before it can activate receptors
2. Induces cytolysis of cells expressing TF-alpha