Inflammatory Bowel Disease

Question 1

What are the two major forms of inflammatory bowel disease

Answer 1

Ulcerative Colitis (UC)
Crohn’s Disease (CD)

Question 2

What are the risk factors for IBD

Answer 2

Genetics

Environmental Factors:
Smoking (more prevalent in CD)
Diet/obesity
Gut microbiome

Question 3

Describe the pathogenesis of IBD

Answer 3

Potentially due to a defective interaction between the mucosal immune system and the gut flora

1. Disrupted innate immunity
2. Uncontrolled inflammation
3. Physical damage to epithelium and leakiness of tight junctions

Question 4

Describe ulcerative colitis (mediators, affected tissues, distribution, continuity)

Answer 4

Th2 mediated, dependent on cytokines IL-5 and IL-13
Affects mucosa and submucosa
Always starts in the rectum and spreads proximally
Continuous

Question 5

Describe Crohn’s disease (medators, affected tissues, distribution, continuity )

Answer 5

Th1 mediated, dependent on cytokine TNF-alpha
Penetrates all the way through the gut
Affects any point in the GI tract – from mouth to anus
Skips lesions

Question 6

Describe how IBD presents clinically

Answer 6

Abdominal pain and crampitng
Diarrhoea, bloody faeces
Bloating
Rectal abscess
Fever
Weight loss

Question 7

What is the first line treatment for IBD patients who present with bloody diarrhoea

Answer 7

Fluid/electrolyte replacement

Blood transfusion/iron replacement

Question 8

What is the first line treatment for IBD patients who appear malnourished

Answer 8

Nutritional support

Question 9

What are the three classes of drugs used in symptomatic treatment for IBD

Answer 9

Glucocorticoids
Aminosalicylates
Immunosuppressives

Question 10

What are glucocorticoid drugs and give examples of glucocorticoids used in IBD treatment

Answer 10

Anti-inflammatory immunosuppressants

Prednisolone, fluticasone, budesonide

Question 11

Describe the pharmacokinetics of glucocorticoids in IBD treatment

Answer 11

High hepatic first pass metabolism means that little active glucocorticoid escapes into the systemic circulation

Question 12

Describe the use of glucocorticoids in ulcerative colitis

Answer 12

Aminosalicylates have been proven to be better

Used topically normally and IV if severe

Question 13

Describe the use of glucocorticoids in Crohn’s disease

Answer 13

Drug of choice in inducing remission

High chance of side effects

Question 14

How are the side effects of glucocorticoids minimised

Answer 14

Topical admin
Low dose combinations
Topical/oral admin with first pass metab

Question 15

Compare budenoside to prednisolone

Answer 15

Budesonide has fewer side effects than prednisolone but prednisolone is better than inducing remission so decisions are made case by case

Question 16

Give examples of aminosalicylates used in IBD treatment and where are they absorbed

Answer 16

Mesalazine or 5-aminosalicylic acid (5-ASA)

Absorbed in the small bowel and colon

Question 17

What gives aminosalicylates their anti-inflammatory effect

Answer 17

Inhibition of IL-1, TNF-alpha and Platelet Activating Factor
Decreased antibody secretion
Non-specific cytokine inhibition
Reduced cell migration (macrophages)
Inhibition of localised immune response

Question 18

Describe the use of aminosalicylate in ulcerative colitis

Answer 18

First line in inducing and maintaining remission

Question 19

Describe the use of aminosalicylate in Crohn’s disease

Answer 19

Effectiveness is questioned in active disease

Thought to help maintain surgically induced remission

Question 20

Give examples of immunosuppressives used in IBD

Answer 20

Azathioprine
Methotrexate
Cyclosporin

Question 21

Describe the use of azathioprine in IBD

Answer 21

Maintains remission in CD and some UC patients

Question 22

Describe how azathioprine is activated

Answer 22

activated in vivo by gut flora to 6-mercaptopurine (purine antagonist) - interferes with DNA synthesis and cell replication

Question 23

What does azathioprine impair

Answer 23

cell- and antibody-mediated responses, lymphocyte proliferation, mononuclear cell infiltration

Question 24

What does azathioprine enhance

Answer 24

T cell apoptosis

Question 25

What proportion of patients stop treatment using azathioprine due to side effects and what might these be

Answer 25

Pancreatitis
Bone marrow suppression
Hepatotoxicity
Increased risk of lymphoma and skin cancer

Question 26

Which drugs is contraindicated for use with azathioprine

Answer 26

Allopurinol (used to treat gout) interacts with Azathioprine

Question 27

What type of drug is methotrexate and what does it do

Answer 27

Folate antagonist

Reduces synthesis of purines, interfering with DNA synthesis and replication

Question 28

Give examples of potential curative therapies of IBD

Answer 28

Manipulation of the gut microbiome
Biological therapies
Anti-TNF alpha e.g. infliximab
Anti-alpha4-inteferin e.g. natalizumab

Question 29

Describe the manipulation of the gut microbiome in IBD

Answer 29

Nutrition Based Therapies (exclusive enteral nutrition EEN)
Probiotic therapy
Faecal Microbiota Replacement Therapies

Question 30

What is rifamixin and how does it work

Answer 30

Antibiotic treatment for IBD
Binds to RNA polymerase and interferes with transcription
Induces and sustains remission in moderate CD

Question 31

Describe biological therapies for IBD

Answer 31

Anti-TNF-alpha antibodies: Infliximab and Adalimumab
Successful in the treatment of CD - Responds within 6 weeks
Potentially curative
Some evidence of effectiveness in UC

Question 32

What is the mechanism of action of biological therapies for IBD

Answer 32

Causes downregulation of many cytokines - reduced leukocyte activation
Induces cytolysis of TNF-alpha cells and apoptosis of activated T cells

Question 33

What are the side effects of using biological therapies for IBD

Answer 33

Increased risk of septicaemia
Worsening heart failure
Increased risk of demyelinating disease
Increased risk of malignancy