Pharmacology

Question 1

What are the aims of treatment for IBD?

Answer 1

Induce remission

Maintain remission

Prevent secondary effects

Question 2

What is the first line of treatment for Ulcerative colitis and what does this drug do?

Answer 2

Aminosalicylates (ASAs)

• induce remission
• maintain remission
• prevent colonic cancer

Question 3

What is the mechanism of action of Aminosalicylates?

Answer 3

Anti inflammatory (note entirely know how)

Inhibit synthesis of inflammatory mediators:

• prostgaglandins
• thromboxane
• platelet-activating factor

Scavenger of oxygen-radicals

Question 4

What role do Aminosalicylates have in Crohn’s disease?

Answer 4

No evidence that is is any better to placebo for maintenance of medically induced remission

Question 5

Give examples of aminosalicylates?

Answer 5

Sulfasalazine

Mesalazine

• Asacol
• Pentasa
• Mezavant

Olsalazine

Balsalazide

Question 6

What are the side effects of sulfasalazine?

Answer 6

Allergic reactions

• rash
• fever (sign of infection)
• leucopenia
• agranulocytosis

Male infertility
- due to oligospermia and reduced sperm motility

Orange discolouration of body secretions

Question 7

What should be done if someone has side effects to sulfasalazine?

Answer 7

Withdraw drug

Note does dependent
- reducing dose doess not rid of allergic reactions

Question 8

Where is Mesalazine absorped in the body?

Answer 8

Completely and rapidly absorbed in the jejunum

• well tolerated

Question 9

How can mesalazine be administered?

Answer 9

Oral and topical

Question 10

How do the three main Mesalazine preparations differ?

Answer 10

Asacol

• pH dpeendent release mechanism
• favours ileum and colon release

Pentasa

• time controlled release
• pH-independent coating - acts throughout GI tract

Mezavant
- Multimatrix delivery system

Question 11

What are the adverse effects of Mesalazine?

Answer 11

Diarrhoea

Headache

Nausea

Rash (1%)

Renal impairment rare but still monitor renal function

Question 12

What interacts with Mesalazine?

Answer 12

Lactulose

Question 13

What are the aim of Corticosteroids in IBD?

Answer 13

Induce remission in both IBDs

Do not play a role in maintenance therapy

Question 14

What is the mechanism of action of corticosteroids?

Answer 14

Potent anti-inflammatory agents

Inhibit inflammatory responses

Question 15

What are the anti-inflammatory and immunosuppresive effects of corticosteroids?

Answer 15

Inactivates pro-inflammatory transcription factors

• NF-KB
• AP-1

Prevent stimulation of inflammatory mediators

• prostaglandins
• leukotrienes
• cytokines
• platelet activating factor

Question 16

What are the adverse effects of corticosteroids?

Answer 16

Symptoms of Cushing’s

Question 17

Why must corticosteroids not be stopped immediately after use?

Answer 17

Risk of addisonian crisis due to feedback mechanisms

Question 18

What else must be given when administrating steroids?

Answer 18

Give bone protection

• Ca2+
• Biphosphonates

Question 19

What are the steroids used and in what order for inducing remission of IBD?

Answer 19

IV hydrocortisone, then reduce to:

Oral prednisolone, then:

Stop

Question 20

What are thiopurines used for in IBD?

Answer 20

Unlicensed medication used in both Crohn’s and UC when ASAs and innefective or untolerated, and steroid use is not having enough effect

Question 21

Give examples of Thiopurines used in IBD?

Answer 21

Azathiprine

Mecaptopurine

Question 22

What is Azathiprine metabolised to?

Answer 22

6-Mecaptopurine

Question 23

What are the adverse effects of Azathioprine?

Answer 23

Allergic reactions

• fever
• arthralgia
• rash

Bone marrow suppression

Leukopenia

Hepatotoxicity

Question 24

What must be done to ensure safety in use of azathiprine?

Answer 24

Blood monitoring: FBCs and LFTs weekly for first 8 weeks then every 3 months

Question 25

What enzyme metabolises Thiopurines?

Answer 25

Thiopurine methyltransferase

Question 26

What is Ciclosporin used for in IBD?

Answer 26

Used to induce remission in active severe Ulcerative colitis in patients who have failed to respond to IV steroids

Question 27

What are the adverse effects of ciclosporin?

Answer 27

Hypertension Infection Renal impairment Increase seizures with IV if: - hypocholesterolaemia - hypomagnesaemia GUM hypertrophy and hirsutism

Question 28

Which drugs do ciclosporin interact with?

Answer 28

Enzyme inhibitors e.g. Macrolides

Question 29

What is Methotrexate used for in IBD?

Answer 29

Induction and maintenance of remission in Crohn's disease 2nd line immunosuppressant in patients resistant or intolerant to AZA or 6-mecaptoupurine

Question 30

What are the side effects of methotrexate?

Answer 30

GI (folic acid may reduce risk of SEs) - nausea, vomiting, diarrhoea Hepatotoxicity Blood dyscrasias

Question 31

What do monoclonal antibodies do and give two examples?

Answer 31

Target specific immunological and inflamamtory pathways e.g. Infliximab and Adalimumab inhibit TNF-alpha

Question 32

What is infliximab? Describe it's mechanism of action

Answer 32

A chimeric (human and mouse) anti-TNF antibody Targets membrane bound TNF Kill host cell by complement induced lysis Anti-inflammatory action

Question 33

What should infliximab be used for?

Answer 33

Severe active Crohn's or fistulating severe active crohn's - surgery innapropriate and unresponsive to AZA and steroids Ulcerative colitis - ciclosporin is contraindicated or clearly innapropriate

Question 34

What are the cautions when using infliximab?

Answer 34

Tuberculosis screening Delayed hypersensitivity reaction Contraindicated in severe infection and severe heart failure

Question 35

What is adalimumab and its indication?

Answer 35

Humanised monoclonal antibody Inhibits TNF-alpha Severe active Crohn's only