Inflammatory Bowel Disease

Question 1

Mechanism of action of 5-aminosalicylates

Answer 1

API: mesalazine

Inhibition of prostaglandin, leukotriene synthesis, inhibiting production of reactive oxygen species

Question 2

What is the main treatment for UC and doses

Answer 2

5-aminosalicylates

4-4.8g a day for treatment and then maintenance 2-2.4g /day

Question 3

How does 5-ASA in sulfasalazine work?

Answer 3

It is poorly absorbed and thus remains in the terminal ileum/coon - induces remission but inhibiting the COX/leukotrienes/cyotkines, TNFa

Question 4

Counselling for aminosalicylates?

Answer 4

• swallow whole not chew or crush as halving would cause premature 5-asa release
• Contact Dr if get sore throat, easily bruised, ever - could indicate a blood disorder caused by drug
• Maintain the brands due to differences in release profile

Question 5

What are the components of sulfasalazine and what they do

Answer 5

sulfapyridine - acetylated in liver, no action in UC. Can also cause folate deficiency, hepatotoxicity.

Mesalazine (5-ASA) is the active component which induces remission

Question 6

Name 3 brands of aminosalicylate

Answer 6

Asacol MR - Enteric coat delayed release pH >7 in terminal ileum and large bowel

Octasa MR - EC delayed release pH >7 in terminal ileum and colon

Ethylcellulose - coated microgranules to allow slow continous release - duodeum to rectum

Sulfasalazine in the colon - cleaved by intestinal bacteria - azoreductase pH >7

Mesavant XL pH>7 in colon

Question 7

What is the licensing for mesalazine preparations in UC?

Answer 7

All mesalazine preps are licensed for tretment of milt to moderate acute exacerbations. EXCEPT salofalk 1g tablets which are only licensed for maintenance of remission

Asacol and Octasa MR are for maintenance AND remission for chrons ileo-colitis too

Question 8

What is salofalk for?

Answer 8

1g tablets, only licensed for maintenance of remission in UC

Question 9

What formulation would be used if a patient has UC that reaches the sigmoid colon?

Answer 9

This is proctosigmoiditis - Use foam 20-30 ml

Question 10

What formulation is used for UC proctitis?

Answer 10

Suppository -reaches the rectum, 1g, 2g, 4,g

Question 11

What formulation would be used for left sided distal colitis?

Answer 11

Enema - up to 100ml, reaches the descending colon –> splenic flexure

Question 12

What is the order of patient preference of formulations?

Answer 12

Suppository > foam > enema

Question 13

What are corticosteroids used for?

Answer 13

Mainstay treatment of Chrons flare up (sometimes UC flare), no role in maintenance

Question 14

What is the main treatment for a chrons flare up and dose?

Answer 14

Corticosteroids - but NO ROLE IN MAINTENANCE - just flare up - Prednisolone 40mg OD, reduced slowly 2 weeks

Question 15

What are long term risks of corticosteroids and when should they be taken

Answer 15

Long term risks of osteoprosis/peptic ulcer disease

Should be taken in the morning as affects natural sleep hormones. Ideally on lowest effective dose, reducing dose

Question 16

What rectal steroids are available and when are they used?

Answer 16

Only really used for patients who are not responding / intolerent to PR mesalazine

• Hydrocortisone foam
• Prednisolone
• Budesonide foam

Question 17

If a conventional glucocorticoid is contraindicated - what can be used for a single inflammatory exacerbation of chrons in a 12 month period?

Answer 17

Budesonide

Question 18

What is budesonide usually restricted to?

Answer 18

Use in UC if 5-ASA are not tolerated/CI

Question 19

Why is budesonide not as effective?

Answer 19

Less effective
Undergo FPM - low systemic bioavailability,
BUT: effects confined to GIT and low toxicity, less side effects and less adrenal suppression

Question 20

What do we need to check before putting a patient on thiopurines e.g Azathioprine/mercaptopurine

Answer 20

If patient is at risk of developing severe s/e - assess Thiopurine Methyltransferase (TPMT) activity, do not offer if TPMT activity is deficient (would cause prodution of toxic purine analogues - cause BM toxicity)
- Can consider it if it is below normal but not deficient.

Question 21

Monitoring in thiopurines

Answer 21

Monitor for neutropenia even if they have normal TPMT activity

Question 22

MoA of azathioprine?

Answer 22

Immunosuppressant - purine analogues.

• It is a pro drug for mercaptopurine which is active metabolite
• Inhibition of purine synthesis

Question 23

What is a s/e of azathioprine?

Answer 23

Bone marrow suppression - DO NOT give in conjunction with purine analogues e.g allopurinol

Question 24

When is methotrexate considered?

Answer 24

In active and relapsing chron’s when other immunosuppressants are not tolerated or CI

Question 25

MoA of methotrexate and dosing

Answer 25

Anti-metabolite/folate

- 25 mg / week PO, IM, SC - initiate lower and titrate up until remission induced, maintenance 15mg

Question 26

S/e of methotrexate and monitoring

Answer 26

S/E - need to take folic acid to reduce, but omit on days taking metho

• Monitor FBC, LFTs

Question 27

When is ciclosporin used

Answer 27

Acute severe UC - with poor improvements in 72hrs of corticosteroids or no improvement at any time.
- 2mg/kg PO or IV - dont use PO if have diarrhoea
Must have baseline BP, FBC, Cholesterol, LFTs, GCR, Mg levels first

Question 28

When are monoclonal antibodies used?

Answer 28

TNFa inhibitors (Anti-TNFa) - Inflixumab, adalumimab.
Severe active chrons and severe UC.
- not responded to steroids or immunosuppressants
- Use until treatment failure / 12 months - whatever is shortest time.
- Check for TB before starting

Question 29

Monitoring when taking TNF-a inhibitors? any counselling?

Answer 29

For infection and skin cancer

Counsel on effective contraception during treatment and for at least 5 months after last dose - both partners

Question 30

MoA of Inflixumab?

Answer 30

TNFa is implicated in many autoimmune diseases . - regulation of inflammation, Inflixumab is a chimeric monoclonal AB that targets and binds to it, inactivtes it and then reduces inflammatory process

Question 31

General counselling points for IBD patients?

Answer 31

• Flu jabs?
• Codeine can be used as a painkiller and also causes constipation so could stop the diarrhoea?
• Nutrition and dieticians
• Awareness of increased risk of clotting due to inflammation
• Do they need to be on bone protective agents or take Calcium agents?

Question 32

What medications are not used when someone has IBD?

Answer 32

NSAIDS, anti-diarrhoeals, opioids - can precipitate toxic megacolon or worsen condition (in colitis). Paracetamol is good.

Question 33

why is it important to maintain brands of mesalazine?

Answer 33

They have differences in release profiles