Week 6- Inflammatory Bowel Disease Treatment

Question 1

what are the different types of drugs used to treat IBD?

Answer 1

• Aminosalicylates =NSAID
• Corticosteroids
• Thiopurines
• Methotrexate
• Ciclosporin
• Anti-TNF therapies
• Others like antibiotics…

Question 2

what are some of the factors that influence the choice of drug and route for IBD?

Answer 2

- Site
– Extent & disease severity
– Response to current or previous treatment
– Patient’s preference
– Acceptability & tolerance
– Side-effects
– Cost
– Dosing schedule

Question 3

what is the first line treatment for IBD?

Answer 3

aminosalicylates they are Non-steroidal anti-inflammatory drugs (NSAID)

Question 4

what is the active ingredient in aminosalicylates?

Answer 4

5-aminosalicyclic acid (5-ASA)

Question 5

what are the 4 drugs that are available from the base modifications of 5-aminosalicyclic acid basic structure?

Answer 5

• sulfasalazine
• mesalazine
• olsalazine
• balsalazide

Question 6

what is the structure of sulfasalazine?

Answer 6

– 5-ASA + Sulfapyridine

– Attached by a diazo bond cleaved by bacteria in colon

Question 7

what is the structure of mesalazine?

Answer 7

• Modified release 5-ASA

Question 8

what is the structure of olsalazine?

Answer 8

– Dimer of 5-ASA – cleaves in the lower bowel

Question 9

what is the structure of balsalazine?

Answer 9

– Pro-drug of 5-ASA, UC only

Question 10

how do aminosalicylates works?

Answer 10

• sulfasalazine is the sulfapyridine diazotized to 5-ASA.
• the sulfapyridien carries it down to the colon where the diazo bond is cleaved by azoreductase liberating sulfapyridine and 5-ASA, which are absorbed.
• then travel to the liver where they are metabolised and half lives of the drugs are around 5-20hrs.

Question 11

how does 5-ASA work in the colon?

Answer 11

-Inhibit production of cyclo-oxygenase, thromboxane
synthase, platelet-activating-factor synthetase &
interleukin 1 by macrophages
- Decrease production of immunoglobulin by plasma
cells
– Acts as a scavenger of superoxide radicals released
by neutrophils at inflammatory site

Question 12

what is aminosalicylates used for ? action

Answer 12

• Primarily used to induce & maintain remission
-can exert a topical action in the colon
- Effectiveness depends on site of inflammation in relation to
dissolution profile

Question 13

what is the second line therapy for IBD?

Answer 13

CORTICOSTERIODS-

Prednisolone is the preferred choice

Question 14

When is corticosteriods used to treat IBD and how are they taken?

Answer 14

• used in moderate to serve relapses
• brings symptoms under control promptly
• not suitable for maintenance
• can be taken orally, rectal, parenterally in emergency
• can be used in combination with aminosalicylates or alone

Question 15

what is the third line of treatment for IBD?

Answer 15

THIOPURINES

Question 16

What is azathioprine and how does it work?

Answer 16

it is a pro-drug of 6-mercaptopurine which is metabolised by the liver
-used if patient is unresponsive to steroids and aminosalcylates
- its an Immunosuppressant, inhibiting ribonucleotide synthesis
-Effective for both active disease and maintaining
remission in CD and UC
- Possesses steroid-sparing properties
- Can be used with corticosteroids or alone

Question 17

what is methrotrexate? when used? how it works? dose

Answer 17

• immunosuppresenat ony given in CD
• Inhibits dihydrofolate reductase (cytotoxic effect)
• Anti-inflammatory effect, inhibits cytokines and eicosanoid sythesis
• can induce and prevent relapse in CD
• normally at 25mg once a week

Question 18

what is ciclosporin?

Answer 18

• Inhibitor of calcineurin= Prevents clonal expansion of T-cell subsets
• rapid onset of action
• Effective in the management of severe acute UC

Question 19

what are monocolonical antibodies?

Answer 19

• anti-TNF antibodies that are given like infliximab, adulimumab and golimumab
• Anti- α4β7 integrin antibody which is Vedolizumab

Question 20

what is infliximab?

Answer 20

-its an anti-TNF monocolonal antibody
-has potent anti-inflammatory effects
-and given intravenously
some side effect ca be anaphylactic reaction so only given in environment where resuscitation equipment is present
-inhibits the inflammatory mediators downstream so can lead to immpunosurpressant lead to TB

Question 21

what is adalimumab?

Answer 21

-A human anti-TNFα monoclonal antibody
- Has potent anti-inflammatory effects
-80mg subcutaneous injection then 40 mg 2 weeks later
OR 40mg x4 over 1-2 days, then 80 mg 2 weeks later
inhibits the inflammatory mediators downstream so can lead to immunosuppersant lead to TB

Question 22

what is vedolizumab?

Answer 22

is an antibody to the α4β7 integrin expressed on gut homing T helper cells, leads to
reduction in inflammation
-given if patients are not responding to conventional therapy
-IV under specialist supervision

Question 23

what are other treatments used for IBD?

Answer 23

-metronidazole= for CD patients with perianal involvement
-antidiarrhoeals= codeine and loperamide used with caution as can mask inflammation, infection or obstruction
-cholestyramine =Decrease diarrhoea associated with bile-acid
malabsorption

Question 24

how does nutrition lay a role in IBD?

Answer 24

-Prone to malnutrition
- Prevalence of protein-energy malnutrition in IBD ranges
from 20-85%
-malnutrition due to, poor nutrient intake, increased metabolism, increased intestinal protein loss(leaky gut), malabsorption

Question 25

how can nutritional support can help IBD patients?

Answer 25

-mild to moderate attacks= normal diet but avoid coarse fibre may cause obstruction

Question 26

how does surgical management?

Answer 26

-80% of patients will require an operation
-only if failure of medical therapy, complications, failure to grow in children
-can be life saving curative & eliminates long-term risk of
cancer