IBD

Question 1

What do corticosteroids do for IBD

Answer 1

Inactivate proinflammatory transcription factors:
eg, NFkB and AP1
prevents activation of inflammatory mediators= IL-6 and leukotrienes
Also inhibit T cell activation

Question 2

How do glucocorticoids work?

Answer 2

Passively go into cells and bind to glucocorticoid receptor (GR). The GR is bound to the heat shock protein complex which contains chaperone molecules.
Glucocorticoids bind to GR and become activated inhibiting promotor regions = no transcription of proinflammatory cytokines

Question 3

How does azathioprine work?

Answer 3

Inhibits new purine synthesis and is antiproliferative
Azathioprone-> 6MP -> TIMP -> incorporation into DNA or inhibits purine synthesis

Question 4

How does azathioprine control Tcell Apoptosis?

Answer 4

Modulates Rac1
6-thio-GTP from azathioprine binds instead of GTP
Supresses Rac1 target genes = apoptosis

Question 5

How do Aminosalicylates work?

Answer 5

Mesalazine, sulphasalazine etc
Affects prostaglandin synthesis and the cyclooxygenase pathway and suppresses pro-inflammatory cytokines
Action via COX Inhibition
Suppresses cytokines via inhibiting PPARgamma NFkB etc
Can also scavange reactive oxygen metabolites during superoxide anion production in neutrophils, inhibiting ROM generation so inhibits oxidative DNA damage

Question 6

What is the arachidonic acid pathway?

Answer 6

Phospholipids-> arachidonic acid and cyclooxygenase = PGG2-> PGH2->other prostaglandins causes increased cell growth and survival
Or phospholipids -> arachidonic acid and lipoxygenase -> HPETE -> leukotrienes

Question 7

How does ciclosporin work

Answer 7

Binds to cyclophilin, CsA specific competitive inhibition of calcineurin Ca2+ and calmodulin dependant phosphates
Cytokine gene expression blocked

Question 8

How does methotrexate work

Answer 8

Dihydrofolate reductase inhibitor
Prevents new thymidylate and purine synthesis therefore less DNA production
Blocks survival of Tcells
Supresses proinflammatory cytokines IL-6, IL-13 , TNFa and IFN-y

Question 9

What does TNFa do in IBD

Answer 9

TNF elevated
Activates macrophages to produce proinflammatory cytokines incr. apoptosis of gut epithelial cells

Question 10

What is Tcell homing?

Answer 10

T cells migrate to gut tissues where secrete cytokines and cause chronic inflammation
Tcells express molecule for emigration-> defects occur in IBD

Question 11

What is Tcell retention?

Answer 11

Tcells retained in gut tissue as bind alpha4B7 integrin to E cadherin on epithelial cells

Question 12

What drugs block Tcell homing and retention for IBD?

Answer 12

Velolizumab- antia4b7 antibody blocking homing of Tcells

Sphingosine 1-phosphate- S1P receptor controls egression of immune cells from lymph nodes.
S1PR1 agonists causes a decrease in lymphocytes

Question 13

How does ustekinumab work

Answer 13

Targets 1l12 and il23
Supresses Th1 and Th17 -? decreases cytokines

Question 14

How does JAK inhibitors work

Answer 14

tofacitinib and filgotinib
INHIBITS—|Causes STAT to form a dimer and be phosphorylated causing a proinflammatory effect

Question 15

What is the treatment guide for proctitis UC

Answer 15

Topical aminosalicylate (supp)
Add oral if remission not in 4 weeks
Further treatment needed = topical/ oral corticosteroid

Question 16

What is the treatment guide for Proctosigmoiditis and left sided colitis UC

Answer 16

Topical aminosalicylate (enema)
if remission not in 4 weeks consider high dose oral aminosalicylate
or switch to high dose oral AS and topical corticosteroid

Question 17

What is the treatment guide for Extensive UC

Answer 17

Topical aminosalicylate and high dose ORAL aminosalicylate
No remission in 4 weeks-> stop topical and offer TL oral corticosteroids

Question 18

How do you induce remission for UC?

Answer 18

Oral corticosteroid or JAKs or biologics

Question 19

ow do you induce remission for UC in hospital?

Answer 19

IV corticosteroids (and IV ciclosporin if after 72hrs no response)

Question 20

What is the maintenance therapy for mild to moderate UC?

Answer 20

Proctitis and proctosigmoiditis
*Topical aminosalicylate
*oral aminoS and topical
*Oral aminoS
Left-sided and extensive
*Low dose of oral aminoS

Question 21

What would you give a patient who isn’t on aminosalicylates or has had 2 or more inflammatory exacerbations in 12 months?

Answer 21

Mecaptopurine or azathioprine

Question 22

How do you induce remission in crohns

Answer 22

Prednisolone, hydrocortisone (IV)
Budesonide of CI^ - not for severe
Add on therapy: azathioprine or mecaptopurine
Methotrexate if cant tolerate azath or mecap.

If no response- infliximab or adalimumab

Question 23

How do you maintain remission in crohns

Answer 23

Azathioprine or mecaptopurine
Consider methotrexate if previously used
Or no treatment but follow up
If surgery - consider these treatments

Question 24

What can prolonged use of corticosteroids do for IBD?

Answer 24

Increase infection risk, osteoporosis, adrenal suppression, weight gain, diabetes, CV disease

Question 25

What should you give a patient who has IBD and is on corticosteroids

Answer 25

800-1000mg calcium and 800 vit D

Question 26

What do pts with IBD have deficiencies of?

Answer 26

Potassium and magnesium

Question 27

What do you check for thiopurines? (mercaptopurine and azathioprine?)

Answer 27

TPMT thiopurine methyl transferase

Question 28

What interacts with azathioprine

Answer 28

Allopurinol. Decr. dose of azath to 1/4

Or switch to mercap.