Gi: Test 2: 19. Maloney : Agents For Ibd

Front 1

mechanism of IBD

Back 1

proinflammatory trigger-->

activates T cells

causes release of:
Cytokines (TNFalpha)
AA metabolites (GP, LT)
Growth Factors
O2 radicals

all leading to inflammation

Front 2

What type of T cells predominate in UC and CD respectively?

Back 2

UC: Type 2 T Cell

CD: Type I T Cell

Front 3

there are 2 goals of inflammatory bowel disease, what are they?

Back 3

Induce remission

Maintain remission

Front 4

in IBD what are the two types of cells that increase? What does increase of these products cause?

Back 4

Prostaglandins -->inflammation

Leukotrienes-->inflammation and Chemotaxis of neutrophils and macrophages

Front 5

Where do prostaglandins and leukotrienes come from?

Back 5

Arachidonic Acid

Front 6

what enzymes turn arachidonic acid into prostaglandins and leukotrienes respectively?

Back 6

Cyclooxygenase-->prostaglandins

5-Lipoxygenase-->Leukotrienes

Front 7

How can you prevent the damaged caused by excess prostaglandins and leukotrienes in patient with IBD?

Back 7

prevent
5-Lipoxygenase and Cyclooxygenase from making them

Front 8

What agent will block both cyclooxygenase and lipoxygenase

Back 8

5-aminosalycic acid

5-ASA aka Mesalamine

Front 9

Sulfasalazine (Azulfidine)
Olsalazine (Dipentum)
Balsalazide (Colazal)
Mesalamine (Asacol, Pentasa, Lialda, Apriso)

what kind of drugs? How are they administered?

Back 9

5-ASA

Oral

Front 10

MOA of 5-ASA

Back 10

Topical effect on the GI tract

Block the production of leukotrienes-->via 5 lipooxygenase (and cyclooxygenase aka prostaglandins)

Front 11

NSAIDs have not been shown
to be beneficial in IBD. What
does this imply?

Back 11

PGs may not play a role in IBD

so the major thing 5ASA does is block 5-lipoxygenase (and thus leukotrienes)

Front 12

90% of an oral dose of5-ASA will be absorbed inthe upper GI and metabolized

How do you preventsystemic absorption ofthese drugs? (such as use for Ulcerative colitis) 3

Back 12

Rectal delivery methods-Mesalamine rectal suppository or enema

OR
Delayed (pH) and/or sustained (Time) release delivery methods

OR

Conjugated to a carrier that is released in the colon
(Sulfasalazine – carrier is sulfapyridine
Olsalazine – carrier is another molecule of 5-ASA
Balsalazide – carrier is an inert molecule)

Front 13

when you give a 5ASA bound with a carrier, such as sulfapyridine, what is responsible for the cleavage to allow the 5ASA to have its therapeutic effect?

Back 13

bacterial azoreductase in the colon

Front 14

What is the rationale for
conjugating 5-ASA with
sulfapyridine?

Back 14

prevents absorbtion of 5ASA in upper GI tract

Front 15

where are the following 5-ASA formulations going to bind

Rectal enema-
Azo bond-
Asacol (pH) -
Pentasa-

Back 15

Rectal enema-end of colon
Azo bond- length of large intestine
Asacol (pH) -end of small intestine
Pentasa (timed release)- throughout most of intestine

Front 16

clinical use of 5ASAs?

Back 16

Mild to moderately active ulcerative colitis (induce and retain remission

inducing remission for Chron's disease (kind of)

Front 17

which 5ASA prep is best for inducing remission with CD?

Back 17

Sulfasalazine

Front 18

side effects of sulfasalazine

Back 18

Male infertility

Allergic rxns

Front 19

Olsalazine is what kind of drug? What is a major side effect?

Back 19

5ASA

Diarrhea

Front 20

Mesalamine/Olsalazine/Balsalazide have a small chance of what tox?

Back 20

nephrotox

Front 21

A 47-year-old male with a history of Crohn’s disease (on no medication currently) presents with an exacerbation of his disease with relatively moderate symptoms. A trial of sulfasalazine is ineffective. He is diagnosed with a perianal fistula. What can you do for him?

Back 21

get him an antibacterial

it is thought that anaerobic bacteria can exacerbate Chrons

Front 22

what 3 anibiotic drugs can be used for Chron's disease

Back 22

Metronidazole
Ciprofloxacin
Rifaximin

Induce remission
Maintenance of remission

Front 23

uses for Antibiotics in IBD?

Back 23

Mild to moderately active Crohn’s disease
Induce remission
Maintenance of remission
Fistulizing Crohn’s disease

Front 24

A 35-year-old female is diagnosed with ulcerative colitis. A trial of sulfasalazine is ineffective. She continues to have 3-5 bloody stools per day. What can you do for her?

Back 24

Corticosteroids

Front 25

Prednisone
Methyprednisolone
Hydrocortisone
Rectal enema or foam
Budesonide (Entocort EC

used for?

Back 25

anti-inflammatory agents in sulfa resistant UC

Front 26

Budesonide works where? how?

Back 26

Controlled ileal release formula

works topically

Front 27

What is the potential
advantage of budesonide
vs. prednisone?

Back 27

less side-effects

the budesonide targets the ileum and is removed 80% by first pass effect of liver

Front 28

clinical uses for Corticosteroids?

Back 28

Moderate to severely active ulcerative colitis or Crohn’s disease
Oral, rectal, or parenteral
Induce remission
Prolonged use in steroid dependent patients

**Not effective for maintaining remission

Front 29

are corticosteroids good at maintaining remission?

Back 29

NO

good for inducing remission

Front 30

3 types of steroid groups?

Back 30

Steroid responsive
Clinical improvement 1-2 weeks
Remain in remission when drug tapered slowly over weeks or months

Steroid dependent
Clinical improvement 1-2 weeks
Relapse when steroid dose is tapered

Steroid unresponsive

Front 31

If a person is unresponsive to steroids, or is steroid dependent, or has severe disease and goes into remission with steroids, what else can you do?

Back 31

immunosuppressive drugs that TNF alpha

Front 32

if you go into remission with a steroid with mild to moderate UC, what would you want to use to maintain remission

Back 32

5ASA

REMEMBER: Corticosteroids do not maintain remission!!

Front 33

Immunosuppressive agents used for serious disease that you want to induce remission that is unresponsive to steroids?

Back 33

Azathioprine (Imuran)
6-Mercaptopurine (Purinethol)
Methotrexate
Cyclosporine

Front 34

clinical uses of immunosuppresive agents

Back 34

For inducing remission in patients unresponsive to steroids
For reducing steroid use in patients that are steroid dependent
For maintenance therapy in severe IBD after inducing remission with steroids
Fistulizing Crohn’s disease

Front 35

Drug: AZA/6-MP

Onset of benefit:?

Use:?

Back 35

Drug: AZA/6-MP

Onset of benefit: 3-6 months

Use: UC or CD induce/maintain remission

Front 36

Drug: MTX

Onset of benefit:

Use:

Back 36

Drug: MTX

Onset of benefit: several weeks

Use: CD induce/maintain remission

Front 37

Drug: Cyclosporine

Onset of benefit:

Use:

Back 37

Drug: Cyclosporine

Onset of benefit: 1-2 weeks

Use: UC or CD to induce remission

Front 38

Infliximab (Remicade)
Adalimumab (Humira)
Certolizumab Pegol (Cimzia)

all do what?

Back 38

TNF alpha inhibitors

INFLIXimab INFLIX pain on TNF alpha

Front 39

Infliximab MOA

Back 39

Binds to membrane bound TNF-a on macrophages or activated T cells and induces cell death
Binds to soluble TNF-a and prevents it from binding to the TNF receptor on target cells
This prevents the inflammatory effects of TNF-a in IBD

Front 40

What is the difference between infliximab, adalimumab, and certolizumab pegol?

Back 40

infliximab is 25% mouse 75% human

Adalimumab is 100% human

Certolizumab 100% human +polyethyline glycol

the more human, the more responsive

Front 41

What other TNF antagonist is available? (besides the mabs)

Back 41

Etanercept

(normally used for RA)

only works on soluble TNF...not good for IBD

Front 42

what is Natalizumab?

Back 42

Monoclonal antibody to a4 integrin

Front 43

MOA of Natalizumab

Back 43

Binds specifically to a4-subunits of a4b1 and a4b7 integrins expressed on the surface of all leukocytes (except neutrophils) and inhibits the a4-mediated adhesion of leukocytes to their counterreceptors.

This prevents leukocyte migration from peripheral blood into the inflamed tissue

Front 44

TH1 makes what?

Back 44

TNF alpha

Front 45

uses for Infliximab?

Back 45

induce, maintain remission for UC

Fistulizing Chron's Disease

Front 46

Breakdown question:

If a pt has CD + fistulas, and a sulfa resistance what can you use?

Back 46

Antibiotics (first) (Metronidizole, Cipro, rifaximin)

Immunosuppresants (Azathiprine/M6P, methotrexate, cyclosporine)

TNF inhibitors (infliximab)

Front 47

Breakdown question:

if a pt has CD that is sulfasalazine resistant, what do you use?

Back 47

Corticosteriods

if those don't work, try immunosuppresants

Front 48

Breakdown question:

Pt has CD... what can you use

Back 48

5ASA

CS

Immunosuppresive

TNF alpha inhibitor

Front 49

Breakdown question:

Pt has UC... what can you use (go down the line)

Back 49

5ASA

Corticosteroid

Immunosupressive

TNF alpha

Front 50

Which immunosuppresive only treats CD?

Back 50

methotrexate

Front 51

Breakdown question:

Pt has UC that is sulfasalazine resistant, what can you use (go down the line)

Back 51

Corticosteroids (FIRST)

Immunosuppresants (minus metronidazole)

TNF alpha inhibitors

Front 52

mild/moderate CD + fistula you would use?

Back 52

Antibiotic

Front 53

severe CD + fistula you would use?

Back 53

immunosuppresant or TNF alpha

Front 54

Antibiotics are useful in CD or UC?

Back 54

CD! ONLY WITH FISTULA