pharmacology of IBD

Question 1

5-ASA derivatives

Location of Action: Large Intestine

Answer 1

Azo bond. The derivative is bound to a carrier molecule with an Azo bond. The azo bond is broken by azoreductase in the colon. It is the carrier molecule that causes the adverse effects

Question 2

what are they bound to?
Sulfasalazine
olsalazine
balsalazide

Answer 2

sulfasalazine is bound to sulfapyridine
olsalazine is bound to another molecule of 5-ASA
balsalazide is bound to an inert molecule

don’t give sulfa drugs to people with sulfa allergies

Question 3

5-ASA derivatives

Location of Action: Small and large Intestine

Answer 3

Time release drugs: mesalamine

Question 4

1st line therapy to induce remission for mild to moderate Crohn’s and UC

Answer 4

5-ASA derivative

Question 5

1st line therapy to maintain remission in mild to moderate crohn’s and UC.
If this doesn’t work?

Answer 5

5- ASA derivative

Steroids (prednisone- oral) only used for induction of remission because of the side effect profile and because the effects diminish after a year

Question 6

If a pt with Crohn disease does not respond to a 5-ASA what is the next choice?

Answer 6

Antimicrobial: especially if there is a fistula
Not effective for UC and not considered a maintenance therapy

Ciprofloxacin- floraquinolone

Question 7

what is the MOA for floraquinolone?

Answer 7

inhibition of DNA gyrase/topoisomerase IV

Question 8

mild to moderate UC/CD: A patient no longer responds to 5-ASA’s to maintain remission. What do you give him to maintain remission?

Answer 8

2nd line are

Question 9

what is the first line therapy to induce remission for severe CD and UC?

Answer 9

Steroids

Question 10

if a pt is given steroids and . . .
remains in remission after they are tapered?
relapses when they are tapered?
does not respond?

Answer 10

if a pt is given steroids and . . .
remains in remission after they are tapered: steroid responsive
relapses when they are tapered: steroid dependent- switch to Immune Modulators
does not respond? try immune modulators

Question 11

Immune Modulators:

4 common drugs:

Answer 11

thiopurine analogues: 6-mercaptopurine, azathioprine
methotrexate
cyclosporine

Question 12

MOA: 6-mercaptopurine and azathioprine
Onset of benefit:
use:

Answer 12

inhibition of purine synthesis. inhibits T-lymphocyte proliferation
Onset of benefit: 3-6 months
Use: UC or CD maintenance

Question 13

MOA: methotrexate
Onset of benefit:
Use:

Answer 13

inhibits dihydrofolate reductase (inhibits T-lymphocyte proliferation)
Onset of benefit: several weeks
Use: induce remission, maintenance

Question 14

MOA: cyclosporin
Onset of benefit:
Use:

Answer 14

calcineurin inhibitor (inhibits T-lymphocyte proliferation)
Onset of benefit: 1-2 weeks
Use: UC or CD induce remission

Question 15

A patient keeps having flare ups despite being on azathioprine. What can we do?

Answer 15

If a pt has flare ups while on an immune modulator, we can switch to Biologic response Modifiers (infliximab)

Question 16

MOA: infliximab

Answer 16

monoclonal antibody to TNF-alpha

Question 17

First line treatment for inducing remission in severe CD/UC?

next:

Answer 17

steroids. then try methotrexate, or cyclosporine

Question 18

First line treatment for maintaining remission in severe CD/UC?
or?

Answer 18

methotrexate, AZA/6-MP

infliximab

Question 19

Adverse Reactions to Biologic Response Modifiers:

Answer 19

reactions at the injection site, rash, neutropenia, demyelinating disease, hepatotoxicity (basically the bad stuff)