Immunomodulatory Medications

Question 1

For immunomodulatory medications what is the main MOA

Answer 1

block T cell activation

Question 2

What drugs are the calcineurin inhibitors

Answer 2

cyclosporine and tacrolimus

Question 3

What protein does cyclosporine bind to, tacrolimus

Answer 3

Cyclophylin, FKBP-12

Question 4

What happens when tacrolimus or cyclosporine bind their respective proteins

Answer 4

The inhibitors and the cytoplasmic receptors bound with complex with calcineurin causing inactivity

Question 5

In cyclosporine what change of an amino acid would hinder the immunosuppressant activity of the drug, how

Answer 5

If MeLeu is changed to MeAla, the affinity for binding to cyclophylin remains unchanged but it can no longer bind calcineurin causing immunosuppresent activity to be loss

Question 6

What is a structural analogue of cyclosporine, what are some advantages

Answer 6

voclosporin, less nephrotoxic and used in treatment for psoraisis

Question 7

What change would cause no binding to calcineurin in tacrolimus

Answer 7

changes to C15 to C22

Question 8

What drugs are mTOR inhibitors

Answer 8

Sirolimus/rapamycin

Question 9

What is the MOA of sirlolimus/rapamycin

Answer 9

binds to FKBP12 and complexes with mTOR to cause inactivity

Question 10

What is an analogue of rapamycin/sirolimus, what is its differeneces

Answer 10

everolimus, more polar and improve the pharmacokinetic characteristics by changing the half life to 20-30 hours

Question 11

What enzyme metabolizes, tacrolimus, sirolimus, and cyclosporine

Answer 11

CYP3A4 isozymes

Question 12

What are some drug interactions that come with using the CYP3A4 metabolized drugs

Answer 12

antibiotics (erythromycin and ketokonazol) and hypertensives (nifedipine and verapamil)

Question 13

Which immunomodulatory drugs are substrates for P-gp

Answer 13

cyclosporine, tacrolimus, sirolimus

Question 14

What drugs are antiproliferative agents

Answer 14

Azathioprone, mycophenolate mofetil

Question 15

What is azathioprine a prodrug of , how is it converted

Answer 15

6-mercaptopurine (6-MP), converts to 6-MP under alkaline conditions

Question 16

What inactive metabolite can 6-MP be converted to, what drug can inhibit this causing a severe drug-drug interactions

Answer 16

6-thiouric acid, allopurinol (xanthine oxidase inhibitor)

Question 17

What is mycophenolate mofetil a prodrug of

Answer 17

mycophenolic acid (MPA)

Question 18

What is the MOA of MPA

Answer 18

potent inhibitor of inosine monophosphate dehydrogenase, the rate limiting step for de novo synthesis of guanosine nucleotides

Question 19

Why is MPA only functionally selective of the immune system

Answer 19

T-cells and B-cells lack the salvage pathway of purine biosynthesis

Question 20

What drug is a structural analog of sphingosine, what is its MPA

Answer 20

FTY 720, inhibits lymphocyte emigration from lymphoid organs

Question 21

What disease is FTY 720 used for

Answer 21

treatment of MS