Glucocorticoids & Immunosuppressants

Question 1

Glucocorticoids…what do they do?

Answer 1

Promote gluconeogenesis, protein catabolism, and lipolysis. (huh?)
– This allows for critters to respond to overwhelmingly stressful situations

Question 2

• THE “Stress Hormone”

Answer 2

cortisol – Vasoconstriction and glucose release
• Therefore a strong insulin antagonist! (<You gotta understand why this is so…) both too much cortisol and insulin cause insulin resisitance

Question 3

Glucocorticoids…what do they Decrease

Answer 3

WBC’s #’s and functionality (what’s this do?)

Question 4

*All glucocorticoids are

Answer 4

immunosuppressive even as a single dose!

Question 5

Glucocorticoids are POTENT

Answer 5

anti-inflammatory (NOT an analgesic!)

Question 6

Glucocorticoids Break down

Answer 6

muscle and fat (lipolysis)to produce more glucose and the need for more glycogenolysis
• So these are catabolic steroids as opposed to anabolic steroids (except for the liver which is busy making glycogen, right?)

Question 7

GLUGlucocorticoids…what do tHEY Cause “feedback inhibition” OF

Answer 7

further glucocorticoid and thyroid-stimulating hormone production.
– What’s this mean for discontinuing glucocorticoid therapy?

Question 8

Glucocorticoids…what do they do? (cont.)

• Myriad other things at high doses (hey, after all, they’re hormones!)

Answer 8

*Bone density loss *Myopathy *”Steroid rage” and personality changes *Gastric ulcers *Diabetogenic *”Moon Face & Humpback”

Question 9

What diseases are hyper- and hypoglucocorticism called?

Answer 9

addisons and cushings

Question 10

Cortisol is the “archetypical

Answer 10

glucocorticoid and given a value of “1” when comparing anti-inflammatory and salt-retaining properties

Question 11

Cortisol half-life is

Answer 11

1-2 hours.

Question 12

hydrocortisone =

Answer 12

Cortisol

Question 13

-Hydrocortisone

Answer 13

(Solu-Cortef)

Question 14

-Prednisolone

Answer 14

nothing

Question 15

-Prednisone

Answer 15

nothing

Question 16

-Methylprednisolone

Answer 16

(medrol)

Question 17

Dexamethasone

Answer 17

Decadron)

Question 18

• Two General Immunosuppressant Categories:

Answer 18

1) Induction Drugs: Used at the time of
transplantation
2) Maintenance Drugs: Required for long- term immunosuppression.

Question 19

Five Major Pharmacological Classes of Immunosuppressives
#1) Glucocorticoids

Answer 19

• A standard component of Induction & Maintenance (high doses initially tapering over time.)
• D.O.C.s for moderate rejection episodes
• Complex mechanism, but profoundly suppress T-lymphocytes (What are these? What do they do? What other kinds of lymphocytes are there?)

Question 20

1) Glucocorticoids

* Most side-effects of

Answer 20

any immunosuppressive

category when given at high doses over the long term!

Question 21

2) Calcineurin Inhibitors

Answer 21

-Calcineurin is the major T-cell activator (what’s this? humoral or cell-mediated?)

Question 22

cyclosporin

Answer 22

Calcineurin Inhibitors (Sandimmune)

Question 23

-Tacrolimus

Answer 23

Calcineurin Inhibitors (Prograf)

Question 24

Cyclosporin

• The“break-through”drug that

Answer 24

allowed transplants to successfully occur

Question 25

Cyclosporin dose dependent

Answer 25

nephrotoxicity,immune suppression (duh!), hepatotoxicity, cardiotoxicity, and many others (what’s that mean for us?) • Cyclosporin levels must be monitored closely. • Used in combination therapy to reduce dosage and side-effects.

Question 26

Tacrolimus | • Orders of magnitude more potent than

Answer 26

Cycylosporins. also more efficacious

Question 27

Tacrolimus nephrotoxicicity and cardiotoxicity compared to cyclosporins

Answer 27

More nephrotoxic/less cardiotoxic than Cyclosporins. | • More efficacious than Cyclosporin

Question 28

#3) mTOR Inhibitors

Answer 28

- Blocking mTOR prevents maturation and proliferation of T-cells. - Side effects: nephrotoxicity, delayed wound healing.

Question 29

-Sirolimus

Answer 29

m tor inhibitor (Rapamune) *Only available orally.

Question 30

#4) Antiproliferative Agents

Answer 30

-By preventing proliferation of cells, rapidly dividing cells (like B- and T- lymphocytes) don’t multiply.

Question 31

Azathioprine

Answer 31

Antiproliferative Agent. (Imuran)

Question 32

Mycophenolate mofetil

Answer 32

Antiproliferative Agent (Cellcept)

Question 33

-Mycophenolate sodium

Answer 33

Antiproliferative Agent (Myfortic)

Question 34

Azathioprine

Answer 34

Prototypical “early” immunosuppressant • Works best on acute rather than chronic immunogenic response (why?) • Numerous & severe side-effects (especially bone marrow suppression...what’s that mean to us?) have dramatically decreased its use. Mycophenolate mofetil • Much less severe side-effects than azathioprine. -Mainly GI and bone- marrow suppression.

Question 35

Mycophenolate mofetil

Answer 35

• Much less severe side-effects than azathioprine. | -Mainly GI and bone- marrow suppression.

Question 36

Mycophenolate Sodium

Answer 36

* Designed to be a “slower-releasing” and “enterically-pleasing” form of Mycophenolate Mofetil. * No real evidence that it is more effective or safer.

Question 37

``` #5) Monoclonal Antibodies -What the heck are these? ```

Answer 37

*Monoclonal antibodies contain ONLY one type of antibody that is derived from a single cloned B-lymphocyte

Question 38

Monoclonal Antibodies | • Directed against a

Answer 38

single cell-surface protein of target cells

Question 39

types of monoclonal antibodies

Answer 39

A) Antithymocyte Antibodies | B) Antilymphocyte antibodies

Question 40

-Muromonam-CD3A

Answer 40

(Othoclone OKT3) Antilymphocyte antibodies