Pharm 20- Glucocorticoids & Immunosuppressants

Question 1

In stress, hypothalamus releases what?

Answer 1

Corticotropin-releasing factor

Question 2

Corticotropin-releasing factor acts on what part of the body?

Answer 2

Anterior pituitary

Question 3

Anterior pituitary releases what?

Answer 3

Cortiocotropin (ACTH)

Question 4

Corticotropin (ACTH) acts on what? Which then releases what?

Answer 4

Adrenal Medulla; aldosterone/cortisol/androgens

Question 5

Whats the classic stress hormone?

Answer 5

Glucocorticoids

Question 6

What do glucocorticoids do?

Answer 6

Promote gluconeogenesis, protein catabolism, and lipolysis; which allows critters to respond to overwhelmingly stressful situations

POTENT anti-inflammatory (NOT analgesic)

Question 7

Glucorticoids result in what physiologically?

Answer 7

Vasoconstriction, glucose release

Break down fat and muscle (lipolysis) to produce more glucose and the need for more glyconeogenesis

Question 8

Why are glucocorticoids insulin antagonists?

Answer 8

They inhibit the uptake of glucose by fat and muscle and increase hepatic glucose output

Question 9

What is an adverse affect of glucocorticoids?

Answer 9

Decrease WBC #’s

All are immunosuppressive even as a single dose

Question 10

Are glucocorticoids catabolic steroids or anabolic steroids? Why?

Answer 10

Catabolic steroids; because they involve the breakdown of complex molecules in living organisms to form simpler ones

Question 11

Anabolic

Answer 11

construct molecules from smaller units

Question 12

Describe the “feedback inhibition” of glucocorticoids.

Answer 12

Causes feedback inhibition of further glucocorticoid and thyroid-stimulating hormone production

Question 13

What’s important to note about discontinuing glucocorticoids, based on the feedback inhibition?

Answer 13

Wean off little by little bc instead of having too much you’ll have none

Question 14

Effects of Glucocorticoids at high doses

Answer 14

Bone density loss
Myopathy
Steroid rage and personality changes
Gastric Ulcers
Diabetogenic
Moon Face & Humpback

Question 15

What is hyperglucocorticism?

Answer 15

Cushing Syndrome

Question 16

What is hypoglucocorticism?

Answer 16

Addison’s Disease

Question 17

What is the archetypical glucocorticoid?

Answer 17

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

Question 18

What is the half-life of cortisol?

Answer 18

1-2 hours

Question 19

Another name for cortisol?

Answer 19

Hydrocortisone

Question 20

List the Glucocorticoids.

Answer 20

Hydrocortisone (Solu-Cortef)
Dexamethasone (Decadron)
Prednisone
Prednisolone
Methylprednisolone (Medrol)

Question 21

Which (Short-acting) glucocorticoids do we care about for bypass?

Answer 21

Hydrocortisone
Cortisone
(1-12 hours)

Question 22

When would we use long acting glucocorticoids? Name them.

Answer 22

Transplant patient; immunosuppressed for a long time. Bethamethasone, Dexamethasone
(36-55 hours)

Question 23

What are the two general immunosuppressant categories?

Answer 23

1. Induction Drugs: Used at the time of transplanation

2. Maintenance Drugs: Required for long term immunosuppresion

Question 24

What are the 5 Major pharmacological classes of Immunosuppressives

Answer 24

1. Glucocorticoids
2. Calcineurin Inhibitors
3. mTOR Inhibitors
4. Antiproliferative Agents
5. Monoclonal Antibodies

Question 25

What is a standard component of induction and maintenance? (high doses initially tapering over time)

Answer 25

Glucocorticoids

Question 26

What is the drug of choice for moderate rejection episodes?

Answer 26

Glucocorticoids

Question 27

What do glucocorticoids suppress?

Answer 27

T-lymphocytes

Question 28

Calcineurin Inhibitors

Answer 28

Cyclosporin (Sandimmune) | Tacrolimus (Prograf)

Question 29

Calcineurin

Answer 29

Major T-cell activator

Question 30

What is the break through drug that allowed transplants to successfully occur?

Answer 30

Cyclosporin

Question 31

Describe the side effects of cyclosporin.

Answer 31

``` Dose-dependent Nephrotoxicity Immune suppression Hepatotoxicity Cardiotoxicity (patients on these if not balanced well will be coming back for second or third kidney transplants) ```

Question 32

What's important to note about monitoring patients on cyclosporin?

Answer 32

Cyclosporin levels must be monitored closely

Question 33

How to reduce dosage and side-effects of cyclosporins?

Answer 33

Use in combination therapy

Question 34

Tacrolimus

Answer 34

Better, safer form of cyclosporin; orders of magnitude more potent than cyclosporins More efficacious than cyclosporin

Question 35

Describe the toxicity of Tacrolimus.

Answer 35

More nephrotoxic/less cardiotoxic than cyclosporins

Question 36

How do mTOR Inhibitors work?

Answer 36

Blocking mTOR prevents maturation and proliferation of T-cells

Question 37

mTOR side effects

Answer 37

Nephrotoxicity | Delayed wound healing

Question 38

mTOR Inhibitor example

Answer 38

Sirolimus (Rapamune); only available orally

Question 39

How to antiproliferative agents work?

Answer 39

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

Question 40

Antiproliferative Agent Examples

Answer 40

``` Azathioprine (Imuran) Mycophenolate mofetil (Cellcept) Mycophenolate sodium (Myfortic) ```

Question 41

Azathioprine (Imuran)

Answer 41

Prototypical "early" immunosuppressant Works best on acute rather than chronic immunogenic response (Why?) Numerous and Severe side effects (bone marrow suppression)

Question 42

Mycophenolate Mofetil (Cellcept)

Answer 42

Much less severe side-effects than azathioprine; mainly GI and bone-marrow suppression

Question 43

Mycophenolate Sodium (Myfortic)

Answer 43

Designed to be a "slower-releasing" and "enterically-pleasing" form of Mycophenolate Mofetil No real evidence that it is more effective or safer (marketed better)

Question 44

Monoclonal Antibodies

Answer 44

Train B lymphocytes to turn into plasma cell and make one antibody against one specific clone antibody. Contain only one type of antibody that is derived from a single cloned B-lymphocyte

Question 45

Monoclonal Antibodies are directed against what?

Answer 45

Single cell-surface protein of target cells

Question 46

Two types of Monoclonal Antibodies

Answer 46

``` Antithymocyte Antibodies- attacks thymocytes; immune cells Antilymphocyte antibodies (Othoclone OKT3) ```