Pharmacology: Steroids II Flashcards Preview

Module 6: Repro/Endocrine > Pharmacology: Steroids II > Flashcards

Flashcards in Pharmacology: Steroids II Deck (17):
1

What are the distinct domains of steroid receptors?


C-terminally located ligand binding domain

H Domain

Centrally positioned DNA binding domain

N-terminally located MOD/IMM Domain

2

What are characteristics of steroid hormones?


Small and Lipophilic

- can traverse plasma membrane without channels or carrier proteins

3

What is the difference between cortisol and cortisone?


Cortisol (active) = binds to Mineralicorticoid R and Glucocorticoid R

Cortisone (inactive) = binds to neither receptor

**Injections of cortisone allows for extended release of cortisol due to active enzymes

4

How do glucocorticoids act as anti-inflammatory agents?


- Increase transcription of anti-inflammatory genes

- Decrease transcription of inflammatory genes
Cytokines
Chemokines
Adhesion molecules
Inflammatory enzyme

- Decrease mRNA stability of other inflammatory genes
TNF-a
IL-6
GM-CSF
COX-2

5

What are the therapeutic uses of adrenal steroids?


Replacement Therapy:
Addison's
Congenital Adrenal Hyperplasia

Anti-inflammatory:
arthritis, rheumatic carditis,
inflammation of eye, skin, bowel, etc

Cancer Chemotherapy

Allergy

Asthma

Fetal lung syndrome

Immunosuppression:
Transplantation
Autoimmune disease

Cerebral edema

And then some...

6

What enzyme activates cortisone and prednisone?


11ß-dehydrogenase

Inactive = 11b-carbonyl

Active = 11b-hydroxyl

7

What are the toxicities associtaetd with adrenal steroids?


Pituitary -adrenal suppression

Hypokalemic, alkalosis, edema

Hyperglycemia (DM)

Increased susceptibility of infxn

Inhibited wound healing

Myopathy

Behavioral disturbances

Peptic ulceration

Cataracts

Growth arrest in children

Osteoporosis

Various other Cushingoid effeccts

8

What can happen if someone doesn't taper off of their prednisone/steroid?


They can get cardiovascular collapse

--> steroids suppres adrenal gland, so when they stop prednisone, the adrenals are still suppressed

--> when they are put under a stressor before the adrenals are working again, they go into cardiovascular collapse

9

How do glucocorticoids cause osteoporosis?


Inhibit osteoblastic activity

Activate osteoclastic activity

10

What are the 5 parameters that can be modulated in order to choose the correct glucocorticoid?


Affinity

Specificity

Bioavailability

Solubility

Metabolism

 

11

What affects the bioavilability of glucocorticoids?


Binding to CBG

--> more CBG binding = less bioavailability

12

Why would you want to change the metabolism of glucocorticoids?

Inhaled steroids should be rapidly metabolized so that they are not systemically available b/c they are taken daily

Budesonide and Beclomethasone have highest first past metabolism

13

What are different approaches to therapy? (there are 4)


1. Replacement (Addison's, adrenalectomy):
Low dose (in the morning)

2. Suppression (congenital adrenal hyperplasia):
Low dose twice (or more) a day to trick pituitary to believing cortisol is being made

3. Induction (giant cell arteritis; acute phase nephrotic syndrome):
High dose daily for immune suppression

4. Maintenance (rheumatoid arthritis):
Alternate day (if possible) to minimize immunosuppression and other side effects

14

What are the glucocorticoid antagonists available?


Mifepristone

Spironolactone

Eplerenone

15

What is Mifepristone?


Glucocorticoid antagonist used to treat hyperglycemia in Cushing's syndrome patients with diabetes whoa re not candidates for surgery

16

What is spironolactone?

Competitive inhibitor of aldosterone bindign to meralocorticoid receptor used to treat HTN and CHF after acute MI

17

What is Eplerenone?


Selective mineralocorticoid receptor antagonist (fewer side effects)