Pharm- Adrenal Steroids

Question 1

What are the 3 general steroid classes (and example)

Answer 1

Mineralocorticoids- aldosterone- stim by ATII and K
Glucocorticoids- cortisol- stim by ACTH
Weak androgens- potent androgens (men) and estrogens (women)

Question 2

Fludrocortisone- action and AE

Answer 2

Fludrocortisone
Analog to aldosterone
Very potent Na retention and some anti-inflammatory effects
AE- edema, HTN, HF, alkalosis, and hypokalemia (paresthesias and tetany)

Question 3

Glucocorticoid drugs/classes/actions/AE/CI

Answer 3

Short acting- cortisones and prednisones- moderate Na retention and anti-inflammatory effects
Intermediate acting- triamcinolone- some anti-inflammatory effects; no Na retention
Long acting- beta/dexamethasone- very potent anti-inflammatory; no Na retention
AE- opportunistic infection, hyperglycemia, HTN, cataracts, and uclers
CI- AIDS, DM, active infection or ulcer, HTN, HF, angina

Question 4

Explain steroid kinetics

Answer 4

Steroids are hydrophobic and transported via carriers
Transcortin (synthesized in liver) transports most cortisol and aldosterone; cortisol over 30 saturates transcortin leading to an inc in free cortisol [ ]
Transcortin synthesis inc in pregnancy, w/ estrogen admin, or hyperthyroidism
Transcortin synthesis dec w/ cirrhosis (inc t1/2 of cortisol)
Albumin carriers remainder of cortisol and aldosterone and is the major carrier for synthetic steroids

Question 5

Steroid (R) MOA and 11b-HSD2

Answer 5

Steroids bind R leading to effects after a lag phase where effects continue even once steroid [ ] has dropped to zero
Steroid R- AR, ER, PR, GR, MR (MR binds aldosterone and cortisol)
11b-HSD2 converts cortisol into MR-inactive cortisone to inc MR sensitivty to aldosterone
11b-HSD2 is dec by licorice (glycyrihizin) and anti-ulcer carbenoxalone as well by autorecessive AME (juvenile HTN) leading to cortisol induced activation of MR and HTN

Question 6

Glucocortoid actions w/ regards to metabolism and immune system

Answer 6

Carb metabolism- hyperglycemia
Lipid metabolism- fat deposition
Protein metabolism- muscle wasting
Immune- anti-inflammatory effects
Glucocorticoids oppose actions of insulin

Question 7

What are the uses of steroids and which steroids do you use?

Answer 7

Hormone Replacement:
Addisons and CAH- fludrocoritisone and hydrocortisone

Immunosuppression- use glucocorticoids

Question 8

Aminoglutethimid

Answer 8

MOA- dec all steroid synthesis by preventing conversion of cholesterol into pregnenolone
Use- adrenocortical carcinoma
AE- drowsy and GI problems

Question 9

Ketoconazole

Answer 9

MOA- inhibits p450 to dec hormone synthesis
Uses- cushings, hair loss, and prostate cancer
AE- hepatotoxicity and gynectomastia

Question 10

Metyrapone

Answer 10

MOA- inhibits 11-hydroxylase to dec cortisol
Uses- pregnant women w/ cushings
AE- inc aldosterone (HTN) and androgens (hirsuitism)

Question 11

Mitotane

Answer 11

MOA- inhibit PKC and AC
Uses- adrenal carcinoma
AE- rash, depression, GI problems

Question 12

Mifepristone

Answer 12

MOA- GR and PR antagonist
Uses- endogenous cushings and abortion
AE- dizzy, fatigue, and GI problems

Question 13

Spironolactone

Answer 13

MOA- AR and MR antagonist
Uses- 1º hyperaldosteronism and hirsuitism
AE- hyperkalemia, menstrual irregularities, and gynecomastia

Question 14

Eplerenone

Answer 14

MOA- competitive aldosterone antagonist
Uses- HTN and HF
AE- Hyperkalemia