Lecture 18: Adrenal Pharmacology

Question 1

What are the causes of hyperaldosterone?

Answer 1

1. Primary hyperaldosteronism
2. Secondary hyperaldosteronism
3. Liddle’s Syndrome
   
   • mutation in epithelial sodium channel
4. Deoxycoritcosterone mediated
5. Licorice ingestion

Question 2

What are the the treatments for hyperaldosteronism?

Answer 2

1. Amiloride (Midamor)
2. Spironolactone (Aldactone)
3. Eplerenone (Inspra)

Question 3

What is the MoA of spironolactone?

Answer 3

Mineralocorticoid antagonist
-blocks androgen and progesterone receptors so NOT specific
Treats ET, congestive heart failure, cirrhosis, nephrosis
PCOS/hirsuitism

Question 4

Why can you use spironolactone in hirsutism and PCOS?

Answer 4

Because as a minieralocroticoid antagonist, it can also block androgen and progesterone receptor

Question 5

What are the side effects of spironolactone (Aldactone)?

Answer 5

1. hyperkalemia
2. renal impairment
3. volume depletion
4. gynecomastia, impaired libido and impotence in men
5. Teratogenic
6. menstrual irregularities in women

Question 6

What is the MoA of fludrocortisone?

Answer 6

Is a synthetic pure mineralocorticoid (so same MoA of aldosterone)
Indications for hypoaldosteronism

Question 7

What are side effects of fludrocortisone?

Answer 7

1. HYPOkalemia

2. volume overload (edema, HTN)

Question 8

What is the significance of Metyrapone?

Answer 8

Inhibits 11Bhydroxylase
Prevents conversion of 11-deoxycortisol to Cortisol
Used to treat Cushings
Expensive

Question 9

What is the significance of Ketoconazole?

Answer 9

Antifungal used to inhibt enzymes in steroidogenesis pathway of glucocorticoids
Blocks 11B hydroxylase AND 17alpha hydroxylase
Former is the penultimate step to cortisol production
Latter prevents progesterone/pregnenolone from going to cortisol production pathway
Fucks with liver and is ineffective

Question 10

What does mifepristone do?

Answer 10

Blocks glucocorticoid receptor

Blocks progesterone receptor so it allows for uterine contractioin

Question 11

How do you treat glucocorticoid deficiency?

Answer 11

Cortisol replacement

1. Hydrocortisone (Cortef)
2. Dexamethasone (Decadrone)
3. Prednisone

Question 12

What is the MoA of hydrocortisone?

Answer 12

Cortisol
Half-life of 8-12 hours
14-30 mg PO every morning
Could do 2/3 in morning and 1/3 in afternoon
Double and triple hydrocortisone if you are sick because you need the cortisol to counteract sickness
Most like diurnal rhythm

Question 13

What do we give patients who is about to go into operation in terms of hydrocortisone?

Answer 13

50mg every 6-8 hours

Question 14

What is the MoA of dexamethasone (decadrone)?

Answer 14

Cortisol, blocks ACTH
Half-life is 36-54 hours
4mg IV every 6-8 hours if you, taper to 2mg and 0.5 mg

Question 15

Why does hydrocortisone have mineralocorticoid activity?

Answer 15

60-80mg
Because it shifts the cortisol to cortisone to the cortisol side
Cortisol then will bind to mineralocorticoid receptors

Question 16

How do you test for primary adrenal insufficiency?

Answer 16

Cosyntropin stimulation test

Question 17

What is cosyntropin?

Answer 17

A synthetic ACTH
If you add cosyntropin and there is over 20mg/dL of cortisol then you DONT have adrenal insufficiency
If it is less than 20mg/dl, then you DO have adrenal insufficiency

Question 18

Know the MoA, Indications and consequences of

Answer 18

A. Spironolactone (mineralocorticoid receptor antagonist, has androgen antagonist actions)
B. Fludrocortisone (synthetic mineralocorticoid agonist)
C. Metyrapone (blocks glucocorticoid genesis, inhibits 11B hydroxylase)
D. Ketoconazole (blocks glucocorticoid genesis, inhibits 11B and 17A)
E. Hydrocortisone (dosing imperative)
-take everyday PO (8-12 hours)
-cortisol agonist
-has mineralocorticoid actions as well
F. Dexamethasone (dosing imperative)
-cortisol agonist
-36-54 hours, 4mg for stresses
G. Cosyntropin
-ACTH agonist

Question 19

What is the site of action of spironolactone?

Answer 19

Mineralocorticoid receptor inhibitor