Lecture 18: Adrenal Pharmacology Flashcards
What are the causes of hyperaldosterone?
- Primary hyperaldosteronism
- Secondary hyperaldosteronism
- Liddle’s Syndrome
- mutation in epithelial sodium channel
- Deoxycoritcosterone mediated
- Licorice ingestion
What are the the treatments for hyperaldosteronism?
- Amiloride (Midamor)
- Spironolactone (Aldactone)
- Eplerenone (Inspra)
What is the MoA of spironolactone?
Mineralocorticoid antagonist
-blocks androgen and progesterone receptors so NOT specific
Treats ET, congestive heart failure, cirrhosis, nephrosis
PCOS/hirsuitism
Why can you use spironolactone in hirsutism and PCOS?
Because as a minieralocroticoid antagonist, it can also block androgen and progesterone receptor
What are the side effects of spironolactone (Aldactone)?
- hyperkalemia
- renal impairment
- volume depletion
- gynecomastia, impaired libido and impotence in men
- Teratogenic
- menstrual irregularities in women
What is the MoA of fludrocortisone?
Is a synthetic pure mineralocorticoid (so same MoA of aldosterone)
Indications for hypoaldosteronism
What are side effects of fludrocortisone?
- HYPOkalemia
2. volume overload (edema, HTN)
What is the significance of Metyrapone?
Inhibits 11Bhydroxylase
Prevents conversion of 11-deoxycortisol to Cortisol
Used to treat Cushings
Expensive
What is the significance of Ketoconazole?
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
What does mifepristone do?
Blocks glucocorticoid receptor
Blocks progesterone receptor so it allows for uterine contractioin
How do you treat glucocorticoid deficiency?
Cortisol replacement
- Hydrocortisone (Cortef)
- Dexamethasone (Decadrone)
- Prednisone
What is the MoA of hydrocortisone?
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
What do we give patients who is about to go into operation in terms of hydrocortisone?
50mg every 6-8 hours
What is the MoA of dexamethasone (decadrone)?
Cortisol, blocks ACTH
Half-life is 36-54 hours
4mg IV every 6-8 hours if you, taper to 2mg and 0.5 mg
Why does hydrocortisone have mineralocorticoid activity?
60-80mg
Because it shifts the cortisol to cortisone to the cortisol side
Cortisol then will bind to mineralocorticoid receptors
How do you test for primary adrenal insufficiency?
Cosyntropin stimulation test
What is cosyntropin?
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
Know the MoA, Indications and consequences of
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
What is the site of action of spironolactone?
Mineralocorticoid receptor inhibitor
