Corticosteroids & Antagonists Flashcards
MOA of fludrocortisone
Strong agonist of mineralocorticoid receptors and moderate activation of glucocorticoid receptors
What is fludrocortisone used for?
Adrenal insufficiency/Addison’s disease
MOA of mifepristone (RU-486)
Pharmacologic antagonist of glucocorticoid and progesterone receptors
What is mifepristone used for?
Medical abortion and very rarely Cushing’s syndrome or other conditions/neoplasms associated with excess glucocorticoids.
- Clinical trials suggest that mifepristone can reverse the hyperglycemia, hypertension and weight gain associated with Cushing’s Syndrome.
Side effects of mifepristone
Vaginal bleeding, abdominal pain, GI upset, diarrhea, headache
MOA of spironolactone/eplerenone
Pharmacologic antagonist of mineralocorticoid receptor, weak antagonism of androgen receptors;
inhibits 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) at high doses
What are the differences between spironolactone and eplerenone?
Eplerenone is more selective for MC receptor and is not associated with gynecomastia like spironolactone is.
What is spironolactone used for?
Aldosteronism from any cause, hypokalemia due to other diuretics, post-MI
Side effects of spironolactone
Hyperkalemia, gynecomastia, additive interaction with other K-retaining drugs
MOA of ketoconazole
Blocks fungal and mammalian CYP450 enzymes; inhibits mammalian steroid hormone synthesis and fungal ergosterol synthesis
MOA of metyrapone
Inhibits adrenal 11B-hydroxylase
What is metyrapone used for?
“Metyrapone challenge test” to assess HPA axis; has some use in diagnosis of primary and secondary adrenal dysfunction
Why is metyrapone not used long-term?
Would cause adrenal hyperplasia with excess androgen and mineralocorticoid secretion
MOA of aminoglutethimide
Blocks cholesterol side chain cleavage/conversion of cholesterol to pregnenolone (the RLS in the synthesis of all steroid hormones).
It also, through an unknown mechanism, increases the clearance of some other steroids (e.g., dexamethasone)
*NB NOT selective for the adrenal
What is aminoglutethimide used for?
Used as an adjunct in the treatment of breast cancer in women (inhibits synthesis of estrogen)
