Glucocorticoids Flashcards
MOA of prednisolone
only one that cant be given orally. intermediate half-life.
MOA of cosynotropin
synthetic corticotropin (ACTH). Preferred because animal product can contain high levels of vasopressin.
What is the second messenger system of ACTH in the adrenal cortex?
binds a G-protein which activates adenylate cyclase to increase intracellular cAMP
What does 11B-hydroxysteroid dehydrogenase type 2 do to cortisol?
converts it to cortisone in kidney, colon and salivary glands.
What are the relative affinities of these to mineralocorticoid receptor? aldosterone, cortisol, corticosterone
aldosterone and cortisol have same affinities but there is much more cortisol in circulation than aldosterone.
Cortisone does not bind to mineralocorticoid receptor.
What are the metabolic effects of glucocorticoids?
keep glucose high by increasing gluconeogenesis and glycogenolysis.
Decreasing peripheral glucose utilization
Increasing proteolysis and lipolysis.
Permissive effects on GH and beta-adrenergic receptor agonists for increasing lipolysis
What effect do glucocorticoids have on eosinophils, monocytes, basophils, lymphocytes, hemoglobin, erythrocytes and PMNs?
Increase hemoglobin, erythrocytes and PMNs.
Decrease lymphocytes, monocytes, eosinophils and almost all other immune cells.
How do glucocorticoids inhibit inflammation?
inhibit release of arachidonic acid and its metabolites (PGE and leukotrienes) by decreasing phospholipase A2.
They also inhibit cytokine and histamine release.
What are the main ADEs of glucocorticoid therapy?
suppression of ACTH and TSH production from pituitary. DO NOT ABRUPTLY STOP THERAPY.
Osteoporosis,
diabetes risk
peptic ulcer risk
CNS effects like arousal and euphoria followed by depression and sleep disturbances.
In MEN: hypogonadism
Women: dysmenorrhea, uterine bleeding, lack of ovulation
Children: decrease linear growth.
What are two main controls of aldosterone release?
RAAS system and plasma potassium levels. High K increases secretion.
ACTH mediated release is only minor to these two
MOA of ketoconazole
antifungal that inhibits P450 to block cortisol in cushings. (Desmolase)
ADE of ketoconazole?
causes adrenal insufficiency for aldosterone, cortisol and testosterone (adrenal) production because it blocks all three.
what are the longest acting glucocorticoids?
dexamethasone, betamethasone, and triamcinolon
What are the shortest acting glucocorticoids?
cortisol/cortisones (hydrocortisone or cortisone acetate)
What is the precursor molecule for ACTH?
proopiomelanocortin (POMC)
