Adrenal Agents Flashcards
Adrenal Gland Cortex synthesis
Mineralocorticoids
Glucocorticoids
Androgens
(all three considered corticosteroids)
Adrenal Gland Medulla Synthesis
Epinephrine
Norepinephrine
Mineralocorticoid?
function?
physiologic importance?
Aldosterone
increases Na reabsoprtion at renal collecting tubule
BP regulation
Glucocorticoid?
function?
Physiologic importance?
Cortisol
Restoring homeostasis after exposure to stresses
Important under normal conditions and is released under a circadian rhythm
Increases blood glucose levels and numerous other metabolic effects
Counter balance to immune system (antiinflammatory actions)
Facilitates epinephrine and norepinephrine responses
Drug Targets for Corticosteroid Biosynthesis
Common genetic disease?
17-alpha hydroxylase
11-beta hydroxylase
21-hydroxylase deficiency
Hypothalamus releases
corticotropin releasing hormone (CRH)
Anterior Pituitary release
activates GPCR’s on corticotropic cells
Rapid secretion of pre-formed ACTH
slower increase in ACTH pre-cursor synthesis
ACTH effect on Adrenal cortex
ACTH activates adrenal cortical cell receptors
Increases steroidogenic enzymes and secretion of cortical steroids
production of CORTISOL AND ADRENAL ANDROGENS
Glucocorticoid and Mineralocorticoid receptors
NUCLEAR HORMONE RECEPTORS
gluco and mineralocorticoids diffuse across cellular membranes to bind
receptors then TRANSLOCATE TO NUCLEUS
INCREASE OR DECREASE GENE EXPRESSION
Cortisol does what?
What enzyme inactivates cortisol? what’s the product?
What enzyme does the opposite?
binds both mineralocorticoid and glucocorticoid receptors and activates
11-beta hydroxysteroid dehydrogenase type II
cortisone
11-beta-hydroxysteroid dehydrogenase type I
11-beta hydroxylase type I important for?
action occurs mainly where?
activation of prodrugs of glucocorticoids
LIVER
Addisons Disease - deficiency of what?
tx?
deficiency in cortisol, aldosterone, and androgens
ACTH, CRH levels ELEVATED
ORAL CORTISOL
FLUDROCORTISONE
Secondary adrenal insufficiency - two types?
characteristics of each?
tx?
pituitary disease - DECREASE IN ACTH - increase in CRH
hypothalamic disease - DECREASE IN CRH - decrease in ACTH
CORTISOL - fludrocortisone not needed
Short acting corticosteroids
hydrocortisone
cortisone
Intermediate acting corticosteroids
prednisone
prednisolone
methylprednisolone
triamcinolone
Long acting corticosteroids
betamethasone
dexamethasone
Mineralocorticoid drug
fludrocortisone
Cushing syndrome
causes?
chronic glucocorticoid excess
Chronic glucocorticoid therapy
Pituitary tumor that causes hypersecretion of ACTH
Ectopic hypersecretion of ACTH by non-pituitary tumors
Adrenal tumor that hypersecretes cortisol
Dexamethasone test for cause of Cushing’s - 3 causes other than chronic glucocorticoid therapy - DIFFERENTIATE
Pituitary hypersecretion of ACTH - DECREASE CRH, INCREASE ACTH - 50% reduction in cortisol
Adrenal adenoma - DECREASES BOTH CRH, ACTH - no cortisol reduction
Ectopic ACTH Production - DECREASE CRH, INCREASE ACTH - no cortisol reduction
Ketoconazole MOA in cushings tx
INHIBITS 17-ALPHA HYDROXYLASE
decrease production of cortisol pre-cursors
liver toxicity
Metyrapone MOA
uses
inhibits 11-beta hydroxylase
diagnostic in ACTH PRODUCTION EVALUATION
off label tx for cushing’s
Mifepristone MOA
GLUCOCORTICOID RECEPTOR ANTAGONIST - higher doses
terminate pregnancy at lower doses
treat INOPERABLE PATIENTS with ectopic ACTH secretion or adrenal carcinoma
Glucocorticoid effects on immune cells (5)
apoptosis of eosinophils
decrease t cell proliferation
inhibit mast cell degranulation and contents release
stabilization of lysosomal membranes in neutrophils
decrease activation of macrophages and cytokine release
Glucocorticoid mechanisms of anti-inflammatory actions (5)
inhibit phospholipase A2
inhibit COX
inhibit NO synthase
inhibit cytokine production
vasoconstriction
Inhaled corticosteroids (4)
Budesonide
Fluticasone
Mometasone
Triamcinolone
MOA of inhaled corticosteroids (4)
decrease leakiness of vascular endothelial cells
reduce growth of airway smooth muscle
decrease adhesion of airway epithelial cell molecule
increase epithelial integrity
Beta-2 agonist and corticosteroid interaction
corticosteroids INCREASE BETA-2 RECEPTOR EXPRESSION - prevents desensitization
beta-2 agonists INCREASE NUCLEAR TRANSLOCATION OF GR’s - increase binding
Metabolism of glucocorticoids occurs mainly in?
LIVER
excreted in urine
Adverse effects of glucocorticoid therapy (name some)
decrease growth in children osteoporosis increased appetite glaucoma increased infection risk emotional disturbances centripetal fat increased diabetes risk hypokalemia HTN peripheral edema
Things that decrease effect of glucocorticoids
p450 inducers - barbiturates, carbamazepine, rifampin
Things that increase effect of glucocorticoids
estrogens, androgens compete for metabolism
concurrent use with cyclosporin - increase levels of each other
