Adrenal Agents

Question 1

Adrenal Gland Cortex synthesis

Answer 1

Mineralocorticoids
Glucocorticoids
Androgens

(all three considered corticosteroids)

Question 2

Adrenal Gland Medulla Synthesis

Answer 2

Epinephrine

Norepinephrine

Question 3

Mineralocorticoid?

function?

physiologic importance?

Answer 3

Aldosterone

increases Na reabsoprtion at renal collecting tubule

BP regulation

Question 4

Glucocorticoid?

function?

Physiologic importance?

Answer 4

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

Question 5

Drug Targets for Corticosteroid Biosynthesis

Common genetic disease?

Answer 5

17-alpha hydroxylase

11-beta hydroxylase

21-hydroxylase deficiency

Question 6

Hypothalamus releases

Answer 6

corticotropin releasing hormone (CRH)

Question 7

Anterior Pituitary release

Answer 7

activates GPCR’s on corticotropic cells

Rapid secretion of pre-formed ACTH

slower increase in ACTH pre-cursor synthesis

Question 8

ACTH effect on Adrenal cortex

Answer 8

ACTH activates adrenal cortical cell receptors

Increases steroidogenic enzymes and secretion of cortical steroids

production of CORTISOL AND ADRENAL ANDROGENS

Question 9

Glucocorticoid and Mineralocorticoid receptors

Answer 9

NUCLEAR HORMONE RECEPTORS

gluco and mineralocorticoids diffuse across cellular membranes to bind

receptors then TRANSLOCATE TO NUCLEUS

INCREASE OR DECREASE GENE EXPRESSION

Question 10

Cortisol does what?

What enzyme inactivates cortisol? what’s the product?

What enzyme does the opposite?

Answer 10

binds both mineralocorticoid and glucocorticoid receptors and activates

11-beta hydroxysteroid dehydrogenase type II

cortisone

11-beta-hydroxysteroid dehydrogenase type I

Question 11

11-beta hydroxylase type I important for?

action occurs mainly where?

Answer 11

activation of prodrugs of glucocorticoids

LIVER

Question 12

Addisons Disease - deficiency of what?

tx?

Answer 12

deficiency in cortisol, aldosterone, and androgens

ACTH, CRH levels ELEVATED

ORAL CORTISOL

FLUDROCORTISONE

Question 13

Secondary adrenal insufficiency - two types?

characteristics of each?

tx?

Answer 13

pituitary disease - DECREASE IN ACTH - increase in CRH

hypothalamic disease - DECREASE IN CRH - decrease in ACTH

CORTISOL - fludrocortisone not needed

Question 14

Short acting corticosteroids

Answer 14

hydrocortisone

cortisone

Question 15

Intermediate acting corticosteroids

Answer 15

prednisone

prednisolone

methylprednisolone

triamcinolone

Question 16

Long acting corticosteroids

Answer 16

betamethasone

dexamethasone

Question 17

Mineralocorticoid drug

Answer 17

fludrocortisone

Question 18

Cushing syndrome

causes?

Answer 18

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

Question 19

Dexamethasone test for cause of Cushing’s - 3 causes other than chronic glucocorticoid therapy - DIFFERENTIATE

Answer 19

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

Question 20

Ketoconazole MOA in cushings tx

Answer 20

INHIBITS 17-ALPHA HYDROXYLASE

decrease production of cortisol pre-cursors

liver toxicity

Question 21

Metyrapone MOA

uses

Answer 21

inhibits 11-beta hydroxylase

diagnostic in ACTH PRODUCTION EVALUATION

off label tx for cushing’s

Question 22

Mifepristone MOA

Answer 22

GLUCOCORTICOID RECEPTOR ANTAGONIST - higher doses

terminate pregnancy at lower doses

treat INOPERABLE PATIENTS with ectopic ACTH secretion or adrenal carcinoma

Question 23

Glucocorticoid effects on immune cells (5)

Answer 23

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

Question 24

Glucocorticoid mechanisms of anti-inflammatory actions (5)

Answer 24

inhibit phospholipase A2

inhibit COX

inhibit NO synthase

inhibit cytokine production

vasoconstriction

Question 25

Inhaled corticosteroids (4)

Answer 25

Budesonide Fluticasone Mometasone Triamcinolone

Question 26

MOA of inhaled corticosteroids (4)

Answer 26

decrease leakiness of vascular endothelial cells reduce growth of airway smooth muscle decrease adhesion of airway epithelial cell molecule increase epithelial integrity

Question 27

Beta-2 agonist and corticosteroid interaction

Answer 27

corticosteroids INCREASE BETA-2 RECEPTOR EXPRESSION - prevents desensitization beta-2 agonists INCREASE NUCLEAR TRANSLOCATION OF GR's - increase binding

Question 28

Metabolism of glucocorticoids occurs mainly in?

Answer 28

LIVER excreted in urine

Question 29

Adverse effects of glucocorticoid therapy (name some)

Answer 29

``` decrease growth in children osteoporosis increased appetite glaucoma increased infection risk emotional disturbances centripetal fat increased diabetes risk hypokalemia HTN peripheral edema ```

Question 30

Things that decrease effect of glucocorticoids

Answer 30

p450 inducers - barbiturates, carbamazepine, rifampin

Question 31

Things that increase effect of glucocorticoids

Answer 31

estrogens, androgens compete for metabolism concurrent use with cyclosporin - increase levels of each other