Adrenal agents

Question 1

what are the drug targets of corticosteroids?

Answer 1

17a-hydroxylase

11B-hydroxylase

Question 2

17a-hydroxylase is responsible for catalyzing what reactions?

Answer 2

pregnenolone to 17-hydroxypregnenolone

progesterone to 17-hydroxyprogesterone

Question 3

11B-hydroxylase is responsible for catalyzing what reaction?

Answer 3

deoxycortisone to cortisone

Question 4

what enzyme is responsible for catalyzing the reactions

pregnenolone to 17-hydroxypregnenolone
progesterone to 17-hydroxyprogesterone?

Answer 4

17a-hydroxylase

Question 5

what enzyme is responsible for catalyzing the reaction

deoxycortisone to cortisone?

Answer 5

11B-hydroxylase

Question 6

what types of receptors are glucocorticoid and mineralocorticoid?

Answer 6

nuclear hormone receptors

Question 7

cortisol binds to what receptors?

Answer 7

glucocorticoid

mineralocorticoid

Question 8

does cortisone bind to mineralocorticoid receptors?

Answer 8

no

Question 9

where is cortisone converted to cortisol? what is the enzyme?

Answer 9

liver

11B-HSD1

Question 10

which enzyme is responsible for converting cortisol back to cortisone?

Answer 10

11B-HSD2

Question 11

what type of drug is fludrocortisone? what effects does it have?

Answer 11

mineralocorticoid

heavy salt retaining
anti-inflammatory

Question 12

what enzyme is important in converting prodrugs into their active forms?

Answer 12

11B-HSD1

Question 13

what are the causes of primary adrenal insufficiency (addison’s disease)?

Answer 13

autoimmune

TB

Question 14

what are the results of primary adrenal insufficiency (addison’s disease)?

Answer 14

deficiency in cortisol, aldosterone, androgens

hypotension from unresponsiveness of vascular smooth muscle to catecholamines

Question 15

primary adrenal insufficiency (addison’s disease) is treated with what agents?

Answer 15

cortisol

fludrocortisone

Question 16

secondary adrenal insufficiency are due to what causes?

Answer 16

pituitary - 1) decrease in ACTH causing increase in CRH, 2) decrease in cortisol

hypothalamic - 1) decrease in CRH causes increase in ACTH, 2) decrease in cortisol

Question 17

secondary adrenal insufficiency (addison’s disease) is treated with what agent?

Answer 17

cortisol (fludrocortisone NOT needed)

Question 18

chronic glucocorticoid (cortisol) excess leads to what condition?

Answer 18

Cushing’s syndrome

Question 19

Cushing’s syndrome is a result of elevation of what compound?

Answer 19

chronic glucocorticoid (corticoid) excess

Question 20

why does increased levels of cortisol cause HTN?

Answer 20

activation of mineralocorticoid receptors

Question 21

determination of the cause of cushing’s syndrome is made by what compound?

Answer 21

dexamethasone

Question 22

what will be the levels of CRH and ACTH in pituitary hypersecretion of ACTH? upon dexamethasone administration?

Answer 22

low CRH
high ACTH

usually 50% reduction in cortisol upon dexamethasone

Question 23

what will be the levels of CRH and ACTH in adrenal adenoma? upon dexamethasone administration?

Answer 23

low CRH
low ACTH

no reduction in cortisol upon dexamethasone (has nothing to do with cortisol)

Question 24

what will be the levels of CRH and ACTH in ectopic ACTH production? upon dexamethasone administration?

Answer 24

low CRH
high ACTH

no reduction in cortisol upon dexamethasone

Question 25

what class of drug is ketoconazole? what is the MOA? what is it used to treat?

Answer 25

antifungal inhibits 17a-hydroxylase cushing's syndrome

Question 26

what is the adverse effect of ketoconazole?

Answer 26

significant liver toxicity

Question 27

what is the clinical application of metyrapone? for what condition is it used to treat?

Answer 27

diagnostic agent used to evaluate ACTH production cushing's syndrome

Question 28

what drugs are used to treat cushing's syndrome?

Answer 28

ketoconazole | metyrapone

Question 29

what is the MOA of mifepristone? for what condition is it used to treat?

Answer 29

glucocorticoid receptor antagonist inoperable patients with ectopic ACTH secretion or adrenal carcinoma

Question 30

what drug is used to treat inoperable patients with ectopic ACTH secretion or adrenal carcinoma?

Answer 30

mifepristone

Question 31

what are the effects of glucocorticoids on the immune cells?

Answer 31

macrophage - decrease activation neutrophils - stabilize lysosomal membrane mast cells - decrease release of histamine eosinophils - decrease release of granules T cells - decrease number and activation

Question 32

what are the anti-inflammatory mechanisms of corticosteroids?

Answer 32

inhibition of phospholipase A2 | COX inhibition

Question 33

inhaled corticosteroids are the first line treatment for what condition? when should they be used?

Answer 33

asthma patients who take inhaled B2 agonists more than twice a week

Question 34

what is the MOA of inhaled corticosteroids on asthma?

Answer 34

reduce vascular permeability reduce growth of airway SMCs reduce adhesion molecules in airway epithelial cells increase epithelial integrity

Question 35

what is the importance of using inhaled glucocorticoids in conjuction with B2 agonists?

Answer 35

corticosteroids - 1) increase B2 receptor expression, 2) prevent desensitization of B2 receptors B2 agonists - 1) increase nuclear translocation of GRs, 2) increase binding of GRs to GREs on genes

Question 36

what is the importance of dexamethasone administration for glucocorticoid effect?

Answer 36

dexamethasone has low affinity for blood proteins - higher free levels in serum

Question 37

what is the effect of glucocorticoids on stomach acid and pepsin production?

Answer 37

gastic acid - stimulation | pepsin - stimulation

Question 38

what is the adverse effect of glucocorticoids on the endocrine system?

Answer 38

HPA axis suppression

Question 39

what is the effect on estrogens and androgens on glucocorticoids?

Answer 39

increased effect

Question 40

why is it necessary to taper a patient off long term glucocorticoid therapy?

Answer 40

reduce HPA axis suppression

Question 41

what is the mechanism by which high doses of cortisol can lead to hypotension or hypokalemia? would this same mechanism be observed with dexamethasone?

Answer 41

aldosterone (mineralocorticoid) receptor effects no - no mineralocorticoid receptor action

Question 42

what is the principle behind the high dose dexamethasone test?

Answer 42

pituitary tumor - dex has some effect of inhibiting ACTH adrenal adenoma - dex isn't regulated by ACTH at all ectopic ACTH production - dex doesn't inhibit ACTH production in lung (does not have the same responsive capabilities)

Question 43

what is the therapeutic use and MOA of ketoconazole?

Answer 43

inhibition of 17a-hydroxylase