Adrenal agents Flashcards Preview

Year 2 Pharmacology > Adrenal agents > Flashcards

Flashcards in Adrenal agents Deck (43):
1

what are the drug targets of corticosteroids?

17a-hydroxylase
11B-hydroxylase

2

17a-hydroxylase is responsible for catalyzing what reactions?

pregnenolone to 17-hydroxypregnenolone

progesterone to 17-hydroxyprogesterone

3

11B-hydroxylase is responsible for catalyzing what reaction?

deoxycortisone to cortisone

4

what enzyme is responsible for catalyzing the reactions

pregnenolone to 17-hydroxypregnenolone
progesterone to 17-hydroxyprogesterone?

17a-hydroxylase

5

what enzyme is responsible for catalyzing the reaction

deoxycortisone to cortisone?

11B-hydroxylase

6

what types of receptors are glucocorticoid and mineralocorticoid?

nuclear hormone receptors

7

cortisol binds to what receptors?

glucocorticoid
mineralocorticoid

8

does cortisone bind to mineralocorticoid receptors?

no

9

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

liver

11B-HSD1

10

which enzyme is responsible for converting cortisol back to cortisone?

11B-HSD2

11

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

mineralocorticoid

heavy salt retaining
anti-inflammatory

12

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

11B-HSD1

13

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

autoimmune
TB

14

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

deficiency in cortisol, aldosterone, androgens

hypotension from unresponsiveness of vascular smooth muscle to catecholamines

15

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

cortisol
fludrocortisone

16

secondary adrenal insufficiency are due to what causes?

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

17

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

cortisol (fludrocortisone NOT needed)

18

chronic glucocorticoid (cortisol) excess leads to what condition?

Cushing's syndrome

19

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

chronic glucocorticoid (corticoid) excess

20

why does increased levels of cortisol cause HTN?

activation of mineralocorticoid receptors

21

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

dexamethasone

22

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

low CRH
high ACTH

usually 50% reduction in cortisol upon dexamethasone

23

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

low CRH
low ACTH

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

24

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

low CRH
high ACTH

no reduction in cortisol upon dexamethasone

25

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

antifungal

inhibits 17a-hydroxylase

cushing's syndrome

26

what is the adverse effect of ketoconazole?

significant liver toxicity

27

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

diagnostic agent used to evaluate ACTH production

cushing's syndrome

28

what drugs are used to treat cushing's syndrome?

ketoconazole
metyrapone

29

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

glucocorticoid receptor antagonist

inoperable patients with ectopic ACTH secretion or adrenal carcinoma

30

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

mifepristone

31

what are the effects of glucocorticoids on the immune cells?

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

32

what are the anti-inflammatory mechanisms of corticosteroids?

inhibition of phospholipase A2
COX inhibition

33

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

asthma

patients who take inhaled B2 agonists more than twice a week

34

what is the MOA of inhaled corticosteroids on asthma?

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

35

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

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

36

what is the importance of dexamethasone administration for glucocorticoid effect?

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

37

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

gastic acid - stimulation
pepsin - stimulation

38

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

HPA axis suppression

39

what is the effect on estrogens and androgens on glucocorticoids?

increased effect

40

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

reduce HPA axis suppression

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?

aldosterone (mineralocorticoid) receptor effects

no - no mineralocorticoid receptor action

42

what is the principle behind the high dose dexamethasone test?

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)

43

what is the therapeutic use and MOA of ketoconazole?

inhibition of 17a-hydroxylase

Decks in Year 2 Pharmacology Class (70):