Corticosteroids

Question 1

Treatment regimen for Cushings Disease (3 pharm)

Answer 1

Surgery is main option
A Aminoglutethimide
K Ketoconazole
M Metyrapone

Question 2

Aminoglutethimide inhibits what CYP?

Answer 2

CYP11A1

Question 3

Mechanism of Aminoglutethimide

Answer 3

inhibits CYP11A1 resulting in inhibition of corticosteroid synthesis

Question 4

Aminoglutethimide side effects

Answer 4

adrenal insufficiency

Question 5

Aminoglutethimide drug interaction

Answer 5

increased metabolism of other drugs such as

warfarin, theopyylline and digitoxin

Question 6

Ketoconazole Mechanism (3)

Answer 6

high doses - inhibits CYP17, inhibiting glucocorticoid and androgen synthesis
even higher doses - inhibits CYP11A1, inhibiting all steroidogenesis
also reduces ACTH secretion at therapeutic doses

Question 7

Another name for CYP11A1 and action

Answer 7

Cholesterol Desmolase

converts Cholesterol to Pregnenolone

Question 8

Use for Ketoconazole?

Answer 8

Treat Cushing’s Disease and fungal infections

Question 9

Drug Interaction of Ketoconazole (2)

Answer 9

inhibits multiple CYPs, many potential interactions

inhibits P-glycoprotein so may increase levels of P-gp substrates

Question 10

Metyrapone mechanism

Answer 10

selective inhibitor of CYP11B1 reducing the biosynthesis of cortisol

Question 11

What CYP does Metyrapone inhibit?

Answer 11

CYP11B1

Question 12

Metyrapone clinical use?

Answer 12

hypercorticism

diagnostic test for Cushings

Question 13

Metyrapone main side effect and why it occurs?

Answer 13

Hirsutism - due to increased synthesis of adrenal androgens upstream from the enzymatic block

Question 14

Mifepristone (RU-486) mechanism (2)

Answer 14

Inhibits the release of the glucocorticoid receptor from the chaperone proteins
Also competitive inhibitor of progestins at progesterone receptors

Question 15

Mifepristone (RU-486) clinical use (2)

Answer 15

controlling hypercortisolism in patients with Cushing’s syndrome due to inoperable ectopic ACTH secreting tumors

abortion pill

Question 16

Mifepristone (RU-486) main side effect

Answer 16

Heavy vaginal bleeding

Question 17

Mifepristone (RU-486) drug interaction

Answer 17

increased metabolism of other drugs such as warfarin, theopyylline and digitoxin

Question 18

Cosyntropin test is used for what?

Answer 18

Determining primary vs secondary adrenal insufficiency

Question 19

Primary Adrenal Insufficiency treatment

Answer 19

hydrocortisone or cortisone

supplementation with fludrocortisone for mineralocorticoid effect

Question 20

Secondary Adrenal Insufficiency treatment

Answer 20

hydrocortisone, cortisone or prednisone

mineralocorticoids are not necessary.

Question 21

Why are Mineralocorticoids only given once a day

Answer 21

because their release does not show circadian

effects normally.

Question 22

Most common cause of Congenital Adrenal Hypoplasia

Answer 22

Deficiency in CYP21

Question 23

Presentation of Congenital Adrenal Hypoplasia males vs females

Answer 23

Males normal at birth precocious puberty

females psedudohermaphroditism

Question 24

Spironolactone Mechanism

Answer 24

Blocks renal aldosterone receptors

Also progesterone agonist and androgen antagonist

Question 25

Spironolactone clinical use

Answer 25

treatment of aldosteronism for non-surgical candidates

Question 26

Spironolactone side effects

Answer 26

breast tenderness and menstrual irregularities in women | impotence, decreased libido, and gynecomastia in men

Question 27

Glucocorticoids have excellent ___ activity and are they curative?

Answer 27

Excellent anti-inflammatory activity | Underlying cause is still present

Question 28

What occurs if you rapidly withdraw glucocorticoids?

Answer 28

adrenal insufficiency, must wean off

Question 29

What demographic must you be careful about with glucocorticoids?

Answer 29

post-menopausal women and osteoporosis patients

Question 30

Corticosteroids inhibit what transcription factor?

Answer 30

NF-kB

Question 31

What does cortisol bind to in blood and what raises the protein's levels?

Answer 31

90% of cortisol binds to corticosteroid binding globulin (CBG) & albumin in the plasma Pregnancy and estrogen therapy

Question 32

Metabolism of corticosteroids?

Answer 32

first pass hepatic conjugation and then renally excreted

Question 33

Why should people with infections or AIDS avoid corticosteroids?

Answer 33

they are highly immunosuppressive

Question 34

What must you supplement post-menopausal woman with when giving corticosteroids?

Answer 34

Vitamin D and Calcium with high protein diet

Question 35

Why use caution giving glucocorticoids to psychotic patients?

Answer 35

may exacerbate condition - side effect of drugs

Question 36

Which corticosteroid can induce cleft palate and still birth

Answer 36

Dexamethasone

Question 37

Why recommend no breast feeding in systemic steroid treatment.

Answer 37

can redistribute in breast milk

Question 38

Why be cautious in treating diabetics with steroids?

Answer 38

induces hyperglycemia

Question 39

Why be cautious in treating heart patients with steroids?

Answer 39

due to potential weight gain and hypertension and hyperlipidemia induced by steroids

Question 40

Hepatic microsomal enzyme inducers (barbiturates, carbamazepine, phenytoin) do what to corticosteroid metabolism?

Answer 40

promote corticosteroid metabolism.