Hormonal agents 2

Question 1

Androgen Biosynthesis inhibitors include

Answer 1

abiraterone

Question 2

Abiraterone MoA

Answer 2

inhibitor of the cytochrome P450 enzyme (17 alpha hydroxylase, CYP17A1) - this enzyme is responsible for the biosythesis of estrogen

Question 3

Abiraterone toxicity

Answer 3

joint swelling, edema, hot flashes, muscle discomfort

Question 4

What is abiraterone used for?

Answer 4

used for androgen deprivation therapy - usually in ben with late stage castration-resistant prostate cancer

Question 5

Continuous administration of abiraterone leads to

Answer 5

increase in ACTH levels - mineralcorticoid excess

Question 6

Abiraterone blocks androgen production from what 3 sources?

Answer 6

testicular, adrenal, prostate tumor tissue

Question 7

GnRH agonists include

Answer 7

Leuprolide and Goserelin

Question 8

GnRH agonists MoA

Answer 8

stimulate a release of FSH and LH, then inhibit their release, suppressing testosterone production in the testes

Question 9

GnRH agonist side effects

Answer 9

hot flashes, impotence, gynecomastia, risk of diabetes and heart disease

Question 10

Castration levels of testosteronce can be achieved with the use of Leuprolide and Goserelin in how long?

Answer 10

2-4 weeks of treatment

Question 11

The initial surge of LH and FSH caused by GnRH agonists can lead to

Answer 11

a flare of disease - this can be avoided with androgen receptor blocks

Question 12

GnRH antagonists include

Answer 12

Degarelix

Question 13

GnRH MoA

Answer 13

bind reversible to the GnRH receptor in the anterior pituitary, inhibits LH and FSH release

Question 14

Side effects GnRH antagonists

Answer 14

hot flashes, weight gain, increase in hepatic transaminases, QT prolongation (long term use)

Question 15

Delgarelix is a

Answer 15

synthetic decapeptide GnRH receptor antagonist used for rapid medical castration - no surge in LH or FSH before inhibition

Question 16

Aromatase inhibitors include

Answer 16

Anastrozole, Letrozole, Exemestane

Question 17

Main MoA of aromatase inhibitors

Answer 17

block function of the aromatase enzyme that converts androgens to estrogens

Question 18

Anastrozole and Letrozole MoA

Answer 18

binds competitively to the heme group of the aromatase enzyme

Question 19

Exemestane MoA

Answer 19

acts as a suicide substrate for the enzyme - binds covalently to its catalytic site resulting in irreversible inactivation

Question 20

Side effects of aromatase enzyme inhibitors

Answer 20

nausea, hot flashes, joint pain, muscle pain

Question 21

When is exemestane used?

Answer 21

When breast cancer treatment using tamoxifen is unsuccessful and as a preventative

Question 22

When are anastrozole and letrozole used?

Answer 22

ER-positive breast cancer, when tamoxifen is unsuccessful to treat tumors