Reproductive pharmacology

Question 1

What is the mechanism of action of luprolide

Answer 1

GnRH agonist- binds GnRH membrane receptor on pituitary gonadotrope cells.
Usually given in long acting form that eliminates pulsatility and thus causes decreased gonadotropin production

Question 2

What are indications for GnRH agonists or antagonists?

Answer 2

• testing for precocious or delayed puberty
• suppressing precocious puberty
• endometriosis
• prostate cancer
• decrease endogenous ovarian function to use exogenous ovulation indcution

Question 3

What are side effects of GnRH agonists?

Answer 3

signs of hypogondadism- hot flashes, bone loss, low libido, amenorrhea

Question 4

What is a difference in the response to GnRH agonists vs antagonists?

Answer 4

agonists do cause LH/ FSH flare then inhibition

antagonists cause immediate inhibition with no flare

Question 5

What would be an indication for pulsatile administration of GnRH?

Answer 5

treatment of hypogonadotropic hypogonadism due to hypothalamic dysfunction, ex Kallman syndrome

Question 6

Daily injections of exogenous ______ stimulate ovarian follicle development

Answer 6

FSH

Question 7

Injection of hCG (or LH) triggers ______

Answer 7

LH surge, ovulation, and progesterone production

Question 8

________ are used to treat prolactinomas

Answer 8

dopamin agonists like cabergoline, bromocriptine

Question 9

Describe the cellular location and biochemistry of the estrogen receptor

Answer 9

nuclear location
bound to heat shock proteins that dissociate upon estrogen binding
receptor dimerizes then can bind estrogen response element in DNA

Question 10

_______ is a weak estrogen produced by the placenta

Answer 10

estriol

Question 11

____ is the principle ovarian estrogen; _____ is an estrogen common in post-menopause

Answer 11

estradiol/ estrone

Question 12

What is the source of most estrogen in post-menopausal women

Answer 12

peripheral aromatization of adrenal androgens

Question 13

What is the effect of estrogen at bone?

Answer 13

maintains bone mass

stimulates closure of epiphyses

Question 14

What is the effect of estrogen in the liver?

Answer 14

Stimulates production of SHBG, thyroid hormone binding globulin, and blood clotting factors

Question 15

What are therapeutic uses of estrogens?

Answer 15

• tx estrogen deficiency in premature ovarian failure, menopause
• prevention, treatment of osteoporosis
• contraception

Question 16

If estrogen is given therapeutically without opposing progesterone, there is increased risk of __________

Answer 16

endometrial carcinoma

Question 17

What is the mechanism of action of clomiphene citrate?

Answer 17

Inhibits estrogen binding in the hypothalamus and anterior pituitary, preventing the normal feedback regulation and causing increased secretion of GnRH and gonadotropins, stimulating ovarian follicle development

technically has weak agonist effects, but clinically acts as a pure antagonist

Question 18

What is the most common use for clomiphene citrate?

Answer 18

ovulation induction

Question 19

What is the mechanism of action of tamoxifen?

Answer 19

estrogen antagonist in breast tissue.

weak agonist at endometrium and bone.

Question 20

What are indications for tamoxifen?

Answer 20

ER+ breast cancer

Question 21

What is a positive side effect of tamoxifen?

Answer 21

anti-resorptive action at bone

Question 22

What are negative side effects of tamoxifen?

Answer 22

endometrial hyperplasia, carcinoma
thromboembolism
hot flashes

Question 23

What is the mechanism of action of raloxifine?

Answer 23

estrogen agonist in bone.
estrogen antagonist in breast tissue.
Does not have action at the endometrium

Question 24

What are indications for raloxifine?

Answer 24

treatment of postmenopausal osteoporosis

Question 25

What are positive side effects of raloxifene?

Answer 25

decreased risk of ER+ breast cancer

Question 26

What are negative side effects of raloxifine?

Answer 26

thromboembolism | hot flashes

Question 27

Inhibition of _____ will result in lower estrogen levels

Answer 27

aromatase

Question 28

Differentiate between type 1 and type 2 aromatase inhibitors

Answer 28

Type 1 agent, exemestane, is steroidal in structure and acts as irreversible inhibitor of aromatase. Type 2 agents, anastrozole and letrozole, are nonsteroidal agents and are reversible inhibitors of the enzyme.

Question 29

What are indications for aromatase inhibitors?

Answer 29

ER+ breast cancer | ovulation induction- type 2/ reversible only

Question 30

Describe the cellular location and biochemistry of the progesterone receptor

Answer 30

cytoplasmic location | bound to heat shock proteins, dissociation when estrogen binds

Question 31

List the physiologic effects of progestins

Answer 31

- Inhibits estrogen-induced proliferation of the endometrium - Prepares endometrium for embryo implantation - Supports maternal and fetal needs throughout pregnancy - Withdrawal from progesterone triggers menses

Question 32

What are therapeutic uses for progestins?

Answer 32

- postmenopausal hormone therapy to avoid effects of unopposed estrogen - contraception - support of pregnancies in assisted reproduction where there is no CL - abortifactants- mifiprisone

Question 33

_______ and ______ act through a single cytoplasmic androgen receptor

Answer 33

testosterone and DHT

Question 34

Why can't testosterone be given orally?

Answer 34

first pass metabolism in the liver

Question 35

What are clinical uses of androgens?

Answer 35

male testosterone deficiency

Question 36

What is the mechanism of action of finasteride?

Answer 36

Inhibitor of the enzyme 5-α reductase, which converts testosterone to DHT

Question 37

What are clinical uses of finasteride?

Answer 37

tx of BPH, male pattern baldness

Question 38

What is the mechanism of action of spironolactone

Answer 38

weakly blocks androgen receptor weakly inhibits testosterone synthesis blocks mineralocorticoid receptor weak agonist at progesterone receptor

Question 39

What are uses of spironolactone?

Answer 39

hirsutism hypertension, CHF primary hyperaldosteronism

Question 40

What are adverse effects of spironolactone?

Answer 40

hyperkalemia irregular menses gynecomastia

Question 41

What is the mechanism of action of flutaminde

Answer 41

competitive antagonist of androgen receptor

Question 42

What are clinical uses of flutamide?

Answer 42

prostate cancer | hirsutism (rarely used)

Question 43

What is the key adverse effect of flutamide?

Answer 43

hepatotoxicity