Reproductive Pharmacology

Question 1

GnRH analog that can be used as antagonist or agonist

Answer 1

Leuprolide (pulsatile–agonist, continuous–antagonist) downregulates GnRH receptor in pituitary –> decreased FSH/LH

Question 2

Uses of leuprolide? Toxicities?

Answer 2

infertility (pulsatile), prostate cancer (continuous use with flutamide), uterine fibroids (continous), precocious puberty (continuous); Has anti-androgen effects

Question 3

What are risks of estrogen use?

Answer 3

increased risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina (DES exposure in utero), increased risk of thrombi

Question 4

What are some SERMS?

Answer 4

clomiphene, tamoxifen, raloxifene

Question 5

Antagonist at estrogen receptors in hypothalamus

Answer 5

Clomiphene; SERM that prevents normal feedback inhibition and increases release of LH and FSH from pituitary to stimulate ovulation; use to treat infertility due to anovulation (PCOS)

Question 6

Antagonist of estrogen receptors at breast tissue

Answer 6

Tamoxifen; SERM that is also agonist at uterus/bone. Ass w/ endometrial cancer, thromboembolic events; Primarily used to treat ER+ breast cancer

Question 7

Antagonist of estrogen receptors at uterus

Answer 7

Raloxifene: SERM that is agonist on bone also; increases risk of thromboembolic events; decrease resorption of bone–>used to treat osteoporosis

Question 8

What are risks of unopposed estrogen therapy?

Answer 8

increased risk of endometrial cancer (thats why you add progesterone); possibly increased cardiovascular risk

Question 9

Anastrazole/exemestane

Answer 9

aromatase inhibitors used in post-menopausal women with breast cancer (decrease conversion of androgens to estrogens)

Question 10

Progestins

Answer 10

bind progesterone receptors to decrease growth and increase vascularization of endometrium—used in OCPs and treatment of endometrial cancer, abnormal bleeding

Question 11

Mifepristone

Answer 11

competitive inhibitor of progestins at progresterone receptor–used to terminate pregnancy; administered with misoprostol (PGE1)

Question 12

Terbutaline

Answer 12

B2 agonist that relaxes the uterus, used to decrease contraction frequency in women during labor

Question 13

Danazol

Answer 13

synthetic androgen used in endometriosis and hereditary angioedema; androgen effects and decreased HDL levels/hepatotoxic

Question 14

What effects to testosterone have on serum lipids?

Answer 14

Increase LDL and decrease HDL

Question 15

Finasteride

Answer 15

5 alpha reductase inhibitor (blocks conversion of testoterone to DHT), used in BPH and promotes hair growth at the cost of gynecomastia and decreased sexual performance

Question 16

Flutamide

Answer 16

competitive inhibitor of testosterone receptor used in Prostate Ca

Question 17

Used in treatment of PCOS to prevent hirsutism

Answer 17

Ketoconazole (inhibits 17,20 desmolase; steroid synthesis), Spironolactone (inhibits steroid binding, 17 alpha hydroxylase, 17,20 desmolase); both cause gynecomastia and amenorrhea

Question 18

Tamsulosin

Answer 18

alpha1 antagonist used to treat BPH by inhibiting smooth muscle contraction; selective for alpha1A,D receptors found only on prostate

Question 19

Sildenafil/vardenafil

Answer 19

PDE5 inhibitors, cause increase cGMP, NO release, smooth muscle relaxation in corpus cavernosum; can cause headache, heartburn, impaired vision, life threatening hypotension in patients also taking nitrates