Repro Drugs

Question 1

Leuprolide: Mechanism

Answer 1

GnRH analog with agonist properties when used in a pulsatile fashion.
ANTAGONIST when used in a continuous fashion (downregulates GnRH receptor in pituitary –> decreased FSH/LH)

Question 2

Leuprolide: Clinical Use

Answer 2

Pulsatile – infertility

Continuous – Prostate cancer, Uterine fibriouds, Precocious puberty

Question 3

For prostate cancer, use continuous or pulsatile leuprolide? Also, with what other drug

Answer 3

Treat prostate cancer with continuous leuprolide and co-administer with flutamide (competitive inhibitor of androgens)

Question 4

Leuprolide: Toxicity

Answer 4

Antiandrogen, nausea, vomiting

Question 5

Testosterone, Methyltestosterone: Mechanism

Answer 5

Agonist at androgen receptors

Question 6

Testosterone: Clinical Use

Answer 6

Treats hypogonaidism and promotes development of secondary sex characteristics; stimulation of anabolism to promote recovery after burn or injury

Question 7

Testosterone: Toxicity

Answer 7

Causes masculinization in females; reduces intratesticular testosterones in males by inhibiting release of LH (via negative feedback), leading to gonadal atrophy. Premature closure of epiphyseal plates.

Question 8

Testosterone effect on cholesterol

Answer 8

Increased LDL; Decreased HDL

Question 9

Enzyme for conversion of testosterone to DHT

Answer 9

5-alpha reductase. DHT is more potent than testosterone

Question 10

Finasteride

Answer 10

5-alpha reductase inhibitor (decreases conversion of testosterone to DHT).

Question 11

Finasteride Uses

Answer 11

Useful for BPH (as DHT is primary mediator that causes hyperplasia in prostate). Also promotes hair growth - used to treat male pattern baldness

Question 12

Flutamide

Answer 12

A non steroidal competitive inhibitor of androgens at the testosterone receptor. Used in prostate carcinoma.

Question 13

Ketoconazole

Answer 13

Inhibits steroid synthesis (inhibits 17, 20 desmolase).

Question 14

Spironolactone

Answer 14

Inhibits steroid binding.

Question 15

Rx for polycystic ovarian syndrome to prevent hirsuitism

Answer 15

Spironolactone and Ketoconazole. Can cause gynecomastia and amenorrhea

Question 16

Estrogens - name them

Answer 16

Ethinyl, Estradiol, DES, mestranol

Question 17

Estrogen: Mechanism

Answer 17

Bind estrogen receptors

Question 18

Estrogen: Clinical Use

Answer 18

Hypogonadism or ovarian failure.
Menstrual abnormalities,
HRT in postmenopausal women;
use in men with androgen dependent prostate cancer

Question 19

Estrogen: Toxicity

Answer 19

Increased risk of endometrial cancer

• bleeding in postmenopausal women
• clear cell adenocarcinoma of vagina in females exposed to DES in utero
• increased risk of thrombi

Question 20

Contraindications of Estrogen use

Answer 20

• ER-positive breast cancer

- history of DVTs

Question 21

Selective Estrogen Receptor Modulators (SERMs)

Answer 21

Clomiphene, Tamoxifen, Raloxifene

Question 22

Clomiphine

Answer 22

SERM - partial agonist at estrogen receptors in hypothalamus.
Prevents normal feedback inhibition and increases release of LH and FSH from pituitary which stimulates ovulation

Question 23

Clomiphine: Use

Answer 23

Treat infertitility and polycystic ovarian syndrome. May cause hot flashes, ovarian enlargement. Multiple simultaneous pregancies, and visual disturbances

Question 24

Raloxifene

Answer 24

SERM. Agonist on bone; Reduces resorption of bone; Used to treat osteoporosis.

Question 25

Tamoxifen

Answer 25

Antagonist at breast tissue; Used to treat and prevent recurrence of ER-positive breast cancer.

Question 26

Hormone replacement therapy

Answer 26

Used for relief or prevention of menopausal symptoms (e.g. hot flashes, vaginal atrophy) and osteoporosis (increases estrogen, decreases osteoclast activity)

Question 27

Discuss risks of HRT of cancer, CV dises

Answer 27

Unopposed estrogen replacement therapy (ERT increases risk of endometrial cancer, so progesterone is added. Possible INCREASED CV risk

Question 28

Anastrozole/ Exemestane

Answer 28

Aromatase inhibitors used in postmenopausal women with breast cancer

Question 29

Progestins : Mechanism

Answer 29

Bind progesterone receptors, reduce growth and increase vascularization of endometrium.

Question 30

Progestin: Clinical Use

Answer 30

Used in oral contraceptive and in the treatment of endometrial cancer and abnormal uterine bleeding

Question 31

Mifepristone (RU-486): Mechanism

Answer 31

Competitive inhibitor of progestins at progesterone receptors

Question 32

Mifepristone (RU-486): Clinical Use

Answer 32

Termination of pregnancy. Administered with misprostol (PGE1)

Question 33

Mifepristone (RU-486): Toxicity

Answer 33

Heavy bleeding, GI effects (nausea, vomiting, abdominal pain)

Question 34

Oral contraception (synthetic progestins, estrogen)

Answer 34

Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge --> no LH surge --> no ovulation

Question 35

Discuss progestins and pregnancy prevention

Answer 35

Progestins cause thickening of cervical mucus, thus limiting access of sperm to uterus. Also inhibit endometrial proliferation, thus making endometrium less suitable for implantation of an embryo.

Question 36

Contraindications of OCP

Answer 36

Smokers > 35 y.o Increased risk of CV events Patients with a hx of thromboembolism and stroke or hx of estrogen dependent tumor

Question 37

Terbutaline

Answer 37

B2 agonist that relaxes the uterus; reduces premature uterine contractions

Question 38

Tamsulosin

Answer 38

Alpha 1 antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective alpha 1AD receptors (found on prostate) vs. vascular alpha 1 B receptors `

Question 39

Sildenafil, vardenafil

Answer 39

Phosphodiesterase inhibitors

Question 40

Sildenafil, Vardenafil: Mechanism

Answer 40

Inhibit phosphodiesterase 5, causing increase in cGMP smooth muscle relaxation in the corpus canvernosum, increased blood flow and penile erection

Question 41

Sildenafil, Vardenafil: Clinical Use

Answer 41

Treatment of erectile dysfunction

Question 42

Sildenafil, Vardenafil: Toxicity

Answer 42

Headache, flushing, dyspepsia, impaired blue-green vision. Risk of life threatening hypotension in patients taking nitrates "Hot and sweaty", but then "Headache", "Heartburn, "Hypotension"

Question 43

Danazol: Mechanism

Answer 43

Synthentic androgen that acts as partial agonist at androgen receptors.

Question 44

Danazol: Clinical Use

Answer 44

Endometriosis and hereditary angiodema

Question 45

Danazol: Toxicity

Answer 45

Weight fain, edema, acne, hirsuitism, masculinization. Decreased HDL levels, hepatotoxicity