Reproductive

Question 1

Leuprolide

Answer 1

MOA:
GnRH analog with agonist properties when used in pulsatile fashion; antagonist properties when used in continuous fashion (downregulates GnRH) receptor pituitary –> dec. FSH/LH

Use: 
Uterine fibroids 
Endometriosis
Precocious puberty
Prostate cancer
Infertility

Question 2

Estrogens

Ethinyl estradiol, DES, Mestranol

Answer 2

MOA: Bind estrogen receptors

Use:
Hypogonadism or ovarian failure, menstrual abnormalities, hormone replacement therapy in postmenopausal women; Use in men with androgen-dependent prostate cancer

Adv. effects:
Increased risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina in females exposed to DES in utero, increase risk of thrombi.
Contraindications - ER + breast cancer, history of DVTs

Question 3

Clomiphene

Answer 3

Antagonist at estrogen receptors in hypothalamus

Prevents normal feedback inhibition & increase release of LH and FSH from pituitary, which stimulates ovulation.

Used to treat infertility due to anovulation (ex. PCOS)
May cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances.

Question 4

Tamoxifen

Answer 4

Antagonist at breast
Agonist at bone, uterus
Increase risk of thromboembolic events & endometrial cancer
Used to treat and prevent recurrence ER/PR + breast cancer

Question 5

Raloxifene

Answer 5

Antagonist at breast, uterus
Agonist at bone
Increased risk of thromboembolic events but no increased risk of endometrial cancer (vs. tamoxifen)
Used primarily to treat osteoporosis

Question 6

Aromatase inhibitors

Anastrozole, Letrozole, Exemestane

Answer 6

Mech:
Inhibit peripheral conversion of androgens to estrogen

Use:
ER + breast cancer in postmenopausal women

Question 7

Hormone replacement therapy

Answer 7

Used for relief or preventation of menopausal symptoms (hot flashes, vaginal atrophy), osteoporosis (increase estrogen, decrease osteoclast activity)

Unopposed estrogen replacement therapy increased risk of endometrial cancer, so progesterone is added.

Possible increased cardiovascular risk

Question 8

Progestins

Levonorgestrel, Medroxyprogesterone, Etonogestrel, Norethindrone, Megestrol when combined w/ estrogen

Answer 8

MOA:
Bind progesterone receptors, decrease growth and increase vascularization of endometrium, thicken cervical mucus

Use:
Contraception
Endometrial cancer
Abnormal uterine bleeding

Progestin challenge:
presence of withdrawal bleeding excludes anatomic defects (Asherman syndrome) and chronic anovulation without estrogen.

Question 9

Antiprogestins

Mifepristone, Ulipristal

Answer 9

MOA:
Competitive inhibitors of progestins at progesterone receptors

Use:
Termination of pregnancy (mifepristone w/ misoprostol)
Emergency contraception (ulipristal)

Question 10

Progestins + Ethinyl Estradiol

Answer 10

pills, patch vaginal ring

Question 11

Estrogen + Progestins

Answer 11

Inhibit LH/FSH and prevent estrogen surge –> no LH surge

Progestins - thicken cervical mucus –> limiting access of sperm to uterus

Progestins - inhibit endometrial proliferation –> endometrium less suitable to implantation

Question 12

Contraceptive Contraindications

Answer 12

Smokers > 35 yrs old (increased risk of cardiovascular events)

Patients w/ h/o venous thromboembolism, coronary artery disease, stroke

Patients w/ migraine (esp with aura)

Patients w/ breast cancer

Question 13

Copper intrauterine device

Answer 13

MOA:
Produces local inflammatory reaction toxic to sperm and ova, preventing fertilization and ovulation
Hormone free

Use:
Long-acting reversible contraception
Most effective emergency contraception

Adv. effects: Heavier or longer menses, dysmenorrhea

Risk of PID with insertion (contra in active pelvic infection)

Question 14

Terbutaline, Ritodrine

Answer 14

B2 agonists

Relax the uterus

Used to decrease contraction frequency in women during labor

Question 15

Danazol

Answer 15

MOA:
Synthetic androgen; acts as partial agonist at androgen receptors

Use:
Endometriosis
Hereditary angioedema

Adv. effects:
Weight gain
Edema
Acne
Hirsutism
Masculinization
Decrease HDL levels
Hepatotoxicity

Question 16

Testosterone, Methyltestosterone

Answer 16

MOA: agonists at androgen receptors

Use:
Hypogonadism
Promote secondary sex characteristics
Stimulate anabolism to promote recovery after burn or injury

Adv. effects:
Masculinization in females
Decrease intratesticular testosterone in male by inhibiting release of LH (neg. feedback) -- > gonadal atrophy
Premature closure of epiphyseal plats
Increase LDL
Decrease HDL

Question 17

Finasteride

Answer 17

Antiandrogen

5a-reductase inhibitor (decrease conversion of testosterone to DHT)

Used for BPH and male-pattern baldness

Question 18

Flutamide

Answer 18

Antiandrogen

Nonsteroidal competitive inhibitor at androgen receptors

Used for prostate carcinoma

Question 19

Ketoconazole

Answer 19

Antiandrogen

Inhibits steroid synthesis (inhibits 17,20-desmolase)

Used for polycystic ovarian syndrome (reduce androgenic symptoms)

Side effects of gynecomastia and amenorrhea

Question 20

Spironolactone

Answer 20

Antiandrogen

Inhibits steroid binding, 17a-hydroxylase and 17,20-desmolase

Used for polycystic ovarian syndrome (reduce androgenic symptoms)

Side effects of gynecomastia and amenorrhea

Question 21

Tamsolusin

Answer 21

alpha 1 antagonist

Selective for alpha1a receptors (on prostate)

Used to treat BPH by inhibiting smooth muscle contractions

Question 22

Phosphodiesterase type 5 inhibitors

Sildenafil, Vardenafil, Tadalafil

Answer 22

MOA:
Inhibit PDE-5 –> Increase cGMP –> prolonged smooth muscle relaxation in response to NO –> increase blood flow in corpus cavernosum of penis. decrease pulmonary vascular resistance

Use:
Erectile dysfunction
Pulmonary hypertension
BPH (tadalfil only)

Adv. effects:
Headache, flushing, dyspepsia, cyanopia (blunt-tinted vision)
Risk of life threatening hypotension in patients taking nitrates

Question 23

Minoxidil

Answer 23

MOA: Direct arteriolar vasodilator

Use:
Androgenetic alopecia
Severe refractory hypertension