HRT pharm

Question 1

Estrogens (mech)

Answer 1

diffuse through mem –> enter nuc –> bind to ER –> receptor dimerization

-dimers bind ERE in promotor regions to initiate transcription

Question 2

what are the developmental physiologic effects of estrogen

Answer 2

• develo of vagina, uterus, breast
• secondary sex char: axillary/pubic hair, fat dist
• accelerated growth phase
• closing of epiphyses of long bones at puberty

Question 3

effects of estrogen on: endometrium
bone
liver

Answer 3

endo- activate during proliferative phase
bone- DECREASE osteoclast activity
liver- decrease LDL, increase HDL, increase clotting factors

Question 4

adverse effects of estrogen

Answer 4

clotting
endometrial/breast cancer
postmenopausal bleeding
HTN
increase migraine freq
gallstones

Question 5

contraindications to est

Answer 5

hx of breast/endometrial CA
vaginal bleeding
acute liver dz
active thrombosis

Question 6

Clinical uses of estrogen HRT

Answer 6

menopausaul hormonal therapy

• vasomotor sx (systemic)
• vulvovaginal and urogenital complaints –>local
• osteoporosis –> only consider if at risk

Question 7

Raloxifene

Answer 7

SERM used to prevent osteoporosis becuase lacks uterine and breast tissue activity
-antagonist at breast, agonist at bone

Question 8

“physiologic replacement” prep

Answer 8

hypoestrogenic menopausal sx

-5-10 mcg ethinyl estradiol

Question 9

“pharmacologic suppression” prep

Answer 9

for ovulation

- 20-25 mcg ethinyl estradiol in oral contracep

Question 10

Medroxyprogesterone

Answer 10

megestrol

• main actions are peripheral on endometral tissue
• less efffect on pituitary

Question 11

progestins in OCPS

Answer 11

1st gen = Norethindrone
2nd gen = Levonorgestrel → increased androgenic actions
3rd gen = Desogestrel-norethynodrel-norgestimate → *lower androgenic actions, higher VTE risk
4th gen = Drospirenone → antimineralocorticoid and antiandrogenic activity → increased VTE risk

Question 12

name 7 effects of progetins

Answer 12

Stimulates LPL activity → fat deposition
Increase insulin levels and insulin response to glucose → promote liver glycogen storage and ketogenesis
Prolonged high levels impair glucose tolerance (pregnancy)
Can cause compensatory increases in aldosterone secretion by adrenal cortex (pregnancy)
Increase ventilatory response to CO2
Increases body temperature at ovulation
*ANTI-ESTROGENIC action on ENDOMETRIAL proliferation

Question 13

clinical uses of progestins

Answer 13

contraception

menopausal therapy –> use with estrogen

Question 14

adverse effects of progestins

Answer 14

• depression/somnolence/HA
• breast enlargement/tenderness
• elevated BP,edema, weight gain
• osteoporosis –> suppress FSH and LH

Question 15

name two SERM (selective estrogen receptor modulation)

Answer 15

raloxifene

tamoxifen

Question 16

raloxifene (mech)

Answer 16

agonist activity- increase bone mineral density and decrease LDL and total C (liver)

antagonist activity - uterine and breast tissue –>

Question 17

how is raloxifene used?

Answer 17

osteoporosis prevention

postmonopausal therapy

Question 18

what are the benefits and adverse effects of raloxifene?

Answer 18

benes: NO effect on breast/ endo tissueso no increased risk of breast CA
risks: clotting, hot flashes

Question 19

tamoxifen

Answer 19

use: breast cancer prevention
risks: increased rate of endometrial cancer, hot flashes, thromboembolism

Question 20

name some drugs that REDUCE the contraceptive effect of oral contraceptives

Answer 20

via induced estrogen metab

-rifampin, phenytoin, carbamezapine, phenobarb, griseofulvin