Reproductive Pharm Flashcards
lecture objectives?
- understand the pharmacology of the reproductive process
- understand the mechanism of contraceptive and erectile dysfunction drugs
- understand the clinical indications for the use of these drugs
- understand the relevant side effects of the use of contraceptive and erectile dysfunction drugs
what are the three major estrogens produced by female body?
- estradiol
- estrone
- estriol
what is the primary source of estradiol in premenopausal women?
the ovary
what cells are responsible for making estrogen?
granulosa cells of ovarian follicle
estradiol can be converted to estrone and estriol in
the liver
estrogens are converted from androstenedione and testosterone
in ovaries or in other tissues (eg - adipose tissue, bone, and brain)
estrogens can also be produced in other tissues such as
- adipose tissue
2. adrenal gland in men and post-menopausal women
during pregnancy, large quantities of estriol are produced by
the placenta
what is the major circulating estrogen in premenopausal women?
estradiol
for men and postmenopausal women what is the major circulating estrogen?
estrone
aromatase in involved in the production of
estrogen
aromatase converts testosterone to
estradiol
aromatase converts androstenedione to
estrone
where is aromatse expressed in our body?
ovaries, placenta, adrenal gland, adipose tissue, testicles, brain
synthetic estrogens include
steroidal and nonsteroidals forms
what are the 3 synthetic steroidal estrogens in therapeutic use?
- estradiol esters
- conjugated estrogens
- alkyl estrogens
nonsteroidal synthetic estrogens
are less commonly used in the clinic
diethylstilbestrol (DES) was reported to increase the risk of
clear cell adenocarcinoma in the vagina and cervix
when does positive feedback on gonadotropin happens?
occurs at high concentrations near the end of the follicular phase, estrogen positively regulated pituitary to trigger the release of FSH and LH that causes the ovary to produce more estrogen.
what is responsible for ovulation?
high levels of estrogen and LH
what are the cardiovascular effects of estrogen
whether estrogens reduce cardiovascular dz is still under debate
what are the effects of estrogen on lipoprotein?
increase HDL and decrease LDL
what is the effect of estrogen on bone?
decrease bone resorption, thus used for the treatment of osteoporosis
what are the uses of estrogen for contraception?
synthetic estrogen, such as Ethinyl estrodiol is frequently used along with Progestin for prevention of pregnancy
what is the other use of estrogen?
primary hypogonadism (reduced or absent secretion of hormones from the sex glands, eg- ovaries)
how is estrogen used for postmenopausal hormone therapy?
used to reduce postmenopause symptoms such as “hot flashes”, atrophic vaginitis, also for the prevention of osteoporosis
what are the other physiological effects of estrogen?
decrease bone resorption –> thus, used for the osteoporosis
side effects of estrogen?
increase body fat, salt, and fluid retention
what are the 3 therapeutic uses of estrogen?
- contraception
- primary hypogonadism
- postmenopausal hormone therapy
what type of estrogen is used for contraception?
synthetic estrogen, such as ethinyl estrodiol, is frequently used along with progestin for prevention of pregnancy
what is primary hypogonadism?
reduced or absent secretion of hormones from the sex glands (eg - ovaries)
why is estrogen used for postmenopausal symptoms?
reduce postmenopause symptoms such as hot flashes, atrophic vaginitis, also for the prevention of osteoporosis
what are the common adverse effects of estrogen?
nausea, breast tension/pain, vaginal bleeding, headache, weight gain, hypertension
what are some less common adverse effects of estrogen?
- breast cancer (controversial)
- 2-3 fold increase in the incidence of DVT and pulmonary embolism
- increase risk of heart attach, stroke, gallbladder dz
- may increase the risk of cervical and endometrial cancers
what are two contradictions of estrogen?
- strongly contraindicated in pts with breast or endometrial cancer, endometriosis, and undiagnosed vaginal bleeding
- generally contraindicated in pts with pregnancy, thromboembolic dz, hypertension , hepatic dz or with family hx of breast or uterine cancer
what are two compounds that are estrogen receptor competitive antagonist?
- tamoxifen
2. clomiphene
tamoxifen is
a nonsteroidal agent
tamoxifen has both
estrogenic and antiestrogenic actions
antiestrogenic effect of tamoxifen is on
mammary epithelium
pro-estrogenic effect of tamoxifen is on
uterine endometrium and bone
how does tamoxifen work on breast?
works as a partial estrogen competitive antagonist in the breast –> blocks estrogen from binding to estrogen receptor and is commonly used for the treatment of ER-positive advanced breast cancers
estrogen binds to
sex hormone binding globulin in cell
estrogen has much higher binding affinity than
tamoxifen
tamoxifen must be used in concentration much
higher than estrogen to maintain inhibition of breast cancer cells
prolonged use of tamoxifen (for prevention of breast cancer)
increases incidence of endometrial carcinoma
clomiphene has two isomers:
cis and trans
cis clomiphene is
a weak estrogen agonist
trans clomiphene is
a potent estrogen antagonist
estrogen feedback on gonadotropin release can be either
positive or negative
the negative feedback of estrogen occurs
when estrogen reaches high level –> it acts in a negative feedback loop on ant. pituitary as well as hypothalamus and thus slows down the release of FSH and estrogen itself
the positive feedback of estrogen occurs
at high conc near the end of the follicular phase, estrogen positively regulates pituitary to trigger the release of FSH and LH that cause the ovary to produce more estrogen –> high level of estrogen and LH are responsible for ovulation
what is the mech of action of clomiphene?
blocks estrogen binding to its receptors in the hypothalamus and inhibits estradiol’s negative feedback on the gonadotropins –> increases in the secretion of gonadotropins and LH –> leads to ovulation
clomiphene blocks
E2 receptor and increases GnRH –> LH and FSH surge –> ovulation
clomiphene is used for
stimulating ovulation in patients with disorder of ovulation who wish to become pregnant
side effects of clomiphene?
symptoms of menopause, multiple pregnancy, hot flashes
progestin is considered as
synthetic progesterone
what are the physiological functions of progesterone?
- stimulate endometrium to develop secretory glands
what is effect of progesterone on growth?
suppress growth and can prevent endometrial cancers
prolonged use of pregesterone has
atrophic effect on endometrium (thus, progesterone is used to oppose estrogen effect)
what are the clinical usages of progesterone?
- contraception
- hormone replacement therapy
3.
what is the abortion pill?
RU-486 (mifepristone)
what is progesterone contraindicated?
similar to estrogen
estrogen-progesteron combination contracepties are the
most affective, reversible contraceptive
progestin only oral contraceptives is called
mini pills and less effective than combination prep
what is the the use for pregestin only oral pill?
useful when estrogens are contraindicated (eg - endometrial cancer)
what is the abortion pill?
mifepristeon (RU-486)
mifepristone is the progestin
antagonist (indicated for the medical termination of early preg. 49 days or less)
what are the mech of sildenafil, verdenafil, tadalafil (cialis)
inhibitors of PDE5
half life for sildenafil and vardenafil
4 h
half life for tadalafil
17.5
what are common side effects of PDE5 inhibitor?
flushing and change in vision
PDE5 inhibitors can cause sudden blood pressure drop to unsafe level when taken with other drugs such as
nitrates and alpha-blocker
PDE5 inhibiros should not be used with
nitrates and alpha blocker
