Reproductive pharmacology Flashcards
What is the mechanism of action of luprolide
GnRH agonist- binds GnRH membrane receptor on pituitary gonadotrope cells.
Usually given in long acting form that eliminates pulsatility and thus causes decreased gonadotropin production
What are indications for GnRH agonists or antagonists?
- testing for precocious or delayed puberty
- suppressing precocious puberty
- endometriosis
- prostate cancer
- decrease endogenous ovarian function to use exogenous ovulation indcution
What are side effects of GnRH agonists?
signs of hypogondadism- hot flashes, bone loss, low libido, amenorrhea
What is a difference in the response to GnRH agonists vs antagonists?
agonists do cause LH/ FSH flare then inhibition
antagonists cause immediate inhibition with no flare
What would be an indication for pulsatile administration of GnRH?
treatment of hypogonadotropic hypogonadism due to hypothalamic dysfunction, ex Kallman syndrome
Daily injections of exogenous ______ stimulate ovarian follicle development
FSH
Injection of hCG (or LH) triggers ______
LH surge, ovulation, and progesterone production
________ are used to treat prolactinomas
dopamin agonists like cabergoline, bromocriptine
Describe the cellular location and biochemistry of the estrogen receptor
nuclear location
bound to heat shock proteins that dissociate upon estrogen binding
receptor dimerizes then can bind estrogen response element in DNA
_______ is a weak estrogen produced by the placenta
estriol
____ is the principle ovarian estrogen; _____ is an estrogen common in post-menopause
estradiol/ estrone
What is the source of most estrogen in post-menopausal women
peripheral aromatization of adrenal androgens
What is the effect of estrogen at bone?
maintains bone mass
stimulates closure of epiphyses
What is the effect of estrogen in the liver?
Stimulates production of SHBG, thyroid hormone binding globulin, and blood clotting factors
What are therapeutic uses of estrogens?
- tx estrogen deficiency in premature ovarian failure, menopause
- prevention, treatment of osteoporosis
- contraception
If estrogen is given therapeutically without opposing progesterone, there is increased risk of __________
endometrial carcinoma
What is the mechanism of action of clomiphene citrate?
Inhibits estrogen binding in the hypothalamus and anterior pituitary, preventing the normal feedback regulation and causing increased secretion of GnRH and gonadotropins, stimulating ovarian follicle development
technically has weak agonist effects, but clinically acts as a pure antagonist
What is the most common use for clomiphene citrate?
ovulation induction
What is the mechanism of action of tamoxifen?
estrogen antagonist in breast tissue.
weak agonist at endometrium and bone.
What are indications for tamoxifen?
ER+ breast cancer
What is a positive side effect of tamoxifen?
anti-resorptive action at bone
What are negative side effects of tamoxifen?
endometrial hyperplasia, carcinoma
thromboembolism
hot flashes
What is the mechanism of action of raloxifine?
estrogen agonist in bone.
estrogen antagonist in breast tissue.
Does not have action at the endometrium
What are indications for raloxifine?
treatment of postmenopausal osteoporosis
What are positive side effects of raloxifene?
decreased risk of ER+ breast cancer
What are negative side effects of raloxifine?
thromboembolism
hot flashes
Inhibition of _____ will result in lower estrogen levels
aromatase
Differentiate between type 1 and type 2 aromatase inhibitors
Type 1 agent, exemestane, is steroidal in structure and acts as irreversible inhibitor of aromatase.
Type 2 agents, anastrozole and letrozole, are nonsteroidal agents and are reversible inhibitors of the enzyme.
What are indications for aromatase inhibitors?
ER+ breast cancer
ovulation induction- type 2/ reversible only
Describe the cellular location and biochemistry of the progesterone receptor
cytoplasmic location
bound to heat shock proteins, dissociation when estrogen binds
List the physiologic effects of progestins
- Inhibits estrogen-induced proliferation of the endometrium
- Prepares endometrium for embryo implantation
- Supports maternal and fetal needs throughout pregnancy
- Withdrawal from progesterone triggers menses
What are therapeutic uses for progestins?
- postmenopausal hormone therapy to avoid effects of unopposed estrogen
- contraception
- support of pregnancies in assisted reproduction where there is no CL
- abortifactants- mifiprisone
_______ and ______ act through a single cytoplasmic androgen receptor
testosterone and DHT
Why can’t testosterone be given orally?
first pass metabolism in the liver
What are clinical uses of androgens?
male testosterone deficiency
What is the mechanism of action of finasteride?
Inhibitor of the enzyme 5-α reductase, which converts testosterone to DHT
What are clinical uses of finasteride?
tx of BPH, male pattern baldness
What is the mechanism of action of spironolactone
weakly blocks androgen receptor
weakly inhibits testosterone synthesis
blocks mineralocorticoid receptor
weak agonist at progesterone receptor
What are uses of spironolactone?
hirsutism
hypertension, CHF
primary hyperaldosteronism
What are adverse effects of spironolactone?
hyperkalemia
irregular menses
gynecomastia
What is the mechanism of action of flutaminde
competitive antagonist of androgen receptor
What are clinical uses of flutamide?
prostate cancer
hirsutism (rarely used)
What is the key adverse effect of flutamide?
hepatotoxicity
