Estrogens Drugs Flashcards
17a-alkylated estrogens
Ethinyl estradiol
Mestranol
Quinestrol
Ethinyl estradiol
17a-alkylated estrogen
Mestranol
17a-alkylated estrogen
Quinestrol
17a-alkylated estrogen
17a-alkylated estrogen MOA
17a-alkylation prevents conversion to estrone -> enhances bioavailability and half life
3-alkylated ether is quickly dealkylated in vivo
Estrogenic esters
Estradiol valerate
Estradiol cypionate
Estradiol valerate
Estrogenic ester
Estradiol cypionate
Estrogenic ester
Estrogenic esters MOA
Esterification decreases solubility and slows the absorption
Slow absorption from the injection site (depot) prolongs the action -> less frequent injections
Prodrugs
Conjugated estrogens
Estrone sulfate
Equilin sulfate
Estrone sulfate
Conjugated estrogen
Equilin sulfate
Conjugated estrogen
Conjugated estrogens MOA
Usually collected from pregnant mares’ urine
Mix of estrogens
50-60% estrone sulfate
20-30% equilin sulfate
Other estrogenic substances
Non-steroidal estrogens:
Diethylstilbestrol
Chlorotrianisene
Diethylstilbestrol
Non steroidal estrogen
Used in 1940-1970 to prevent miscarriages
Increased risk of vaginal adenocarcinoma in women exposed in utero
Used in advanced prostate cancer
Chlorotrianisene
Non-steroidal estrogen
Postpartum breast engorgement
Menopause symptoms
Prostate cancer
SERMS
Selective estrogen receptor modulators
Partial estrogen agonists - block the action of stronger estrogens
Estrogenic in some tissues and antiestrogenic in others
Mostly nonsteroidal estrogens
Hold promise as the alternative for estrogen replacement therapy
SERM types
Tamoxifen
Toremifene
Ospemifene
Raloxifene
Bazedoxifene
Clomiphene
Tamoxifen
SERM
Prodrug: Oxidized in vivo
Partial estrogen agonist
Antiestrogen actions:
Tx breast cancer; prevents breast cancer in high risk women
Estrogenic actions:
Weak estrogen agonist at endometrial cells
Increases the risk for thromboembolic events
Prevents osteoporosis
Toremifene
SERM
Structurally similar to tamoxifen
Used to treat advanced breast cancer
Ospemifene
SERM
Structurally similar to toremifene
Estrogenic effects on the vaginal epithelium
Used to treat dyspareunia in post menopasual women
Raloxifene
SERM; partial estrogen agonist
Tissue-specific activities
Estrogen actions:
Prevents osteoporosis in postmenopausal women (Approved)
Does not stimulate endometrial cells
May cause hot flashes
Bazedoxifiene
SERM
Recently approved analog of Raloxifene with similar activities
Clomiphene
SERM; partial estrogen agonist
Increases secretion of FSH and LH by inhibiting negative estradiol feedback
Used to stimulate ovulation in women with oligomenorrhea or amenorrhea and ovulatory dysfunction (frequently from PCOS)
PCOS:
7% of women of reproductive age
Gonadotropin-dependent ovarian hyperandrogenism
Anovulation and infertility
Fulvestrant
SERD (downregulator)
Pure estrogen receptor antagonist for the treatment of breast cancer
Somewhat more effective than SERM in patients who have become resistant to tamoxifen
Aromatase inhibitors
Anastrozole
Letrozole
Exemestane
Anastrozole
Aromatase inhibitor
Letrozole
Aromatase inhibitor
Exemestane
Aromatase inhibitor
Aromatase inhibitors MOA
Block the biosynthesis of estrogens
Effective in some patients whose breast cancer has become resistant to tamoxifen
Ovulation induction (off-label use)
Gynecomastia
Clinical uses of estrogens
Hormone replacement therapy in postmenopausal women (Relief of CNS disturbances, relief of urogenital atrophy symptoms, relief of psychological effects)
Osteoporosis
Hormonal contraception
Replacement therapy in patients with primary hypogonadism
Castration
