Drugs Flashcards
17B-estradiol
- most potent of human estrogens
- oral preparation, patches, or creams; transdermal route minimizes hepatic effects of estrogens.
- in body it is in equilibrium with estrone
- both are produced by aromatization of testosterone and andosenedione, respectively (testosterone–>17B estradiol and androstenedione–>estrone)
- high first pass effect–>poor bioavailability with oral preparations
Conjugated equine estrogens
- sulfate esters of estrone
- esters are cleaved in the body
Ethinyl estradiol
- most potent estrogen available
- semisynthetic steroid
- C17 ethinyl inhibits first pass metabolism
Mestranol
-is converted to ethinyl estradiol
Therapeutic Uses of Estrogens
- combination oral contraceptives
- postmenopausal hormone replacement therapy
- failure of pituitary function/ovarian development
Adverse effects of estrogens
- gall bladder disease: increase cholesterol levels in bile and cause a 2-3-fold increase in gallbladder disease
- increase risk of thromboembolic disease
- nausea and vomiting
- breast swelling
- migraine headaches
Estrogen therapy contraindications
- pregnancy
- estrogen-dependent cancer
- undiagnosed abnormal genital bleeding
- history/active thrombophlebitis or thromboembolic disorders
Clomiphene
- two isomers: a weak estrogen agonist and a potent antagonist combined (racemic mixture)–antagonizes feedback suppression of GnRH by estrogen
- first-line therapy for infertility due to anovulation
- increases LH and FSH pulse amplitude without changing pulse frequency
- blocks inhibitory action of estrogen on gonadotropin release from pituitary
- side effects: ovarian hyperstimulation, multiples, hot flashes, ovarian cysts, blurred vision
- prolonged use may increase risk of ovarian cancer
Selective Estrogen Receptor Modulators
Interact with ERs and can change interactions with co-activators and co-repressors. ER ligands that can be anti-estrogenic in all tissues, partially estrogenic in some tissues, or anti-estrogenic in some but not others, or purely estrogenic in all tissues
Tamoxifen
-oral, non-steroidal SERM
-competitive antagonist of ER in breast tissue
-treatment of breast cancer in women with ER-positive tumors
treatment of choice for early/advanced breast cancer in women of all ages
-reduces risk of contralateral breast cancer
-can be used as prevention of breast cancer in women at high-risk
-adverse effects: hot flashes, increases risk of endometrial cancer, increase in risk of thromboembolic disease
Raloxifene
- oral
- competitive, partial ER agonist in bone
- treatment and prophylaxis of osteoporosis in postmenopausal women and breast cancer.
- adverse effects: hot flashes, DVT, leg cramps
Aromatase inhibitors
- Letrozole (non-steroidal)–bind reversibly to heme group of CYPs
- Anastrozole (non-steroidal)–bind reversibly to heme group of CYPs
- Exemestane (steroidal)–suicide inhibitor, binds aromatase irreversibly
- treatment of breast cancer, off-label use for ovulation induction and suppression of endometriosis
- side effect: hot flashes
Progestins
- progesterone (natural progestin)–high first pass effect and poor bioavailability
- medroxyprogesterone
- norethindrone–ethinyl substituent at C17 significantly slows hepatic metabolism
Norgestrel
- oral progesterone
- more potent progestin with less androgenic activity
Drospirenone
- synthetic progestin
- new progestin used in combo OC
- spironolactone analog
- anti-MC and progestin activity
- because of MC antagonism, can cause hyperkalemia–monitor in women at high-risk.
