Leuprolide mechanism
-GnRH analog with agonist properties when used in a pulsatile fashion; antagonist properties when used continuously (downregulates GnRH receptor in the pituitary leading to decreased FSH/LH)
Clinical use of Leuprolide
infertility prostate cancer uterine fibroids precocious puberty
Clinical use of estrogens (ethinyl estradiol, DES, mestranol)
-hypogonadism or ovarian failure -mesntrual abnormalities -HRT in postmenopausal women -used in men with androgen dependent prostate cancer
Toxicity of estrogens
-increased risk of endometrial cancer -bleeding -clear cell adenocarcionma of vagina (DES) -increased risk of thrombi
Estrogens are contraindicated in…
ER + breast cancer and those with a hx of DVTs
Selective Estrogen Receptor Modulators (SERMs)
-Clomiphene -Tamoxifen -Raloxifene
Clomiphene is an…
antagonist at estrogen receptors in the hypothalamus that prevents normal feedback inhibition leading to increaed release of LH and FSH from the pituitary which stimulates ovulation.
CLompihene is used to treat…
infertility due to anovulation (PCOS).
Clomiphene may cause…
hot flashes, ovarian enlargement, multiple simultaneous pregnancies and visual disturbances.
Tamoxifen is an…
antagonist on breat tissue and agonist in bone and the uterus.
Tamoxifen is associated with…
endometrial cancer and thromboembolic events.
Tamoxifen is primarily used to treat and prevent recurrence of…
ER + breast cancer.
Raloxifene is an…
agonist on bone and antagonist at the uterus.
Raloxifene increases risk of…
thromboemblic events.
Raloxifene is used to treat…
osteoporosis bc it decreases resorption of bone.
HRT is used for…
relief of menopausal symptoms and osteoporosis.
Unopposed estrogen replacement therapy increases risk of…
endometrial cancer so progesterone is added.
Anastrozole/Exemestane are…
aromatase inhibitors used in postmenopausal women with breast cancer
Progestins MOA
bind progesterone receptors to decrease growth and increase vascularization of the endometrium
Progestins Use
used in oral contraceptives and in treatment of endometrial cancer and abnormal uterine bleeding
Mifepristone MOA
competitive inhibitor of progestins
Clinical use of mifepristone
termination of pregnancy (administered with misoprostol (PGE1))
In OCPs, estrogen and progestins inhibit…
LH/FSH and thus prevent the estrogen surge. No estrogen surge means no LH sruge means no ovulation.
In OCPs, progestins cause…
thickening of the cervical mucus (limiting access to sperm) and they inhibit endometrial proliferation making it less suitable for implantation.
Contraindications for OCPs
smokers > 35 hx of thromboembolism, stroke or estrogen-dependent tumors
Terbutaline is a…
beta2-agonist that relaxes the uterus; usted to decrease contraction frequency in women during labor.
Danazol MOA
synthetic androgen that acts as a partial agonist
Use of Danazol
endometriosis and angioedema
Toxicity of Danazol
-weight gain -edema -acne -hirsutism -masculinization -decreased HDL -hepatotoxicity
MOA of Testosterone and Methyltestosterone
agonist at androgen receptors
Use of Testosterone and Mehtyltestosterone
-hypogonadism -promotes development of secondary sex characteristics -stimulation of anabolism to promote recovery after burn or injury
Toxicity of testosterone
-masculinization -decrease intratesticular testosterone (gonadal atrophy due to decreased LH) -premature closure of epiphyseal plates -increased LDL, decreased HDL
Finasteride is a…
5alpha-reductase inhibitor that decreases the conversion of testosterone to DHT
Finasteride uses
-BPH -male pattern baldness
Flutamide is a…
nonsteroidal competitive inhibitor of androgens at teh testoterone receptor.
Flutamide is used in…
prostate carcinoma.
Ketoconazole inhibits…
steroid synthesis (inhibits 17,20-desmolase).
Spironolactone inhibits…
steroid binding, 17alpha-hydroxylase and 17,20-desmolase.
Ketoconazole and spironolactone are used in the treatment of…
PCOS to prevent hirsutism. Both have side effects of gynecomastia and amenorrhea.
Tamsulosin is an…
alpha1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for alpha1A,D receptor found on prostate.
Sildenafil and Vardenafil MOA
inhibit phosphodiesterase-5 causing increased cGMP, smooth muscle relaxation, increased blood flow and penile erection
Toxicity of Sildenafil and Vardenafil
-dyspepsia -impaired blue-green color vision -risk of life-threatening hypotension in pts taking nitrates (since they block teh breakdown of NO)
