Reproductive Pharmacology Flashcards
Leuprolide–mechanism pulsatile vs. continuous
- pulsatile: GnRH analog with agonist properties
- “Leuprolide can be used in lieu of GnRH”
- continuous: antagonist properties
- downregulates GnRH receptor in pituitary –> decrease FSH/LH
Leuprolide–use
- uterine fibrinoids
- endometriosis
- precocious puberty
- prostate cancer
- infertility
name the estrogens
- ethinyl estradiol
- DES
- mestranol
estrogens–mechanism
- bind estrogen receptors
estrogens–use
- hypogonadism or ovarian failure
- menstrual abnormalities
- hormone replacement therapy in postmenopausal women
- use in men with androgen dependent prostate cancer
estrogens–toxicity
- inc risk of endometrial cancer
- bleeding in postmenopausal women
- clear cell adenocarcinoma of vagina in demales exposed to DES in utero
- inc risk of thrombi
what are the contraindications for estrogens?
- ER + breast cancer
- history of DVTs
name 3 selective estrogen receptor modulators
- clomiphene
- tamoxifen
- raloxifene
clomiphene–mechanism
- antagonist at estrogen receptors in hypothalamus
- prevents normal feedback inhibition and increase release of LH and FSH from pituitary which stimulate ovulation
clomiphene–use
- infertility due to anovulation
- ie. PCOS
clomiphene–toxicity
- hot flashes
- ovarian enlargement
- multiple simultaneous pregnancies
- visual disturbances
tamoxifen–mechanism
- antagonist at breast
- agonist at bone, uterus
- increase risk of thromboembolic events and endometrial cancer
tamoxifen–use
- treat and prevent recurrence of ER/PR + breast cancer
raloxifene–mechanism
- antagonist at breast, uterus
- agonist at bone
*
raloxifene–use
- osteoporosis
raloxifene–toxicity
- inc risk of thromboembolic events but no increased risk of endometrial cancer (vs tamoxifen)
name 3 aromatase inhibitors
- anastrozole
- letrozole
- exemestane
aromatase inhibitors–mechanism
- inhibit peripheral conversion of androgens to estrogens
aromatase inhibitors–use
- ER + breast cancer in post menopausal women
hormone replacement therapy–use
- used for relief or prevention of menopausal symptoms (ie. hot flashes, vaginal atrophy)
- tx of osteoporosis
- inc estrogen, dec osteoclast activity
why is progesterone added to hormone replacement therapy?
- unopposed estrogen replacement therapy inc risk of endometrial cancer, so have to add progesterone
hormone replacement therapy–toxicity
- possible cardiovascular risk
name the progestins
- levonorgestrel
- medroxyprogesterone
- etonogestrel
- norethindrone
- megestrol
- others when combined with estrogen
progestins–mechanism
- bind progesterone receptors
- decrease growth and increase vascularization of endometrium
- thicken cervical mucus
progestins–use
- contraception–pill, IUD, implant, depot injection
- endometrial cancer
- abnormal uterine bleeding
- progestin challenge
explain the progestin challenge
- presence of withdrawal bleeding excludes anatomic defects (ie. Asherman syndrome) and chronic anovulation without estrogen
name the antiprogestins
- mifepristone
- ulipristal
antiprogestins–mechanism
- competitive inhibitors of progestins at progesterone receptors
antiprogestins–use
- termination of pregnancy
- mifepristone with misoprostol
- emergency contraception
- ulipristal
what do you have to administer with Mifepristone?
misoprostol
Mifepristone–toxicity
- (antiprogestin)
- heavy bleeding
- GI effects
- nausea
- vomiting
- anorexia
- abdominal pain
explain combined contraception
- progestins + ethinyl estradiol
- estrogens and progestins inhibit LH/FSH and thus prevent estrogen surge
- no estrogen surge –> no LH surge –> no ovulation
- progestins cause thickening of cervical mucus, so limit access of sperm to uterus
- progestins also inhibit endometrial proliferation –> endometrium is less suitable to the implantation of the embryo
- estrogens and progestins inhibit LH/FSH and thus prevent estrogen surge
- forms include pill, patch, and vaginal ring
what are contraindications for combined contraception?
- smokers > 35 yo
- inc risk of cardiovascular events
- pts with increased risk of cardiovascular dz
- including history of venous thromboembolism, coronary artery dz, stroke
- migraine (especially with aura)
- breast cancer
copper intrauterine device–mechanism
- produces local inflammatory rxn toxic to sperm and ova
- prevent fertilization and implantation
- hormone free
copper intrauterine device–use
- long acting reversible contraception
- most effective emergency contraception
copper intrauterine device–toxicity
- heavier or longer menses
- dysmenorrhea
- risk of PID with insertion
what is a contraindication for copper intrauterine devices?
- active pelvic infection
terbutaline, ritodine–use
- decrease contraction frequency in women during labor
terbutaline, ritodine–mechanism
- beta 2 agonists that relax the uterus
danazol–mechanism
- synthetic androgen that acts as a partial agonist at androgen receptors
danazol–use
- endometriosis
- hereditary angiodema
danazol–toxicity
- weight gain
- edema
- acne
- hirsutism
- masculinization
- decrease HDL levels
- hepatotoxicity
testosterone, methyltestosterone–mechanism
- agonists at androgen receptors
testosterone, methyltestosterone–use
- treat hypogonadism
- promote develop of secondary sex characterisitcs
- stimulate anabolism to promote recovery after burn or injury
testosterone, methyltestosterone–toxicity
- causes masculinization in females
- decrease intratesticular testosterone in males by inhibiting release of LH (negative feedback) –> gonadal atrophy
- premature closure of epiphyseal plates
- increase LDL
- decrease HDL
name 4 antiandrogens
- finasteride
- flutamide
- ketoconazole
- spironolactone
what enzyme is used to convert testosterone to DHT?
5alpha reductase
finasteride–mechanism
- 5 alpha reductase inhibitor
- decrease conversion of testosterone to DHT
finasteride–use
- BPH
- male pattern baldness
flutamide–mechanism
- nonsteroidal competitive inhibitor at androgen receptors
flutamide–use
- prostate carcinoma
ketoconazole–mechanism
- inhibits steroid synthesis
- inhibits 17, 20 desmolase
ketoconazole–use
- polycystic ovarian syndrome
- to reduce androgenic symptoms
ketoconazole–toxicity
- gynecomastia
- amenorrhea
spironolactone–mechanism
- inhibits steroid binding, 17 alpha hydroxylase, and 17, 20 desmolase
spironolactone–use
- polycystic ovarian syndrome
- to reduce androgenic symptoms
spironolactone–toxicity
- gynecomastia
- amenorrhea
tamsulosin–mechanism
- alpha 1 antagonist
- inhibits smooth muscle contraction
- selective for alpha1A, D receptors found on prostate vs. vascular alpha1B receptors
tamsulosin–use
- treat BPH
name 3 phosphodiesterase type 5 inhibitors
- sildenafil
- vardenafil
- tadalafil
phosphodiesterase type 5 inhibitors–mechanism
- inhibit PDE-5 –> inc cGMP –> prolonged smooth muscle relaxation in response to NO –> increase blood flow in corpus cavernosum of penis
- “sildenafil, vardenafil, and tadalafil fill the penis”
- decrease pulmonary vascular resistance
phosphodiesterase type 5 inhibitors–use
- erectile dysfunction
- pulmonary hypertension
- BPH
- tadalafil only
phosphodiesterase type 5 inhibitors–toxicity
- headache
- flushing
- dyspepsia
- cyanopia (blue tinted vision)
- risk of life threatening hypotension in pts taking nitrates
- “Hot and sweaty,” but then Headache, Heartburn, Hypotension
minoxidil–mechanism
- direct arteriolar vasodilator
minoxidil–use
- androgenetic alopecia
- severe refractory hypertension
