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126 Cards in this Set
- Front
- Back
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what are the estorgen receptor agonists?natural
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estradiol and its ester
estrone conjugated estrogens |
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what are teh semi-synthetic estrogen rec. agonists
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ethinylestradiol
mestranol |
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what are the synthetic estrogen rec. agonssti?
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diethylstibiestrol
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what are the progesterone rec. agonists?
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pregnanes-progesterone, medroxyprogesterone acetate
synthetics- 19-nortestosterones -norethynodrel -norethindrone/norethindrone acetate -ethynodiol -nogestrel -desogestrel, gestodene, norgestimate |
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what are the estrogen rec antagoinst/SERMs?
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tamoxifen
clomiphene raloxifene |
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what is the prototype progesterone receptor antagonist?
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mifepristone
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what are the antiestrogenics?
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aromatase inhibitors-anastrzole, exemestane, letrozole
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what are the xenoestrogens?(foreign)
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envrionmental estrogen/phytoestrogens- isoflavones, resertrol
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what are the gonadotropins?
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FSH(urofolliculin)
HCG menotrophins(hMG=FSH+LH) |
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what are the antigonadotropins?
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danazol
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what are the GnRH analogs?
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leuprolide
gonadorelin nafarelin goserlin remember relin for GnRH analogs |
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what releases GnRH? and what is it?
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hypothalamus releases gonadotropin releaseing hormone(GnRH)
its a decapeptide that goes to the pituitary and sims increased synthesis and release of gonadotropins |
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what is important about the release of GnRH?
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its pulsatile over a course of a few mins
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what are the two gonadotropins?
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FSH and LH
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what is the structure of FSH and LH?
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they are alphabeta dimers
the alpha units is common to hCG, TSH, FSH, and LH the beta subunit confers biological specificyt |
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what are the actions of FSH?
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stimulates ovarian follicular development
increases estradiol output promotes matureation of ovum induces LH receptors |
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what are the actions of LH?
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supports corpus luteal function
midcycle surge of LH leads to ovulation |
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what does ovary secrete ?
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estrogen
progesterone androgens |
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what are three parts of the ovary that secrete and what do they secrete?
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follicle-estrogen
corpus lueteum-estrogen/progesterone stroma secretes androstenedione/testosterone |
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what are the feed back relationships of the female hormones?
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all products feedback to inhibit the pituitary and hypothalmus
BUT at midcycle there is a LH surge even in the presence of high estradiol levels, this leads to ovulation |
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what are the effects of estrogen?
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growth development and maintence of primary and secondary sex characteristic
proliferation of the endometrium increase uterine and tubal motility watery cervical secretions suppression of FSH ***************below are the pertinent side effects that estrogens cause medically Na and water retention increased in clotting factors(eps,. if orally given) lipid alterations decreased LDL increased HDL decreased cholesterol |
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what is the dominant control fo estrogen?
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everything is set up for fertilization
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what are the effects of progestins?
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develop of secretory endometrium
viscous, low volume cervical secretions decreased uterine motility thermogenic effect(1degree F increase) suppression of LH release |
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what occurs under dominent progesterone effects?
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condition in the feamle reproductive tract are optimzed for implantation
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what are the phases of ovulatory cycle?
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follicular phase-development
ovulation leuteal phase-corpus leuteum |
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what phase produces the greates variablity in length that can make a cycle more irregular?
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follicular phase
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what hormone sustains the corpus leuteum? and what is the relations btw them?
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LH sustains corpus
coprus release progesterone progesterone inhibits LH loss of LH cause death of corpus |
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what occurs after menses?
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progesterone is low, and estrogen is low as well as LH and FSH low.
all these are low so there is no feedback inhibition on pituitary. so it starts to amp back up its production and starts cycle over again. |
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how must you take temp to check for ovulation?
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very carefully dont even get out of bed little movement at all can lead to increased temp. use of special thermometer
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what is an important enzyme in synthesis of estrogen?
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all estrogens are synthesyzed from an androgen by the action of aromatase.
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what are the sites of estrogen production?
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ovary primary source
adrenal secondary source-this is where men and postmenopausal women get estrogen from) they are secreted as androgen and converted peripherally to estrogen |
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what is the interaction of LH and FSH with the granulosa/theca cells?
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LH stims theca cell to produce androstenodione(androgen)
the androgen floats over to a granulos cells which is stimulated by FSH to produces estrogen from the androgen. |
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how is GnRH suplemented?
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can be made synthetic'
given parentally or nasally cant take orally |
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how is FSH, LH and hCH given?
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derived from natural, cant synthesize
not given orally, must be parentally |
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how is estrogen found in blood?
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most bound to proteins main protein is Sex hormone binding globulin. only 2% is free and available for action.
therefore there is a huge resouire for estrogens. |
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how is progesteron found in blood?
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just like estrogen except its bound to coticosteroid binding globulin mainly
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how is estrogen and progesterone metabolized?
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phase 1 oxidations
phase 2 conjucation with sulfates and glucuronides |
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how are estrogens and progesterones excreted?
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urinary and fecal as conjugates
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what are the conjugates of estrgen found?
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premarin and CEE
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how long does it take for the estrogen/progestones to effect after release/administration?
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minutes to hours to be turned on and to be turned off
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how long does it take for FSH/LH/GnRH to work?
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seconds to minutes to turn on and turn off.
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what is the most important estrogen receptor agonists?
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the ones the have ethine addition to the 17 alph carbon. this prevents liver metabolism of them and allow them to survive first pass metabolism when given orally. normal estrogen will be almost entirely metabolized in first pass if given orally so they arent.
mestranol quiestrol ethyl estradiol |
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what is another name for mestranol?
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17 ethinylestradiol
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what is important about synthetic estrogen receptor agonsist and pregnancy?
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they are teratogenic so you must make sure they are not pregnant when you give them.
especially diethylstibestrol.(DES) |
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what are the estrogens found in the environment?
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phytoestrogens-soy flavones often taken as dietary supplement
DDT- not on market but still present in enrivonement as pesticide bisphenol- found in some plastics genistien- one of the soy derived phytoestrogens |
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what are the three major ways to inhibit estrognic action?
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interfere with gonadotropin release and susequent ovarian estrogen production
inhibit synthesis (aromatase inhibitors) block estrogen receptors |
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what are the two estrogen receptor antagonist?
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clomiphene
tamoxifen |
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what is clomiphen used fore?
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anovulatory inhertility treatment
helps people get pregnant originally created to be used as a contraceptive but ended up making people have twins and triplets instead! |
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what is tamoxifen used for?
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useful fro the manegment of estrogen dependent cancers but it is being replaced by the aromatase inhibitors
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what are the aromatase inhibitors?
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anastrozole
exemestane Ietrozole used in treatment of estrogen dependent cancers as well as just overall decreasing of endogenous estrogens. |
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what is a SERM?
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selectie estrgen recepotr modulator
RALOXIFENE- SERMs are drugs that have a selective affinity for sublasses of estrogen receptors. |
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what is Raloxifene used for?
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targets the bone estrogen receptors to prevent post menapausal osteoporosus, but it does not stimulate breast or uterine tissue which could cause increased risk for estrogen induced cancers.
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what is diference btw progestin and progesterone?
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progestin is name of class of agents and progesterone is the name of a specific molecule that is in that class (the main biologic one)
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what are the progesterone receptor agonists?
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natureal-progesterone
semi-synthetic medroxyprogesterone and derivatives synthetic 19-notestosterones |
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what drugs are used primarily as the oral progesterone contraceptives?
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19-nortestosterones
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what are the synthetic progestin?
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....gestrels
.....drone nore..... norg...... norethindrone norethyndodrel norethindrone acetate ethynodiol diacetate levonorgetrel di-Nogestrel desogestrel gestodene norgestimate |
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what is important to know about the generations of the synthetic progestins?
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increasing progestin potency and decreaseing androgenic effects as you get to higher and higher generations
4th gen drugs desogetrel and gestodene have high levels of cardiac negative effects than any of the prior gen drugs. |
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what are the pregnane progestins?
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chlormadinone acetate
megestrol acetate medroxyprogesterone acetate more closely resemble chemical progesterones. |
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what is mifepristone(RU486)
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pregesterone receptor antagonist
inhibits the uterine quieting effects of progesterone which leads to less ability to implant or maintain a pregancy used as early term abortion pill. |
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what is needed alone with mifepristone to induce abortion more effiecently?
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alone only 75% effective
usually given with a prostaglandin-prostaglandins direclty stimulate uterine contractions which in combo with mifepristone will cause abortion |
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what are some other uses for mifeprisone?
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it has some level of corticosteroid activity so it may have some potential utility in treatment of cushign, glaucoma, and other OB/gyns stuff
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what is a major source of gonadotropins?
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derived from urine and placenta
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what is the antigonadotropin?
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danazol
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what is danazol used for?
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endometriosis
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what are the GnRH analogs?
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gonadorelin
leuprolide nafarelin goerelin |
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what are oral estrogens used for?
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hormone replacement in menopause
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who is more likely to have fractures caused by loss of bone density in menopause?
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white female
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what is the controversy in hormone replacment therapy?
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improves bone strength may help cognitive, but does increase risk of cardiovascular problems
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what is important when giving progestin to woman to help prevent loss of pregnancy?
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must be careful with doseing too much can virilize the fetus
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progestin only has what problem
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33% intolerance due to break through bleeding sporadically at unexpected times
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what is important in choosing oral contraceptive?
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estrogen cause anovulation as well as cardiac problems
so must find right amount of estrogen to get effect but not cardiac issues, pair that with progesterone for increased effect. |
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what are the main interactions of oral contraceptives
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increased clotting factors-so causes issues with anticoagluants doses
p450 inducers will make these drugs ineffective broad sprectrum antibiotics- sterilzes the gut and net estrogen decreases and loss of efficacy of oral contraceptive |
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what is importatn about oracl contraceptive and T4 measures?
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oral contraceptives increase TBG which lead to increased T4 bound to TBG which results in a raised total T4 but normal free T4 our tests measure total T4
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what are serious contra indications to oral contraceptives?
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history of throboembolic
imparied hepatic function/obst. jaundice estrogen dependent neoplasia pregancy smking greater that 15 cigs a day and older than 35 |
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what is treatment of hyperprolactinemia?
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bromocyptine
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what is treatment of polycytic ovary syndrome?
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cycling OCs clomiphene
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unfavorable cercical mucus treatment
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topical estrogen
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oyxtocis are what?
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agenst that simtulate uterine contraction
Also stims milk ejection(not production) |
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what are toclytics?
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agents that inhibit uterine contraction
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what is oxytocin similar to?
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ADH
has about 1/10 effect of ADH |
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what is good about oxytocin half life?
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very short half life allow for us to use it to induce labor and if we give to much we can just stop it and it will break down fast.
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labor inductino indications
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?
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labor induction contraindications?
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?
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effects of ergot alkaloids?
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bleeding???
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importance of cervix role in induction?
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cervix must be ripened or it will rupture can do this with prostaglandins
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what are tocoyltics used for?
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to prevent preterm labor
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what are the tocolytics?
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MgSO4
beta-2 adrenergic agonists indomethacin nifedipine-ca channel antagonist |
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how do you reverse MgSO4?
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calcium gluconate
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what is risk in beta 2 adrenergics?
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stimulation of heart bc no such thing as pure alpha 2 agonist
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what is norethindrone?
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is the prototype of the 19-nortestosterone family of progestins. 17-ethinylation yields an orally acting agent; removal of C-19 changes an androgen to a progestin
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why is urine used to get gonadotropins
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The urine of postmenopausal women is rich in gonadotropins because they do not have estrogen suppressing their release from the pituitary.
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13. Describe the periodic patterns of secretion for GnRH and the relationship to the therapeutic uses of synthetic analogs: intermittent versus continuous administration
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a. Under normal conditions, GnRH is released in a pulsatile pattern from the hypothalamus.
b. GnRH analogs can be used to either increase or inhibit gonadotropin release. The effect that the analogs will have depends on the rate/frequency of administration. |
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how GnRH used to stimulate pituitary gnadotropin secretions and increase ovarian functino?
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c. To stimulate pituitary gonadotropin secretion and increase ovarian function you want to mimic endogenous GnRH release (give pulsatile doses). Typically use an infusion pump. May be used to “kick-start” delayed puberty.
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To decrease pituitary gonadotropin release using GnRH?
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constant or depot administration is necessary. This is usually given in the form of a depot injection or as a nasal spray. This is used in endometriosis, prostatic cancer, and precocious puberty.
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what are the GnRH analogs?
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i. Gonadorelin
ii. Leuprolide iii. Nafarelin iv. Goserelin |
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b. Dysmenorrheal: difficult and painful menstruation. May be treated with
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oral contraceptives, but the drug of choice is more likely to be an NSAID.
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d. Hirsutism: due to excess androgen production is treated how?
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If the source is ovarian, you can use oral contraceptives to decrease LH output. LH stimulates androgen production, so androgen levels will decrease.
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f. Suppression of postpartum lactation?
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Bromocryptine is the drug of choice (dopamine agonst, decreases prolactin release).
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a. Decreased ovarian function in menopause leads to
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vasomotor symptoms, paresthesias, muscle cramps, arthralgia, anxiety, and dizziness. Strategy for treatment is replacement therapy with hormones.
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what is the progression of bone density with age and how is it dealt with?
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b. Bone density reaches its max around age 30. It decreases in both men and women after this, but more rapidly in women, especially after menopause. The most effective way to maintain bone density is to start with more at age 30. Another goal is to extend the time to fracture threshold by slowing loss of bone density.
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what are some therapuetic alternatives to estrogen as hormone replacement in post menapause
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as bisphosphonates and SERMs
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16. Explain the rationale for the use of estrogen receptor antagonists and aromatase inhibitors for the treatment of breast cancer
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a. Breast cancer is often a hormone responsive tumor. Estrogen signaling stimulates proliferation of the tissue in these tumors. Therefore, blocking estrogen receptor stimulation either directly or by inhibiting the synthesis of estrogen can decrease the growth of breast cancer tumors.
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why are a. The naturally occurring steroids are not useful as routine oral contraceptives
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Modification of C-17 enhances oral activity. otherwise it undergoes 90% first pass metabolism
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mechanisms of action a. Estrogen or post-coital combination pills (“morning after”):
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the mechanism is uncertain, but these probably alter tubal and uterine motility sufficiently to interfere with implantation. Not used in an attempt to influence ovulation.
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MOA Progestin only: contraceptive strategies
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can be taken either as a minipill or in parenteral depot administration. These do inhibit ovulation but this effect does not sufficiently explain their efficacy. Effects on endometrial lining, uterine motility and cervical secretions contribute to efficacy.
issue of intolerance due to bleeding |
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c. Combination type MOA contraceptive
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these are combinations of a semi-synthetic estrogen and a 19-nortestosterone. These are given in low constant doses for days 5-25 of the menstrual period and inhibit gonadotropin release. Thus no ovum matures or is released. The estrogen is primarily effective for inhibition of ovulation and the progestin ensures proper withdrawal bleeding.
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d. Progesterone receptor antagonistsMOA contraceptive
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increased uterine mobility (inhibiton of implantation), some inhibition of ovulation.
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19. List the effects of estrogens on laboratory tests, including liver function, clotting factors, and thyroid hormone disposition.
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a. Increased clotting factors
b. Lipid alterations c. Increased TBG and total T4 (pt is not actually hyperthyroid, oral contraceptives just increase liver synthesis of TBG) |
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20. List the most significant drug interactions with estrogens and progestins.
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a. Anticoagulants: due to an increase in plasma clotting factors, the effect of oral anticoagulants may be diminished.
b. Hepatic microsomal enzyme inducers: since hepatic metabolism plays a large role in the elimination of steroids, agents that induce these enzymes may increase the rate of inactivation of oral contraceptives, diminishing their efficacy. This is especially problematic because as a rule of thumb, you chose the lowest possible dose of estrogen. Any increase in metabolism may bring estrogen levels below the therapeutic range. Inducers = Phenobarbital, phenytoin. c. Enterohepatic cycling alterations: long term broad spectrum antibiotics may reduce intestinal flora which normally produce enzymes that regenerate active steroids from inactive Phase II conjugates. Advise patients to use alternative form of contraception during such therapy. |
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21. Discuss major adverse effects/contraindications for estrogens and progestins and explain known causes for these
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a. Estrogen excess: cervical mucorrhea, edema, nausea, bloating, breast tenderness, vascular headache, hypertension
b. Estrogen deficiency: early/mid-cycle breakthrough bleeding c. Progestin excess: acne, hirsutism, depression, fatigue, increased appetite (and weight gain other than fluid retention), vaginitis, alopecia d. Progestin deficiency: delayed withdrawal bleeding, late-cycle bleeding e. In general: i. If the problem is a menstrual irregularity, you probably have a deficiency in one or the other components. ii. If the problem is due to excess estrogen – think salt and water retention. iii. If the problem is due to excess progestin – think anabolic side-effects of the 19-nortestosterones. f. Significant adverse effects of combination oral contraceptives: i. Thrombophlebitis, thromboembolism (due to increased clotting factors) ii. Increased risk of MI iii. Increased risk of stroke iv. Risk of cardiovascular disease is greatly compounded by other risk factors including age over 35, obesity, hypertension, family history, and smoking v. Increased glucose intolerance vi. Hypertension (usually responsive to diuretics) vii. Increased incidence of hepatoma viii. Increased incidence of gall bladder disease ix. Principle: both the efficacy as an anti-ovulatory agent and the serious cardiovascular side effects of the contraceptives are due to the estrogenic component. |
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what are contraindications for estrogens and progestins?
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g. Absolute contraindications:
i. History of thromboembolic disease ii. Impaired hepatic function/obstructive jaundice iii. Estrogen dependent neoplasia/breast CA/genital bleeding iv. Pregnancy v. Smoking tobacco h. Relative contraindications i. Migraine, hypertension, DM, epilepsy |
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22. Discuss the relationship between hyperprolactinemia and anovulatory infertility. Describe the mechanism of action of dopaminergic agonists used to treat this.
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a. Hyperprolactinemia is one of the causes of anovulatory infertility. Dopamine from the hypothalamus normally inhibits prolactin secretion from the pituitary. Therefore, dopamine agonists such as Bromocriptine can be used to decrease prolactin secretion and allow ovulation to occur.
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23. Describe the use of drugs such as clomiphene for the treatment of anovulatory infertility.
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a. Clomiphene is a SERM that acts as an antagonist in the hypothalamus and pituitary and as a weak agonist in the ovaries. In patients who have low gonatropin levels due to abnormal feedback communication, it can be used to interrupt negative feedback to the hypothalamus and pituitary and increase gonadotropin secretion from the pituitary. Blockade at the estrogen receptor in the pituitary and hypothalamus disrupt feedback inhibition to GnRH, LH/FSH secretion increased secretion of GnRH, LH/FSH increased gametogenesis and steroidogenesis in ovaries.
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23. Describe the use of drugs such as gonadotropic drugs for the treatment of anovulatory infertility.
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b. In patients who are anovulatory due to pituitary hypofunction (not abnormal feedback communication), you can use FSH/LH to stimulate the ovary directly.
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Oxytocin stimulate ?
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i. Endogenous oxytocin is synthesized by the paraventricular nucleus and secreted by the posterior pituitary. Secretion is stimulated by mechanical forces – uterus, breast, vagina. It elicits milk ejection in lactating women and increases the rate and force of uterine contractions.
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24. State the usual route of administration ii. Oxytocin
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ii. Oxytocin injection: can be given IM or IV. Short plasma half-life (5-15 minutes) allows for excellent control of uterine contractility using infusion during labor. Post-partum blood loss can be minimized by injection of oxytocin to simulate sustained contraction. Only the gravid uterus will respond to oxytocin.
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what are the oxytotic agents?
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oxytocin
prostaglandins ergot alkaloids |
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character of prostaglandins?
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i. Somewhat more difficult to control than oxytocin, but still excellent oxytocic agents that will contract both the gravid and non-gravid uterus.
ii. Prostaglandin E2 - Dinoprostone: useful as abortifacient and for ripening of the uterine cervix. Also useful for post-partum bleeding. Often given by vaginal suppository. iii. 15-Methylprostaglandin F2 – IM iv. Misoprostol |
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use of ergot alkaloids?
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i. Ergonovine: IM or IV administration. Difficult to control so used for post-partum bleeding control.
ii. Methylergonovine iii. Not for induction of labor. |
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25. Describe the sensitivity of the uterus to the various oxytocics and how this changes during pregnancy.
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a. Uterine sensitivity to oxytocin increases dramatically in the third trimester of pregnancy. Oxytocin not a very active uterine stimulant in early pregnancy. If you want to stimulate the non-gravid uterus or in the first 2 trimesters, a better choice would be direct stimulation with a prostaglandin.
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26. Discuss the clinical use of the oxytocics
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a. The oxytocics are used for induction of labor, induction of therapeutic abortions and treatment of incomplete abortions, and control of postpartum bleeding.
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indications for induction of labor and contraindications.
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b. In general labor induction is indicated only when the risks of continuing the pregnancy are greater than the risks of induction.
c. Indications: i. Diabetes Mellitus ii. History of intrauterine demise iii. Prolonged pregnancy (>40 wk) iv. HTN v. Bleeding complications vi. Preeclampsia (HTN, edema, proteinuria) d. Contraindications: i. Fetopelvic disproportion ii. Unfavorable presentation iii. Invasive cervical ca iv. If vaginal delivery not desirable – don’t induce |
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27. State the mechanism of action for mifepristone (RU 486) and other abortifacients
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a. Mifepristone is a progesterone antagonist that blocks the activity of progesterone at its receptors. Since progesterone is necessary for the maintenance of pregnancy, this can lead to termination of the pregnancy. It is often given in combination with Misoprostol, a prostaglandin analog. Misoprostol causes strong myometrial contractions, leading to expulsion of tissue.
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a. Toxolytics are agents that
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relax the uterus. They are used to prolong pregnancy until the fetus is viable
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Toxolytics agents
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i. MgSO4
ii. Beta-2 adrenergic agonists 1. Ritodrine 2. Terbutaline iii. Indomethacin iv. Nifedipine |
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28. List appropriate indications for using pharmacological tocolysis to forestall labor
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b. Treatment includes bedrest first, then if premature labor occurs, the fetus is less than 34 weeks, there is cervical dilation of 3-4 cm, and there are no contraindications, you can use pharmacologic therapy to forestall the labor.
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