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80 Cards in this Set
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Indications for estrogens
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• Oral contraceptives
• Post-menopausal hormone replacement therapy infertility, lack of puberty cancer osteoporosis abnormal endo bleeding lyeomyoma Uterine stimulant/tocolytic |
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natural Estrogens
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Estradiol -17 β
Modifications(dec 1st pass, doa Micronized estradiol Esterified estrogens estropipate Estrone (and maybe equine congugated estrogens) |
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modifications to estadiol
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Modifications(dec 1st pass, ^doa)
Micronized estradiol Esterified estrogens estropipate |
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Synthetic Estrogens
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Ethinyl estradiol
Mestranol (coverted to above in body) (and maybe conjugated Synthetic Es) |
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Synthetic Estrogens
uses |
Ethinyl estradiol
Mestranol highly used for OCT |
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equine congugated estrogens
indications |
• Isolated form pregnant equine urine
• Post-menopausal hormone replacement therapy(#1 used) |
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conjugated Synthetic Es
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• Derived from yam and soy bean plants
• Contains 9 of 10 natural estrogens (modified) • Not bioequivalent to natural estrogens |
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Diethylstilbestrol
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-Synthetic, oral, nonsteroidal estrogen
-was used for threatened abortion (was found to be teratogenic after 30 years of use-clear cell carcinoma and REPRO DEV probs) -now for metastatic prostate cancer |
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Sx of E deficiency
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Vag/urethral atrophy, emotional change, osteoporosis, dec. REM, inc. CV disease, fatique hotflash (and other vasomotor probs.
(LH, FSH levels go way up due to loss of - feedback- the increase in weak androgens creates some estrone but is not adequate) |
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E indications in menopause
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early Sx of E def (hotflash, U tract atrophy)
-osteoporosis prevention |
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why use combo E & P therapy
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unapposed E cause bigtime endometrial cancer. need the P to alow differention of the endo not just growth
(so no hysterectomy = combo) |
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E therapy
Adverse Reactions |
GB disease
thromboembolis in healthy and non (oral route worse but better for lipid prophile) increased Breast cancer (E is cancer Promotor, not carcinogen) can increase CV disease in ALLREADY sick hearts (paradoxical) |
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synthetic Es are worse in what side effects
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more liver, clotting and BP problems with ethynyl. E, mestranol, and DES
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E MoA
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intracellular-R
E-R complex acts as TF to mod. gene expression |
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paradoxical effect of Es on CV sytem
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good for healthy, premenopasal no cv probs--=cardioprotective
at incraesed dose or with CV disease =makes thing worse (trigger) |
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Nonsteroidal Estrogens
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• Isoflavones (soy beans)
• Lignans (flax seeds) • Appears to have agonist/antagonist activity in natural supplements conc. are varied |
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SERMS
named |
Tamoxifen
Raloxifene Clomiphene |
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E doses replace Vs. OCT
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dose is much lower in replacement therapy (20%)
goal is red. Sx not restore |
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primary indications Of Es
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Replacement in failure of ovarian
development (say turners) -Postmenopausal hormone replacement therapy -Contraceptives |
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Tamoxifen
Moa |
SERM
• Estrogenic in … Endometrium, CV system Bone • Anti-estrogenic in … Breast there are alpha and beta E-r in various tissues plus specific co-activators/repressors & TFs giving E a tissue specific response |
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important tissue specific E responses
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ENDO/MYOmetrium-growth, cervix-thin mucus,
Vag-growth Keratinization breast-growth bone-density cv-varied liver and brain |
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Tamoxifen
indications |
E + in bone, endo, antag in breast
prophyl tx E sensitive • Breast cancer (male also)- now even used premenopausal in high risk) • Decreases risk of breast CA in high risk women • Fibrocystic breast disease |
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TAmoxifen SEs
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• Symptoms of menopause
• Drug interaction with warfarin • Increased risk of endometrial CA & thromboembolism • Retinopathy |
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Raloxifene
actions indications SEs |
SERM
• Estrogenic in … Bone • Anti-estrogenic in … Breast Endometrium indic. • Osteoporosis in post meno (prophyl, Tx) • Symptoms of menopause • Drug interaction with warfarin • Increased risk of blood clots equal to estrogen |
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Raloxifene Vs. Tamoxifen
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invasive cancer same
non invasive cancer dec w/Tamox uterine CA,DVT,PE- dec w/ralox so a tradeoff tamox usually used for BR. cancer- because it is older and more predictable |
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CLomiphene
moa |
SERM
Anti-estrogenic in … Hypothalamus • Blocks negative feedback of estradiol • Increases GnRH • Increases LH & FSH • Increases stimulation of gonads |
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CLomiphene
indications |
• Infertility
Increase ovulation rate Must have responsive ovaries Increase sperm count Blocks negative feedback of testosterone ---will thicken cervical mucus (?) |
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CLomiphene
Ses |
• Thick cervical mucus
• Ovarian enlargement • Symptoms of menopause (hot flashes) • Visual disturbances • Drug interaction with warfarin • Multiple births When used to stimulate ovulation |
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SERMS all
SE |
all increase the symptoms of menopause
being hugely researched |
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Estrogen Receptor Antagonist
named |
Fulvestrant (2nd line drug)
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Fulvestrant
indication SEs |
Estrogen Receptor Antagonist
• Metastatic breast cancer Newly approved for the treatment for estrogen receptor positive metastatic beast CA (NOT RESPONSIVE ON TAMOXIFEN) given as DEPO injection 1/month causes menopausal Sx |
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Progestins from T
named |
Levonorgestrel Norgestrel (high potent high androgen, some anti E)
Norethindrone, Ethynodiol diacetate (slight andro, slight E) Norgestimate Desogestrel (very low andro, some anti E) |
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Progestins from T
indications |
most common • Oral contraceptives
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Progestins
• Derived from 17α-hydroxyprogesterone named |
Hydroxyprogesterone
Megestrol acetate Medroxyprogesterone acetate |
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Progestins
indications |
• Test for continuous estrogen synthesis in amenorrhea
• Dysfunctional uterine bleeding • Endometriosis • Endometrial CA • Renal cell CA • Contraception • Luteal phase defect and adjunct in postmenopausal H replacement |
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Progestins
SEs |
minimal usually well tollerated
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Drospirenone
MOA INDIcations |
Synthetic P, related to SPIRonolactone
w/ antiandro,anti ALDO used in contracepitives (YAZ) and in hormone replacement may have benifit in PMS,HTN) |
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ANTI Progestins
named |
Mifepristone
(RU486) also antiglucocorticoid |
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Mifepristone
MOA indications |
Progesterone Receptor Antagonist
• Glucocorticoid receptor antagonist • Pregnancy Termination Effective until day 49 From 1st day of last menstrual period Typically used w/ misoprostol Prostaglandin agonist • Off label Cushing’s syndrome Emergency contraception Endometriosis Uterine leiomyomata Breast CA (Progesterone +) BUT VERY TIGHT REGUlation and thus hard to use |
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Mifepristone
CIs |
Pregnancy & breastfeeding
Anti-coagulant therapy Bleeding disorders Adrenal insufficiency |
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GNrH agonists
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Gonadorelin
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Gonadorelin
MOa indications |
GNrH agonists
• Amenorrhea • Infertility (given pulsatile)---in • Used when there is no GnRH (rare) |
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GnRH SUPERagonists
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Leuprolide (• SubQ, IM, Depot)
Goserelin (IV) Nafarelin (intranasl) histerilin acetate(new for suppress precocious puberty) |
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Leuprolide
Moa |
(Goserelin Nafarelin)also
GnRH SUPERagonists- • Continuous administration Down regulates GnRH receptors in pituitary Inhibits LH & FSH Inhibits Gonads • Inhibits Pituitary without CV risks of high estrogens (prostate CA) |
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Nafarelin
indications |
GNRH superago (=ANTAGONIST)
• Prevention of LH surge in women undergoing controlled ovarian hyperstimulation Endometriosis • BPH • Precocious puberty • PMS • Uterine leiomyoma (Estrogen-dependent) Shrink tumor before surgery • Breast CA (tamoxifen-resistent) • Prostate CA |
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GnRH SUPERagonists
SEs |
• Brief stimulation of gonads before down regulation
“Flare” of steroidogenesis Giver testosterone or estrogen receptor antagonist to prevent the flare • Chemical castration or chemical menopause • Osteoporosis with long-term use Due to loss of steroids • Hot flashes Think: Chemical castration = menopause (Osteoporosis & hot flashes assoc w/ menopause) |
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GnRH antagonists
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Ganirelix
Cetrorelix Abarelix |
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histerilin acetate
indications |
gnrh super agonist
histerilin acetate(new for suppress precocious puberty) |
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Ganirelix
Cetrorelix indications |
GnRH antagonists
• Prevention of LH surge in women undergoing controlled ovarian hyperstimulation short DOA than abarelix) |
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Aborelix
indications |
GnRH Antagonists
• Advanced Prostate Cancer In pituitary, immediate receptor antagonism DEPOT-stays in muscle---1/month |
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gnrh antagonists
SEs |
the RELIX family
• gani and cetro) NOT approved for long-term treatment • Chemical castration • IMMEDIATE allergic reaction (anytime) |
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gonadotropins
named |
Menotropin (lh/fsh)
Urofollitropin (FSH)folli Follitropin (FSH) Chorionic gonadotropin (lh like) |
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gonadotropins
indications SEs |
fsh/lh + AC---cAMP
• Hypogonadism (♂ or ♀) • Oligospermia (♂) • Stimulate follicular growth in infertile women Due to FSH activity Monitor ovaries daily (ultrasound) SEs Watch out for multiple follicles (multiple births) ovarian hyperstimulation syndrome) |
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Chorionic gonadotropin
actions indications |
LH like activity (stim ovulation)
• Stimulate ovulation when follicular growth was simulated by menotropin, follitropin, urofollitropin • Cryptorchidism • Infertility • Hypogonadism • Oligospermia |
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ASSISTED REPRO TeCHNOLOGIES
drugs and the actions |
-Leuprolide, Ganirelix, Cetrorelix:
to inhibit endogenous LH surge -Menotropin, Urofollitropin, Follitropin: to stimulate follicular growth -Chorionic gonadotropin: to stimulate ovulation |
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Aromatase Inhibitors
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Aminoglutethimide (not as specific as others)also adrenal-)not as widely used)
Anastrozole Letrozole Exemestane (IRREversible) |
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Anastrozole
indications |
Aromatase Inhibitors (Anastrozole, Letrozole, Exemestane)
for • Tamoxifen-resistant Breast CA Where tamoxifen has failed |
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Letrozole
SEs |
Aromatase Inhibitors (Anastrozole, Letrozole, Exemestane)
all create symptoms of E deprivation (hotflash, osteopor....) |
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Endometriosis:
defined |
Endometrial tissue escapes from the
uterus and implants in the abdominal cavity. It then responds to cyclic changes in estrogen and progesterone during the ovarian cycle. Patients have dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. |
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Endometriosis
Tx |
Surgery (Dx usually requires it)
•Oral contrac. continuously instead of cyclically •Progestins (in preg ENDO decidualizes these last two trigger this) •GnRH superagonists (dec E=dec growth)(watch osteoporosis etc. use SHORT TERM) |
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Fibrocystic breast condition (cyclic):
Tx |
-Bromocriptine: dopaminergic
-Oral contraceptives -Progestins -Tamoxifen: anti-E -Danazol: weak andro |
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Hirsutism:
causes |
If sudden Rapid--needs med attn.
(Ovarian and adrenal neoplasms, polycystic ovary syndrome, ACTH- secreting tumors, and late-onset CAH)ALL INCREASE ANDROGENS all woman have some androgens (facial hair is a cultural...) |
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Hirsutism:
TX |
if rapid blah
-surgery for tumors -OCT- (decr. endogenous steroidogen.) -glucocorticoids (when caused by CAH-turns off by feedback) -eflornithine -spironolactone: androgen receptor blockers |
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eflornithine
MOA uses |
Ornithine decarboxylase inhibitor
-Don’t understand mechanism • Hirsutism Hair growth slows and hair lightens and becomes finer but comes back when stop used as topical cream (effective 20-40%) |
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prevention of post partum lactation
Tx |
Estrogen or estrogen/androgen agonists
were used in the past, but rebound lactation can occur with them. FDA says--no drug should be routinely used for this---PrL only up for a week |
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DRugs that interact with Reproductive function
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• Anti-neoplastics
• Nicotine (premature Ovarian Failure) • Heroine, cocaine, marijuana • DES • Sprionolcatone (esp MALE) • Metoclopramide • Excess levothyroxine • Methyldopa • Thioridizine (incr PrL - LH FSH) |
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herbals/ naturals that interact with Reproductive function
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ST. John's wart-- (+)CYP 3A4 (-) natural steroids (decrease OCT effect
black cohosh-used for dysmennorea,PMS , menopause may be a SERM GRAPEFRUIT- (-)CYP 3A4 + endogenous steroids |
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Uterine STimulants
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Oxytocin
Misoprostol Donoprostone Carboprost (prostaglandins) Ergonovine Methylergonovine (fungus) |
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OXYTOCIN
MOA indications SEs |
• Augmentation of labor
• Prevention/Control of uterine bleeding after delivery MOA (IV IM) • Stimulate uterine contractions works via own Receptor (upregulated by(?) must be ready) SEs- • Uterine rupture • Maternal/fetal death |
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Misoprostol
indication MoA |
• NSAID-induced ulcer prophylaxis
• Off label Induce cervical ripening (soft enlarge) Induction of labor Pregnancy termination with mifepristone *Cheaper than Donoprostone (1.50 vs 150.00) MOA Prostaglandins • Stimulate uterine contractions PGE1 Agonist |
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Donoprostone
MOA INDIcations |
Donoprostone
PGE2 Agonist • Induce cervical ripening • Intrauterine fetal death (induce labor of unborn) • Hydatidiform mole • Pregnancy termination |
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Misoprostol
SEs |
• Diarrhea
• Menstrual irregularity Prostaglandins cause regression of the corpus luteum |
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Donoprostone
SEs |
• Uterine rupture
• Cervical laceration • Transient fever (opposite of ASA) • Contraction of vascular, GI, bronchial smooth mm. • Nausea, vomiting, diarrhea |
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Carboprost
everything about it |
PGF-2a
Ind-• Refractory postpartum bleeding • Pregnancy termination AVAILABLE only through the hospital |
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ERgonovine
moa indications |
• Stimulate uterine contractions
Obtained from fungus (ergot) uses • Expulsion of placenta (not routine) • Prevent uterine bleeding & atony after delivery |
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best drugs for
Labor induction, cervical ripening: (2) Augmentation of labor:(1) Prevent uterine bleeding after delivery:(3) |
Labor induction, cervical ripening:
1. Misoprostol 2. Dinoprostone Augmentation of labor: 1. Oxytocin Prevent uterine bleeding after delivery: 1. Oxytocin 2. Ergonovine, Methylergonovine 3. Carboprost |
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Uterine tocolytics:
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progesterone
Beta adrenergic agonists Ritodrine Terbutaline Magnesium sulfate Indomethacin NONE are very effective (P is good if started early in a woman with a previous history of premature labor) |
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magnesium Sulfate
MoA indications SEs |
• Uncouples excitation-contraction of uterine myometrium smooth mm.
Halt premature labor Mg is very toxic--fatal--must monitor |
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Indomethacin
moa,indications,SEs |
(-) Prostaglandin sythesis
• Halt preterm labor • Premature closure of ductus arteriosus in fetus |
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Beta adrenergics in premature labor
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Ritodrine
Terbutaline can halt for 48-72 hours but with B agonist SEs |
