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39 Cards in this Set
- Front
- Back
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MOA of estrogens?
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Estrogen enters cells and binds to intracellular receptors altering their conformation.
The receptor – estrogen complex binds to estrogen response elements (ERE) on various genes and regulates their transcription, resulting in protein synthesis. The types of response elements on the genes transcription factors vary from cell to cell and determine the response to estrogen in that cell. There are two estrogen receptors, Era and ERb, with different tissue distributions, different responses to estrogenic substances, and different biological functions. In addition, the specific transcription factors that are recruited by the estrogen receptor seem to be tissue dependent, and probably account for some of the target specificity of estrogen action. |
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physiological/pharmalogical effect of estrogens
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Female maturation – estrogens are necessary for normal maturation.
They stimulate the development of the vagina, uterus, and fallopian tubes, as well as secondary sex characteristics. Stimulate growth and closure of epiphysis at puberty. |
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what stimulates the development of endometrial lining?
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Estrogens
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maintenance of normal structure of skin and blood vessels
Decreases bone resorption increases HDL decreases bile acid secretion are the metabolic effects of what? |
Estrogens
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What effect do estrogens have on blood coagulation?
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Increased factors II, VII, IX, and X (vitamin K dependent factors), and decreased antithrombin III
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how does estrogen travel in the blood?
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bound to sex steroid binding globulin and albumin (to prevent metabolism)
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natural estrogens and their esters are not effective orally...why?
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significant first pass hepatic metabolism
Ethinyl estradiol and non-steroidal estrogens are metabolized very slowly by liver and are active orally |
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Excretion of estrogens occurs by what method(s)? what is important about this?
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primarily renal and biliary excretion of conjugated metabolites
bacteria in GI will deconjugate the metabolite and it will be reabsorbed (enterohepatic recirculation) |
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why were transdermal patches of estradiol made?
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FEWER metabolic alterations
oral prep can cause changes in synthesis of blood clotting factors and other liver proteins |
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what kind of estrogen is used in transdermal and vaginal estrogen preps?
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estradiol 17B (active form)
because it is not going through the liver you don't have to worry about breakdown |
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vaginal rings (estrogen) use? 2
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maintain mucus membrane in the vagina (menopausal)
systemic effect: prevent osteoporosis |
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Most frequent adverse reaction of estrogens?
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– nausea is most frequent; may be accompanied by anorexia and vomiting
MORNING SICKNESS others: Weight gain Chloasma Hypertension Decreased glucose tolerance Thromboembolism Cancer (breast, uterine) Migraine headache GERD |
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Cancer (breast, uterine) can be a side effect of what drug? so who is contraindicated?
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Estrogen
DO NOT GIVE TO ANYONE WHO ALREADY HAS TUMOR--IT WILL STIMULATE IT TO GROW |
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2 main uses of estrogen?
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mainly replacement therapy and oral contraception
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What are the 2 ways estrogens are used as replacement therapy?
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Failure of ovarian development (helps with breast development, social factors)
Menopause (HRT: hormone replacement therapy) – combination of estrogen and progestin-to lower the rate of endometrial carcinoma) |
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You can use estrogen to treat vasomotor symptoms of menopause (such as hot flashes, night sweats, ect) but what would contraindicate this use?
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Consider the woman’s age, risk factors for CV disease, stroke, and breast cancer
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estrogens can be used for osteoporosis, but what is preferred?
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Bisphosphonates
(-dronates) |
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T/F
Estrogen replacement therapy protects women from CV disease and increased risk of strokes/MI/DVT |
FALSE
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what are some of the herbals that can have weak estrogenic effects?
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Soy/isoflavone
black cohash advise women who have had breast cancer not to use it |
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What does Raloxifine do? adverse effects?(2)
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it is a Selective Estrogen Receptor Modulator
but stimulates or blocks the action of estrogen depending on the organ system it is an agonist in bone, but an antagonist in breast and endometrium Therapeutic use – replacement therapy to prevent osteoporosis in post-menopausal women; reduce breast cancer risk in post-menopausal women Adverse reactions – most common are hot flashes and leg cramps. Also increased incidence of venous thrombeombolism |
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What does Tamoxifen do? clinical use?
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Selective Estrogen Receptor Modulator
Blocks estrogen receptors in breast, but has agonist activity in bone, liver, and endometrium Tamoxifen may cause endometrial cancer (partial agonist at uterine estrogen receptors) but benefits probably outweigh risk Used to treat women post tumor/mastectomy--REDUCE OCCURRENCE OF BREAST CANCER (5 years) |
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what type of drug is tamoxifen? what blocks it?
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Prodrug
must be activated by metabolism by CYP2D6. Some drugs (eg. fluoxetine (Prozac) inhibit activation |
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using +/- list the effects of the drugs
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what is Clomid/Clomiphene used for? How does it do this?
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treats infertility by inhibiting estrogen receptor (primary drug used to do this, inhibiting negative feedback on the hypothalamus, inhibiting the action of estrogen on the pituitary)
this increases GnRH (removing negative feedback)-->increased LH/FSH-->Ovulation |
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side effects of Estrogen receptor antagonist – clomiphene (Clomid)
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Multiple births
Ovariain hyperstimulation syndrome |
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in addition to infertility, what can comiphene be used for?
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Fibrocystic breast disease
estrogen receptor antagonist |
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what does Fulvestrant do? treats?
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E2 receptor antagonist used in treatment of metastatic breast cancer.
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what type of drug is anastrozole? used to treat?
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Aromatase inhibitors (blocks the production of estrogen)
tx breast cancer |
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what type of drug is letrozole? used to treat?
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Aromatase inhibitors (blocks the production of estrogen)
tx breast cancer |
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as compared to tamoxifen, what do the aromatase inhibitors have a decreased risk for? But what problem is there with the aromatase inhibitors?
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decreased risk of endometiral cancer
but they induce menopause-->osteoporosis |
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what does danazol do? used to tx?
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a synthetic derivative of 17-ethinyl-testosterone with weak progestational, androgenic, and glucocorticoid activities.
It induces a pseudomenopausal state by suppressing LH and FSH release. This results in a decrease in estrogen and progesterone synthesis resulting in amenorrhea, anovulation, and atropy of the uterine endometrium Danazol is used to treat endometriosis |
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what hormones control the synth/release of progesterone?
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FSH/LH/hCG
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physiological actions of progestins?4
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Development of secretory endometrium during luteal phase of cycle. Decline of progesterone causes onset of menstruation.
Pregnancy – important for maintenance of pregnancy Mammary gland – aids in development of secretory tissues CNS thermogenic action – increases body temperature ~ 1°F. Also produces sedation |
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MOA for progestins
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Mechanism of action – steroid type mechanism resulting in increased protein synthesis.
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do progestins undergo the first pass effect?
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yeppers
Derivatives have greater oral effectiveness |
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what can you use to treat dysfunctional uterine bleeding?
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Progestins
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adverse effects of progestins?
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Weight gain,
cramps, acne, pigmentation changes, drowsiness, and depression |
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What kind of drug is Mifepristone? Use?
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Progestin Antagonist (blocking progesterone receptors)
Used to terminate early pregnancy (along with misoprostol-induce uterine contraction) |
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side effects of mifepristone?
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Side effects include vaginal bleeding, crampy abdominal pain, nausea, vomiting, diarrhea, and headache
Progestin Antagonist |
