Female Pharmacology Flashcards
converts the androgens (Testosterone, Androstenedione and Hydroxyandrostenedione) to the respective estrogens, Estradiol, Estrone and Estriol)
the aromatase enzyme
What are the three natural estrogens and which is the most potent?
Estradiol>Estrone>Estriol
67% of circulating estrogens are bound to:
Where is estrogen metabolized?
sex steriod binding globulin and albumin
in the liver
There are two nuclear estrogen receptors: _______and_____.They are ligand-activated transcription factors that increase or decrease the transcription of target genes. They have different tissue distributions and transcriptional regulatory effects on a wide number of target genes
ER-alpha and ER-beta.
Both ERs exist as multiple mRNA isoforms due to differential promoter use and alternative splicing. This concept of _________in ER conformation is central to understanding the mechanism of action of estrogen agonists and antagonists.
There is evidence of a cell membrane receptor for estrogen that signals non-transcription estrogenic effects.
ligand- mediated changes
enhances skeletal maturation and epiphyseal growth plate closure to limit linear growth and a role in feedback regulation of gonadotropin release
Estrogen
Estrogen has positive effects on bone mass mainly by decreasing the number and activity of
osteoclasts
Estrogens alter a number of pathways affecting the clotting cascade. Estrogens slightly____ a number of coagulation factors II, VII, IX, X, and XII, and________ the anticoagulation factors protein C, protein S, and antithrombin III. Fibrinolytic pathways also are affected, with decreased levels of plasminogen-activator inhibitor 1 (PAI-1) protein with a concomitant increase in fibrinolysis. Thus, estrogens______ both coagulation and fibrinolytic pathways – an imbalance in these opposing activities could cause adverse effects.
increase
decrease
increase
Estrogens role in cervical mucus and endometrium
increases amount of cervical mucus and its water content to facilitate sperm penetration as well as promoting endometrial proliferation
The naturally occurring hormone,______ is secreted by the ovary, mainly from the corpus luteum during the second half of the menstrual cycle. It’s synthesis is a component of corticosteroid biosynthesis cascade.
progesterone
Progesterone acts on the progesterone receptor (a steroid receptor). It is a single gene that encodes two isoforms, PR-A and PR-B. How are they distributed?
ratios of each depend on tissue type and actvity depends on target tissue. MOstly results in stimulatory effect but sometimes inhibitory
In plasma progesterone binds to _______ and ______ while some progestins bind to SHBG
Progesterone has a RAPID first pass effect
corticosteroid binding globulin and albumin
Effect progesterone on GnRH pulses
Decreases frequency of GnRH
Effect of progesterone on estrogen driven endometrial proliferation
decreases estrogen-driven endometrial proliferation and leads to development of a secreatory endometrium.
*abrupt decline in progesterone at end of cycle is main determinant of the onset of menstration
AFfect of progesterone on cervical mucous and pregnancy
makes mucous viscid and maintains pregnancy
Effect of estrogen and progestin on endometrium
estrogen: proliferation
Progestin: secreatory to limit proliferation
Affect of estorgen and progestin on cervical mucous
Estrogen decreases viscosity and increases amount of cervical mucous
Progestin **increases **and decreases amount
Effect of estrogen and progestin on uterine contractions
Estrogen will favor rhythmic contractions and the progestin will decrease contractions
collected from mare’s urine and contains sulfate esters of estrone, equilin, and other naturally occuring compounds
Conjugated equine estrogens
is the most potent of the natural estrogens in humans.
Preparations: Oral (micronized prep, because of first pass effect) patches, creams. The transdermal route minimizes hepatic effects of estrogens.
17B-estradiol
(PREMARIN) contain sulfate esters of estrone, equilin and other equine compounds - **oral, esters are cleaved in the body. **
Conjugated equine estrogens
(estradiol valerate or estradiol cypionate) are available and are dissolved in oil and injected I.M. resulting in slow release.
Estrogen esters
(a semisynthetic steroid) is the most potent estrogen available. (Oral) – C17
ethinyl inhibits first pass metabolism (t 1⁄2 = 13 to 27 hours).
Ethinyl estradiol
Therapeutic uses of estrogens
* Combination oral contraceptives
* Postmenopausal hormone replacement therapy
Failure of pituitary function/ovarian development
Toxic side effects of estrogen therapy
Gall Bladder disease (2-3 fold increase)
Oral estrogen increases risk of thromboembolic disease
nausea and vomiting
breast swelling
migraine headaches
When is estrogen therapy contraindicated?
pregnancy, estrogen-dependent cancers, undiagnosed uterine bleeding, thromboembolic disorders
orally active with two isomers: a weak estrogen agonist and a potent estrogen antagonist
***works as a partial agonist at estrogen receptors.