Pharm Ch. 30
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What activate estrogen receptors on bone and vascular tissue while antagonizing estrogen receptors on uterine and breast tissue?
- SERMs (Selective Estrogen Receptor Modulators)
- Tamoxifen (Nolvadex)
- Rolaxafene (Evista)
What is the primary risk factor from estrogen and progesterone?
What was the 1st SERM that doesn't completely block estrogen receptors on uterine tissue and may stimulate endometrial proliferation (increases uterine cancers)?
What does Raloxafene (Evista) do?
- Blocks estrogen receptors on breast and uterine tissues
- Treating osteoporosis
- Side effects: hot flashes depression, insomnia, GI disturbances, joint muscle pain
What do antiestrogens do?
- Antagonize all estrogen receptors
- High levels of estrogen inhibit FSH and LH
- Treat infertility
- Clomiphene (Clomid, Serophene)
What do antiprogestins do?
- Antagonist to progesterone receptors in uterus
- Causes detachment of placenta
- Used to terminate pregnancy/ abort
- Mifepristone (Mifeprex): morning after pill (RU486)- w/in 1st 7 wks of pregnancy
How do contraceptives work?
- Inhibit ovulation and impair development of endometrium
- High levels of est/progest limit release of FSH and LH (limiting LH prevents ovulation)
- Birth control pill typically has fixed amount of est/progest
- Progesterone only: Norplant and Depo Provera
What are rehab considerations of taking hormones?
- Monitor BP
- Education about androgen abuse
What are male and female sex hormones and where are they made?
- Androgens: testes
- Estrogens and progestins: ovaries
- (Made in gonads)
Where is testosterone made? How is it regulated?
- LEYDIG CELLS located in interstitial space betw seminiferous tubules where spermatogenesis occurs
- Regulated by gonadotropins LH and FSH from anterior pituitary
- GH, prolactin, and other homrones also have influence
What does LH do in men?
- Both LH and FSH control spermatogenesis
- Primary hormone that stimulates testosterone production
What does FSH do in men?
- Controls spermatogenesis along with LH
- Stimulates growth and function of Sertoli cells
- Responsible for development and maturation of normal sperm
What are clinical uses of Androgens?
- Replacement therapy
- Catabolic states
- Delayed puberty
- Breast cancer
- Hereditary angioedema
What is used to inhibit the synthesis of effects of endogenous androgen production? (and in prostate cancer or BPH)
What helps treat hirsutism in women or treat prostate cancer?
- Flutamide (Eulexin)
- Antagonist of cellular androgen receptor
What is Buserelin?
- GnRH analog: desensitizes GnRH receptors to decrease LH and testosterone production
What inhibits conversion of testosterone to dihydrotestosterone?
- Finasteride (Proscar)
- Dutasteride (Avodart)
- Accelerates growth of prostate gland
What is Abarelix?
- Directly blocks GnRH receptor on pituitary (decreases LH production)
How are androgens abused?
- Anabolic steroids taken to enhance athletic performance
- 7-14 wk cycles with increase in dosage
- Promote skeletal muscle growth and increase lean body mass
- increased aggressiveness
- Many side effects, even fatal
What do estrogen and progesterone do?
- Promote sexual differentiation and maturation
- Estrogen (Estradiol): initiates growth and development of female reproductive system
- Progesterone: facilitates and maintains pregnancy
What is the menstrual cycle?
- 28 days
- Stimulates ovaries to produce an ovum available for fertilization
- Prepares endometrium for implantation of ovum
- Follicular (Proliferative), Ovulation, and Luteal (Secretory) Phases
What is the Follicular phase?
- Proliferative phase
- 1st half
- Ant pituitary releases FSH which stimulates maturation of several follicles in the ovary (one follicle fully matures and yields ovum)
- Developing follicle secretes estrogen (causes endometrial growth)
What occurs during Ovulation?
- LH release causes ovum release
- Mature follicle ruptures releasing ovum from the ovary
- Travels down fallopian tubes to uterus
- Follicle is corpus luteum after release of ovum
What occurs during the Luteal phase?
- Secretory phase
- 2nd half of cycle
- Corpus luteum grows and develops for 1 week after ovulation and secretes est/progest (this thickens uterine lining)
- Uterus gets ready for implantation
What happens if egg in not fertilized/implantation doesn't occur?
endometrium sloughs off creating menstrual bleeding
What are conditions treated with Estrogen and Progesterone?
- Replacement Therapy
- Failure of ovarian development
- Menstrual irregularities
- Conjugated estrogens (Premarin): oral, transdermal
What happens if fertilization occurs?
- Corpus luteum continues to produce progesterone
- Human chorionic gonadotropin (HCG) is released fron the fertilized ovum and takes over role of LH and rescues corpus luteum from destruction
- Corpus luteum degenerates betw weeks 9 and 14 of gestation
- Placenta produces estrogen and progesterone
- Progest. increases growth of mammary glands
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