Pharm Block II Estrogens Flash Cards

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Title: Pharm Block II Estrogens
Description: pharm, block II, Sept 23, 8am
Number of Cards: 47
Save Count: 3
Author: cohey0311
Created: 2005-09-23
Tags: blockii estrogens pharmacology syapin
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    • Question
    • Answer
    • Side 3
    • natural estrogens
    • -17 beta estradiol (most potent), estrone, estriol
      -aromatized steroid A ring
      -produced in ovary in premenopausal women, testis and adrenal for males, adipose in postmenopausal women
    • regulation of female steroids
    • -cyclical secretion due to LH and FSH
      -early phase feedback inhibition on GnRH, LH and FSH
      -late phase high levels of estrogen stimulate LH and FSH surge
      -progesterone only does feedback inhibition
    • estrogen pharmacokinetics
    • -67% bound to albumin or sex steroid binding globulin
      -estradiol converted to estrone and estriol in liver
      -liver conjugates with sulfuric acid for excretion in the urine
    • effects of estrgen
    • -primary and secondary female sex characteristics
      -skin and blood vessel structure
      -increased coagulability
      -increases HDL/LDL, decreases cholesterol
      -edema by Na and water retention
      -modulation of sympathetic smooth muscle control
    • mechanism of estrogen action
    • -nuclear receptors alpha and beta
      -distribution leads to differential gene expression
      -also a 7 transmembrane G protein receptor
    • natural estrogens in use
    • -given as lipophilic esters in oil, in transdermal patches, or in oral micronized preparations
      -also used sulfate esters of equine esstrone and equilin
    • other estrogen in use
    • -orally active synthetics and non-steroidals
      -ethinyl estradiol (synthetic) is most potent
      -mastranol converts to ethinyl estradiol in body
      -diethylstilbestrol (DES) first cheap potent non-steroidal
      -different plant estrogens
    • common threapeutic uses of estrogens
    • -hormone replacement (HRT): most effective in early menopause
      --used to prevent osteoporosis, vasomotor symptoms, urogenital atrophy
      --CV effects still controversial
      -oral contraception
    • estrogens in contraceptives
    • oral contraceptives usaully include ethinyl estrdiol or mastranol
    • estrogens for menopause relief
    • -small doses of conjugated estrogens or ethinyl estradiol
      -SERMs (selective estrogen receptor modulators) are more selective an may be better
    • other therapeutic uses of estrogens
    • -female hypogonadism
      -ovarian dysgenesis
      -dysmenorrhea or amenorrhea
      -hirsutism
    • estrogens in cancer therapy
    • -superceded by anti-estrogen therapy
      -high doses block GnRH for protatic adenocarcinoma
      --now continuous GnRH preferred
    • adverse effects and toxicity of estrogens
    • -common: nausea/vomit, vaginal bleeding, breast tenderness, endometrial hyperplasia/carcinoma
      -risk of thromboembolic disease, stroke, migraine, cholestasis, gall bladder disease
      -breast cancer risk still controversial
    • contraindications of estrogen use
    • -pregnancy
      -estrogen-dependent breast/uterine cancer
      -idiopathic genital bleeding
      -thrombophlebitis or thromboembolic disorder
    • tamoxifen citrate
    • SERM
      -competative estrogen inhibitor in breast tissue BUT agonist in bone and on lipid metabolism
      -treatment of metastatic breast cancer in postmenopause with tumors with estrogen receptors
      -induce ovulation
      --may cause hot flashes, nausea/vomit, uterine cancer, thromboemoblic events
    • Raloxifene
    • -orally active non-steroidal SERM
      -agonist in bone and lipid
      -antagonist in uterus
      -treat/prevent postmenopause osteoporosis
      -may cause: hot flashes, abdominal pain, infertility, peripheral edema, teratogenesis, thromboembolism, weight gain
    • Clomiphene citrate (enclomiphene)
    • -orally active non-steroidal anti-estrogen (possible SERM)
      -first choice to stimulate ovulation
      -blocks estrogen negative feedback of GnRH
      -also a weak agonist is some responsive tissues
    • side effects of clomiphene
    • -risk of ovarian hyperstimulation syndrome
      -overian cysts or enlargement
      -abdominal discomfort
      -abnormal uterine bleeding
      -breast tenderness
      -blurred vision
    • Danazol
    • -17 β alkyl testosterone derivative
      -pure estrogen inhibition to block LH/FSH surge
      -blocks steroidoenic enzymes
      -also binds to androgen, progesterone, and glucocorticoid receptors (same superfamily)
      -only androgen activity is relevant
    • Danazol pharmacokinetics
    • -long, 15 hr half life
      -mainly used for endometriosis
      -causes: weight gain, edema, breast reduction, hot flashes, headache, cramps, hirsutism, ance, deep voice
    • Anti-aromatase drugs
    • -aminoglutethimide
      -exemestane
      -imidazole inhibitors
    • Exemestane
    • -orally active
      -steroidal enzyme inhibitor
    • Aminoglutethimide
    • -also inhibits P450scc at high doses
    • Imidazole Inhibitors
    • -anatrozole and letrozole
      -orally active, rapid onset
      -total estrogen suppression
      -no angrogen effects
    • Progesterone synthesis
    • -cholesterol to pregnenolone to progesterone
      -metabolized in liver
    • Progesterone Pharmacokinetics
    • -only natural progestin
      -short, 5 min half life
      -inactivated by conversion to pregnanekiol and pregnanolone then conjugation with glucuronic acid
      -index of production is total 3α,20α pregnanediol
    • Mechanism of Progestin Action
    • -one gene gives two receptors: A and B
      -bind progesterone equally
      -A inhibits B action
    • Progestins
    • -17α hydroxyprogesterone metabolites
      -19 nortestosterone derivatives
    • 17α hydroxyprogesterone metabolites
    • -hydroxyprogesterone caproate
      -medroxyprogesterone acetate (MPA)
      -megestrol acetate
    • 19 nortestosterone derivatives
    • -nerethindrone
      -ethylnodiol diacetate
      -norgesterol (gonanes)
      -least androgenic
    • Synthetic progenstin pharmacokinetics
    • -orally active
      -long half lives
      --norethindrone 7 hr
      --nergestrel 16 hr
      --MPA 24 hr
    • Progestin effects in Females
    • -changes endometrium from proliferative to secretory
      -decreases myometrial contractility
      -alveolobular development in mammary gland
      -high doses inhibit ovulation
    • General effect of Progestin
    • -raise body tempurature (not in synthetics)
      -weak aldosterone antagonist leading to Na, Cl, and water loss
      -synthetics have estrogenic, androgenic, anabolic, anti-estrogenic, and anit-androgenic properties
      -potent progestins may decrease HDL
    • Therapeutic Uses of Progestins
    • -usually used with estrogens
      -prevent postmenopausal symptoms
      -oral contrceptives
      -progesterone and hyproxyprogesterone caproate suppress ovary function
      --stop uterine bleeding
      --treat dysmenorrhea
      --treat endometriosis (continuous application)
      --treat hirsutism
    • Toxicity of Progestin
    • -increase blood pressure
      -reduce HDLs by androgenic and anti-estrogenic effects
    • Mifepristone
    • -competative antagonist of progestin
      -used to terminate pregnancy
      -high doses block glucocorticoid binding
    • Norplant Contraceptive system
    • -implanted rubber capsule
      -uses levonorgesterol
      -lasts up to 5 years
      -reguires local anesthesia
      -early in use may cause: breakthrough bleeding, dermatitis, breast discharge, weight gain, anorexia, hirsutism
    • Depo-Provera
    • -medroxyprogesterone acetate
      -150 mg every 3 months
      -may lead to amenorrhea for up to a year after discontinuing
      -increased osteoperosis risk
    • Lunelle
    • -monthly injections
    • Preven
    • -emergency contraceptive
      -ethinyl estradiol (50ug x4 tablets)
      -OR levonorgesterol (0.25mg x4 tablets)
      -contraindicated in pre-existing pregnancy (WHY??)
    • Plan B
    • -emergency contraceptive
      -levonorgestrol (0.75mg x2 tablets
      -first dose within 72 hrs
      -next dose 12 hr later
    • Actions of Oral Contraceptives
    • -thicken cervical mucus
      -alter endometrium
      -decrease motility and secretions of fallopian tubes
      **to block implantation
      -progestin minipills don't block ovulation
    • Other uses of Oral Contraceptives
    • -treat dysmenorrhea or endometriosis that don't respond to estrogen or progestins alone
      -delay menses in hemolytic or hemorrhagic anemia
    • Adverse effects of Oral Contraceptive
    • -first cycle effects:
      --nausea/vomit, headache, dizziness, fatigue
      --abdominal cramps, backache
      --breakthrough bleeding
      --increased appetite, fluid retention, weight gain
      -6% develop clinical depression
      -low doses have low risk of side effects
      -low risk of MI and hypertension
      -increase in thromboembolism
      -amenorrhea may last up to 12 mo, but is responsive to clomiphene
      -high dose may lead to hepatic dysfunction
      -breast cancer risk controversial
      -decrease in ovarian and endometrial cancer
    • Contradindications for Oral Contraceptives
    • -thromboembolic disease
      -cerebral vascular disease
      -MI or coronary artery disease
      -congenital hyperlipidemia
      -hormone-sensitive carcinoma
      -idiopathic vaginal bleeding
      -pregnancy (for real??)
      -liver dysfunction or tumor
    • Contraindications for Progestrin-only Preparations
    • FROM PILLS
      -undiagnosed vaginal bleeding
      -liver disease
      -breast cancer

      DEPOT
      -thrombophlebitis
      -thromboembolic disorders
    • Risk factors with Contraceptives
    • -risk of CV problems if over 35 and heavy smoker
      -hypertension
      -migraines
      -breast cancer