female reproduction Flashcards
Potency of natrual estrogens
Estradiol> Estrone> Estriol
Estrogen preps
17B- estradiol- oral (micronized prep) because of 1st pass effect (IM, patch , creams) Ethinyl estradiol (a semisynthetic steroid) most post available, oral C 17 ethinyl inhibits first pass metabolism- slower metabolism Mestranol- converted to ethinyl estradiol Conjugated equine estrogens (Premarin)- sulfate esters of estrone oral, injectable, cream, esters cleaved in the h=guy
pharmacokinetics
Lipophilic majority of circulating estrogens are bound to sex steroid binding globulin and albumin, rapidly metabolized in the liver to estrone and estriol, 2 intracellular estrogen receptors ER alpha and ER Beta
Estrogen effects
Dev- epiphyseal closure
During menstrual cycle- Endometrial proliferation, peristalsis, cervical mucous, feedback (neg and pos)
metabolic effects- increased bone density, increased HDL and decrease LDL, increase coagulation
Therapuetic uses of estrogens
Como oral contraceptive- Ethinyl estradiol, mestranol
Failure of pituitary function and ovarian development- Equine estrogens, ethinyl estradiol, mestranol
Failure of pit function and ovarian development- equine estrogens, thinyl estradiol
Post meno hrt, conjugated equine e
SE and contraindications
SE: thromboembolic events, endometrial hyperplasia, breast changes
Contraindications: pregnancy, estrogen dependent cancers - progesterone modulates risk, undiagnosed uterine bleeding, thromboembolic disorders
Clomiphene
Anti estrogen,
Indication- infertility
MOA- inhibits estrogen negative feedback, increases gonadotropin release
SE- ovarian hyperstimulation syndrome, hot flushes
Tamoxifen
SERM (selective estrogen receptor modulator
MOA: mixed estrogen antagonist in breast, agonist in bone, uterus
Indication- treats/ prevent breast cancer
SE- uterine cancer, thromboembolism, hot flushes
Raloxifen
SERM
MOA- estrogen agonist in bone, antagonist in breast and uterus
Indication- treats breast cancer in postmenopausal women with high risk of osteoporosis
SE- thromboembolism, hot flushes, muscle cramps
letrozole, anastrozole
aromatase inhibitors
MOA- Non steroidal reversible inhibitors of aromatase
indication - treats breast cancer in post menopausal women
letrozole- also trrats infertility, increase FSH, se- decreased bone density, hypercholesterolemia
anastrozole- SE hot flushes, weakness arthritis
no risk of thromboembolism
exemestane
Aromatase inhibitor
MOA- Steroid, suicide substrate, IRREVERSIBLE inhibition of aromatase
Indicatedsd in post meno breast cancer
SE- hot flushes and fatigue
Progesting
Cholesterol to pregnenolon (scc)
Preg-> progesterone (3 b hsd)
Binds to corticosteroid binding globulin and albumin, some binding to SHBG
Rapid first pass elimination- low oral bioavailability
2 isoform of progesterone receptor (PRA and PRB)
progestin preparations
progesterone- low oral bioavailability (Micronized, injection, suppositories, gels)
Medroxyprogesterone acetate- modified progesterone esters injected some oral
Norethindrone, levonorgesterel, etonogesterl- testostesterone derivatives, good oral activity, implantable, prolonged plasma half lives
Drospirenone- a spironolactone analogue, has antimineralocorticoids, and progestin activity
Progestin Effects
Aka progestation
secretory endometrium, decreased oviduct peristalsis, thinken mucus, mammary gland development
therapuetic uses- Contraceptives- norethindrone, levonorpgestresl, etonogestrel, drospirenone, medroxyprogesterone acetate
Post meno HRT- Norethindrone, levonorgestrel, Medace
SE- Blood lipid alterations- increased LDL, edema and weight gain, androgenic action, headache and breakthru bleeding
Mifeprestone
Progesterone antagonist-
Mechanism- competitive progesterone receptor modulator, primarily antagonist use
Pregnancy termination- FDA approved thru 70th day, follow later with misoprostol or dinoprostone to promote expulsion of the blastocyst
SE- abdominal pain, nausea, may have serious bleeding
GC antagonist
Ulipristal
Partial agonist at progesterone receptors, MOA- inhibits ovulation and alters endometrium
Use- emergency contraception effective for 5 days post intercourse
hormonal contraception goals
effective, easy to use, limited side effects, reversible
Combo- estrogen and progestin or Progestin only
Combined oral contraceptives
COC- pill- highly effective
Estrogen- ethinyl estradiol or mestranol
Progestin- Norethindrone, levonorgestrel, etonogestral, drospirenone
Mono or multiphasic, multiphasic variations of dosing allows decrease in hormone concentrations
MOA of COC Action
Disrupts feedback, inhibits ovulation (negative feedback on hypothalamus, decreased gonadotropin levels (LH surge))
Disrupts the conditioning of endometrium, thickens cervical mucus, decreases oviduct peristalsis
Progestin only contraception
MOA- suppress ovulation, thicken cervical mucous, block implantation
Oral- norethindrone, Implant (levonorgestrel, etonogestrel), IUD (Levonorgestrel), Medroxyprogesterone SE- bone lossd
Emergency conraception- postcoital
Combined oral contraceptives (levonorgestrel and ethunyl estradiol - 2 doses)
Levonorgestrel alone (2 doses)
Ulipristal
Contraceptive Adverse effects
Combination oral contraceptives- thromboembolic disorders, migraine headaches, others
Progestin- only Contraceptives- breathru bleeding, acne, headaches, bone thining for depot (Medroxyprogesterone)
Drug interactions
Drugs that reduce the effects of OCs- penicillin V, Ampicillin, tetracycline, rifampin, Carbamazipine, phenytoin
Drugs whose effects are reduced by OCs- Warfarin, insulin and other hypoglycemic agent
Contraindications of COCs
Thromboembolic or cerebrovascular disease, MI, CV disease, Cervical, endometrial or breast cancer (estrogen dependent), undiagnosed abnormal genital bleeding, pregnancy or suspected preganncy
Uterine Fibrinoids and endometriosis treatment
Leuprolide
MOA- GnRH analog (agonist if pulsatile, antagonis if continuous)
Initial surge of estradiol then declines
Use- uterine fibrinoids, endometriosis central precocious puberty
SE- hot flushes, decreased libido
Contraindication- pregnancy CAt X, breast feeding
Danazol
Testosterone orally active,
MOA- suppresses LH reelase, testicular, ovarian functions
Indication- Treat endometriosis and hereditary angioedema
SE- hepatotoxic, acne
Druga to prevent labor (preterm)
Prevention of preterm labor- progesterone, inhibits cervical ripening and uterine contraction
Tocolytic agents- used for short term delay of labor, decrese uterine contractile activity:
Nifedipine, CCb, antihypertesnsivc, indomethacin, magnesium sulfate, tervutaline (beta agonist, No
drugs for labor induction
dinoprostone- PGE2 analog, causes cervical ripening
Misoprostol- PGE1 analog, peptic ulcer, ripens cervix, increases uterine contraction
Oxytocin- enhances uterine contraction, decreases postpartum blood loss, cross reacts with vasopressin receptor
Methylergonovine- third stage of labor, strongly increases uterine contractions, decreases pospartum blood loss, contraindicated in HTN
