Female Pharm [last years material...do paper notecards too!] Flashcards
(28 cards)
What should we use to promote folliculogenesis in women with hypothalamic anovulatory [dys]fxn?
daily injxn of both FSH & LH
What should we use to promote superovulatory folliculogenesis in women with hypothalamic anovulatory [dys]fxn?
inject **FSH & LH **on day 2-3 of menstrual cycle
What should we use to promote folliculogenesis in women with endogenous estrogen activity & normal hypopit-ovarian fxn?
clomiphene citrate: estrogen antagonist that induces FSH secretion
- MC used
What are menotropins and urofolitropin?
urinary derived human gonadotropins [FSH & LH] pooled from postmeopausal women, concentr8d and purified
menotropins: injected, w/ FSH & LH activity (Pergonal)
- pergonal & hCG given in sequence for ovulation in anovulatory women & for prodxn of multiple follicles
Urofolitropin: injected, w/ FSH activity ONLY (Metrodin)
- metrodin & hCG given in sequence to induce ovulation in PCOS
- in pt’s w/ high FSH/LH & IF clomiphene Tx FAILED
What are recombinant human gonadotropins?
what are they used for?
available immediately & are consistent
follitropin** a (Gonal-f; FSH) & follitropin b **(Follistim; FSH)
- a & b are synthesized the same, making identical dimeric a-FSH & B-FSH subunits that differ in glycosylation & purification
- induce follicle development
- w/ hCG = induce ovulation
Which has a better rate of pregnancy?
Mixed gonadotropins or FSH [recombinants] only dosing?
neither; they have similar pregnancy rates
What are the side effects of the folliculogenesis inducing drugs and recombinant gonadotropins?
Hyperstimulation
Multiple Fetuses
Ovarian hyperstimulation syndrome
What is ovarian hyperstimulation syndrome?
shift of vascular fluids to abdominal & thoracic cavities
-usually mild Sx’s, occassionally severe
Clomiphene citrate!
Its the one to know!!! See paper notecard
What is/are 2 Step Ovulation Induxn?
- follicular stimulation using combined FSH +/- LH or clomiphene followed by:
-
hCG to stimulate LH surge
- induces follicular maturation
- follicle aspiration or ovulation if desired
What is the role of hCG?
- binds LH/CG-R so has LH-like indxn of ovulation
- stimulates estrogen primed follicle to induce meiotic resumption of oocytes
- used following follicle stimulation by clomiphene or gonadotropins
What is a synthetic GnRH agonist?
Leuprolide [See paper NC]
What are Cetrorelix and Ganirelix?
GnRH Antagonists
- competitive antagonists–> suppress gonadotropin release
-
Use: fertility, prevents endogenous LH surge while promoting folliculogenesis w/ exogenous gonadotropins
- in prostate & breast cancer Tx to inhibit steroid prdxn
- in benign uterine disease [fibroids]
***DO NOT see transient increase in FSH & LH as w/ GnTH agonists
Describe the formation of natural estrogens
What do estrogens do?
Fxns?
- development, growth, & maintenance of sex accessory tissues
- skeletal growth & body shape development
- key regulator in HPO axis & thus; in maintenance of mense cycle
- metabolic: Na+ & H2O retention, ^^HDL & decrease LDL
What are the 3 major uses for estrogen?
- oral contraceptives
- usually in combo w/ progestin
- interfere w/ LH surge & ovulation
- H replacement therapy
- usually with progesterone
- Dysmenorrhea
Which is the principal/primary form of natural estrogen?
what biochemical addition can be made to it?
Estradiol 17b
- readily absorbed in tissues
- 1st pass metabolism limits oral effectiveness
- Addition at C-17 reduces metabolism & makes orally active
What are some pharmokinetics of estrogens in general?
What does esterification do to estrogens?
- 1st pass metabolism limits oral efectiveness [add C-17 decreases this problem]
- esterification decreases abdorption rate from parenteral site
- use: patch, gel, vaginal ring = BC
-
metabolism: LIVER
- metabolites conjugated
- conjugates excreted in K or bile
- circulating estradiol is bound to steroid hormone binding globulin {SHBG]
- estrogens increase synthesis of SHBG
- androgens decrease synthesis of SHBG
What are examples of a SERM?
Tamoxifen [selective estrogen R modulator]
Raloxifene & Toremifene
[see paper NC]
What is Fulvestrant?
MOA?
Use?
SE’s?
SERD: selective estrogen R Down Regulator
- PURE estrogen antagonist [blox R binding & down regulates R in al tissues]
-
Use: also ER+ breast cancer Tx
- IM injxn [1 month?]
- oxidized & conjugated, excreted in feces
- SE’s: GI disturbances, hot flashes, thromboembolism
What are the axns/fxns of progesterone?
what gene is involved?
- develop & maintain secretory endometrium
- promote uterine relaxation in prego
- w/drawal during late prego ids part of parturition
- preps breast for lactation
- 2 R’s: PR-a & PR-b on one gene
What are the 5 major uses for synthetic Progestins?
- oral contraceptive
- alone or w/ estrogens
- Emergency contraception =/- estrogens
- H Replacement Therapy
- alone or w/ estrogens
- Dysmenorrhea
- Luteal support for implantation & pregnancy
What is the main form of Progestin?
How is it synthesized?
Progesterone, C21 Steroid
Synthesis:
- corpus luteum makes it during 2nd half of menstrual cycle
- Placenta makes it in 2nd & 3rd trimester
- Other tissues: Testes & adrenal…anytime/always?
What is a synthetic form of:
C21 Progestin/Pregnanes?
19-nor-testosterones/Estrane?
19-nor-testosterone/Gonane?
C21/Pregnane= Medroxyprogesterone acetate
19NT/Estrane= Norethindrone
19NT/Gonane= Levonorgestrel
- more potent & used at lower doses than others
