Flashcards in Reproductive Pharmacology Deck (23):
What are the indications for pulsatile administration of GnRH v. long acting or continuous administration of GnRH agonists?
pulsatile: used to establish follicular development and ovulation in hypogonadtropic hypogonadism/Kallmann Syndrome
long acting/continuous: initial stimulation with following inhibition which is used in treatment of precocious puberty, endometriosis, fibroids, fertility treatment (with assistive technology) or androgen deprivation for prostate cancer
*also in LHRH testing for precocious and delayed puberty
What are the adverse effects of GnRH agonists?
non-pulsatile agonists create a chemical menopause and side effects include hot flashes, low-libido, amenorrhea and infertility
in certain cases "add-back" therapy may supplement a small amount of estrogen to support bone health
What are the therapeutic uses of FSH, LH and HCG?
used in futility treatment and endocrine support
FSH injections stimulate ovarian follicle development and sperm production
hCG can be used in place of LH to stimulate ovulation and progesterone production, enhances spermatogenesis and testosterone secretion
Give two expamples of dopamine receptor agonists.
bromocriptine and cabergoline- these dopamine receptor agonists inhibit prolactin production
Describe the general mechanism by which nuclear receptor superfamily function and which of hormones work via nuclear receptor mechanism.
receptors, located in the nucleus of target cells are bound by hormone and release heat shock proteins
two receptors dimerize and subsequently bind to target DNA sequences and regulate gene transcription
hormones acting by this mechanism: estrogen
Where are estradiol, estriol and estrone produced?
estradiol E2 principal ovarian estrogen potency+++
estriol E3 principle placental estrogen potency +
estrone E1 major ovarian estrogen post menopause potency ++
What is the effect of estrogen at the liver?
stimulates hepatic production of sex hormone binding globulin, thyroid hormone binding globulin and blood clotting factors
What are the three major therapeutic uses of estrogens?
estrogen deficiency as in premature ovarian failure or menopause (stimulate development of secondary sex characteristics, or tx. of symptoms of estrogen deficiency)
prevention and treatment of osteoporosis and contraception (normally as part of a combo OC)
What is the MOA of selective estrogen receptor modifiers? Name 3 examples.
drugs have mixed agonist/antagonist activity and their action varies from tissue to tissue
examples include clomiphene, tamoxifen and raloxifine
What is the therapeutic indication for clomiphene? What are the adverse effects?
works centrally at hypothalamus
prevents normal feedback regulation of estrogen leading to increased secretion of GnRH and gonadotropins, stimulating ovarian follicle development, used in ovulation induction
adverse effects: multiple births, hot flashes, thick mucous/thick endometrium
What is the therapeutic indication for tamoxifen? What are the adverse effects?
acts as an estrogen antagonist in breast tissue, acts as week agonist at endometrium, used as treatment in breast cancer (ER+)
adverse effects: endometrial hyperplasia, hot flashes, multiple births
What is the therapeutic indication for reloxifene? What are the adverse effects?
acts as an estrogen agonist in bone and an estrogen antagonist in breast tissue, used in prevention and treatment of osteoporosis
When is use of an aromatase inhibitor indicated? What are the adverse effects?
type 1 irreversible inhibitors are often used to reduce endometrial hyperplasia and breast cancer and type 2 reversible inhibitors can be used in ovulation induction
adverse effects: hot flashes, bone loss
What's important to remember regarding the route of progesterone administration?
progesterone undergoes extensive first pass metabolism and can be administered high dose PO, IM infection or as a vaginal preparation
What type of progesterone is included in combination OC and why?
progestins are structural derivatives of progesterone with better pharmacokinetics , can also be used in HRT
older agents have more androgenic activity (contraindicated in pregnancy) while drospirenon is antiandrogenic
What are the therapeutic uses of progestins? (3)
can be used to prevent endometrial hyperplasia with postmenopausal hormone therapy
as part of a combined contraceptive
in support of pregnancies (with donor egg/embryo when CL is not present)
**mifiprisone is a progesterone and glucocorticoid receptor antagonist
What are the risks of HRT?
HRT associated with increased risk of DVT and stroke, no protective against heart disease and increases risk of breast cancer---usually given at the lowest possible dose for the shortest period of time
(does improve bone mineral density)
Describe the receptor that testorone and DHT act through.
both act through a single androgen receptor which is present in the cytoplasm working through the same mechanism of the nuclear receptor superfamily
What are the therapeutic uses of androgens?
replacement in males with testosterone (DOES NOT HELP WITH FERTILITY)
other effects: virilization, development of secondary sexual characteristics in men, stimulates linear growth and enhances sex drive and libido
**monitor for erthryocytosis and PSA for occult prostate cancer
What are the different vehicles for androgens?
injection (high levels for day(s)
patch and topical (more steady application)
CANNOT BE GIVEN ORAL (first pass)
What is the MOA of anti androgen spironolactone? When is it used?
acts as a weak blocker of AR and weak inhibitor of testosterone synthesis as well as blocker of the mineralocorticoid receptor
used in: tx of hirsutism in women, hypertension and CHF, primary hyperaldosteronism
adverse effects: hyperkalemia, irregular menses, gynecomastia
What are the clinical uses of flutamide?
acts as a competitive antagonist of the AR, used in hormonal therapy for prostate cancer and hirsutism
can cause hepatotoxicity