Term
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Definition
it is the loss of ovarian follicle function, followed by the cessation of menses
what happens with sex hormones?
decrease, loss of sex hormones
how are the sex hormones related to postmenopausal health?
bone loss, urogenital athrophy, etc.
sex hormones are not only used for reproduction
a lot of changes occur in women going through menopause
postmenopausal ovarian secretes androstenedione and testosterone -> increase in androgens |
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Term
| what is the primary source of estrogens in postmenopausal women? |
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Definition
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Term
| what happens with estradiol when administered orally |
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Definition
| not stable when administered orally |
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Term
| what is a micronized form (micronized estradiol, micronized progesterone)? |
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Definition
| micronized progesterone is very small particles to increase surface area of the drug exposed |
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Term
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Definition
growth periods -> bone formation > bone loss
adulthood -> bone formation = bone loss
after 40 -> bone formation < bone loss |
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Term
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Definition
loss of bone mass
microarchitectural deterioration of bone tissue
deficiency in well mineralized bone production
three types: pstmenopausal (type I), senile (type II), and secondary (type III)
postmenopausal osteoporosis:
accelerated rate of bone loss via enhanced resorption at the onset of menopause
trabecular bone loss >>> cortical bone: vertebral crush fractures more common, wrist and ankle fracture more common
estrogen deficiency is related to postmenopausal osteoporosis |
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Term
| estrogen deficiency and osteoporosis |
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Definition
estrogens regulate skeletal homeostasis
estrogens inhibit bone turnover:
reduce osteoclast-mediated bone resorption
enhance osteoblast-mediated bone production |
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Term
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Definition
physiological effect: to block activation of the bone metabolic unit
regulation of osteoclast apoptosis
retardation of bone resorption effects of parathyroid hormone
estrogen analogs for estrogen replacement therapy:
17beta-estradiol
estrone
17-ethinyl estradiol |
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Term
| selective estrogen receptor modulators (SERMs) |
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Definition
SERMs can have agonistic or antagonistics effects depending on where the estrogen receptor is or what type of estrogen receptor it is (alpha or beta):
conformation of the estrogen receptor - conformation of the receptor may be different in different tissues
co-activators or co-repressors - in tissues will have either or these that lead to the agonistic or antagonistic effects o these drugs
ERalpha/ERbeta - ratio of alpha to beta in the tissues can cause agonists or antagonist effects
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raloxifene
first drug approved for the treatment of osteoporosis
agonist in bone and cardiovascular
antagonist in breast and uterus
it does not prevent hot flashes |
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Term
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Definition
[image]
[image]
pyrophosphate
ATP -> AMP + pyrophosphate
pyrophosphate in the blood and urine inhibits mineralization
bisphosphonates act to directly repair the bone
replace some of the bone units and form a bone-like structure
they contain pyrophosphate forms (also found in the urine and blood and these forms INHIBIT mineralization) have to be careful with the structure of these drugs
bisphosphonates selectively bind to the hydroxyapatite portion of the bone
bisphosphonates effectively inhibit osteoclast proliferation, decrease osteoclast activity, reduce osteoclast lifespan
decrease the number of sites along the bone surface where bone resorption occurs
these drugs become part of the bone |
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Term
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Definition
[image]
one substituent needs to be an OH group!
the other substituent: a carbon linear chain is good (4 is the best length); having an amino group increases potency; substitution of the amino groups also increases potency |
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Term
| pharmacokinetics of bisphosphonates |
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Definition
absorptioN: compounds are very polar, will easily get in circulation b/c of polarity, but to get to the bone is more difficult
uptake is better in areas of bone loss
b/c of the high polarity, these drugs are cleared very quickly |
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Term
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Definition
32 aa peptide (human)
postmenopausal osteoporosis and PD
main source is salmon
pharmacokinetics:
bioavailability (variable), absorbed rapidly
metabolized in the kidneys
analgesic effect |
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Term
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Definition
drug therapy used to treat osteoporosis: bone forming agent
short acting and it responds to hypocalcemic state and it opposes calcitonin effects
low serum Ca -> increased PTH and decreased CT -> decreased renal excretion of Ca, increased vitamin D production -> increased intestinal absorption of Ca -> increased bone resorption of Ca
increased serum Ca -> increased CT and decreased PTH -> increased bone resorption of Ca, decreased vitamin D, decreased intestinal absorption of Ca -> increased renal excretion of Ca |
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Term
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Definition
[image]
vitamin D is produced by starting with cholesterol (or other steroidal structures)
light is needed for vitamin D to be formed in vivo
vitamin D is needed to keep bone structure (indirectly) |
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Term
| inorganic salts used for osteoporosis |
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Definition
calcium (carbonate, phosphates, chloride, citrate, lactate, gluconate):
helps prevent bone loss
absorption under acidic conditions is better
water solubility
sodium fluoride:
promotes proliferation and activity of osteoblast
narrow therapeutic window
bone not well mineralized
not approved for osteoporosis |
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