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82 Cards in this Set

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  • Back
Diganostic Use only for Hypothyroidism
Thyrotropin Releasing Hormone
Gonadotropin Releasing Hormone is used to
diagnose infertility and delayed puberty
used to treat prostate and breast cancer, treat endometriosis, help thin endometrium prior to a hysterectomy
Gonadotropin antagonists
prevent ovulation and the LH surge
an example of a GnRH antagonist
Corticotropin Releasing Factor is used
diagnotist use for cases of pituitary defects that present as Cushing's Disease
Growth Hormone Releasing Factor is used diagnostically for
kids with idiopathic growth hormone deficiency
Growth Hormone Releasing Hormone is used treatment wise for:
GHD where the pituitary workds fine, but the hypothalamus doesn't secret adequate GRF
Dopamine is also knowns at
Prolactin Release Inhibitory Factor
Dopamine is not used in hormone therapy because:
too many peripheral effects of dopamine in blood vessels and it is broken down by MAO's or other enzymes
a type of dopamine that was used in women with pituitary tumors
a type of dopamine that had less side effects than bromocriptine
somatostatin does not treat
cancer itself
inhibition of glucagon secretion by somatostain is _______ than its inhibition of insulin secretion
a condition that has too much growth hormone and causes an enlargemetn of large bones in the hands, feet, and face, with an enlargement of the nose and lips
Why is 111 Indium added?
the agent is administed such that radioactivity is selectively delivered to kill the cells overexpressing somatostatin receptors
70 times more effective than native somatostain
is being tested for use in cancer and it seems to be 2 to 3 times more potent than octreotide
for Somatostain, replacing a L-AA with a D-AA makes the analog how many more times active
6-8 times
in somatostatin, D-AA at position 14 makes an analog that is much more selective for inhibition of growth hormone and of glucagon than for inhibiting insuline release, which suggests
that the peripheral receptors for somatostatin are structurally different
the reasons why growth hormone has a long half life
1/ the hormone is much larger than its active region, so the extra size protects the active region from enyzmatic destruction.
2/ it does not move in the blood as a free molecule, rather it is adsorbed onto plasma proteins
Some uses of growth hormone
1/ children whose growth is abnormally slow,
2/ adults with GH deficiency
3/ girl's with turner's syndroms
4/ body wasting due to HIV
5/ cardiac insufficiency
insulin like growth factors
somatomedins act together with GH to:
promote cartilage growth, stimulated protein synthesis, stimulate thymidine incorporation into DNA, and stimulate cell division
prolactin has what with GH?
16% homology
why are proteins glycosylated?
1/ to increase stability or half life-longer duration of action
2/ to faciliate the secreton of proteins from a cell
3/ to create recognition sites for other molecules
effects of prolactin
1/ promote mammary gland proliferation
2/ release progesterone which renders the uterus suitable for imbedding of the ovum
oxytocin is:
a synthetic peptide given only with strict medical supervison to induce labor or delivery
lypressin is:
given as a nasal spray and is used to treat diabetes insipidus- pituitary release of ADH doesnt occur properly
desmopressin is:
given as a nasal spray, orally, or parenteraly. used to treat the symports of diabetes insipidus, and used to treat children who experience uncontrolled bed wetting.
Cys removed and D-Arg replaces L-Arg
terlipressin is:
given to treat bleeding of the esophagus that may result in cirrohis of the liver. also causes an increase in blood pressure which causes bulges that can rupture
function of Throid Stimulating Hormone from the pituitary:
promote release of T4 and T3 from thyroid gland and stimulate uptake of iodide from blood into acinar cells
thyroxin-binding globulin
only have 1 high-affinity binding site for homrone
also called t4- binding pre-albumin since it only carries one of the hormones. it has an affinity 1000 times less affinity for t4 than thyroxin binding globulin, but theres more of it
carries 10% t4 and 30% of t3
from a single tg molecule, only ______ hormones are released
2 to 5
transthyretin binds where
the cooh end of the hormone binds a pair of lys residues at the mouth of the funnel, even bound by t4, also binds four molecules of vitamin A
details about the binding of the nuclear receptor of t3 and t4
1/ the I at postitions 3 and 5 on the inner ring keep the 2nd ring perpendicular
2/ the spacer atom between the rings keeps the second ring at an angle of 120
3/ the cooh end of the hormone forms half of an ion pair with the receptor
4/ the 4-oh is also a crutial part of the binding site of the hormome
5/ better binding if 3' has an isopropyl group or a lipophilic halogen
normal functions of t3 and t4
promote oxygen uptake , gluclose availability, protein synthesis, generate heat, and growth and development
hypothyroidism consequences
non toxic goiter: lack of hormone from thyroid causes increased release of TSH that stimulated the thyroid to enlarge in order compensate
may have to do with lack of I2 diet
a lack of iodine during early childhood means lack of CNS development and a stunting of growth due to abmormal bone formation

lack of iodine, or loss of the thyroid, or lack of TSH can cause mucopolysaccharide infiltration of the spaces between cells of the skin and muscle, also anemia, mental apathy, and sensitivity to cold

hyperthyroidism consequences
increased heart rate and cardiac output, anorexia, poor thermoregulation, toxi goiter
graves disease
autoantibodies against one's own TSH receptors on acinar cells of the thyroid lead to and overproduction and release of t4 and t3

hashimoto's disease
autoantibodies against Tg or other thyroid cell proteins lead to infiltration of cytotoxic t-cells, and also plug up the machinery needed for iodine uptake and incorportation to hormones. - lack of hormone, resulting in overproduction of TSH and goiter

for hypothyroidism what kind of hormone replacement do you need?
1/ thyroid USP= acetone powder of cow or pig thyroid gland
2/ synthetic t4 (levothyroxine)- slower onset of action since higher affinity for carrier proteins
3/ synthetic t3 (liothyronine)rapid onset of action, and short duration
hyperthyroidism needs what?
a hormone antagonist to block the peroxidase enzyme so th atless hormone is made
prodrug of MMI that is converted to MMI in vivo
synthesized by the adrenal cortex
glucocorticoids and mineralcorticoids
primarily regulate water and sodium ion retention to maintain blood volume and electrolyte balance
bile acids are trans or cis
beta orientation are represented by
solid line, or solid wedge
alpha orientation are represented by
dashed line or wedge made of short dashed lines
have to remove 6 C's two hydroxylation steps followed by cleavage of the side chain in front of c22 by enzyme
five major classes of steroid hormones
progesterone, glucocorticoids, mineralcorticoids, andrgens, and estrogens
oxidize 3-oh to a ketone and then osimerize the double bond
four steps from progesterone- three additions of oh then oxidation to 11-keto
adrenal cortex hormones
cortisol and aldosterone
from progesterone, oh at 21 and oh at 11, followed by oh at 18 and oxidation to 18 aldehyde
too much cortisol can lead to:
muscle wasting or retarded growth
cortisols function:
maintain blood glucose availability, primary target is liver and then brain
cortisols main therapeutic interest
to conrol inflammation and associated redness, swelling, pain, local vasodialation
essential for activity of aldosterone or cortisol
double bond-delta 4, 3 keto and 20 keto
essential for glucocorticoid activity
21-oh and 11-B-oh
analogs for anit-inflammatory activity
9-alpha-fluoro greatly enhances activity- has greater glucocorticoid activity, but way toooo much mineralcorticoid activity
what does adding a double bond at the c-1 do?
selectively increases glucocorticoid activity by a factor of 5 without any change in the mineralcorticoid activity
what does a c-16 methyl group do to activity?
either alpha or beta increases glucocorticoid activity and decreases mineralcorticoid activity
has 25 x the activity of cortisol
betamethasone - beta solid methyl
has 30 x activity of cortisol
dexamethasone- alpha is dotted wedge
aldosterone antagonists
progesterone, series or spirolactones
how to avoid the anti-androgen effect
replace the thioester with a different ester 7alpha-C-O-CH3
short acting glucocorticoids
cortisone acetate and hydrocortisone (cortisol)

treat insufficient output by the adrenal cortex: rheumatic arthritis or joint pain and inflammatory disorders
intermediate acting glucocorticoids
prednisone, prednisolone, methyprednisolone, triamcinolone (esp for asthma)

for more severe conditions that often require chronic treatment
long acting glucocorticoids
betamethasone, dexamethasone

for chronic inflammation, chronic allergic diseases, autoimmune diseases, and some cancers
one of the most serious adverse effects of long term glucocorticoid therapy
steroids ususally have _____ net charge
does a steroid have the same conformation when bound to its receptor is when it is in a crystal?
about the same.... yes - can do computer assissted "rationa" drug design of steroid analogs
glucocorticoid receptors and mineralcorticoid receptors start where?
in the cytoplasm
estrogen, androgen, and progesterone receptors are where?
only in the nucleus
steroids have threee principle active regions
a hormone binding region, a DNA binding region, and an N-terminal region used to allow binding of other proteins that enhance or repress DNA binding
6 hypothalamic hormones
thyrotropin releasing hormone, gonadotropin releasing hormone, corticotropin releasing hormone, growth hormone releasing hormone, prolactin release inhibiting hormone, somatostain
secreted from the posterior pituitary
vasopressin and oxytocin