thyroid drugs Flashcards
steps of thyroid hormone biosynthesis
iodide enters follicular cell
iodide(I-) is “organified” to I2
tyrosines on TG get iodinated in the colloid producing MITs and DITs
iodityrosines combine:
MIT+DIT = T3
DIT+DIT = T4
T4, T3(5:1) are released via excytosis and proteolysis
T4 can be metabolized peripherally into the more potent form: T3
thyroid hormones bind to what types of receptors?
nuclear receptors – activate transcription factors to increase RNA and protein synthesis of Na/K ATPase
this means: thyroid hormone takes a while to work! –takes hours/days to see effects
tissues/organs most responsive to thyroid hormone
pituitary
kidneys
heart
skeletal muscles
lungs
intestine
levothyroxine
synthetic T4 – single dose
indicated for hypothyroidism
liothyronine
synthetic T3
fast action but short half-life(1.5hr)
liotrix
T4:T3 hormone mix w/4:1 ratio
why do pregnant women with hypothyroid need an increase in normal dose of thyroid medication?
thyroid binding globulin is increased during pregnancy which binds up more T3(less free T3)
myxedema coma presentation, treatment
untreated thyroid state – medical emergency
weakness, stupor, hypothermia, hypoventilation, hyponatremia, water intoxication, shock
treatment:
loading dose of T4 – fills empty TBG
IV T3 – be careful…difficult to monitor
management options for graves disease
antithyroid therapy - if mild
thyroidectomy - treatment of choice
radioactive iodine - preferred for pt 21+ yo
risk factors for thyroid replacement
arrhythmias, angina, accelerated osteoporosis
and the usual other hyperthyroid symptoms: heat intolerance, palpitations, tachycardia, wt loss
thioamides: names, indication, mechinism
PTU
methimazole - longer t1/2 than ptu
antithyroid meds for hyperthyroidism!
mechanism:
inhibit T4-T3 conversion
inhibit TPO catalyzed reactions
- iodide organification
- coupling of iodotyrosines
anion inhibitors: name,indications, mechanism
perchlorate(ClO4-), thiocyanate(SCN-)
antithyroid drugs for hyperthyroidism
block uptake of iodide via competing for uptake
- can be overcome by large dose iodide
vitamin D precursor in the skin
7-dehydroxycholesterol
what is used to measure vitamin D levels?
25OH Vit.D3(cholecalciferol) – storage form
effects of calcitonin; where is it produced
made in parafollicular cells of thyroid
acts to lower serum calcium and phosphate by acting @ bone and kidney
- not part of normal physiologic regulation
- used sometimes in hypercalcemia and pagets
negative effects of glucocorticoids on bones
decrease intestinal calcium reabsorption (antagonize Vitamin D here)
stimulate renal calcium excretion
block bone collagen synthesis
increase PTH stimulated bone resorption
mechanism of estrogen preservation of bone
reduce resorptive action of PTH
raloxifene
selective estrogen receptor modulator(SERM)
ER agonist at bone
ER antagonist at breast/uterus – as effective as tamoxifen
adverse effects: hot flashes, blood clots, teratogenic
bisphosphonates: nitrogenous vs non-nitrogenous action
deposited in bone(hydroxyapetite); osteoclasts come by and eat them when restructuring bone
there are nitrogenous and non-nitrogenous with slightly differing mechanisms, but they both end up killing/stopping osteoclasts from reabsorbing more bone
adverse effects of bisphosphonates
atypical femure fractures — on the shaft instead of head
consensus is that these patients with atypical fractures are likely predisposed and overall occurence is rare
osteonecrosis of jaw - rare
denosumab
rankL inhibitor
rankL is what osteoblasts produce to activate osteoclast precursors
no rankL means no active osteoclasts == less bone reabsorption
synergy with BPs
indications for denosumab
use when bisphosphonates dont work(5 years), there is an intolerance to them, breast cancer with hormonal therapy, prostate cancer with androgen deprivation
*rankL inhibitor
plicamycin
med used for pagets and hypercalcemia
inhibits RNA sythesis
much smaller dose than cytotoxic
