thyroid drugs

Question 1

steps of thyroid hormone biosynthesis

Answer 1

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

Question 2

thyroid hormones bind to what types of receptors?

Answer 2

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

Question 3

tissues/organs most responsive to thyroid hormone

Answer 3

pituitary

kidneys

heart

skeletal muscles

lungs

intestine

Question 4

levothyroxine

Answer 4

synthetic T4 – single dose

indicated for hypothyroidism

Question 5

liothyronine

Answer 5

synthetic T3

fast action but short half-life(1.5hr)

Question 6

liotrix

Answer 6

T4:T3 hormone mix w/4:1 ratio

Question 7

why do pregnant women with hypothyroid need an increase in normal dose of thyroid medication?

Answer 7

thyroid binding globulin is increased during pregnancy which binds up more T3(less free T3)

Question 8

myxedema coma presentation, treatment

Answer 8

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

Question 9

management options for graves disease

Answer 9

antithyroid therapy - if mild

thyroidectomy - treatment of choice

radioactive iodine - preferred for pt 21+ yo

Question 10

risk factors for thyroid replacement

Answer 10

arrhythmias, angina, accelerated osteoporosis

and the usual other hyperthyroid symptoms: heat intolerance, palpitations, tachycardia, wt loss

Question 11

thioamides: names, indication, mechinism

Answer 11

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

Question 12

anion inhibitors: name,indications, mechanism

Answer 12

perchlorate(ClO4-), thiocyanate(SCN-)

antithyroid drugs for hyperthyroidism

block uptake of iodide via competing for uptake
- can be overcome by large dose iodide

Question 13

vitamin D precursor in the skin

Answer 13

7-dehydroxycholesterol

Question 14

what is used to measure vitamin D levels?

Answer 14

25OH Vit.D3(cholecalciferol) – storage form

Question 15

effects of calcitonin; where is it produced

Answer 15

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

Question 16

negative effects of glucocorticoids on bones

Answer 16

decrease intestinal calcium reabsorption (antagonize Vitamin D here)

stimulate renal calcium excretion

block bone collagen synthesis

increase PTH stimulated bone resorption

Question 17

mechanism of estrogen preservation of bone

Answer 17

reduce resorptive action of PTH

Question 18

raloxifene

Answer 18

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

Question 19

bisphosphonates: nitrogenous vs non-nitrogenous action

Answer 19

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

Question 20

adverse effects of bisphosphonates

Answer 20

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

Question 21

denosumab

Answer 21

rankL inhibitor

rankL is what osteoblasts produce to activate osteoclast precursors

no rankL means no active osteoclasts == less bone reabsorption

synergy with BPs

Question 22

indications for denosumab

Answer 22

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

Question 23

plicamycin

Answer 23

med used for pagets and hypercalcemia

inhibits RNA sythesis

much smaller dose than cytotoxic