Pharmacotherapy of Thyroid Disease Flashcards
levothyroxine
T4
liothyronine
T3
methimazole
antithyroid agent
propylthiouracil
PTU
antithyroid agent
potassium iodide
antithyroid agent
NIS
sodium iodine symporter
-transport of iodine into thyroid gland
inhibited by SCN-, TcO4-, ClO4-
pendrin
transport of iodide to follicular lumen
thyroidal peroxidase
oxidizes iodide to iodine
then to MIT and DIT (organification)
thyroglobulin
combines with iodine to form thyroid hormones
two DIT in TH - T4
DIT and MIT in TH - T3
thyroid hormone release
exocytosis and proteolysis of thyroglobulin at apical colloid border
high levels of iodide blocks the proteolysis
ratio of T4 to T3
5:1
thyroid hormone transport
plasma protein bound
-to thyroxine binding globulin (TBG)
0.04% in free form
3-5-3 triiodothyronine
T3
3-4x more potent
3-3-5 triiodothyronine
rT3
inactive
amiodarone
inhibits 5’ deiodinase for T4 to T3
low T3 and high rT3
block conversion of T4 to T3
amiodarone iodinate contrast media beta blockers corticosteroids illness starvation
TSH signaling
adenylyl cyclase
T4 and T3 feedback
negative on hypothalamus and pituitary
acute psychosis or cold
activate thyroid axis
somatostatin and dopamine
inhibit TSH release
large amounts of iodine
inhibit TSH release
thyroid hormone MOA
T4 to cytoplasm - 5 deiodinase converts to T3
T3 to nucleus
thyroid receptor bound to DNA at TRE
T3 binds TR - displaces corepressor and allows binding of coactivator
binds RXR on TRE - activates gene transcription
thyroid effects
activation of nuclear receptors lead to protein synthesis
lag time of effects - hours or days
warm, sweaty, tachycardia, increased appetite, nervous
hyperthyroid
cool, pale, bradycardia, decreased appetite, lethargic
hypothyroid
hyperthyroid T3 and T4
clearance increased
half life decreased
hypothyroid T3 and T4
clearance decreased
half life increased
agents increase CYP and enhance thyroid hormone degradation
rifampin phenobarbital carbamazepine phenytoin HIV protease inhibitor
agents interfere T4 absorption
oral bisphosphanate bile acid sequestrant cipro PPIs sucralafate antacids bran soy coffee
agents induce autoimmune thyroid disease
IFN-alpha
IFN-beta
lithium
amiodarone
agents inhibit conversion T4 to T3
radiocontrast amiodarone beta-blocker corticosteroid PTU
levothyroxine
T4
-preferred - cheaper, easy lab monitoring, long half life
liothyronine
T3
- 3-4x more potent
- shorter half life
risk of cardiotoxicity
cardiac disease
no T3
thioamides
methimazole
PTU
methimazole MOA
inhibit thyroid peroxidase
-block organification
block coupling MIT and DIT
propylthiouracil MOA
inhibit thyroid peroxidase
-block organification
block coupling MIT and DIT
methimazole vs. PTU
methimazole is DOC
-10x more potent
both cross placenta - to fetal thyroid - risk hypothyroidism
pregnancy antithyroid drug
PTU - first trimester
more protein bound - so crosses placenta less readily
thyroid storm
PTU
severe hepatitis
PTU black box warning
agranulocytosis
in PTU and methimazole
anion inhibitors
perchlorate
pertechnetate
thiocyanate
competitively inhibit iodide transport
potassium iodide MOA
inhibit iodide organification and hormone release
inhibit hormone release and decrease size and vascularity of hyperplastic gland
reduction in size of hyperplastic gland
potassium iodide
acneiform rash and swollen salivary glands
seen with potassium iodide - adverse effect
radioactive iodide MOA
emission of beta rays
-destruction of thyroid gland
concentrates in thyroid and stored in follicles
DOC for hashimotos
levothyroxine - T4
drug levels reached in 6-8 weeks
restlessness, insomnia and accelerated bone grwoth
thyroxine in children
nervous, heat intolerance, palps, tachy, weight loss
thyroxine in adults
myxedema coma
end stage of untreated hypothyroid
-medical emergency
intubation, ventilation - drugs IV**
a fib and osteoporosis
overtreatment with T4
hypothyroid women
often infertile
pregnancy
important to replace thyroid hormones in hypothyroid mother
-important for fetal brain
young patient, small gland, mild graves tx
medical - methimazole (or PTU)
old patient, large gland, MNG graves tx
surgical - thyroidectomy
treat with antithyroid until euthyroid**
potassium iodide - to diminish vascularity
radioiodine tx o fgraves
without heart disease over 21yo
adjuncts to antithyroid meds
beta blockers
diltiazem (CCB)
tx of thyroid storm
beta blockers potassium iodide PTU hydrocortisone supportive therapy
