63: Thyroid/Antithyroid Drugs Flashcards
iodide uptake into thyroid gland by the…
sodium iodide symporter
oxidation of iodide to iodine
peroxidase mediated
iodination of tyrosine molecules within..
thyroglobulin molecule
“iodide organification”
can either be MIT or DIT
MIT + DIT =
DIT + DIT =
T3
T4
most thyroid hormone is released as…
T4
majority is bound to thyroxine-binding globulin in blood
without thyroid hormone bound..
receptor is bound to tyroid response element and corepressors to INHIBIT gene transcription
T3 will bind directly to monomer of TR but T4 needs to be converted to T3 (5’ deiodinase)
with T3 bound to TR, retinoid x receptor and TR form hetero-dimer and increase gene trx
hypothalamus releases TRH –>
pituitary gland –> TSH –> thyroid –> T3 and T4
high T3 and T4 ______ secretion of TRH and TSH
inhibit - negative feedback loop
high iodide concentrations _____ thyroid hormone synthesis
inhibit (short term)
low promote
impact of TH on sympathetics?
- increase B adrenergic receptors
- decrease alpha adrenergic receptors
impact of TH on growth and development?
- brain development, neurogenesis
- bone growth and skeletal maturation through activation of osteoblast/clast
impact of TH on thermogenics?
- increase energy consumption resulting in heat production
impact of TH on respiratory system?
- increase O2 consumption in most tissues, thereby increasing CO2 formation –> RR increases
impact of TH on CNS?
- rapidity of thinking and reasoning
- effect spinal cord synapses that control m. tone
impact of TH on GI?
increase secretions and motility
impact of TH on skin and hair?
- growth promotion of hair, skin, nails
- prevent accumulation of glycosaminoglycans in interstitial space
impact of TH on cardiovascular?
- increase HR
- increase force of contraction
- increase Co
- increase blood volume
- decrease vascular resistance
(due to changes in gene expression of prtns including b-adrenergic receptors)
impact of TH on metabolism?
- decrease circulating cholesterol by increases LDL and lipolysis
- increase absorption of carbs, increase glycolysis, increase gluconeogenesis, increase insulin secretion
- increase prtn synthesis and catabolism
- increase need and usage of vit
- *increase basal metabolic rate
s/s hyperthyroidism
increase BP tachycardia sweating tremors rapid growth heat intolerance high RR increased breakdown muscle weight loss weakness and fatigue insomnia diarrhea *exopthalmos
grave’s disease
hyperthyroidism (autoimmune)
autoantibodies stimulate TSH receptors and increase the production of T3 and T4
*TSH levels will be low
s/s hypothyroidism
delayed development bradycardia cold intolerance hypoventilation depression *puffy eyes sleepy increased body weight dry and scaly skin atherosclerosis
cretinism
congenital defect - primary hypothyroidism
- lack of thyroid development, lack of TSH receptor, lack of TH synthesis
Hashimotos disease
autoimmune primary hypothyroidism
may see initial hyperthyroidism with release from glands being destroyed
iodide deficiency
primary hypothyroidsim
impaired hormone production
observe goiter
why is levothyroxine tx of choice for hypothyroidism?
- stable
- low cost
- easily measured
- long half life
- similar to normal physiology
liothyronine
T3 agonist
more potent, but shorter half-life
thyroid storm
acute episode of thyroid activity brought on by stress in a pt with undiagnosed/untreated hyperthyroidism
excess iodide –>
normally will inhibit hormone production but with underlying disease can cause hyperthyroidism
thioamides =
methimazole
propylthiouracil
- contra in preggers
- rash/GI side effects
MOA methimazole and propylthiouracil
inhibit peroxidase, iodination, and coupling of iodotyrosines
concentrate in thyroid gland
BBW for propylthiouracil
hepatitis
treat thyroid storm with which thioamide
propylthiouracil because faster absorption
iodides =
potassium iodide
lugol’s solution
can be used for thyroid storm
MOA iodide
inhibit hormone release by inhbiting proteolysis of Tgb
side effects of iodides
“sick” feeling
only work 2-8 wks
withdrawal = thyrotoxicosis
MOA radioactive iodine
b ray destroy parenchymal cells of thyroid
gamma rays pass through tissue and detect concentration of RAI remaining in thyroid gland
anion inhibitors
perchlorate
pertechnetate
thiocyanate
adverse effect perchlorate
aplastic anemia
MOA perchlorate, pertechnetate, thiocyanate
competitively inhibit the uptake of iodide via Na/I transporter
MOA propanolol
beta blcoker (Cardioprotective in thyroid storm) blocks T4--> T3
cant be used with athma, hypotension, bradycardia
MOA diltiazem
calcium channel blocker
control tachycardia in asthmatic
MOA barbiturates and bile acid sequestrants
increase T4 metabolism
increase T4 excretion
