Thyroid and antithyroid agents Flashcards
where does thyroid hormone synthesis take place?
cell itself and colloid
how does iodide get into the thyroid gland?
sodium / iodide symporter (NIS)
what enzyme is responsible for converting iodide to iodine?
peroxidase
what is iodide organification? what are the results?
iodination of tyrosine residues within thyroglobulin molecule
monoiodotyrosine (MIT)
diiodotyrosine (DIT)
how are the thyroid hormones formed?
molecules of MIT and DIT are combined to form:
MIT plus DIT - T3
DIT plus DIT - T4
what is the typical ratio of thyroid hormones?
T4: T3 - 5:1
the majority of thyroid hormones are bound to what molecule?
thyroxine bound globulin (TBG)
what is the MOA of thyroid hormone in the absence of thyroid hormone?
homodimer of receptor is sitting on response element of gene - NO activation of transcriptional processes
what is the MOA of thyroid hormone in presence of thyroid hormone?
hormone is transported into cell
RXR and TR form heterodimer and increases gene transcription
what is the function of 5’-deiodinase (5’-DI)?
conversion of T4 to T3
what is the result of inhibition of 5’-DI?
hypothyroidism type symptoms
what is the regulation of thyroid secretion? what type of feedback is involved?
TRH - TSH
TSH promotes synthesis of T4 and T3
negative feedback
what are the result of high blood concentrations of iodide on hormone synthesis? low blood levels?
inhibition
promotion of synthesis
what are the metabolic effects of thyroid hormone on fat?
- decrease circulating cholesterol via increase in LDLr expression
- increased lipolysis
what are the metabolic effects of thyroid hormone on carbohydrates?
- increased intestinal absorption of carbohydrates
- increased glycolysis
- increased gluconeogenesis
- increased insulin secretion
what are the metabolic effects of thyroid hormone on protein?
increased protein synthesis and catabolism
what are the metabolic effects of thyroid hormone on vitamins?
increase need and usage for cofactors to enzymes as a result of a general increase in enzyme secretion
definition: myxedema
when is it seen in relation to thyroid metabolism?
puffy, baggy eyes from retention of fluids in interstitial spaces
hypothyroidism
what are the causes of hypothyroidism?
congenital autoimmune thyroiditis (hashimoto's) iodide deficiency
what are the treatment options for hypothyroidism?
levothyroxine (T4)
liothyronine (T3)
liotrix (mixture T3 and T4)
what is the treatment of choice for hypothyroidism? why?
levothyroxine
more stable, low cost, long half life, more physiological
what is the MOA of thyroid hormone?
activation of T3 receptors
what considerations should be made when treating elderly patients for hypothyroidism? why?
must check for underlying CV disease (decreasing contractility and BP)
hypothyroidism is protective for potential coronary artery disease
what are the adverse effects of thyroid hormone in children?
restlessness, insomnia, accelerated bone maturation
what are the adverse effects of thyroid hormone in adults?
nervousness, heat intolerance, palpitations, tachycardia, weight loss
which thyroid hormone is more potent? why?
T3
already in ligand-active form
what is the mechanism of grave’s disease? what are the levels of TSH?
autoantibodies stimulate TSH receptors and increase the production of T3 and T4
TSH levels will be low
what are the thioamide antithyroid agents for hyperthyroidism?
methimazole
propylthiouracil (PTU)
what is the MOA of the antithyroid agents?
inhibition of peroxidase reaction, iodineorganification, and coupling of iodotyrosines
which antithyroid agent is appropriate for use in pregnant women? why?
propylthiouracil (PTU)
75% protein binding
what is the significant adverse effect of PTU?
severe hepatitis
what are the iodide antithyroid agents?
potassium iodide
lugol’s solution
what is the MOA of the iodide antithyroid agents?
- inhibition of TGB proteolysis
2. decreases vascularity, size, and fragility of hyperplastic gland
which class of antithyroid agents are useful against iodide storm? why?
iodide agents
rapid onset
which class of antithyroid agents are useful for hyperplastic gland and preop preparation? why?
iodide agents
decreases vascularity, size, and fragility of hyperplastic gland
what is the radioactive antithyroid agent? what is the MOA?
radioative iodine 131-I
destruction of parenchymal cells
what are the anion inhibitor antithyroid agents?
perchlorate
pertechenate
thiocyanate
what is the MOA of the anion inhibitor antithyroid agents?
inhibition of energy dependent uptake of iodide into the thyroid cells that is mediated by sodium / iodide symporter
what is the main adverse effect of radioactive iodine 131-I?
hypothyroidism
what agents can be used to treat iodide-induced hyperthyroidism (eg amiodarone induced thyrotoxicosis)
anion inhibitors
what are the key adjuncts antithyroid agents?
propanolol
diltiazem
barbiturates
bile acid sequestrants
what are the clinical uses of beta blockers for hyperthyroidism?
adjunct to control tachycardia, HTN, aF
what is the clinical use for diltiazem?
control tachycardia in asthmatic
what is the clinical use for barbiturates?
increase T4 metabolism
what is the clinical use for bile acid sequestrants?
increase biliary T4 excretion
