Pharmacology of Thyroid Hormone Flashcards Preview

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Flashcards in Pharmacology of Thyroid Hormone Deck (61)
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1

Colloid contains

thyroglobulin

2

Synthesis and release of thyroid hormone

1. Uptake of iodide ion by the gland
2. Oxidation of iodide ion and the iodination of tyrosyl groups
3. Condensation of iodotyrosyl residues to iodothyronyl residues in thyroglobulin
4. Proteolysis of thyroglobulin and release of thyroxine and triiodothyronine into blood
5. The conversion of thyroxine to triiodothyronine in peripheral tissues

3

Iodide uptake from the circulation occurs by

sodium-iodide symporter located in the basolatedral plasma membrane of thyroid follicle cell

4

Sodium-iodide symporter is inhibited by

complex anions such as perchlorate, thiocyanate, pertechnetate

5

Iodide is extruded from the thyroid follicle cell by

the protein pendrin (sodium-indepedent chloride/iodide transporter) located in the apical membrane

6

Pendred's syndrome

the hereditary syndrome of goiter and deafness due to a deficiency or absence of pendrin

7

Oxidation of iodide to iodine is catalyzed by

the thyroid peroxidase enzyme complex in the presence of hydrogen peroxide

8

Secretion of thyroid hormone

1. Endocytosis of colloid
2. Proteolysis
3. Release of hormones

9

80% of T3 is produced by

metabolism of T4 in peripheral tissues by types I, II and III 5' deiodinases

10

Type I deiodinase catalyzes

the formation of circulating T3 used by peripheral tissues; requires selenium to function

11

Type II deiodinase is present/catalyzes

present in brain, hypothalamus, pituitary, placenta and brown adipose tissues; catalyzes the formation of intracellular T3

12

Type III deiodinase inactivates

inactives both T4 and T3 with preference for T3; metabolizes T4 to inactive rT3; high expressed in CNS, skin, fetal brain, and liver

13

Conditions and factors that inhibit 5' deiodinase activity

1. Acute and chronic illness
2. Caloric deprivation
3. Malnutrition
4. Glucocorticoids
5. beta-adrenergic blocking drugs
6. Oral cholecystographic agents
7. Amiodarone/PTU
8. Fatty acids

14

Agents that increase metabolism of T4 and T3

1. Rifampin
2. Phenobarbital
3. Carbamazepin
4. Phenytoin
5. Rifabutin

15

Major carrier of thyroid hormones

thyroxine binding globulin

16

Transthyretin

Tyroxine binding pre-albumin (TBPA)

17

Factors that increase the binding of thyroxine to thyroxin-binding globulin

estrogens, methadone, clofibrate, 5-fluorouracil, heroin, tamoxifen, liver disease, porphyria, HIV

18

Factors that decrease the binding of thyroxine to thyroxin-binding globulin

glucocorticoids, androgens, L-asparaginase, salicylates, mefenamic acid, fenclofenac, antiseizure medications, furosemide, acute and chronic illness

19

Allan-Herndon-Dudley syndrome

mutations in the transmembrane transporters of thyroid hormones that leads to an X-linked inherited syndrome of mental retardation and myopathy with low serum T4 levels

20

Symptoms of hypothyroidism

1. Sluggish (progressive weakness)
2. Low metabolic rate in many organs
3. Complain about feeling cold
4. Puffy face, doughy skin
5. Hypercholesterolemia
6. Decreased HR, SV, CO, and pulse pressure

21

Thyroid hormone deficiency before birth may lead to

cretinism (dwarfism with mental retardation)

22

Endemic cretinism

due to extreme deficiency of iodine; goiter may or not be present; high incidence of nerve deafness

23

Sporadic cretinism

due to failure of thyroid gland to develop normally; due to defect in synthesis of thyroid hormone; goiter present if defect in synthesis is the cause

24

Simple goiter

TSH levels are very high due to deficient secretion of thyroid hormone; may be due to iodine deficiency; may also be caused by a goitrogen

25

Hashimoto's disease

chronic autoimmune thyroiditis; autoantibodies produced against thyroid peroxidase and less often thyroglobuline; thyroxine levels are low; TSH ishigh

26

Diffuse toxic goiter

thyroid enlargement with hyperthyroidism (Graves' disease)

27

Nodular goiter

thyroid enlargment with nodules;
non-toxic: without thyroid hormone production
toxic: with thyroid hormone production (Plummer's disease)

28

Thyroid preparations

1. Levothyroxine Sodium (Synthroid, Levothyroid, L-T4)
2. Liothyronine Sodium (Cytomel, Triostat)
3. Liotrix (Euthyroid, Thyrolar)

29

Levothyroxine sodium (Synthroid, Levothyroid, L-T4, Levoxyl, Tirosint)

Sodium salt of synthetic thyroxine available in tablets and for injection

30

Liothyronine sodium

Sodium salt of triiodothyronine (T3) available in tablets or injection