L34- Thyroid and Antithyroid Drugs (intro + hypothyroid)

Question 1

briefly review TH biosynthesis

Answer 1

1) Iodide ion uptake (I-)
2) oxidation, I- –> I2 (iodine, in colloid)
3) iodination of tyrosyl groups on Thyroglobulin
4) iodotyrosine residue coupling –> THs
5) TH resorption from colloid
6) thyroglobulin proteolysis –> thyroxine and triiodothyronine in blood

Question 2

(T3/T4) is more rapid/potent because of (2) and (3)

Answer 2

1- T3
2- T3 bind plasma proteins less tightly
3- T3 bind TH nuclear receptors more tightly

Question 3

list methods of TH metabolism

Answer 3

• deiodoination (most important)
• glucuronidation
• sulfation

Question 4

(1) is the most important method of TH metabolism. (1) process usually occurs in (2) manner. Inhibition of (3) will result in (4).

Answer 4

1- deiodonation

2-
T4 –> T3, more potent than T4
T4 –> rT3 (reverse), inactive

3- 5’-deiodinase

4- low T3 in serum

Question 5

5’-deiodinase enzymes are inhibited by…..

Answer 5

• drugs: propylthiouracul, propanlol, corticosteroids, amiodarone
• severe illness / starvation
• iodinated compounds –> radiographic agents iopnanoic acid, ipodate

Question 6

describe the alternate method of TH metabolism

Answer 6

T3/T4 –> liver –> sulfation, glucuronidation –> enters bile –> intestine –> hydrolyzed –> reabsorbed or excreted in stool

Question 7

describe how metabolism of TH can be targeted

Answer 7

Deiodinase and UDP glucuronosyltransferase enzymes are inducible

drugs that are enzyme inducers –> inc T3/T4 metabolism (if on replacement therapy, higher T4 dose is required)

Question 8

describe hypothyroidism thyroid preparation classification

Answer 8

Synthetics:

• levothyroxine, T4
• liothyronine, T3
• liotrix (T4/T3 mix)

Natural: via animal, desiccated thyroid

Question 9

Synthetic TH:

• (Y/N) protein Ag
• (un-/stable)
• (uniform/variable) hormone concentrations
• (easy/difficult) lab monitoring
• (high/low) cost
• (not/preferred)

Answer 9

1- No
2- stable
3- uniform
4- easy
5- high cost
6- preferred

Question 10

Natural TH:

• (Y/N) protein Ag
• (un-/stable)
• (uniform/variable) hormone concentrations
• (easy/difficult) lab monitoring
• (high/low) cost
• (not/preferred)

Answer 10

1- Yes
2- unstable
3- variable
4- difficult
5- low cost
6- not preferred

Question 11

Levothyroxine (vs liothyronine):

• (more/less) potent
• (long/short) 1/2 life
• (3) dosing frequency
• (easy/difficult) lab monitorig
• (higher/lower) cardiotoxicity risk
• (not/preferred)

Answer 11

T4
1- less
2- longer
3- po qd
4- easy
5- lower
6- preferred

Question 12

Liothyronine (vs levothyroxine):

• (more/less) potent
• (long/short) 1/2 life
• (3) dosing frequency
• (easy/difficult) lab monitorig
• (higher/lower) cardiotoxicity risk
• (not/preferred)

Answer 12

T3
1- more
2- shorter
3- multiple times daily
4- difficult
5- higher
7- not preferred

Question 13

(T/F) Liotrix is the preferred option for thyroid hormone replacement therapy

Answer 13

F- liotrix (T3/T4) is equally or less efficacious as levothyroxine (T4), but more expensive

Question 14

Thyroid replacement therapy AEs

Answer 14

• hyperthyroidism

- higher risk of AFib, osteoporosis

Question 15

(1) is a severe complication of long-standing hypothyroidism, with (2) as the cardinal features. (1) is treated / managed by (3).

Answer 15

1- Myxedema coma

2- hypothermia, respiratory depression, dec consciousness

3- IV levothyroxine (maybe liothyronine until Pt is stable and conscious) + supportive measures

Question 16

_____ is the drug of choice for hypothyroidism in pregnancy (and its importance)

Answer 16

-adequate (maybe increasing) dose of levothyroixine

Fetal brain development depends on maternal thyroxine

Question 17

why is a higher dose of levothyroxine required in pregnancy

Answer 17

1) inc serum [thyroxine binding globulin / TBG] induced by estrogen
2) placental expression of 5’-deiodinase (D3)
3) small amount of transplacental passage of levothyroxine to fetus

Question 18

what is the important factor in treating congenital hypothyroidism

Answer 18

start w/in 1st two weeks of life –> normal physical and mental development

-development may be affected if started later