Lecture 1 - Thyroid Drugs

Question 1

What is TSHs direct effect on the follicle cell?

Answer 1

activate NIS to increase iodine intake

Question 2

Which conditions/drugs inhibit D1 activity?

Answer 2

acute and chronic illness
caloric deprivation 
malnutrition
glucocorticoids
BB (used in hyperthyroidism) 
amiodarone 
propylthiouracil (used in yperthyroid) 
fatty acids 
selenium deficiency

Question 3

TBG

Answer 3

thyroxin binding globulin is the protein that is bound to T4 and T3 in circulation

Question 4

What proteins bind to T3 and T4 for transport through circulation?

Answer 4

TBG
transthryetin (TBPA)
albumin

TBG is just to most common

Question 5

What drugs can cause an increase in transport proteins?

Answer 5

estrogen
methadone
pregnancy

this means there will be a decrease in free thyroid hormone

this decrease in free hormone will cause the pituitary to increase TSH

Question 6

What are the indications for thyroid replacement therapy?

Answer 6

adult hypothyroidism
- usually primary

infantile hypothyroidism
endemic goiter

Question 7

What is the drug of choice for hypothyroidism?

Answer 7

Levothyroid sodium - L-thyroxin, T4

Question 8

How often is the dosing for T4?

Answer 8

once daily

Question 9

What are the adverse effects of T4?

Answer 9

cardiac sxs
angina
palpitations

use with care, particularly in elderly

Question 10

Why don’t we use T3 as much as we use T4 for replacement therapy?

Answer 10

more expensive
shorter half life –must be given more often

worse CV risk

Question 11

What are the two main antithyroid drugs given for hyperthyroidism?

Answer 11

MMI - methimazole
PTU - propyltiouracil

thioamide class

Question 12

What is the MOA of MMI and PTU?

Answer 12

prevent hormone synthesis by inhibiting TPO catalyzed reactions to block iodine organification (binds to and inactivates TPO)

also block coupling of iodotyrosines

PTU has the added effect of blocking D1s conversion of T4 to active T3

Question 13

How long does it take for MMI and PTU to take effect?

Answer 13

3 - 4 weeks because you have a storage of hormones

Question 14

What are the adverse effects for MMI and PTU?

Answer 14

skin rash, joint pain, agranulocytosis in 0.2% of pts

hepatotoxicity is seen with both but WORSE with PTU

MMI has greater risk of BIRTH defects

Question 15

Which has worse hepatotoxicity PTU or MMI?

Answer 15

PTU

Question 16

Which has greater risk of birth defects, PTU or MMI?

Answer 16

MMI

Question 17

Thyroid storm recommended drug?

Answer 17

PTU

Question 18

Which hyperthyroidism drug is best for pregnancy?

Answer 18

PTU in the first trimester

MMI after that

Question 19

Anion Inhibitors

Answer 19

antithyroid drugs

thiocyanate competes with iodine for uptake, so there is less iodine taken up

thiocyanate can be a byproduct of smoking

Question 20

What are the uses of anion inhibitors?

Answer 20

major clinical use for potassium perchlorate is to block thyroidal uptake of iodine in pts with iodine induced hyperthyroidism (ex. amiodarone induced hyperthyroidism)

the use is RARE d.t side effects of aplastic anemia

Question 21

What are the adverse effects of anion inhibitors?

Answer 21

aplastic anemia

Question 22

When do you use iodides?

Answer 22

in hyperthyroidism
rare
using the iodine to precipitate the Wolff-Chaikoff effect (suppression of thyroglobulin synthesis and release)

was used when people were exposed to radioactive iodine

Question 23

What preop treatment is used for thyroidectomy?

Answer 23

thioamide drug till euthyroid (6 weeks)
KI 10 days prior to surgery to reduce size and vascularity
give BB to antagonize catecholamines for symptomatic relief of thyotoxcosis that mimics manifestations of Beta receptor stimulation

Question 24

MOA of iodines (KI)?

Answer 24

participates the Wolff-Chaikoff effect

Question 25

I131

Answer 25

Radioactive iodide

used to treat thyrotoxicosis

MOA: PO, concentrates in thyroid follicle cells, where Beta particles selectively destroy gland w/o injury to adjacent cells

pt becomes euthyroid 6-8 weeks

Question 26

What are the adverse reactions to I131?

Answer 26

eventually causes hypothyoridism

but this is likely part of natural progression of disease

Question 27

What are contraindications of radioactive iodide?

Answer 27

children and pregnancy

no evidence of cancer risk increase with treatment

Question 28

Enzyme D function

Answer 28

activates T4 into T3 via deionization

recall that deionizing you need selenium

Question 29

What happens with there is an increase in binding protein?

Answer 29

a decrease in “free” hormone (since it’s now bound to the binding protein)
the pituitary is stimulated by “Free” hormones so it takes this decrease in free hormone as a stimulus to increase TSH and thus increase in free T4

Question 30

Thioamides

Answer 30

antithyroid drugs

PTU and MMI

onset of action is slow because mechanism to inhibit hormone synthesis:
takes 3-4 weeks to deplete hormone

concentrate in thyroid and excreted in urine

Question 31

What is the treatment course of action for pts with hyperthyroid?

Answer 31

ideally if it is mild to moderate you can manage them with MMI or PTU
60-70% incidence of relapse
most will require surgery or radioactive iodine tx at some point

Question 32

When in hx have they given iodide as a treatment for something?

Answer 32

to compete with the radioactive iodide they gave regular iodide for survivors of
churnobel
japan tsunami

Question 33

What are the adverse effects of iodides?

Answer 33

antithyroid drugs

uncommon and usually reversible when discontinued
acniform rash
swollen salivary glands
mucous membrane ulcerations

Dont use in pregnancy –can cause fetal goiter

Question 34

What is the treatment prep for a pt whom you will be removing their thyroid?

Answer 34

thioamide drug till euthyroid (~6 weeks)
potassium iodide prior to surgery to reduce size and vascularity (aim to reduce surgical risk)
give BB to antagonize catecholamines for sxs relief of thyrotoxicosis that mimic manifestations of Beta receptor stimulation

you could also use radioactive iodide (concentrates in the follicle cells of the thyroid) to destroy the thyroid (euthyroid in 6-8 weeks)