Thyroid Drugs

Question 1

What are the 2 thyroid hormones and what is their relationship?

Answer 1

L-thyroxine (T4) and Liothyronine (T3). T4 is the precursor to T3 which is the active hormone.

Question 2

Describe the steps in thyroid hormone synthesis.

Answer 2

Peroxidase (enzyme) –> oxidation of dietary iodine –> iodination of tyrosine –> thyroid hormone

Question 3

How and where is thyroid hormone stored?

Answer 3

Stored as thyroglobulin in the thyroid

Question 4

Describe the hypothalamic-pituitary-thyroid axis.

Answer 4

Hypot releases TRH –> AP releases TSH –> thyroid releases T4 –> T4 deiodinated to T3 in periphery.

Question 5

How is the majority of T3 and T4 present in the blood?

Answer 5

Bound to plasma protein (inactive) –> thyroxine binding globulin (TBG)

Question 6

What increases and decreases TBG?

Answer 6

Inc: pregnancy and oral contraceptives
Dec: anabolic steroids (T inc metabolic requirements which increases need for free T3)

Question 7

Why are most thyroid meds given PO?

Answer 7

T4 and T3 are lipophilic meaning they are well absorbed in the gut.

Question 8

What is the basic mechanism of Graves disease?

Answer 8

Autoimmune antibodies that agonize TSH receptors

Question 9

Describe the pharmacological effects of T3 and T4.

Answer 9

Activating hormones –> stimulate protein synthesis, inc metabolic rate and O2 consumption, inc sensitivity to catecholamines

Question 10

State and describe the drug most used to treat hypothyroid.

Answer 10

Levothyroxine (T4, aka Synthroid) –> slow on and slow off. Max effect of one dose reached in 10 days.

Question 11

What is the name of T3 and why is it not used in the treatment of hypothyroid?

Answer 11

Liothyronine –> 5x as potent as T4, max effect in 24h. Its potency makes it too unpredictable.

Question 12

What lab value indicates hypothyroidism (cretinism)?

Answer 12

High TSH, low T3 and T4

Question 13

What is the dosing regimen for hypothyroidism?

Answer 13

50-100 mcg synthroid qd titrated up to normal TSH

Question 14

In dosing synthroid what considerations are given to pregnant females and to cardiac patients?

Answer 14

pregnant: need higher dose (TBG increases)
cardiac: need lower dose (don’t overstimulate heart)

Question 15

Why is synthroid taken on an empty stomach?

Answer 15

Synthroid sticks to food, dec absorption

Question 16

When would T3 be administered as treatment for hypothyroid?

Answer 16

Emergency –> myxedema coma

Question 17

What are potential adverse effects of Synthroid?

Answer 17

inc metabolic rate (pseudohyperthyroidism)

atrial fibrillation

Question 18

T/F: Brand Synthroid is preferred over generic.

Answer 18

True

Question 19

What happens if synthroid is dosed too high and thyroid hormone levels rise too much?

Answer 19

D/C drug for 7 days then recommence at lower dose

Question 20

T/F: Hyperthyroid disease is much easier to treat than hypothyroid disease.

Answer 20

False –> hypothyroid easy to manage by titrating Synthroid. Hyperthyroid often involves surgical removal of the thyroid gland.

Question 21

What is the mechanism of action of methimazole?

Answer 21

Blocks formation of thyroid hormones by inhibiting oxidation of dietary iodine.

Question 22

T/F: Methimazole reduces conversion of T4 to T3 in peripheral tissues.

Answer 22

False –> has no effect on T4 - T3 conversion

Question 23

Why is methimazole not typically used in the first trimester of pregnancy?

Answer 23

It easily crosses the blood-placenta barrier.

Question 24

What is the effect of plasma albumin concentration on the action of methimazole?

Answer 24

No effect –> methimazole is not plasma protein bound.

Question 25

What is the typical dose of methimazole?

Answer 25

5 - 15 mg PO, QD

Question 26

What is the mechanism of action of propylthiouracil (PTU) and why are its effects delayed?

Answer 26

Inhibits oxidation of thyroid hormone. Max effects not seen until all previously formed T4/T3 is exhausted.

Question 27

Why is a high dose of PTU the treatment of choice in thyroid storm?

Answer 27

PTU blocks peripheral conversion of T4 to T3

Question 28

When in pregnancy is PTU preferred over methimazole?

Answer 28

During the 1st trimester –>PTU still crosses blood-placenta barrier and may enter breast milk.

Question 29

Why is methimazole preferred over PTU in most patients?

Answer 29

More AE’s with PTU –> rash, dysphagia, agranulocytosis (low WBC)

Question 30

What is the typically dose of PTU?

Answer 30

100 - 200 mg PO, TID

Question 31

Why is high doses of iodine used to treat hyperthyroidism?

Answer 31

When given a lot of iodine, there is a negative feedback on the thyroid which causes it to produce less thyroid hormone.

Question 32

What is the primary use of iodine? In what form is it given? And why is it used?

Answer 32

It is used properatively as potassium iodide - 60 mg, Q8h, for 10-14 days. The iodine firms up the thyroid making it more amenable to surgical procedures.

Question 33

Describe Lugol’s solution.

Answer 33

SSKI –> Saturated Solution of Potassium Iodine

Question 34

What is the purpose of giving radioactive iodine?

Answer 34

Iodine goes straight to the thyroid, taking the radiation with it to destroy thyroid tissue. This is used to treat hyperthyroidism.

Question 35

What antiarrhythmic medication has iodine in it? What other products used in medicine contain iodine?

Answer 35

Amiodarone –> monitor TSH levels in patients taking amiodarone. Some contrastst dyes and antiseptics contain iodine.

Question 36

Other than PTU, what 2 medications are the ideal treatment of thyroid storm?

Answer 36

IV or PO propranolol –> non-selective beta blocker

High dose dexmethasone –> inhibit T4 - T3 conversion (monitor BGL in Pt’s on dexmethasone)

Question 37

Why must BGL be monitored in patients taking steroids?

Answer 37

Steroids can cause hyperglycemia