"Pharmacology Thyroid Ying Huang"

Question 1

What enzymes convert T4 to T3?

Answer 1

D1 and D2 deiodinases
D1 - liver and kidney
D2 - CNS, pituitary gland, thyroid, heart, brown adipose tissue, skeletal muscle

Question 2

What is D3?

Answer 2

D3 deiodinase - predominantly in brain and skin and placenta

Inactivates T3 to T2

Question 3

What is the cause of congenital hypothyroidism?

Answer 3

Mutations in the sodium-iodide symporter gene affecting iodide transport

Question 4

What causes Hashimoto’s thyroiditis?

Answer 4

Autoantibodies attack the sodium-iodide symporter and cause hypothyroidism

Question 5

Hyperthyroidism has what levels of TSH and T4?

Answer 5

Hyperthyroidism:
Low TSH
High T4

Question 6

Primary hypothyroidism has what levels of TSH and T4?

Answer 6

Primary hypothyroidism:
High TSH
Low T4

Question 7

Secondary hypothyroidism has what levels of TSH and T4?

Answer 7

Secondary hypothyroidism:
Low TSH
Low T4

Question 8

What are common causes of hypothyroidism?

Answer 8

Hashimoto's
Iodine deficiency
Thyroid ablation
Secondary hypothyroidism (pituitary disorder, hypothalamic disorder such as adenoma or radiotherapy)
Myxedema
Cretinism

Question 9

Class: Levothyroxine

Answer 9

Synthetic thyroid hormone (T4)

Question 10

MOA: Levothyroxine

Answer 10

Converted to T3 in liver; T3 binds to TR complex to influence gene expression
Half life of 6-7 days

Question 11

Uses: Levothyroxine

Answer 11

Drug of choice for hypothyroidism (longer half-life than T3)

Question 12

Side effects: Levothyroxine

Answer 12

Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss

Question 13

Class: Liothyronine

Answer 13

Synthetic thyroid hormone (T3)

Question 14

MOA: Liothyronine

Answer 14

T3 binds to TR complex in nucleus to influence gene expression
Half life of 1 day

Question 15

Uses: Liothyronine

Answer 15

Acute management of hypothyroidism (rapid effect); myxedema coma (IV formulation)

Question 16

Side effects: Liothyronine

Answer 16

Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss

Question 17

Class: Liotrix

Answer 17

Synthetic thyroid hormone (T4 & T3)

Question 18

MOA: Liotrix

Answer 18

Converted to T3 in liver; T3 binds toTR complex to influence gene expression

Question 19

Uses: Liotrix

Answer 19

Thyroid hormone replacement therapy (4:1 mix of T4:T3; not used much)

Question 20

Side effects: Liotrix

Answer 20

Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss

Question 21

Levothyroxine is not indicated in patients with:

Answer 21

Chronic Fatigue Syndrome bc they have difficulty converting T4 to T3
Use Liothyronine in these patients

Question 22

What is the drug of choice for acute hypothyroidism, such as myxedema coma?

Answer 22

IV formulation of Liothyronine

Question 23

What causes Grave’s disease?

Answer 23

Thyroid-stimulating antibodies which bind to and activate the thyrotropin receptor on thyroid cells

The second most common cause of hyperthyroidism is nodular goiter (older age group). Other causes include thyroiditis or thyroid cancer.

Question 24

Why would a beta blocker such as propranolol be indicated for hyperthyroidism?

Answer 24

It would dampen the sympathetic effects of the hyperthyroid function

Question 25

Class: Propylthiouracil

Answer 25

Thioamide (thyroid peroxidase inhibitors)

Question 26

MOA: Propylthiouracil

Answer 26

Inhibit organification of iodide and coupling of iodotyrosine; also reduces peripheral deiodination of T4 to T3 by D1

Question 27

Uses: Propylthiouracil

Answer 27

Hyperthyroidism; thyrotoxicosis (high dose); drug of choice for hyperthyroidism during pregnancy

Question 28

Side effects: Propylthiouracil

Answer 28

Rare side effects: hepatitis, agranulocytosis (higher than methimazole), lupus-like syndrome

Question 29

Class: Methimazole

Answer 29

Thioamide (thyroid peroxidase inhibitors)

Question 30

MOA: Methimazole

Answer 30

Inhibit organification of iodide and coupling of iodotyrosine; active metabolite of carbimazole; less effect on T4 to T3 conversion

Question 31

Uses: Methimazole

Answer 31

Hyperthyroidism; thyrotoxicosis (high dose)

Question 32

Side effects: Methimazole

Answer 32

Rare side effects: hepatitis, agranulocytosis (less than propylthiouracil), lupus-like syndrome

Question 33

Class: Carbimazole

Answer 33

Thioamide (thyroid peroxidase inhibitors)

Question 34

MOA: Carbimazole

Answer 34

Prodrug converted to methimazole; Inhibits organification of iodide and coupling of iodotyrosine; less effect on T4 to T3 conversion

Question 35

Uses: Carbimazole

Answer 35

Hyperthyroidism; thyrotoxicosis (high dose)

Question 36

Side effects: Carbimazole

Answer 36

Rare side effects: hepatitis, agranulocytosis, lupus-like syndrome

Question 37

In thyrotoxicosis, what route of administration may be necessary?

Answer 37

Rectal

Question 38

Which antithyroid drug has a higher risk of agranulocytosis, propylthiouracil or methimazole?

Answer 38

Propylthiouracil

Question 39

Propylthiouracil is the preferred antithyroid drug in what patient population?

Answer 39

Pregnant and breast-feeding patients

Question 40

Patients taking an anti-thyroid who develop agranulocytosis are then candidates for what therapies?

Answer 40

Radioactive iodine or surgery

Question 41

Class: Radioactive Iodine

Answer 41

Radioactive isotope

Question 42

MOA: Radioactive Iodine

Answer 42

Radioactive agent that emits beta particles and gamma rays that destroy thyroid cells

Question 43

Uses: Radioactive Iodine

Answer 43

Treatment of choice for hyperthyroidism after antithyroid drug therapy; ablation after cancer

Question 44

Side effects: Radioactive Iodine

Answer 44

Transient or permanent hypothyroidism; increases cancer risk

Question 45

Radioactive iodine is contraindicated in what patient population?

Answer 45

Pregnant and breastfeeding patients