Thyroid and Antithyroid Drugs

Question 1

How much thyroid hormone is absorbed, taken up by the thyroid, bound to thyroglobulin and excreted?

Answer 1

• 80-90% absorbed from diet
• 50% is taken up by the thyroid
• T4:T3 –> 5:1 ratio in thyroglobulin
• 60-80% excreted in the urine: 20-40% feces

Question 2

What are the drugs for treatment of hypothyroidism?

Answer 2

Thyromimetic drugs
- levothyroxine
- liothyronine

Question 3

What is the MOA for the Thyromimetic Drugs?

Answer 3

• Levothyroxine: Synthetic T4 → converted to T3 in tissues; activates nuclear T3 receptors
• Liothyronine: Synthetic T3; directly stimulates nuclear thyroid hormone receptors for gene transcription

Question 4

levothyroxine ADME

Answer 4

oral bioavailability is 80%
t1/2 is 6-7 days
99% bound to TGB

Question 5

What are the adverse effects of Levothyroxine

Answer 5

hyperythyroidism symptoms
- insomnia
- anxiety
- fever
- tachycardia
- urticaria

Question 6

What are the drug-drug interactions for Levothyroxine and what can they lead to?

Answer 6

• estrogens and heroine –> increased TGB
• androgens –> decreased TGB
• salicylates –> displacemenet
• rifampin, nicardipine –> increased metabolism
• PTU, beta-blockers –> decreased metabolsim
• antacids, PPIs, cholestryamine –> decreased absorption

Question 7

What is the treatment for thyroid cancer?

Answer 7

Surgery or Radioactive Iodine
- then treat with levothyroxine

Question 8

What are the drugs for treatment of hyperthyroidism?

Answer 8

Antithyroid drugs
- Potassium iodide
- Radioactive iodide (I-131)
- Thioamides: Propylthiouracil , Methimazole

Question 9

What is the MOA for the Thioamines?

Answer 9

Inhibits thyroid peroxidase (↓ T3/T4 synthesis) & blocks peripheral T4 → T3 conversion

Question 10

What is the MOA for Radioactive Iodine?

Answer 10

Taken up by thyroid → beta radiation destroys thyroid tissue

Question 11

What is the MOA for Potassium Iodine?

Answer 11

High doses inhibit thyroid hormone release (Wolff-Chaikoff effect)

Question 12

What are the adverse reactions for Potassium Iodide?

Answer 12

allergic reactions
head-cold like symptoms
acne
swollen tender salivary glands
** not used for long term therapy

Question 13

How long does it take for Radioactive Iodine to have clinical effects?

Answer 13

6-12 weeks

Question 14

How long does it take for Thioamides to have clinical effects?

Answer 14

3-4 weeks

Question 15

What are the adverse effects of Thioamides?

Answer 15

• maculopapular pruritic rashes
• GI upset
• hypothyroidism
• agranulocytosis
• cross placenta: gets into breastmilk

Question 16

What are the adjuncts in treatment of Hyperthyroidism and either MOA?

Answer 16

• Propranolol, Atenolol: Beta-blockers
• Diltiazem: Calcium channel blocker

Question 17

What is the treatment for Thyroid Eye Disease (associated w/ Graves Disease)?

Answer 17

Teprotumumab IV once every 3 weeks for 8 doses

Question 18

What is the MOA for Teprotumumab and what are the therapeutic effects?

Answer 18

monoclonal antibody that inhibits the Insulin-like Growth Factor-1 Receptor (IGF-1R) on fibrocytes in orbital tissue
- Reduces proptosis (bulging of the eyes)
- Decreases inflammation
- Improves diplopia (double vision)

Question 19

What are the adverse effects of Teprotumumab?

Answer 19

Muscle spasms
Nausea and/or diarrhea
Hair loss
Fatigue
High blood sugar (hyperglycemia)

Question 20

What are the symptoms most expected from chronic overdose of levothyroxine?

Answer 20

Tachycardia
Dry puffy skin
Large tongue & drooping eyelids Lethargy, sleepiness
Weight gain