Wooten - TH drugs

Question 1

Which two enzymes are common targets of drugs that treat hyperthyroidism?

Answer 1

TPO (thyroperoxidase)
- inhibiting this enzyme inhibits the oxidation of iodide to iodine, so coupling of iodine/tyrosine cannot occur

5’ deiodinase
- inhibiting this enzyme prevents the conversion of T4 –> T3 in the periphery

Question 2

What is the MOA of propylthiouracil, and what is it used to treat?

Answer 2

Propylthiouracil (PTU) works by inhibiting BOTH TPO and 5’ deiodinases:

TPO inhibition = prevention of oxidation of iodide –> iodine, so coupling cannot occur

5’ deiodinase inhibition = reduces peripheral conversion of T4 –> T3

PTU is used to treat hyperthyroidism and thyroid storm.

Question 3

What is the MOA of methimazole, and what is it used to treat?

Answer 3

Methimazole inhibits TPO, so oxidation of iodide to iodine does not occur. This prevents the coupling of iodine and tyrosine, decreasing thyroid hormone production.

Methimazole is used to treat hyperthyroidism.

Question 4

What drug is the commonly preferred agent to treat hyperthyroidism?

Answer 4

Methimazole

Question 5

Which drug is preferred to treat hyperthyroidism in a patient in the first trimester of pregnancy?

Answer 5

PTU

Question 6

What drugs are commonly used in conjunction with radioactive iodine prior to surgical thyroidectomy?

Answer 6

PTU or methimazole

Question 7

What are some AE associated with PTU and methimazole?

Answer 7

Leukopenia/agranulocytosis
- monitor WBC, watch for infections

Also: rash, urticaria, arthralgia, N/V, bleeding

PTU specifically has risk of ANCA-related vasculitis and hepatotoxicity/liver failure

Methimazole is teratogenic

Question 8

What drugs can be used to address symptoms of hyperthyroidism (as opposed to excess production of thyroid hormone)?

Answer 8

B-blockers - reduce the adrenergic-related symptoms; slow conversion of T4 –> T3 via 5’ deiodinase

Glucocorticoids - Slow the conversion of T4 –> T3 via 5’ deiodinase; also helps reduce inflammation (helps with moon face and exopthalamos)

Question 9

What drugs are used during thyroid storm?

Answer 9

• PTU (preferred over methimizole due to action on 5’ deiodinase)
• B-blockers
• Glucocorticoids
• Lugol’s or potassium iodide
  (makes thyroid gland less vascular and inhibits T3/T4 synthesis via Wolff-Chaikoff effect)

Question 10

What are some drugs that have adverse effects on thyroid synthesis and can lead to iatogenic hypothyroidism?

Answer 10

Lithium
Amiodarone
Anti-seizure drugs

Question 11

What are three drugs that can be used to treat hypothyroidism?

Answer 11

Levothyroxine - exogenous T4

L-triiodothyroixine - exogenous T3

Thyroid USP/Armour TH - desiccated bovine/porcine thyroid gland

Question 12

What is the drug of choice to treat hypothyroidism?

Answer 12

Levothyroxine

Question 13

What are some drugs that can inhibit levothyroxine?

Answer 13

• Iron (including multivitamins)
• Ca++
• Aluminum-containing antacids, including sucralfate
• Some cholesterol meds (cholestyramine and colestipol)
• Estrogen

Question 14

Which drugs have effects that can be enhances by high levels of TH or administration of levothyroxine?

Answer 14

• Epinephrine
• Warfarin (reduce dose in patients on levothyroxine and monitor INR)
• Antidepressants

Question 15

What are some things that can decrease the bioavailability of levothyroxine?

Answer 15

• PPI therapy (used in GERD/ulcers)
• Autoimmune gastritis
• H. pylori infection
• Various foods, coffee, or medications that can decrease absorption

Question 16

What are some adverse effects of levothyroxine?

Answer 16

Anything associated with hyperthyroidism, including:

• Tachycardia; palpitations
• Increased appetite; weight loss
• Nervousness; insomnia
• Sweating; heat intolerance; fever
• Headache