Pharmacotherapy of Thyroid Diseases - SRS

Question 1

What are the thryoid agents we need to know? (2 bold, 4 total)

Answer 1

1. Levothyroxine [T₄]
2. Liothyronine [T₃]
3. Liotrix [4:1 ratio of T₄:T₃]
4. Desiccated thyroid

Question 2

What are the antithyroid agents we need to know? (3 bold, four total)

Answer 2

1. Methimazole
2. Propylthiouracil [PTU]
3. Potassium iodide
4. Radioactive iodine (¹³¹I) sodium

Question 3

Peripheral metabolism is responsible for deiodination of T4 and T3. What are some drugs (4) and conditions (2) that can inhibit this process?

Answer 3

1. Amiodarone
2. iodinated contrast media
3. Beta blockers
4. corticosteroids
5. severe illness
6. Starvation

Question 4

What are two hormones that inhibit release of TSH?

Answer 4

Somatostatin

Dopamine

Question 5

Small amounts of iodide are needed for thyroid hormone synthesis, but large amounts of iodide produce?

Answer 5

Wolf-Chaikoff effect - reduced Thyroid hormone production and release

Question 6

What is the mechanism of action for the following?

• Levothyroxine
• liothyroinine
• liotrix
• desiccated thyroid

Answer 6

Serve as synthetic or xenograft (sort of) source of thyroid hormone, directly stimulate thyroid hormone receptors and thyroid hormone response elements.

Question 7

What is important to know about how our body handles a dose of thyroid agents (levothyroxine or other)?

Answer 7

After absorption, we bind these synthetic or foriegn substances to thyroid binding proteins just as we would endogenous thyroid hormone. Then, we procede to decouple the proteins and hormones at the target tissues.

Question 8

What impact would the following have on thyroid agents?

• rifampin
• phenobarbitol
• carbamazepine
• pheytoin
• HIV protease inhibitors

Answer 8

All increase hepatic metabolism and enhance degredation of thyroid hormone,

Question 9

What are some examples of agents that impair T4 absorption? (9)

Answer 9

1. Oral bisphosphonates
2. bile acid sequestrants (cholestyramine)
3. ciprofloxacin
4. PPIs
5. sucralfate
6. antacids
7. bran
8. soy
9. coffee

Question 10

What are four agents known to induce autoimmune thyroid disease with hypo-or hyperthyroidism?

Answer 10

Amiodarone

Interferon-alpha

interferon-beta

Lithium

Question 11

Why is levothyroxine the preparation of choice? (6)

Answer 11

1. Stability
2. uniform content
3. low cost
4. hypoallergenic
5. easy lab monitoring
6. long T1/2

Question 12

Why is the long half life of levothyroxine a boon?

Answer 12

• Less frequent dosing - once per day
• A missed dose will have minimal impact

(overall better patient compliance and results)

Question 13

Levothyroxine is a synthetic preparation of what hormone?

Answer 13

T4

Question 14

What is the bioavailability of levothyroxine?

Answer 14

70%

Question 15

What is the T1/2 for levothyroxine?

Answer 15

7 days

Question 16

What is the half life for T3?

Answer 16

1 day

Question 17

Despite generally good availability, oral preparations must be swapped for IV in some patients. What patients are these?

Answer 17

Those with severe myxedema and ileus

Question 18

Though more potent, levothyronine is not recommended for therapy for what reasons?

4

Answer 18

1. Shorter T1/2
2. Multiple daily doses
3. Higher cost
4. difficult lab monitoring

Question 19

In what patients would you use liotrix or dessicated thyroid rather than levothyroxine?

Answer 19

In no cases.

1. As oral administration of T₃ is unnecessary, use of more expensive mixture of T₃ and T₄ (liotrix) instead of levothyroxine is never required.
2. Use of desiccated thyroid rather than synthetic preparations is not justified. Disadvantages: protein antigenicity, product stability, variable hormone concentration, and difficulty in lab monitoring far outweigh advantage of lower cost.

Question 20

What are 6 ADR’s associated with levothyroxine? 6

Answer 20

1. Palpitations
2. tremor
3. anxiety
4. weight loss
5. tachycardia
6. increased bowel movement frequency

Question 21

What is the MOA for the thioamides?

Answer 21

Prevent thyroid hormone synthesis via…

3 - Iodide conversion to iodine

4 - organification reaction

5 - coupling reaction

Question 22

What additional step does PTU inhibit beyond the 3 MOA common to thioamides?

Answer 22

Peripheral deiodination of T4 to T3

Question 23

Describe the onset of action for thioamides and explain why it is what it is.

Answer 23

1. Thioamides affect the synthesis of thyroid hormones rather than the release. Onset of action is slow and often requires 3-4 weeks before stores of T₄ are depleted.

Question 24

What is the thioamide drug of choice?

Why?

Answer 24

1. Methimazole: drug of choice; 10x more potent than PTU.

Question 25

Apart from the potency, what other advantages does methimazole have over PTU? What is the half life?

Answer 25

Complete absorption slower excretion Accumulates in thyroid so once daily in spite of T1/2 = 6 hrs.

Question 26

PTU is generally a second line antithyroid drug, in what patients does this move up to first line? Why?

Answer 26

First trimester of pregnancy d/t limited ability to cross the placental barrier. Thyroid storm d/t peripheral T4 to T3 inhibition.

Question 27

What are the big deal ADR's associated with the antithyroid meds?

Answer 27

1. maculopapular pruritic rash (4-6%) 2. Severe hepatitis (black box warning) - may result in death 3. Agranulocytosis - most dangerous complication

Question 28

If a patient develops agranulocytosis what must be done?

Answer 28

Discontinue medication - this usually results in rapid reversal. May need to tx with broad spectrum antibiotics for complicating infections. Consider giving Filgrastim - granulocyte colony stimulating factor

Question 29

If a patient develops agranulocytosis with methimizole, can you switch them to PTU after the crisis is over?

Answer 29

No, d/t the fact that there is 50% cross reactivity between the two drugs and thus a recurrance of agranulocytosis is a significant possibility.

Question 30

What are the anion inhibitors? None bold

Answer 30

1. perchlorate (ClO₄^-), pertechnetate (TcO₄^-), and thiocyanate (SCN^-).

Question 31

What is the MOA for the anion inhibitors?

Answer 31

1. competitively inhibits iodide transport mechanism blocking iodide uptake.

Question 32

While limited, therapeutic uses do exist for anion inhibitors of the thyroid. What is one?

Answer 32

block thyroidal reuptake of iodide in patients with iodide-induced hyperthyroidism (e.g., amiodarone-induced hyperthyroidism).

Question 33

What is the MOA of potassium iodide?

Answer 33

1. inhibit iodine organification and hormone release (possibly inhibition of thyroglobulin proteolysis); decrease size and vascularity of hyperplastic gland.

Question 34

What are three therapeutic uses for potassium iodide?

Answer 34

1. Thyroid storm – improvement in symptoms within 2-7 days. 2. Preoperative reduction of hyperplastic gland. 3. Block thyroidal uptake of radioactive isotopes of iodine in a radiation emergency or other exposure to radioactive iodine.

Question 35

What is **Radioactive Iodine (¹³¹I) used for?** ## Footnote **How does it do this?**

Answer 35

Thyroid ablation effect depends on emission of β rays. Within a few weeks, destruction of thyroid parenchyma evidenced by epithelial swelling and necrosis, follicular disruption, edema, and leukocyte infiltration.

Question 36

What are some contraindications to thyroid ablation?

Answer 36

pregnancy or breast-feeding: Crosses placenta and excreted in breast milk, destroys fetal or infant thyroid gland.

Question 37

In what cases would we use B-blockers in thyroid disease?

Answer 37

1. Cause clinical improvement of hyperthyroid symptoms but do not typically alter thyroid hormone levels (exception: high doses of propranolol may inhibit peripheral conversion of T₄ to T₃, lowering T₃ levels ~20%).

Question 38

How and when should levothyroxine be administered?

Answer 38

1. Administer levothyroxine on an empty stomach, 60 minutes before meals, 4 hours after meals, or at bedtime. Due to many drug interactions/effects separate drug administration times.

Question 39

What toxicities can arise from thyroxine in children?

Answer 39

1. Children – restlessness, insomnia, accelerated bone maturation and growth.

Question 40

What toxicities can arise from thyroxine tx in adults?

Answer 40

1. Adults – increased nervousness, heat intolerance, episodes of palpitations and tachycardia, or unexplained weight loss.

Question 41

Chronic overtreatment with T4 can result in what toxic effect, especially in the elderly?

Answer 41

Atrial fibrillation osteoporosis acceleration

Question 42

What is the end stage of untreated hypothyroidism?

Answer 42

Myxedema coma

Question 43

If a patient presents with the following, what should you suspect? What should you administer? progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock,

Answer 43

Consider Myxedema coma - Admit to ICU and initiate large loading dose of levothyroxine via IV followed by daily maintenance doses.

Question 44

How should you approach tx of a hypothyroid patient with coronary artery disease?

Answer 44

Cautiously, since low levels of thyroxine are cardio protective against increasing demands which could result in angina, A fib, or MI.

Question 45

What is the treatment protocol for a thyroid storm?

Answer 45

1. β-blocker to control severe cardiac manifestations (or calcium-channel blocker if contraindicated). 2. Potassium iodide to prevent release of thyroid hormones from gland. 3. PTU to block hormone synthesis. 4. Hydrocortisone IV to protect against shock (also blocks peripheral conversion of T₄ to T₃). 5. Supportive therapy to control fever, heart failure, or underlying disease states. 6. In rare instances where above measures fail, oral bile acid sequestrants, plasmapheresis, or peritoneal dialysis may lower circulating thyroxine.