Kruse - Thyroid and Antithyroid Drugs DSA

Question 1

Longer half life: T4 or T3? Which is more potent?

Answer 1

T4 (7 days) > T3 (1 day).

T3 is more potent, but T4 is preferred therapy for hypothyroidism as thyroid replacement.

Question 2

T4 and T3 absorption may be affected by myxedema with ileus, but not by mild ____?

Answer 2

hypothyroidism

Question 3

Agents that inhibit conversion of T4 to T3 (via inhibition of 5’-deiodinase in cytoplasm) and increase reverse-T3 (inactive) levels.

Answer 3

Radiocontrast agents iopanoic acid and ipodanate

***Amiodarone, B-blockers, Corticosteroids

Question 4

Patients experiencing ____ are administered agents that inhibit T4 to T3 conversion to reduce T3 levels?

Answer 4

Thyroid storm (thyrotoxic crisis)

Question 5

What drugs decrease T4 absorption?

What instructions should be given to someone who is taking T4?

Answer 5

Cholestyramine, colestipol, cipirofloxin, PPI, ferrous sulfate, bran, soy, coffee, antacids (aluminum hydroxide, calcium carbonate)
-Instruct to take on an empty stomach

Question 6

Drugs that induce hepatic CYP450s, thus increasing metabolism of T4 and T3 are ____.

Answer 6

Rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, imatinib, protease inhibitors

Question 7

Advantages of T4 (levothyroxine) for thyroid replacement therapy

Answer 7

Stability, low cost, lack of allergic foreign protein, easy lab measurement of serum levels, long 1/2 life –> 1x/day dose

Question 8

Agents that interfere with production of thyroid hormone

Answer 8

• Thioamides (block iodide organification/oxidation in the thyroid)
• Anion inhibitors (block thyroid uptake of iodide)
• Iodide (inhibit organification, decrease size/vascularity of gland)

Question 9

Agents that modify tissue response to thyroid hormone

Answer 9

?

Question 10

Thyroid gland destruction with radiation or surgery

Answer 10

Radioactive iodine

Question 11

Name the thioamides and function.

Answer 11

Methimazole, Propylthiouracil (PTU)

Used for hyperthyroidism

Question 12

MOA of methimazole and Propylthiouracil (PTU)

Answer 12

Inhibit thyroidal peroxidase-catalyzed reactions and BLOCKS IODIDE ORGANIFICATION (Inhibit TH synthesis by blocking oxidation of iodide in the thyroid gland.)

Question 13

Two pregnant woman have hyperthyroidism and need agents that interfere with production of thyroid hormone. One is in her 1st trimester, one is in her 2nd/3rd trimester. What drug is given to each?

Answer 13

1st trimester, give PTU

2nd/3rd trimester, give methimazole

Question 14

Methimazole and Propylthiouracil (PTU) - half lives and dosing.

Answer 14

Methimazole - half life = 6hrs; 1x/day dose

Propylthiouracil (PTU) - half life = 1.5 hours; 3-4x/day dose

Question 15

How does PTU MOA differ from methimazole?

Answer 15

PTU blocks peripheral conversion of T4 to T3, allowing for a significantly greater fall in T3 concentration.

Question 16

Most common adverse effects of methimazole and propylthiouracil (PTU).

Answer 16

Maculopapular pruritic rash with possible fever, nausea, GI distress

Question 17

Adverse effect that is more common in PTU than methimazole?

Answer 17

Hepatitis

Question 18

Adverse effect that’s more common in methimazole than PTU?

Answer 18

Cholestatic jaundice

Question 19

Most serious adverse effect of methimazole and propylthiouracil (PTU).

Answer 19

Agranulocytosis (

Question 20

Treatment for agranulocytosis induced by PTU or methimazole.

Answer 20

Discontinue drug and give colony-stimulating factor (pegfilgrastim or filgrastim).

Question 21

What population (taking thioamide) has especially increased risk for agranulocytosis?

Answer 21

Especially in older patients receiving high dose methimazole

Question 22

MOA of anion inhibitors (perchlorate, pertechnetate, thiocynate)

Answer 22

Block thyroid uptake of iodide by competitive inhibition of iodidie transport.

Question 23

MOA of iodides.

Answer 23

Inhibit organification and hormones release, decreases size and vascularity of the hyperplastic thyroid gland.

Question 24

In what three clinical settings would iodide be of use for a person with hyperthyroidism?

Answer 24

1. Thyroid storm
2. Pre-operative reduction of hyperplastic thyroid gland
3. Block thyroidal uptake of radioactive isotopes of iodine in radiation emergency or exposure to radioactive iodine.

Question 25

Mother did not stop taking iodide for her hyperthyroidism and it crossed the placenta. What would the fetus present with?

Answer 25

Fetal goiter

Question 26

A person presents with an acneiform rash, swollen salivary glands, mucous membrane ulcerations, conjuctivitis, and metallic taste - what are they on?

Answer 26

Iodide for hyperthyroidism

Question 27

What is the MOA of radioactive iodine?

Answer 27

It is rapidly absorbed and concentrated by the thyroid and incorporated into the follicles where the B-radiation destroys thyroid parenchyma.

Question 28

Evidence of radioactive iodine B-radiation destroying thyroid parenchyma.

Answer 28

epithelial swelling and necrosis, follicular disruption, edema, leukocyte infiltration

Question 29

Advantages of radioactive iodine treatment.

Answer 29

Ease of administration, effectiveness, low expense, absence of pain (no surgery).

Question 30

Administration of of radioactive iodine treatment is contraindicated in what type of people?

Answer 30

pregnant women or those breastfeeding

Question 31

What types of B-blockers are effective in management of thyrotoxicosis?

Answer 31

Those without sympathomimetic activity - metoprolol, PROPANOLOL, atenolol

Question 32

What is the result of B-blocker use?

Answer 32

Improves symptoms of hyperthyroid but does not typically alter thyroid levels.

Question 33

DOC for hypothyroidism - both for (1) replacement therapy and (2) drug-induced hypothyroid that is not alleviated stoppage of offending agent.

Answer 33

Levothyroxine (T4)

Question 34

A person presents with progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock, and death. What is this and what do you treat with?

Answer 34

Myxedema coma (end state of untreated hypothyroidism), treat with IV Levothyroxine (large loading dose, then smaller dosing).

Question 35

Treatment of myxedema coma with T4 for someone with what ___ concomitant condition must be taken into account.

Answer 35

Coronary artery disease - T4 can provoke arrhythmia, angina, and acute MI

Question 36

A woman wants to conceive, but cannot. What could be the cause and what is cruicial to make sure is administered once she becomes pregnant?

Answer 36

If hypothyroid, women are typically infertile until normal thyroid levels restored. Maternal T4 crucial for fetal brain development.

Question 37

Potential treatments for Grave's Disease (hyperthyroid)

Answer 37

1. Antithyroid therapy - TxOC in young pts with small glands and mild dz; methimazole preferred over PTU) 2. Thyroidectomy - TxOC for pts with large glands or multinodular goiter) 3. Radioactive iodine - TxOC for most people over 21 4. Adjunct tx - B-blockers to control tachycardia, HTN, afib.

Question 38

TxOC in young pts with Graves with small glands and mild dz

Answer 38

Antithyroid therapy

Question 39

TxOC for pts with large glands or multinodular goiter.

Answer 39

Thyroidectomy | *80-90% will require replacement therapy

Question 40

TxOC for most people over 21, esp those with underlying heart disaese, severe thyrotoxicosis, or elderly.

Answer 40

Radioactive iodine | *80% will require replacement therapy

Question 41

A person is taking antithyroid therapy, but needs adjunct to control tachycardia and B-blockers are CI. What drug can be used?

Answer 41

diltiazem (Ca-channel blocker)

Question 42

Tx regimen for thyrotoxicosis

Answer 42

1. B-blocker for arrhythmia 2. Potassium iodide - prevent TH release from gland 3. IV hydrocortisone - protect from shock and decraese T4 to T3 converstion in peripheral tissues/blood 4. Potentially plasmapharesis or peritoneal dialysis to lower T4 levels.