Thyroid & Antithyroid Drugs

Question 1

Drugs for treatment of hypothyroidism

Answer 1

Levothyroxine (T4)
Liothyronine (T3)
Liotrix (T4 and T3)

Question 2

Drug of choice for treatment of Grave’s disease (due to longer half-life and lower adverse effect profile)

Answer 2

Methimazole

Question 3

Drug of choice for treatment of thyroid storm, because of it’s additional action to prevent peripheral conversion of T4->T3

Answer 3

Propylthiouracil (PTU)

Question 4

MOA of antithyroid drugs (PTU and methimazole)

Answer 4

Irreversibly inhibit the peroxidase enzyme. The content of thyroglobulin gradually decreases due to:

1. The continued secretion and inhibition of synthesis
2. Suppression of hormone secretion
3. PTU (ONLY!!) prevents peripheral conversion of T4 -> T3

Question 5

Explain why antithyroid drugs are goitrogenic.

Answer 5

There is a compensatory increase in TSH secretion with continued decrease of thyroid hormone synthesis and secretion.
*NB: because of this, it is necessary to administer T4 to prevent goiter.

Question 6

Adverse effects of PTU and methimazole

Answer 6

Most common: Rash
Other: Nausea, headache, pain/stiffness of joints. Mild, transient leukopenia is common in children.
Most serious: Agranulocytosis

Question 7

Monovalent anions that competitively inhibit the iodide/sodium pump (symport).

Answer 7

Perchlorate, thiocyanate, fluoborate

Question 8

High doses of perchlorate can cause?

Answer 8

Fatal aplastic anemia

Question 9

Mood stabilizer that inhibits thyroid hormone secretion and may interfere with Ca2+ metabolism

Answer 9

Lithium

Question 10

MOA of iodide (aka Lugol’s solution, potassium iodide)

Answer 10

Primary MOA at therapeutic doses is inhibition of T3/T4 release.
High concentrations will decrease (but not ABOLISH) thyroid hormone synthesis through inhibition of iodine organification.
Reduce size and vascularity of thyroid gland

Question 11

Used in diagnosis of thyroid function and as means of definitive treatment of hyperthyroidism

Answer 11

Radioactive iodine (131-I)

Question 12

Which particles of 131-I cause necrosis of the thyroid gland?

Answer 12

Beta particles

Question 13

Which particles of 131-I pass through soft tissues and can be detected by an external counter?

Answer 13

Gamma particles

Question 14

Control thyrotoxic symptoms associated with increased sensitivity to catecholamines; useful in thyrotoxic crisis.

Answer 14

Beta blockers: propranolol, metoprolol, atenolol

Question 15

Beta blocker that has the additional effect of preventing the peripheral conversion of T4 –> T3 at high doses through inhibition of hepatic 5’-deiodinase I

Answer 15

Propranolol

Question 16

Contraindications for the use of beta blockers in thyroid disease

Answer 16

Cardiac failure, bronchial asthma

Question 17

Control tachycardia and decrease the incidence of supra ventricular arrhythmias in thyroid storm; not used with beta blockers

Answer 17

CCBs (verapamil and diltiazem appear to be the most effective)

Question 18

MOA of glucocorticoids in thyrotoxic crisis

Answer 18

1. Decrease peripheral conversion of T4 to T3; increase the conversion of T4 to rT3.
2. Inhibit TSH secretion, decrease plasma TBG levels, inhibit iodide uptake and T4/T3 release

Question 19

MOA of cholestyramine and other bile acid-binding resins in thyrotoxic crisis

Answer 19

Bind thyroid hormone conjugates secreted in bile and prevent their enterohepatic recycling.