Anti Thyroid Drugs

Question 1

4 classes of drugs that help achieve a “euthyroid” state

Answer 1

1. Iodide transport blockers
2. Thyroid peroxidase (TPO) inhibitors
3. Inhibitors of thyroid hormone secretion
4. Thyroid hormone replacement therapy

Question 2

What are 3 agents that inhibit iodide accumulation?

Answer 2

1. ClO₄^- high affinity for transporter, used for acute inhibition of I- transport during diagnostic procedures
2. SCN^- intereferes with I- uptake (present in braccaca
3. **I^- **in large amounts can be used to limit accumulation of radioactive I- during nuclear accidents. Also can block TPO

ClO₄ > I > SCN > ClO₃

Question 3

What are 2 agents that inhibit thyroid peroxidase? (anti-thyroid drugs)

Answer 3

• Thionamides
  
  • Propylthiouracil
  • Methimazole
  • Carbimazole
• I- in high concentrations, but TPO escapes from the block within 2 weeks = not used for chroonic treatment

Question 4

Side effects of Thyroid Peroxidase inhibitors

Answer 4

Propylthiouracil: inhibits deiodinase activity, may cause hepatic failure

Propylthiouracil and Methimazole (+ Carbimazole, which converts to MMI in vivio) pruritic rash, lupus like symptoms, most severe is agranulocytosis (severely low neutrophil, basophil, eosinophil)

Methimazole is not hepatotoxic

Question 5

What is the agent that inhibits thyroid hormone secretion?

What’s it used for?

Answer 5

LUGOL solution: a mix of KI and I₂

• the KI keeps the I₂ in solution so to get high concentration
• net effect: blocking TPO, blocking T3 and T4 (unknown mech), and constricting blood vessels supplying thyroid gland
• used to quickly reduce thyroid hormone supply to the body (used to be utilized to prepare hyperthyroid pts for throidectomy)

Question 6

What is given for thyroid hormone replacement? 2 reasons why

(hypothyroidism treatment)

Answer 6

T4

• longer half life
• tissue is able to adjust T3 supply by regulating deiodinase activity

Question 7

Wolf-Chaikoff effect

Answer 7

• increased levels of iodide inhibit thyroid hormone
• protects against thyrotoxicosis when iodine is high
• due to inhibition of dual oxidase (generates H202 , electron acceptor) and of thyroid peroxidase (adds iodine, iodide oxidation and binding to tyrosine in follicle lumen)

Question 8

amiodarone (anti arrythmia drug) association with thyroid

Answer 8

has lots of iodine, inhibits deiodinases (T4–>T3), can damage thyroid, and causes hyper or hypo thyroidism

Question 9

What drug does not cross the placental barrier?

Answer 9

Propylthiouracil (PTU)

• good for pregnant women with grave’s to avoid potentially damaging the fetal thyroid gland
• recall that fetus needs to produce T4 and T3 for normal development
• supplement with B-blocker

think of “propio” - your own, so keeps to yourself and wont cross over

Question 10

what indicates that a patient is euthyroid?

Answer 10

normal TSH levels (the pituitary thyrotroph is the endogenous biosensor for T4)

Question 11

For a pt with thyroid cancer who had a total surgical thyroidectomy followed by radioidine treatment, what do you adjust the T4 to?

Answer 11

Important that pt receiving T4 replacement is slighlyyy hyperthyroid so that plasma TSH levels are low/minimal. Maliganant thyroid cells, if still harbors any, grows better in the presence of TSH. So best to keep them low just in case.

Question 12

If pt taking methimazole for 2 months (for her hyperthyroidism) develops a rash (large area, itches), what should you do next?

Answer 12

• DISCONTINUE and consider radioiodine treatment
• rash indicates hypersensitivity aka she will not tolerate any of the thionamide drugs in future (so cant use PTU or carbimazole either)
• radiothyroidectomy is good option since not pregnant, if she develops hypothyroidism after, you can give her daily T4 replacement therapy