Antithyroid Drugs: Propylthiouracil, Carbimazole & Methimazole

Summary

This video explains the role of antithyroid drugs like propylthiouracil, carbimazole, and methimazole in managing hyperthyroidism. These drugs inhibit thyroid peroxidase, preventing the synthesis of thyroid hormones, with effects taking around three weeks to show. Propylthiouracil also blocks the conversion of T4 to T3, making it useful in thyroid storm and during pregnancy. Common side effects include hypothyroidism and rash, while more severe risks like agranulocytosis and liver damage are noted. Carbimazole and methimazole are preferred for their fewer side effects and once-daily dosing. The video is a comprehensive guide to the uses, mechanisms, and side effects of these vital medications.

Takeaways

• 😀 These antithyroid drugs (propylthiouracil, carbimazole, and methimazole) are taken orally and have good gastrointestinal absorption.
• 😀 Carbimazole is converted into methimazole after absorption, so they are often considered together in treatment.
• 😀 These drugs inhibit thyroid peroxidase, preventing the synthesis of new thyroid hormones. However, the thyroid gland stores already synthesized hormones, leading to a delayed effect (about three weeks).
• 😀 These drugs accumulate in the thyroid gland, making their effects last longer than predicted by their plasma half-life.
• 😀 Propylthiouracil has a short plasma half-life (1-2 hours) but its effects last around 8 hours, requiring dosing 2-3 times a day.
• 😀 Carbimazole has a longer plasma half-life (8 hours) and its effects last for an entire day, so it's usually taken once daily.
• 😀 Propylthiouracil also inhibits the peripheral conversion of T4 to T3, providing immediate effects by depleting T3 levels.
• 😀 These drugs are primarily used to treat hyperthyroidism, including conditions like Graves' disease, toxic nodular goiter, and subacute thyroiditis.
• 😀 Propylthiouracil is particularly used in thyroid storm (due to its T3 depletion action) and during pregnancy (due to less placental penetration).
• 😀 Common side effects include hypothyroidism, goiter, rash, joint pain, and a rare but serious side effect of agranulocytosis. Propylthiouracil may also cause liver damage, while carbimazole and methimazole can cause fetal toxicities.
• 😀 For treatment, carbimazole or methimazole is preferred in most cases, but propylthiouracil is used in special situations like thyroid storm or pregnancy.

Q & A

What is the primary mechanism of action of antithyroid drugs like propylthiouracil, carbimazole, and methimazole?

These drugs inhibit the enzyme thyroid peroxidase, which plays a critical role in the synthesis of thyroid hormones. This prevents the production of new thyroid hormones.

Why do antithyroid drugs take about three weeks to show effects despite being absorbed quickly?

Antithyroid drugs take about three weeks to show effects because the thyroid gland stores already synthesized hormones, which are released over time. The drugs prevent the synthesis of new hormones, but the stored hormones continue to be secreted for about three weeks.

How do the plasma half-lives of propylthiouracil and carbimazole compare to the duration of their effects?

Propylthiouracil has a plasma half-life of 1-2 hours, but its effect lasts for about 8 hours, requiring 2-3 doses daily. Carbimazole has a plasma half-life of 8 hours, but its effect lasts for an entire day, so it is taken once daily.

What is the additional mechanism of action of propylthiouracil, and how does it affect thyroid hormone levels?

Propylthiouracil inhibits the enzyme deiodinase (D1), which is responsible for converting T4 to T3 in peripheral tissues. This action depletes T3 levels immediately, making propylthiouracil effective in rapidly reducing T3.

What are the main therapeutic uses of antithyroid drugs like propylthiouracil, carbimazole, and methimazole?

These drugs are primarily used to treat hyperthyroidism, such as in Graves' disease, toxic nodular goiter, and subacute thyroiditis. They are used either alone for moderate disease, in combination with radioactive iodine, or before surgery to achieve a euthyroid state.

Why is propylthiouracil preferred in certain special cases, like thyroid storm and pregnancy?

Propylthiouracil is preferred in thyroid storm due to its inhibition of T4 to T3 conversion, which is crucial in managing the storm. In pregnancy, it is preferred because it is more protein-bound, leading to less placental penetration and thus lower risk of fetal toxicity compared to carbimazole and methimazole.

What are some common side effects of antithyroid drugs like propylthiouracil, carbimazole, and methimazole?

Common side effects include hypothyroidism, goiter, rash, joint pain, and agranulocytosis. Propylthiouracil can also cause liver damage, and carbimazole and methimazole can cause fetal toxicities such as fetal goiter and coanal atresia.

How do antithyroid drugs cause goiter, and why does this occur?

Antithyroid drugs can lead to goiter due to reduced thyroid hormone levels, which stimulate the pituitary to release thyroid-stimulating hormone (TSH). Increased TSH causes the thyroid gland to enlarge in an attempt to produce more hormones.

What are the potential fetal toxicities associated with carbimazole and methimazole during pregnancy?

Carbimazole and methimazole can cross the placenta and cause fetal toxicities such as fetal goiter, coanal atresia, scalp defects, and aplasia cutis, making these drugs less preferable during pregnancy compared to propylthiouracil.

Why is propylthiouracil specifically avoided in children and young adults despite its effectiveness?

Propylthiouracil is avoided in children and young adults because it can cause severe liver damage, which is a serious and potentially fatal side effect. This risk outweighs its benefits in these age groups.