The pharmacology of thyroid drugs encompasses a range of medications used to treat disorders of the thyroid gland. The thyroid gland secretes two types of hormones: iodine-containing amino acids (thyroxine [T4] and triiodothyronine [T3]) and a peptide (calcitonin). T4 and T3 have broad effects on growth, development, and metabolism, while calcitonin is involved in calcium metabolism .
Thyroid Hormone Synthesis
– The thyroid secretes T4 and T3, the synthesis of which depends on dietary iodine or iodide supplements.
– Iodide ion is actively taken up by the thyroid, where it is converted to elemental iodine by thyroidal peroxidase.
– The protein thyroglobulin acts as a scaffold for thyroid hormone synthesis, with the iodination of tyrosine residues forming monoiodotyrosine (MIT) or diiodotyrosine (DIT), leading to the formation of T4 and T3.
– After synthesis, T4 and T3 are released into the blood and transported by thyroxine-binding globulin (TBG) .
Thyroid Function Control
– Thyroid function is regulated by the pituitary gland through the release of thyrotropin (TSH), which stimulates iodide uptake, thyroid hormone synthesis, and release.
– High levels of thyroid hormones inhibit TSH release, providing negative feedback control.
– In Graves’ disease, an autoimmune disorder, antibodies can interfere with this regulation .
– Thyroid disorders are broadly categorized into hypothyroidism (decreased thyroid hormones) and hyperthyroidism (increased thyroid hormones).
– Hypothyroidism is treated with thyroid hormone replacement therapy using synthetic forms of T4 (levothyroxine) and T3 (liothyronine), which mimic the actions of thyroid hormones.
– Common side effects of thyroid hormone replacement therapy include headaches, insomnia, nervousness, weight loss, excessive sweating, heat intolerance, and cardiovascular effects like tachycardia and palpitations .
– Antithyroid drugs either decrease thyroid hormone synthesis (thionamides) or thyroid hormone release (iodides).
– Thionamides, including methimazole, carbimazole, and propylthiouracil, inhibit thyroid peroxidase, thus blocking thyroid hormone synthesis.
– Propylthiouracil also lowers peripheral conversion of T4 to T3.
– Iodides, containing potassium iodide, inhibit thyroid hormone release and decrease the vascularity of the thyroid gland .
Indications and Side Effects
– Thionamides are used for hyperthyroidism, thyroid storm, and as preoperative preparation in Graves’ disease.
– Methimazole is preferred due to its faster onset and fewer side effects compared to propylthiouracil.
– Common side effects of thionamides include allergy/hypersensitivity reactions, hematologic effects like agranulocytosis, and hepatotoxicity.
– Iodides’ side effects are usually mild, including oral/gastric mucosal irritation and hypersensitivity reactions .
– In pregnancy, propylthiouracil is recommended in the first trimester, while carbimazole or methimazole are preferred in the second and third trimesters .
These drugs play a crucial role in managing thyroid disorders, with their specific use dependent on the condition being treated and individual patient factors.