The mechanisms of action of antithyroid drugs are not completely understood. Based on their mechanisms of action, the drugs are classified into following six classes.
Thyroid hormone synthesis inhibitors These drugs probably inhibit the enzyme
thyroid peroxidase ( thyroperoxidase), decreasing iodide oxidation,
iodination of tyrosyl residues in
thyroglobulin, and coupling of iodotyrosyl and iodothyronyl residues. It is thought that they inhibit the thyroperoxidase-catalyzed oxidation reactions by acting as substrates for the postulated peroxidase-iodine complex, thus competitively inhibiting the interaction with the amino acid
tyrosine. The most common drugs in this class are
thioamides, which include propylthiouracil, methimazole and its
prodrug carbimazole. Additionally, propylthiouracil may reduce the de-iodination of
thyroxine (T4) into
triiodothyronine (T3) in peripheral tissues.
Lugol's iodine is used to temporarily block thyroid hormone synthesis before surgeries. It is also used to treat patients with thyroid storm or, more commonly, to reduce thyroid vascularity before
thyroidectomy (surgical removal of the
thyroid gland).
Iodide uptake inhibitors They decrease uptake of
iodide ions (I−) into
follicular cells of the thyroid gland. Since their molecules have structural similarities with the iodide ion, they compete with iodide for being transported by the sodium/iodide symporter, which is a
transporter protein that co-transports Na+ and I− ions. Iodide transport is a key step in the biosynthesis of the thyroid hormones T4 and T3. Besides
perchlorates, other examples of iodide uptake inhibitors include
pertechnetates,
thiocyanates,
nitrates. These drugs are no longer used due to high toxicity and adverse effects.
Thyroid hormone release inhibitors They inhibit release (
secretion) of thyroid hormones by the thyroid gland. The most studied drug in this class is
lithium, which inhibits thyroid hormone secretion by inhibiting iodotyrosine coupling, thyroidal iodide uptake, and alteration in structure of
thyroglobulin, a protein which acts as a substrate for the synthesis of thyroid hormones and storage of inactive forms of T3, T4 and iodine within the lumen of thyroid follicular cells. Since lithium is neither metabolized nor protein-bound, its bioavailability usually is close to 100%. Hence, there are risks of serious side effects such as
lithium toxicity,
hypothyroidism, and
diabetes insipidus.
Excess iodine Excessive iodine intake can temporarily inhibit production of thyroid hormones. This occurs because of the
Wolff-Chaikoff effect, which is a phenomenon of rejection of large quantities of iodine by the thyroid gland, therefore preventing it from synthesizing large quantities of thyroid hormones.
Iodine radiopharmaceuticals They are
radioisotopes of iodine. In small doses, when they are taken up by overactive thyroid follicular cells, they emit small amounts of
beta radiation that destroys not all, but many thyroid follicular cells, thereby reducing thyroid hormone production. This is a form of targeted therapy for hyperthyroidism. Since even low levels of ionizing radiation are highly mutagenic and can cause cancer, less toxic iodine isotopes such as
iodine-123 are more commonly used in
nuclear imaging, while
iodine-131 is used for its
cytolytic (cell-destroying) effects in hyperthyroidism and
thyroid tumors. Antagonist 1-850 has also been found to inhibit binding of [125I]T3 to TRs in intact GH4 cells. ==Adverse effects==