Antithyroid agents

Thyroid Hormone Synthesis and Actions Effects of Antithyroid Agents 

Active accumulation of iodide into gland Basis for selective cell destruction of I 

Coupling reactions to form DIT, Tj, and T Inhibited by thioamides and high levels of iodide 

I Coupling reactions of MIT and DIT to form Tjt and T Inhibited by iodide and high-dose ipodate 

Conversion of T to Tj via 5 deiodinase in peripheral tissues Inhibited by ipodate, propranolol, and at high-dose propylthiouracil  

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Hyperthyroidism, that is, the overproduction of thyroid hormones, is usually treated by surgical removal of the thyroid gland. Before such a procedure is undertaken, the hyperthyroidism is usually first brought under control by treatment with so-called antithyroid agents. 

Antithyroid agent. An agent that decreases the synthesis and/or release of thyroid hormones. 

Like sulfur, selenium based electron donors are heavily studied due to their potential as antithyroid agents. Of the 28 complexes reported, the majority (20) are diiodine based, and most of these (16) are simple adducts. One diiodine complex is bridged, one contains only extended adducts, one contains only bridged adducts, and one contains both bridged and extended adducts. All of the interhalogen complexes are simple adducts except one with iodine monobromine, which forms an extended adduct. 

Fukayama H, Nasu M, Murakami S, et al. 1992. Examination of antithyroid effects of smoking products in cultured thyroid follicles only thiocyanate is a potent antithyroid agent. Acta Endocrinol (Copenh) 127(6) 520-525. 

Antithyroid agent Bioavailability (%) Protein binding (%) Transplacental passage Breast milk levels (M P)2 Half-life (h)... 

Drugs that may interact with antithyroid agents include anticoagulants. 

Methimazole (Tapazole) [Antithyroid Agent] Uses Hyperthy-roidism, thyrotoxicosis, pr for thyroid surgery or radiation Action Blocks T3 T4 formation Dose Adults. Initial 15-60 mg/d PO tid Maint 5-15 mg PO daily Peds. Initial 0.4-0.7 mg/kg/24 h PO tid Maint V h- U h of initial dose PO daily w/ food Caution [D, +/-] Contra Breast-feeding Disp Tabs SE GI upset, dizziness, blood dyscrasias Interactions t Effects OF digitalis glycosides, metoprolol, propranolol X effects OF anticoagulants, theophylline X effects W/ amiodarone EMS None OD May cause N/V, HA, abd pain, fever, and pale skin symptomatic and supportive... 

Propylthiouracil [PTU] [Antithyroid Agent/Thyroid Hormone Antagonist] Uses HypCTthyroidism Action X Production of Tg T4 conversion of T4 to Tg Dose Adults. Initial 100 mg PO q8h (may need up... 

Aggravation of the extrapyramidal effects of antipsychotic agents have been described and it has been reported that the use of lithium in combination with haloperidol may result in irreversible neurological toxicity. Lithium can increase the hypothyroid effects of antithyroid agents or iodides. 

Antithyroid agents are used for the management of hyperthyroidism. The different agents are equally effective and have the same toxic potential. Their commonest adverse effects are skin rashes, while the most serious reaction is the occurrence in about 0.5% of the patients of a potentially fatal agranulocytosis. 

Biosynthetic defects in thyroid hormonogenesis may also result in an inability of the thyroid gland to produce sufficient hormone and may be due to inherited enzymatic deficiencies or the ingestion of natural or therapeutically administered antithyroid agents. An example in the latter category is lithium, widely used to treat psychiatric disorders and associated with the development of hypothyroidism and goiter. It is concentrated by the thyroid, where it inhibits thyroidal I uptake, incorpora-... 

In addition, the metabohsm of OCAs results in the release of large amounts of E into the circulation. As described for KI, I released from OCAs may have effects at the thyroid gland and if used alone to treat hyperthyroidism, OCAs carry the same potential to induce increased secretion of thyroid hormone and exacerbation of thyrotoxicosis. When an OCA is used in the treatment of hyperthyroidism, large doses of antithyroid agents are usually administered concomitantly. However, the combination of OCAs and antithyroid drugs may cause resistance to the antithyroid drugs with time, presumably because of the elevation in intrathyroidal 1 content. Thus, it is recommended that the use of OCAs be reserved for short-term treatment of patients with severe thyrotoxicosis and significant comorbidity (e.g., myocardial infarction, sepsis, stroke) for rapid control of plasma Tj concentrations. 

Details are discussed in chapter Thyroid antithyroid agents. ... 

These are used to inhibit the functional activity of hypersecretive thyroid gland. The hypersecretion leads to the development of thyrotoxicosis. The antithyroid agents acts by interfering with the synthesis and release of thyroid hormones. They are classified as in table 8.4.1. 

Prior to the introduction of the thioamides in the 1940s, iodides were the major antithyroid agents today they are rarely used as sole therapy. 

A potential biomarker of exposure to PBDEs relates to their effect on the thyroid gland. As discussed in Sections 3.2.2.2, Endocrine Effects, thyroid changes in rats and mice include reduced serum thyroxine (T4) levels w itli no changes in scrum TSH (Damerud and Sinjari 1996 Fowles et al. 1994 Hallgren and Damemd 1998 WIL Research Laboratories 1984 Zhou et al. 2001, 2002). Additional studies are needed to characterize thyroid effects of PBDEs in humans and develop specific correlations between levels and duration of exposure and alterations in senun levels of T4. This potential biomarker is not specific to PBDEs because PBBs and other antithyroid agents can have similar effects. 

Polybrominated Diphenyl Ethers. The thyroid is a critical target for PBDEs in animals and, based on these data (see Section 3.2.2.2 Endocrine Effects), serum T4 level is a potential biomarker of effect in humans. Although this biomarker is not specific to PBDEs because other antithyroid agents can have similar effects, changes in T4 can be considered to indicate potential impairment of health. 

Bliddal H, Hansen JM, Rogowski P, Johansen K, Friis T, Siersbaek-Nielsen K. 131I treatment of diffuse and nodular toxic goitre with or without antithyroid agents. Acta Endocrinol (Copenh) 1982 99(4) 517-21. 

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