抗甲状腺薬, antithyroid agent

WordNet

use recreational drugs (同)do drugs
administer a drug to; "They drugged the kidnapped tourist" (同)dose
a substance that is used as a medicine or narcotic
having the effect of counteracting excessive thyroid activity; "antithyroid drugs"

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『薬』,薬品,薬剤 / 『麻薬』,麻酔剤 / 〈人〉‘に'薬(特に麻酔剤)を与える / 〈飲食物〉‘に'(麻酔薬・毒薬などの)薬を混ぜる

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/29 17:02:21」(JST)

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An antithyroid agent is a hormone antagonist acting upon thyroid hormones.

The main antithyroid drugs are carbimazole (in the UK), methimazole (in the US), and propylthiouracil/PTU. A less common antithyroid agent is potassium perchlorate.

Graves' disease

In Graves' disease, treatment with antithyroid medications must be given for six months to two years, in order to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells.

A randomized control trial testing single dose treatment for Graves' found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthyouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups).^[1] But generally both drugs are considered equivalent.

A study has shown no difference in outcome for adding thyroxine to antithyroid medication and continuing thyroxine versus placebo after antithyroid medication withdrawal. However, two markers were found that can help predict the risk of recurrence. These two markers are an elevated level of thyroid stimulating hormone receptor antibodies (TSHR-Ab) and smoking. A positive TSHR-Ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% (sensitivity 39%, specificity 98%), a negative TSHR-Ab at the end of antithyroid drug treatment is associated with a 78% chance of remaining in remission. Smoking was shown to have an impact independent to a positive TSHR-Ab.^[2]

Competitive antagonists of thyroid stimulating hormone receptors are currently being investigated as a possible treatment for Grave's disease.

Adverse effects

The most dangerous side-effect is agranulocytosis (1/250, more in PTU); this is an idiosyncratic reaction which generally resolves on cessation of drug. It occurs in about 0.2 to 0.3% of cases treated with antithyroid drugs.^[3] Others include granulocytopenia (dose dependent, which improves on cessation of the drug) and aplastic anemia, and for propylthiouracil severe, fulminant liver failure.^[4] Patients on these medications should see a doctor if they develop sore throat or fever.

The most common side effects are rash and peripheral neuritis. These drugs also cross the placenta and are secreted in breast milk. Lugol's iodine is used to block hormone synthesis before surgery.

Mechanism of action

The mechanisms of action are not completely understood. Some scientists believe that anti-thyroids inhibit iodination of tyrosyl residues in thyroglobulin. 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. Propylthiouracil additionally may reduce the de-iodination of T4 into T3 in peripheral tissues.^[5]

References

^ Homsanit M, Sriussadaporn S, Vannasaeng S, Peerapatdit T, Nitiyanant W, Vichayanrat A (2001). "Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism". Clin. Endocrinol. (Oxf) 54 (3): 385–90. doi:10.1046/j.1365-2265.2001.01239.x. PMID 11298092.
^ Glinoer D, de Nayer P, Bex M (2001). "Effects of l-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves' hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study". Eur. J. Endocrinol. 144 (5): 475–83. doi:10.1530/eje.0.1440475. PMID 11331213.
^ Zambrana, J.; Zambrana, F.; Neto, F.; Gonçalves, A.; Zambrana, F.; Ushirohira, J. (2005). "Agranulocytosis with tonsillitis associated with methimazole therapy". Brazilian journal of otorhinolaryngology 71 (3): 374–377. PMID 16446945. edit [1]
^ Bahn RS, Burch HS, Cooper DS, Garber JR, Greenlee CM, Klein IL, Laurberg P, McDougall IR et al. (July 2009). "The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration.". Thyroid : official journal of the American Thyroid Association 19 (7): 673–4. doi:10.1089/thy.2009.0169. PMID 19583480.
^ Manna D, Roy G, Mugesh G (2013). "Antithyroid Drugs and their Analogues: Synthesis, Structure and Mechanism of Action". Acc. Chem. Res. 11: 2706–15. doi:10.1021/ar4001229. PMID 23883148.

External links

Antithyroid agents at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. チオナミドによるバセドウ病（グレーブス病）の治療 thionamides in the treatment of graves disease
2. チオナミドの薬理学および毒性 pharmacology and toxicity of thionamides
3. 妊娠していない成人におけるグレーブス甲状腺機能亢進症：治療の概要 graves hyperthyroidism in nonpregnant adults overview of treatment
4. 妊娠中の甲状腺機能亢進症：治療 hyperthyroidism during pregnancy treatment
5. 甲状腺クリーゼ thyroid storm

English Journal

Anti-inflammatory effects of methylthiouracil in vitro and in vivo.

Ku SK1, Baek MC2, Bae JS3.
Toxicology and applied pharmacology.Toxicol Appl Pharmacol.2015 Nov 1;288(3):374-86. doi: 10.1016/j.taap.2015.08.009. Epub 2015 Aug 20.
The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Here, methylthiouracil (MTU), an antithyroid drug, was examined for its effects on lipopolysaccharide (LPS)-mediated vascular inflammatory
PMID 26298005

Valuable predictive features of relapse of Graves' disease after antithyroid drug treatment.

Liu X1, Shi B2, Li H1.
Annales d'endocrinologie.Ann Endocrinol (Paris).2015 Oct 26. pii: S0003-4266(15)01083-5. doi: 10.1016/j.ando.2015.08.004. [Epub ahead of print]
PURPOSE: Antithyroid drug treatment (ATDT) effectively achieves euthyroidism in patients with Graves' disease (GD). However, apparently successful treatment may be followed by relapse. We investigated the outcome of ATDT in Chinese patients with GD to identify predictive features of relapse.METHODS:
PMID 26514949

RADIOACTIVE IODINE THERAPY WITHOUT RECENT ANTITHYROID DRUG PRETREATMENT FOR HYPERTHYROIDISM COMPLICATED BY SEVERE HYPERBILIRUBINEMIA DUE TO HEPATIC DYSFUNCTION: EXPERIENCE OF A CHINESE MEDICAL CENTER.

Ding Y1, Xing J1, Qiu Z2, Wang Y1, Zhang Y1, Fang Y3, Peng X2, Long Y1, Deng P2.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.Endocr Pract.2015 Oct 22. [Epub ahead of print]
OBJECTIVE: The objective of this work is to report our experience with 131I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction.METHODS: Five patients with refractory severe hyperthyroidism were
PMID 26492542

Japanese Journal

Ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hyperthyroidism: effects of treatment on oxidative stress

, , , , , , ,
Endocrine Journal advpub(0), 2015
… The main purpose of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with OHyper and SHyper, to assess the effects of antithyroid drug (ATD) therapy on the oxidative stress (OS) parameters. …
NAID 130005060868

母体バセドウ病治療薬の減量により改善をみた胎児甲状腺腫の1例

安達将隆,坊岡順香,林優 [他]
神奈川産科婦人科学会誌 = Kanagawa journal of obstetrics and gynecology : official journal, Kanagawa Society of Obstetrics and Gynecology 50(1), 35-38, 2013-07
NAID 40020249230

The relationship between bone marrow characteristics and the clinical prognosis of antithyroid drug-induced agranulocytosis

YANG Jing,ZHONG Jing,XIAO Xin-Hua,ZHOU Ling-Zhi,CHEN Ya-Jun,LIU Jiang-Hua,CAO Ren-Xian,WEN Ge-Bo
Endocrine journal 60(2), 185-189, 2013-02-01
NAID 10031156740

Related Pictures

★リンクテーブル★

リンク元	「抗甲状腺薬」「antithyroid agent」
関連記事	「drug」「antithyroid」

「抗甲状腺薬」

　　[★]

英: antithyroid drug
同: 甲状腺阻害薬
関: 甲状腺中毒症、薬理学、甲状腺、甲状腺ホルモン

種類

チアミド系の化合物が用いられる(SPC.323)

作用機序

甲状濾胞内に能動的に取り込まれ、濾胞内でヨードの有機化と縮合を抑制
甲状腺濾胞内に浸潤しているリンパ球の自己抗体産生を抑制

副作用

チアミド系化合物の副作用

皮疹(2-3週後)が最多、甲状腺機能低下症、甲状腺腫、まれに白血球減少症/顆粒球減少症(治療開始後3-12週)

副作用に対する対処

無顆粒球症

症状：突然の咽頭痛、発熱
処置：

抗甲状腺薬の中止。副腎皮質ホルモン、抗菌薬、輸血、G-CSF (医学辞書改変)
無顆粒球症(好中球＜500/ul)と判断されたらすぐに抗甲状腺薬の中止。

薬物動態の比較

文献不明

	チアマゾール thiamazole メチマゾール methimazole methylmercaptoimidazole MMI	プロピルチオウラシル PTU
商品名	メルカゾール(5mg/錠)	プロパジール(50mg/錠)
薬効	13-14	1
初回量	30-45 mg	300-600 mg
維持量	5-10 mg	50-200 mg
血中半減期	約6時間	約2.5時間
作用持続時間	24時間	4-8時間
吸収	ほぼ100%	ほぼ100%
アルブミン結合	5%以下	約80%
末梢作用	なし	T4→T3への変換を抑制
作用発現(T4正常化)	1-2ヶ月	2-3ヶ月
胎盤移行	多い	少ない
乳汁移行	多い	ほとんどなし
尿中排泄	48時間で約70%	24時間で約80%
肝・腎不全時	代謝不変	代謝低下

SPC.1528

	チアマゾール	プロピルチオウラシル
血漿タンパクとの結合	結合しない	0.75
血漿半減期	4?6時間	75分
分布容積	40 liters	20 liters
甲状腺での濃縮	濃縮	濃縮
重症な肝臓病患者での代謝	減少	普通
重症な腎臓病患者での代謝	普通	普通
投与頻度	1-2回/日	1-4回/日
胎盤の通過	低	低
母乳への移行	低	低