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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/09/09 01:11:26」(JST)

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Methimazole (also known as Tapazole or Thiamazole or MMI) is an antithyroid drug,^[2] and part of the thioamide group. Like its counterpart propylthiouracil, a major side effect of treatment is agranulocytosis.

Indications

Methimazole is a drug used to treat hyperthyroidism, a condition that occurs when the thyroid gland begins to produce an excess of thyroid hormone. The drug may also be taken before thyroid surgery to lower thyroid hormone levels and minimize the effects of thyroid manipulation. Additionally, methimazole is used in the veterinary setting to treat hyperthyroidism in cats.

Mechanism of action

Methimazole inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I⁻) to iodine (I₂), hypoiodous acid (HOI), enzyme linked hypoiodate (EOI) facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin, a necessary step in the synthesis of triiodothyronine (T₃) and thyroxine (T₄).

It does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate.

It acts at CXCL10.^[3]

Adverse effects

It is important to monitor any symptoms of fever or sore throat while taking methimazole; this could indicate the development of agranulocytosis, an uncommon but severe side effect resulting from a drop in the white blood cell count (to be specific, neutropenia, a deficiency of neutrophils). A complete blood count (CBC) with differential is performed to confirm the suspicion, in which case the drug is discontinued.^[4] Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) may increase recovery.

Other known side effects include:

skin rash
itching
abnormal hair loss
upset stomach
vomiting
loss of taste
abnormal sensations (tingling, prickling, burning, tightness, and pulling)
swelling
joint and muscle pain
drowsiness
dizziness
decreased platelet count (thrombocytopenia)
aplasia cutis congenita (prenatal exposure)

Drug interactions

Adverse effects may occur for individuals who:

Take anticoagulants ('blood thinners') such as warfarin (Coumadin), diabetes medications, digoxin (Lanoxin), theophylline (Theobid, Theo-Dur), and vitamins
Have ever had any blood disease, such as decreased white blood cells (leukopenia), decreased platelets (thrombocytopenia) or aplastic anemia, or liver disease (hepatitis, jaundice)
Are pregnant, or going to become pregnant, or are breast-feeding.

Methimazole has been demonstrated to potently inhibit all CYP450 enzymes, meaning that the plasma concentration of all hepatically metabolized drugs will be significantly increased when taken with, or after, methimazole.^[5] This must be considered when starting a patient on methimazole, increasing their dose, or starting a methimazole patient on another drug. Many drugs will need their doses lowered and dosing-time intervals increased when co-administered with methimazole. For some hepatically metabolized drugs with very low therapeutic indexes, co-administration with methimazole may not be possible at all.

References

^ "DrugBank: Methimazole (DB00763)". drugbank.ca. Retrieved 21 July 2015.
^ Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N (June 2007). "Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease". The Journal of Clinical Endocrinology and Metabolism. 92 (6): 2157–62. doi:10.1210/jc.2006-2135. PMID 17389704.
^ Crescioli C, Cosmi L, Borgogni E, et al. (October 2007). "Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes". J. Endocrinol. 195 (1): 145–55. doi:10.1677/JOE-07-0240. PMID 17911406.
^ Fumarola, A; Di Fiore, A; Dainelli, M; Grani, G; Calvanese, A (Nov 2010). "Medical treatment of hyperthyroidism: state of the art.". Experimental and Clinical Endocrinology & Diabetes. 118 (10): 678–84. doi:10.1055/s-0030-1253420. PMID 20496313.
^ Guo Z, Raeissi S, White RB, Stevens JC (March 1997). "Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes.". Drug Metab. Dispos. 25 (3): 390–3. PMID 9172960.

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. 妊娠中の甲状腺機能亢進症：治療 hyperthyroidism during pregnancy treatment
4. 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
5. 小児および思春期におけるグレーヴス病の治療および予後 treatment and prognosis of graves disease in children and adolescents

English Journal

Antithyroid Drug Treatment for Graves' Disease in Children: A Long-term Retrospective Study at a Single Institution.

Ohye H, Minagawa A, Noh JY, Mukasa K, Kunii Y, Watanabe N, Matsumoto M, Suzuki M, Yoshihara A, Ito K, Ito K.SourceIto Hospital, Internal Medicine, 4-3-6 Jingumae, Tokyo, Shibuya-ku, Japan, 1508038, 81-3-3402-7411, 81-3-3402-7439 ; h-ohye@ex.ito-hospital.jp.
Thyroid : official journal of the American Thyroid Association.Thyroid.2013 Aug 8. [Epub ahead of print]
Background: The management of Graves' disease (GD) in children entails a dilemma. Although the established initial treatment for GD in children is antithyroid drug (ATD) treatment, the remission rate in children is said to be lower than in adults and severe propylthiouracil-induced adverse events (A
PMID 23926918

Mechanisms of permanent loss of olfactory receptor neurons induced by the herbicide 2,6-dichlorobenzonitrile: Effects on stem cells and noninvolvement of acute induction of the inflammatory cytokine IL-6.

Xie F, Fang C, Schnittke N, Schwob JE, Ding X.SourceLaboratory of Molecular Toxicology, Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, NY 12201.
Toxicology and applied pharmacology.Toxicol Appl Pharmacol.2013 Aug 3. pii: S0041-008X(13)00329-3. doi: 10.1016/j.taap.2013.07.020. [Epub ahead of print]
We explored the mechanisms underlying the differential effects of two olfactory toxicants, the herbicide 2,6-dichlorobenzonitrile (DCBN) and the anti-thyroid drug methimazole (MMZ), on olfactory receptor neuron (ORN) regeneration in mouse olfactory epithelium (OE). DCBN, but not MMZ, induced inflamm
PMID 23921153

Inhibition of lactoperoxidase-catalyzed oxidation by imidazole-based thiones and selones: a mechanistic study.

Roy G, Jayaram PN, Mugesh G.SourceDepartment of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012 (India); Department of Chemistry and Center for Informatics, School of Natural Sciences, Shiv Nadar University, Dadri 203207, Uttar Pradesh (India). gouriprasanna.roy@snu.edu.in.
Chemistry, an Asian journal.Chem Asian J.2013 Aug;8(8):1910-21. doi: 10.1002/asia.201300274. Epub 2013 Jun 4.
Herein, we describe the synthesis and biomimetic activity of a series of N,N-disubstituted thiones and selones that contain an imidazole pharmacophore. The N,N-disubstituted thiones do not show any inhibitory activity towards LPO-catalyzed oxidation reactions, but their corresponding N,N-disubstitut
PMID 23737077

Japanese Journal

複数の疾患特異的自己抗体の早期陰性化を認めた多腺性自己免疫症候群3型の1例

糖尿病 59(5), 376-384, 2016
NAID 130005155340

Does low-normal serum TSH level adversely impact cognition in elderly adults and might methimazole therapy improve outcomes?

Endocrine Journal 63(5), 495-505, 2016
NAID 130005154202

Does low-normal serum TSH level adversely impact cognition in elderly adults and might methimazole therapy improve outcomes?

Endocrine Journal advpub(0), 2016
NAID 130005143575

Related Pictures

★リンクテーブル★

リンク元	「抗甲状腺薬」「チアマゾール」「MMI」
拡張検索	「methimazole-induced agranulocytosis」

「抗甲状腺薬」

Methimazole
Systematic (IUPAC) name
	1-methyl-3H-imidazole-2-thione
Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a682464
Pregnancy; category	D (US);
Routes of; administration	Oral
Legal status
Legal status	AU: S4 (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	93%
Protein binding	None
Metabolism	Hepatic
Biological half-life	5-6 hours
Excretion	Renal
Identifiers
CAS Number	60-56-0
ATC code	H03BB02 (WHO)
PubChem	CID 1349907
IUPHAR/BPS	6649
DrugBank	DB00763
ChemSpider	1131173
UNII	554Z48XN5E
KEGG	D00401
ChEBI	CHEBI:50673
ChEMBL	CHEMBL1515
Chemical data
Formula	C4H6N2S
Molar mass	114.17 g/mol
	SMILES Cn1cc[nH]c1=S ;
	InChI InChI=1S/C4H6N2S/c1-6-3-2-5-4(6)7/h2-3H,1H3,(H,5,7) ; Key:PMRYVIKBURPHAH-UHFFFAOYSA-N ;
Physical data
Melting point	146 °C (295 °F)
Solubility in water	275 mg/mL (20 °C)
(verify)

　　[★]

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

参考

uptodate

1. [charged] チオナミドによるバセドウ病（グレーブス病）の治療 - uptodate [1]
2. [charged] チオナミドの薬理学および毒性 - uptodate [2]
3. [charged] 患者情報：抗甲状腺剤 - uptodate [3]

「チアマゾール」

　　[★]

英: thiamazole
ラ: thiamazolum
同: メチマゾール methimazole、メルカプトメチルイミダゾール mercaptomethylimidazole MMI
商: メルカゾール、Tapazole
関: 薬理学、甲状腺機能亢進症。プロピルチオウラシル propylthiouracil PTU

抗甲状腺薬

thioamide系薬

作用機序

薬理作用

甲状腺濾胞細胞内に取り込まれ、甲状腺濾胞においてペルオキシダーゼの活性を阻害し、甲状腺ホルモンの合成を抑制

ペルオキシダーゼは濾胞内でO₂からH₂O₂を生成し、H₂O₂によりI^-がI^･となりサイログロブリン上のチロシンの3位or5位につく

プロピルチオウラシルのようにT₄→T₃の変換を阻害する作用無し

動態

胎盤を通過
乳汁中に分泌　→　妊婦には投与しない方がよい

適応

注意

禁忌

副作用

皮膚の発疹：よく見られる
甲状腺機能低下症
甲状腺腫
顆粒球減少症 (0.2%) (SPC.323)

「MMI」

　　[★] チアマゾール thiamazole, メチマゾール methimazole, メルカプトメチルイミダゾール mercaptomethylimidazole

「methimazole-induced agranulocytosis」

　　[★] メチマゾール誘発性無顆粒球症

[1] "DrugBank: Methimazole (DB00763)". drugbank.ca. Retrieved 21 July 2015.

[pmid17389704-2] Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N (June 2007). "Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease". The Journal of Clinical Endocrinology and Metabolism. 92 (6): 2157–62. doi:10.1210/jc.2006-2135. PMID 17389704.

[pmid17911406-3] Crescioli C, Cosmi L, Borgogni E, et al. (October 2007). "Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes". J. Endocrinol. 195 (1): 145–55. doi:10.1677/JOE-07-0240. PMID 17911406.

[4] Fumarola, A; Di Fiore, A; Dainelli, M; Grani, G; Calvanese, A (Nov 2010). "Medical treatment of hyperthyroidism: state of the art.". Experimental and Clinical Endocrinology & Diabetes. 118 (10): 678–84. doi:10.1055/s-0030-1253420. PMID 20496313.

[5] Guo Z, Raeissi S, White RB, Stevens JC (March 1997). "Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes.". Drug Metab. Dispos. 25 (3): 390–3. PMID 9172960.

匿名

検索

案内

案内

methimazole

Wikipedia preview

wiki en

Contents

Indications

Mechanism of action

Adverse effects

Drug interactions

See also

References

UpToDate Contents

English Journal

Japanese Journal

Related Links

Related Pictures

★リンクテーブル★

「抗甲状腺薬」

種類

作用機序

副作用

副作用に対する対処

薬物動態の比較

参考

uptodate

「チアマゾール」

作用機序

薬理作用

動態

適応

注意

禁忌

副作用

「MMI」

「methimazole-induced agranulocytosis」

v t e Sulfur compounds

Al₂S₃ As₂S₂ As₂S₃ As₅S₂ As₄S₄ Au₂S₃ B₂S₃ BaS BeS Bi₂S₃ Br₂S₂ CS₂ C₃S₂ CaS CdS CeS SCl₂ S₂Cl₂ CoS Cr₂S₃ CuS D₂S Dy₂S₃ Er₂S₃ EuS SF₄ SF₆ FeS₂ GaS H₂S HfS₂ HgS InS LaS LiS MgS MoS₃ NiS SO₂ SO₃ P₄S₇ PbS PbS₂ PtS ReS₂ SrS TlS SV SeS₂ S₂U WS₂ Sb₂S₅ Sm₂S₃ Y₂S₃ Ag₂SO₄ SOBr₂ CSTe C₂H₄S C₂H₆S₃ C₄H₄S CaSO₄ C₃₂H₆₆S₂ CuFeS₂ H₂SO₄ H₂SO₃ F₂OS NaHS K₂SO₃ O₃S₃Sb₄ Yb₂(SO₄)₃ AlKO₈S₂ CHCl₃S KSCN CdSO₃ PSCl₃ SOCl₂ Cs₂O₄S Re₂S₇ Na₂S K₂S H₂S₂O₇ H₂SO₅ NH₅S HgSO₄ K₂SO₄ RaSO₄ SnSO₄ SrSO₄ Zr(SO₄)₂ Ti(SO₄)₂ Tm₂(SO₄)₃ AlNa(SO₄)₂ Er₂(SO₄)₃ Eu₂(SO₄)₃ CHNS Co(SCN)₂ C₂H₃SN PSI₃ ZrS₂ SiS CSSe

Chemical formulas