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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/18 13:09:09」(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 (I0), 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 white blood cells
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

^ http://www.drugbank.ca/drugs/DB00763
^ 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 : official journal, German Society of Endocrinology [and] German Diabetes Association 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. バセドウ病（グレーブス甲状腺機能亢進症）の治療 treatment of graves hyperthyroidism
4. 妊娠中の甲状腺機能亢進症：治療 hyperthyroidism during pregnancy treatment
5. 中毒性腺腫および中毒性多結節性甲状腺腫の治療 treatment of toxic adenoma and toxic multinodular goiter

English Journal

Treadmill exercise ameliorates symptoms of methimazole-induced hypothyroidism through enhancing neurogenesis and suppressing apoptosis in the hippocampus of rat pups.

Shin MS, Ko IG, Kim SE, Kim BK, Kim TS, Lee SH, Hwang DS, Kim CJ, Park JK, Lim BV.SourceDepartment of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience.Int J Dev Neurosci.2013 May;31(3):214-23. doi: 10.1016/j.ijdevneu.2013.01.003. Epub 2013 Jan 14.
Thyroid hormones play a crucial role in new neuron production and maturation during brain development. Physical exercise is known to promote cell survival and functional recovery after brain injuries. In the present study, we investigated the effects of treadmill exercise on short-term memory, spati
PMID 23328696

Tryptophan-47 in the active site of Methylophaga sp. strain SK1 flavin-monooxygenase is important for hydride transfer.

Han A, Robinson RM, Badieyan S, Ellerbrock J, Sobrado P.SourceDepartment of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA.
Archives of biochemistry and biophysics.Arch Biochem Biophys.2013 Apr 1;532(1):46-53. doi: 10.1016/j.abb.2013.01.004. Epub 2013 Jan 25.
Flavin-dependent monooxygenase (FMO) from Methylophaga sp. strain SK1 catalyzes the NADPH- and oxygen-dependent hydroxylation of a number of xenobiotics. Reduction of the flavin cofactor by NADPH is required for activation of molecular oxygen. The role of a conserved tryptophan at position 47 was pr
PMID 23357278

Japanese Journal

薬物療法の基本と有害事象への対策 (特集甲状腺疾患 : 診断・治療の最新動向) -- (主要疾患の病態・診断・治療)

中村浩淑
日本臨床 70(11), 1915-1921, 2012-11
NAID 40019468684

小児期発症バセドウ病治療についての最近の知見 (特集小児科領域の甲状腺疾患・甲状腺関連遺伝子変異)

佐藤浩一
日本甲状腺学会雑誌 3(2), 80-83, 2012-10
NAID 40019484794

Related Pictures

★リンクテーブル★

リンク元	「薬理学」「抗甲状腺薬」「チアマゾール」「MMI」

「薬理学」

Methimazole
Systematic (IUPAC) name
	1-methyl-3H-imidazole-2-thione
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682464
Pregnancy; category	D (US);
Legal status	AU: Prescription Only (S4); US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	93%
Protein binding	None
Metabolism	Hepatic
Half-life	5-6 hours
Excretion	Renal
Identifiers
CAS Registry Number	60-56-0
ATC code	H03BB02
PubChem	CID 1349907
DrugBank	DB00763
ChemSpider	1131173
UNII	554Z48XN5E
KEGG	D00401
ChEBI	CHEBI:50673
ChEMBL	CHEMBL1515
Chemical data
Formula	C4H6N2S
Molecular 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)
(what is this?) (verify)

　　[★]

英: pharmacology
関: drug entries

定義

生物系と化学物質の選択的な相互作用を研究する学問 (SPC.2)

生物系と薬の相互作用

薬の生物系に対する相互作用：薬理作用 <-化学の視点
生物系の薬に対する相互作用：薬物動態 <-生物の視点

薬品の命名

Ending of the drug name	Category	Example
～afil	Erectile dysfunction	sildenafil
～ane	Inhalatinal general anesthetic	halothane
～azepam	Benzodiaizepine	diazepam
～azine	Phenothiazine (neuroleptic, antiemetic)	chlorpromazine
～azole	Ailtifungal	ketoconazole
～barbital	Barbiturate	phenobarbital
～caine	Local anesthetic	lidocaine
～cillin	Penicillin	methicillin
～cycline	Antibiotic, protein syntlesis inhibitor	tetracycline
～ipramine	TCA	iimipramine
～navir	Protease inhibitor	saquinavir
～olol	β-antagonist	propranolol
～operidol	Butyrophenone ( neuroleptic )	haloperidol
～oxin	Cardiac glycoside ( inotropic agent )	digoxin
～phylline	Methylxanthine	theophylline
～pril	ACE inhibitor	captopril
～terol	β₂ agonist	albuterol
～tidine	H₂ antagonist	cimtidine
～triptyline	TCA	amitriptyline
～tropine	Pituitary hormone	somatotropine
～zosin	a₁ antagonist	prazosin

薬一覧

薬物代謝

薬理動態

神経伝達物質

貧血治療薬

甲状腺関連物質

甲状腺ホルモン製剤

レボチロキシン levothyroxine
リオチニシン liothyronine

抗甲状腺薬

痛風治療薬

痛風発作予防薬

コルヒチン colchicine

尿酸排泄促進薬

尿酸生成抑制薬

アロプリノール allopurinol

「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

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

[1] ttp://www.drugbank.ca/drugs/DB00763

[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 : official journal, German Society of Endocrinology [and] German Diabetes Association 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

thiamazole

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★

「薬理学」

定義

生物系と薬の相互作用

関連分野

薬品の命名

薬一覧

薬物代謝

薬理動態

神経伝達物質

神経筋接合部遮断薬(筋弛緩薬)

交感神経作動薬

交感神経遮断薬

副交感神経作動薬

副交感神経遮断薬

貧血治療薬

甲状腺関連物質

痛風治療薬

「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」