WordNet

a complex consisting of an organic base in association with hydrogen chloride

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/06/21 21:17:57」(JST)

wiki en

Midodrine (brand names Amatine, ProAmatine, Gutron) is a vasopressor/antihypotensive agent. Midodrine was approved in the United States by the Food and Drug Administration (FDA) in 1996 for the treatment of dysautonomia and orthostatic hypotension. In August 2010, the FDA proposed withdrawing this approval because the manufacturer, Shire plc, has failed to complete required studies after the medicine reached the market.^[1]^[2]

In September 2010, the FDA reversed in decision to remove Midodrine from the market and has allowed it to remain available to patients while Shire plc collects further data regarding the efficacy and safety of the drug.^[3] Shire plc announced on September 27, 2011 that it was continuing the process to work with the FDA towards a final approval of the drug.^[4]

Chemical properties

Midodrine is an odorless, white, crystalline powder, soluble in water and sparingly soluble in methanol.

Mechanism of action

Midodrine is a prodrug which forms an active metabolite, desglymidodrine, which is an α₁-receptor agonist and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. Desglymidodrine does not stimulate cardiac beta-adrenergic receptors. Desglymidodrine diffuses poorly across the blood–brain barrier, and is therefore not associated with effects on the central nervous system.

Metabolite desglymidodrine

Metabolism

After oral administration, midodrine is rapidly absorbed. The plasma levels of the prodrug peak after about half an hour, and decline with a half-life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of midodrine and has a half-life of about 3 to 4 hours. The absolute bioavailability of midodrine (measured as desglymidodrine) is 93%.

Indications

Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic hypotension. In a critical care settings, it is widely used as an adjunctive therapy to weaning patients off of intravenous vasopressive medications. It has been suggested also as a treatment for chronic fatigue syndrome^[5] as well as for hepato-pulmonary syndrome. It is also used with octreotide for hepatorenal syndrome; the proposed mechanism is constriction of splanchnic vessels and dilation of renal vasculature.

Contraindications

Midodrine is contraindicated in patients with severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma or thyrotoxicosis. Midodrine should not be used in patients with persistent and excessive supine hypertension.

Side effects

Headache; feeling of pressure/fullness in the head, vasodilation/flushing face, confusion/thinking abnormality, dry mouth; nervousness/anxiety and rash.^{[citation needed]}

References

^ U.S. proposes withdrawal of Shire hypotension drug, Aug 16, 2010.
^ O'Riordan, Michael. "FDA recommends withdrawal of midodrine". Food and Drug Administration. FDA proposes withdrawal of low blood pressure drug [press release]. August 16, 2010.. TheHeart.org. http://www.theheart.org/article/1110411.do. Retrieved 1 April 2011. .
^ Midodrine (ProAmatine, generic) Proposed Market Withdrawal – Update September 10, 2010.
^ Shire Announces Update on ProAmatime September 27, 2011.
^ Naschitz J, Dreyfuss D, Yeshurun D, Rosner I (April 2004). "Midodrine treatment for chronic fatigue syndrome". Postgrad Med J 80 (942): 230–2. DOI:10.1136/pgmj.2003.011429. PMC 1742969. PMID 15082846. http://pmj.bmj.com/cgi/pmidlookup?view=long&pmid=15082846.

External links

Midodrine at drugs.com

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 起立性低血圧および食後低血圧の治療 treatment of orthostatic and postprandial hypotension
2. 肝腎症候群 hepatorenal syndrome
3. 肝硬変患者における腹水の治療：利尿剤抵抗性腹水 ascites in adults with cirrhosis diuretic resistant ascites
4. 透析時以外血圧の安定した患者における透析中の低血圧 intradialytic hypotension in an otherwise stable patient
5. 体位性頻脈症候群 postural tachycardia syndrome

English Journal

Treatment to improve acute kidney injury in cirrhosis.

Wong F1.
Current treatment options in gastroenterology.Curr Treat Options Gastroenterol.2015 Jun;13(2):235-48. doi: 10.1007/s11938-015-0050-2.
OPINION STATEMENT: Acute kidney injury (AKI) is an ominous complication of decompensated cirrhosis, which can be fatal if not treated promptly. It is important that clinicians recognize that AKI has occurred and institute timely treatment. Recent establishment of diagnostic criteria and treatment gu
PMID 25773606

Development and validation of LC-MS/MS assay for the determination of the prodrug Midodrine and its active metabolite Desglymidodrine in plasma of ascitic patients: Application to individualized therapy and comparative pharmacokinetics.

Ali AA1, Al-Ghobashy MA2, Farid SF3, Kassem MA4.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.J Chromatogr B Analyt Technol Biomed Life Sci.2015 Jun 1;991:34-40. doi: 10.1016/j.jchromb.2015.03.032. Epub 2015 Apr 7.
Midodrine (MD) is a prodrug that is converted after oral administration to Desglymidodrine (DMD). In this study, an LC-MS/MS assay was developed and validated for investigation of the pharmacokinetics of MD and DMD in non azotemic patients with liver cirrhosis and tense ascites. Results were compare
PMID 25910235

Topically Applied Midodrine, 0.2%, an α1-Agonist, for the Treatment of Erythromelalgia.

Davis MD1, Morr CS1, Warndahl RA2, Sandroni P3.
JAMA dermatology.JAMA Dermatol.2015 May 6. doi: 10.1001/jamadermatol.2015.0511. [Epub ahead of print]
PMID 25946117

Japanese Journal

Midodrine Hydrochloride Is Effective in the Treatment of Children With Postural Orthostatic Tachycardia Syndrome

CHEN Li,WANG Li,SUN Jinghui,QIN Jiong,TANG Chaoshu,JIN Hongfang,DU Junbao
Circulation journal : official journal of the Japanese Circulation Society 75(4), 927-931, 2011-03-25
… Background: The study was carried out to examine the effect of selective α1 adrenoceptor agonist midodrine hydrochloride vs. β-adrenergic blockade metoprolol in the treatment of children with postural orthostatic tachycardia syndrome (POTS). … Methods and Results: Fifty-three children with POTS were divided into group I (midodrine hydrochloride plus conventional therapy), group II (metoprolol plus conventional therapy) and group III (conventional therapy). …
NAID 10028103473

洞機能不全症候群および起立性頻脈症候群をきたした多発性硬化症の1例

谷掛万里,降矢芳子,形岡博史 [他],川原誠,平野牧人,上野聡
リハビリテーション医学 : 日本リハビリテーション医学会誌 45(8), 535-540, 2008-08-18
… Before the lesion disappeared, she was able to begin rehabilitation by wearing elastic stockings and treatment with midodrine hydrochloride. …
NAID 110006862639

A Case of Neurally Mediated Syncope Induced by Laughter Successfully Treated With Combination of Propranolol and Midodrine

Amaki Makoto,Kamide Kei,Takiuchi Shin,Niizuma Shinichiro,Horio Takeshi,Kawano Yuhei
International Heart Journal 48(1), 123-127, 2007
… Propranolol and midodrine hydrochloride, an alpha1-adrenergic stimulant, were effective at preventing his laughter-induced syncope. … This is a case report of laughter-induced syncope with a familial predisposition successfully treated with the combination of the nonselective beta-blocker propranolol and the alpha1-stimulator midodrine. …
NAID 130000068832

「ミドドリン」

Midodrine
Systematic (IUPAC) name
	(RS)- N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]glycinamide
Clinical data
Trade names	Proamatine
AHFS/Drugs.com	monograph
MedlinePlus	a602023
Pregnancy cat.	?
Legal status	?
Identifiers
CAS number	133163-28-7
ATC code	C01CA17
PubChem	CID 4195
DrugBank	DB00211
ChemSpider	4050
UNII	6YE7PBM15H
KEGG	D08220
ChEBI	CHEBI:6933
ChEMBL	CHEMBL1076
Synonyms	2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxy-ethyl]-acetamide
Chemical data
Formula	C12H18N2O4
Mol. mass	254.282 g/mol
	SMILES O=C(NCC(O)c1cc(OC)ccc1OC)CN;
	InChI InChI=1S/C12H18N2O4/c1-17-8-3-4-11(18-2)9(5-8)10(15)7-14-12(16)6-13/h3-5,10,15H,6-7,13H2,1-2H3,(H,14,16) ; Key:PTKSEFOSCHHMPD-UHFFFAOYSA-N ;
(what is this?) (verify);

　　[★]

英: midodrine
化: 塩酸ミドドリン, midodrine hydrochloride
商: アバルナート、シュプレース、ナチルジン、ミドドリン塩酸塩、メトドリン、メトリジン、メトリジンD
関: アドレナリン受容体。血管収縮剤。

選択的α1アゴニスト。起立性低血圧の治療に用いられる。
ジメトキシフェニルアミノエタノール(DMAE)をグリシンで修飾したプロドラッグ。
肝、腎、空腸、血球など種々の臓器で脱グリシン化されて活性本体となり、交感神経α1-受容体を直接刺激し細動脈を収縮して全末梢血管抵抗を増大することにより血圧を上昇させる。
心機能にはほとんど影響せず、起立時の血圧低下を抑制する。
中枢への影響はなく、また正常血圧に影響を及ぼさない。
本態性低血圧症、起立性低血圧症の治療に用いられ、1日量4～8mgである。1回2-4mg 1日2回で用いられる。
禁忌：甲状腺機能亢進症、褐色細胞腫

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[0] U.S. proposes withdrawal of Shire hypotension drug, Aug 16, 2010.

[1] O'Riordan, Michael. "FDA recommends withdrawal of midodrine". Food and Drug Administration. FDA proposes withdrawal of low blood pressure drug [press release]. August 16, 2010.. TheHeart.org. http://www.theheart.org/article/1110411.do. Retrieved 1 April 2011. .

[2] Midodrine (ProAmatine, generic) Proposed Market Withdrawal – Update September 10, 2010.

[3] Shire Announces Update on ProAmatime September 27, 2011.

[pmid15082846-4] Naschitz J, Dreyfuss D, Yeshurun D, Rosner I (April 2004). "Midodrine treatment for chronic fatigue syndrome". Postgrad Med J 80 (942): 230–2. DOI:10.1136/pgmj.2003.011429. PMC 1742969. PMID 15082846. http://pmj.bmj.com/cgi/pmidlookup?view=long&pmid=15082846.

匿名

検索

案内

案内

midodrine hydrochloride