isoproterenol

イソプロテレノール ISP 　

WordNet

1. drug (trade name Isuprel) used to treat bronchial asthma and to stimulate the heart (同)Isuprel

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/07 14:39:54」(JST)

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Isoprenaline

Systematic (IUPAC) name
(RS)-4-[1-hydroxy-2-(isopropylamino)ethyl]benzene-1,2-diol
Clinical data
AHFS/Drugs.com	International Drug Names
MedlinePlus	a601236
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	inhaled 80-120μg
Identifiers
CAS number	7683-59-2 Y
ATC code	C01CA02 R03AB02 R03CB01
PubChem	CID 3779
IUPHAR ligand	536
DrugBank	DB01064
ChemSpider	3647 Y
UNII	L628TT009W Y
KEGG	D08090 Y
ChEMBL	CHEMBL434 Y
Chemical data
Formula	C11H17NO3
Mol. mass	211.258 g/mol
SMILES Oc1ccc(cc1O)C(O)CNC(C)C
InChI InChI=1S/C11H17NO3/c1-7(2)12-6-11(15)8-3-4-9(13)10(14)5-8/h3-5,7,11-15H,6H2,1-2H3 Y Key:JWZZKOKVBUJMES-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Isoprenaline (INN) or isoproterenol (USAN, trade names Medihaler-Iso and Isuprel) is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective beta-adrenergic agonist and structurally similar to adrenaline.

Uses

Its primary use is for bradycardia or heart block. By activating β₁-receptors on the heart, it induces positive chronotropic, dromotropic, and inotropic effects.

It can be used as an inhaled aerosol to treat asthma, although this is currently a rare treatment. Although it activates all beta adrenergic receptors, it works in a similar fashion to the more selective β₂-adrenergic agonists e.g. salbutamol, by relaxing the airways to increase airflow.

It is also supplied in ampoules under the brand name Isuprel for injection and in sublingual pill form for treatment of asthma, chronic bronchitis and emphysema.

Used with caution, it can also be used to treat torsades de pointes by acquired defect, in conjunction with overdrive pacing and magnesium.

Pharmacology

Isoprenaline is a β₁- and β₂-adrenoreceptor agonist which was commonly used to treat asthma before the more widespread use of albuterol, which has more selective effects on the airways. Its route of administration is either intravenous, oral, intranasal, subcutaneous, or intramuscular, depending on use. The plasma half-life for isoprenaline is approximately two minutes.

Isoprenaline's effects on the cardiovascular system (non-selective) relate to its actions on cardiac β₁ receptors and β₂ receptors on smooth muscle within the tunica media of arterioles. Isoprenaline has positive inotropic and chronotropic effects on the heart. β₂--adrenoceptor stimulation in arteriolar smooth muscle induces vasodilation. Its inotropic and chronotropic effects elevate systolic blood pressure, while its vasodilatory effects tend to lower diastolic blood pressure. The overall effect is to decrease mean arterial pressure due to the β₂ receptor's vasodilation.

The adverse effects of isoprenaline are also related to the drug's cardiovascular effects. Isoprenaline can produce an elevated heart rate (tachycardia), which predisposes patients to cardiac dysrhythmias.

Warnings and contraindications

Isoprenaline should not be administered to patients with myocardial ischemia.

According to Code of Federal Regulations (CFR) Title 21 Section 201.305, use of isoprenaline has been regulated by mandating the inclusion of the following warning label: "Occasional patients have been reported to develop severe paradoxical airway resistance with repeated, excessive use of isoprenaline inhalation preparations. The cause of this refractory state is unknown. It is advisable that in such instances the use of this preparation be discontinued immediately and alternative therapy instituted, since in the reported cases the patients did not respond to other forms of therapy until the drug was withdrawn. Deaths have been reported following excessive use of isoprenaline inhalation preparations and the exact cause is unknown. Cardiac arrest was noted in several instances"

Chemistry

Isoprenaline is synthesized by an analogous scheme of making epinephrine. Interaction of ω-chloro-3,4-dihydroxyacetophenone (chloroacetylpyrocatechol) with isopropylamine gives ω-isopropylamino-3,4-dihydroxyacetophenone, reduction of the carbonyl group of which by hydrogen using a palladium on carbon catalyst gives isoprenaline.

Structure-activity relationship

The isopropyl amine group in isoprenaline makes it selective for β receptors. The free catechol hydroxy groups keeps it susceptible to enzymatic metabolism.

History

An epidemic of deaths within a group of individuals who were being treated for asthma was detected between 1963 and 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand. This was later found to be largely attributed to isoprenaline inhalers which were being used at 5 times the dose USA and Canada were using it at, subsequently, USA and Canada did not add to this epidemic. Shortly after realizing overdose of the drug was causing many deaths, the medication was withdrawn and the number of asthmatics dying quickly decreased.

References

UpToDate Contents

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• 1. 昇圧剤および強心剤の使用 use of vasopressors and inotropes
• 2. 洞不全症候群の診断および評価 diagnosis and evaluation of the sick sinus syndrome
• 3. 失神評価における立位チルト試験 upright tilt table testing in the evaluation of syncope
• 4. 後天性ＱＴ延長症候群 acquired long qt syndrome
• 5. 喘息におけるβ刺激剤：急性期投与および予防的使用 beta agonists in asthma acute administration and prophylactic use

English Journal

• Erratum to: Isoproterenol Cytotoxicity is Dependent on the Differentiation State of the Cardiomyoblast H9c2 Cell Line.

• Branco AF, Pereira SL, Moreira AC, Holy J, Sardao VA, Oliveira PJ.SourceCenter for Neuroscience and Cell Biology, Department of Life Sciences, University of Coimbra, 3004-517, Coimbra, Portugal.
• Cardiovascular toxicology.Cardiovasc Toxicol.2011 Sep;11(3):284.
• PMID 21779752

• Isoproterenol-Induced Cardiomyopathy in Rats: Influence of Acorus calamus Linn. : A. calamus Attenuates Cardiomyopathy.

• Singh BK, Pillai KK, Kohli K, Haque SE.SourceDepartment of Pharmacology, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi, 110062, India.
• Cardiovascular toxicology.Cardiovasc Toxicol.2011 Sep;11(3):263-71.
• Acorus calamus has been used as a traditional remedy since ancient days but its cardioprotective effect is not yet well characterized. The aim of this study was to assess the effect of A. calamus rhizome extract in isoproterenol-induced cardiomyopathy in rats. Male Wistar rats were treated with norm
• PMID 21695526

Japanese Journal

• Exercise preconditioning initiates late cardioprotection against isoproterenol-induced myocardial injury in rats independent of protein kinase C

• Shen Yu-Jun,Pan Shan-Shan,Zhuang Tao [他]
• The journal of physiological sciences 61(1), 13-21, 2011-01
• NAID 40017437145

• The potential benefits of a garlic and hydrochlorothiazide combination as antihypertensive and cardioprotective in rats

• Asdaq Syed Mohammed Basheeruddin,Inamdar Mohammed Naseeruddin
• Journal of natural medicines 65(1), 81-88, 2011
• NAID 40017429398

Related Links

• Isoprenaline - Wikipedia, the free encyclopedia

Isoproterenol, 1-(3,4-dihydroxyphenyl)-2-iso-propylaminoethanol, is synthesized by an analogous scheme of making epinephrine. Interaction of ω-chloro-3,4- dihydroxyacetophenone (chloroacetylpyrocatechol) with isopropylamine gives ...

Related Pictures

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★リンクテーブル★

リンク元	「イソプロテレノール」「カテコール」「isoprenaline sulfate」「dl-isoprenaline hydrochloride」「l-isoprenaline hydrochloride」
拡張検索	「isoproterenol sulfate」「dl-isoproterenol hydrochloride」「isoproterenol hydrochloride」「dichloroisoproterenol」

「イソプロテレノール」

　　[★]

英

isoproterenol, ISP

化

硫酸イソプロテレノール isoproterenol sulfate, 硫酸イソプレナリン isoprenaline sulfate、塩酸イソプレナリン isoprenaline hydrochloride、塩酸イソプロテレノール isoproterenol hydrochloride

同

イソプレナリン

商

イソメニール、プロタノール。ストメリン(イソプロテレノール、デキサメタゾン、メチルアトロピン)

関

アドレナリン受容体、受容体。強心剤

• アドレナリン受容体アゴニスト

• β受容体作動薬

作用機序

• アドレナリンより強力なβ1、β2受容体アゴニスト

薬理作用

プロタノールL注0.2mg／＊プロタノールL注１mg

• 1. 心収縮力増強（Positive inotropic）作用

• イソプレナリン塩酸塩は、交感神経のβ受容体に作用し、心収縮力を増強して、心拍出量を増加する。
• これに伴って、左心室駆出速度の増大及び左心室拡張末期圧の低下をもたらし静脈還流を改善し、心拍出量を更に増加するが、この場合の心筋酸素消費量の増加は比較的軽度である（イヌ、ヒト）3)～8)。

• 2. 心拍数増加（Positive chronotropic）作用

• イソプレナリン塩酸塩は、心臓の刺激伝導系に作用して心拍数を増加する。その作用部位は、上位中枢にあり、洞機能を亢進し、房室伝導を促進する作用が強いので心ブロック時に使用して洞調律に回復させる作用がある（イヌ、ヒト）3)5)～7)。

• 3. 組織循環促進作用

• イソプレナリン塩酸塩は、強力な心拍出量の増加とともに末梢血管の抵抗を減少して、各組織や重要臓器の血流量を増大するので、組織循環が促進される。これは異常に増加した乳酸値の低下や尿量増加がみられることからも確認される（イヌ、ヒト）9)～12)。

• 4. 気管支拡張作用

• イソプレナリン塩酸塩は、気管支平滑筋に作用し、気管支内腔を拡張する作用がある。また、そのdl体はアドレナリンの約10倍の強さをもっている（イヌ）13)。

禁忌

プロタノールL注0.2mg／＊プロタノールL注１mg

• 1. 特発性肥大性大動脈弁下狭窄症の患者〔心収縮力を増強するため、左室からの血液流出路の閉塞が増強され、症状を増強させるおそれがある。〕
• 2. ジギタリス中毒の患者〔重篤な不整脈が起こる可能性がある。〕
• 3. カテコールアミン製剤（アドレナリン等）等との併用は避けること。（「相互作用」の項参照）

効能又は効果

プロタノールL注0.2mg／＊プロタノールL注１mg

• アダムス・ストークス症候群（徐脈型）の発作時（高度の徐脈、心停止を含む）、あるいは発作反復時
• 心筋梗塞や細菌内毒素等による急性心不全
• 手術後の低心拍出量症候群
• 気管支喘息の重症発作時

添付文書

• プロタノールL注0.2mg／＊プロタノールL注１mg

http://www.info.pmda.go.jp/go/pack/2119400A1036_1_03/2119400A1036_1_03?view=body

「カテコール」

　　[★]

英

cathechol, 3'4'-dihydroxybenzene

関

 ／＼
| ○ |￣OH
|   |
 ＼／ ￣OH

cathechol + ethanolamine	catechol-CH(OH)-CH2-NH2-CH(CH3)2	isoproterenol
	catechol-CH(OH)-CH2-NH-CH3	adrenaline
	catechol-CH(OH)-CH2-NH2	noradrenaline
cathechol + ethylamine	catechol-CH2-CH2-NH2	dopamine

英

[[]]

同

catechol

英

catechol

同

ピロカテキン pyrocatechine

同

catechol

「isoprenaline sulfate」

　　[★]

• 硫酸イソプレナリン

関

dl-isoprenaline hydrochloride、dl-isoproterenol hydrochloride、isoprenaline、isoproterenol、isoproterenol hydrochloride、isoproterenol sulfate、l-isoprenaline hydrochloride

「dl-isoprenaline hydrochloride」

　　[★]

• dl-塩酸イソプレナリン

関

dl-isoproterenol hydrochloride、isoprenaline、isoprenaline sulfate、isoproterenol、isoproterenol hydrochloride、isoproterenol sulfate、l-isoprenaline hydrochloride

「l-isoprenaline hydrochloride」

　　[★]

• l-塩酸イソプレナリン

関

dl-isoprenaline hydrochloride、dl-isoproterenol hydrochloride、isoprenaline、isoprenaline sulfate、isoproterenol、isoproterenol hydrochloride、isoproterenol sulfate

「isoproterenol sulfate」

　　[★]

• 硫酸イソプロテレノール

関

dl-isoprenaline hydrochloride、dl-isoproterenol hydrochloride、isoprenaline、isoprenaline sulfate、isoproterenol、isoproterenol hydrochloride、l-isoprenaline hydrochloride

「dl-isoproterenol hydrochloride」

　　[★]

• dl-塩酸イソプロテレノール

関

dl-isoprenaline hydrochloride、isoprenaline、isoprenaline sulfate、isoproterenol、isoproterenol hydrochloride、isoproterenol sulfate、l-isoprenaline hydrochloride

「isoproterenol hydrochloride」

　　[★]

イソプロテレノール

塩酸イソプロテレノール

「dichloroisoproterenol」

　　[★] ジクロロイソプロテレノール