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

WordNet

convert into a sulfate
a salt or ester of sulphuric acid (同)sulphate
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）』「2015/11/13 01:45:45」(JST)

wiki en

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. In humans, it is a non-selective beta-adrenergic agonist and TAAR1 agonist that is structurally similar to adrenaline.^[1]^[2]

Uses

Its primary use is for bradycardia or heart block. By activating β₁-receptors in the heart, it induces positive chronotropic, dromotropic, and inotropic effects.^[2]

It can be used as an inhaled aerosol to treat asthma, although this is currently a rare treatment.^[2] Although it activates all beta adrenergic receptors, it works in a similar fashion to 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 sulfate.

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 agonist effects at TAAR1 provide it with a pharmacodynamic effects that resemble those of the endogenous trace amines, like tyramine,^[1] although its short half-life prevents it from producing persistent psychoactive effects from TAAR1 activation in the central nervous system. 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"

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.^[3]

History

Between 1963 and 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand there was an increase in deaths among people using isoprenaline to treat asthma. This was attributed to overdose: the inhalers produced in that area were dispensing five times the dosage dispensed by inhalers produced in the US and Canada, where the deaths were not observed.^[4]

References

^ ^a ^b Kleinau G, Pratzka J, Nürnberg D, Grüters A, Führer-Sakel D, Krude H, Köhrle J, Schöneberg T, Biebermann H (October 2011). "Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists". PLoS ONE 6 (10): e27073. doi:10.1371/journal.pone.0027073. PMC 3205048. PMID 22073124.
"Table 1: EC₅₀ values of different agonists at hTAAR1, hADRB1 and hADRB2."
^ ^a ^b ^c Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 5. ISBN 1-59541-101-1.
^ Medicinal Chemistry of Adrenergics and Cholinergics
^ Pierce, Neil and Hensley, Michael J. (1998). "Epidemiologic Studies of Beta Agonists and Asthma Deaths" (PDF). Epidemiologic Studies 20 (2).

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. 不整脈原性右室心筋症の臨床症状および診断 clinical manifestations and diagnosis of arrhythmogenic right ventricular cardiomyopathy
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. Sick sinus syndrome: Clinical manifestations, diagnosis, and evaluation
5. 後天性ＱＴ延長症候群 acquired long qt syndrome

English Journal

Protective effects of the standardized extract of Zingiber officinale on myocardium against isoproterenol-induced biochemical and histopathological alterations in rats.

Amran AZ1, Jantan I, Dianita R, Buang F.
Pharmaceutical biology.Pharm Biol.2015 Dec;53(12):1795-802. doi: 10.3109/13880209.2015.1008147. Epub 2015 Apr 14.
CONTEXT: Ginger [Zingiber officinale Roscoe. (Zingiberaceae)] has been universally used as a spice as well as for its health benefits.OBJECTIVE: The present study evaluates the protective effect of the standardized extract of ginger against isoproterenol (ISO)-induced myocardial infarction (MI) in r
PMID 25868620

Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial injury in rats.

Geng ZH1, Huang L1, Song MB1, Song YM2.
Carbohydrate polymers.Carbohydr Polym.2015 Nov 5;132:638-42. doi: 10.1016/j.carbpol.2015.06.086. Epub 2015 Jul 10.
In this study, we investigated the cardioprotective effect of one purified polysaccharide (SMP1) from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. ISO-treated rats showed severe myocardial damage and high lipid peroxidation level, as well as decreased endoge
PMID 26256391

Impaired mitochondrial energy supply coupled to increased H2O2 emission under energy/redox stress leads to myocardial dysfunction during Type I diabetes.

Tocchetti CG1, Stanley BA2, Sivakumaran V2, Bedja D3, O'Rourke B2, Paolocci N2, Cortassa S2, Aon MA4.
Clinical science (London, England : 1979).Clin Sci (Lond).2015 Oct 1;129(7):561-74. doi: 10.1042/CS20150204. Epub 2015 Jun 11.
In Type I diabetic (T1DM) patients, both peaks of hyperglycaemia and increased sympathetic tone probably contribute to impair systolic and diastolic function. However, how these stressors eventually alter cardiac function during T1DM is not fully understood. In the present study, we hypothesized th
PMID 26186741

Japanese Journal

Stereoselective sulfate conjugation of isoproterenol in humans : comparison of hepatic, intestinal, and platelet activity

PESOLA G. R.
Chirality 5, 602-609, 1993
NAID 30009033628

Increased Uncoupling of β-, β1-and β2-Adrenoceptor to Myocardial Contraction in Failing Human Myocardium : CLINICAL EVALUATION OF CARDIAC PERFORMANCE

TAKAHASHI MASAYUKI,SHICHIRI GENSHOU,AMANO MOTOYA,KANAMORI TOSHIYUKI,KINOSHITA MASAHIKO
Japanese circulation journal 56(7), 701-709, 1992-07-20
… β-AR mediated contraction,ΔVcfc by infusion of a β-AR agonist, isoproterenol, declined with the advancement of heart failure from 0.41 Circ/sec (NYHA I) to 0.31 (NYHA II), 0.22 (NYHA III) and 0.12 (NYHA IV). … Dobutamine, a β 1-AR full agonist, mediatedΔVcfc was 92-97% of that of isoproterenol. … On the other hand, terbutaline sulfate, a full agonist to β2-AR, increasedΔVcfc partially in comparison with isoproterenol; …
NAID 110002587537

「イソプロテレノール」

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; category	C;
Legal status	℞ (Prescription only);
Routes of; administration	inhaled 80-120μg
Identifiers
CAS Registry Number	7683-59-2
ATC code	C01CA02 R03AB02; R03CB01
PubChem	CID: 3779
IUPHAR/BPS	536
DrugBank	DB01064
ChemSpider	3647
UNII	L628TT009W
KEGG	D08090
ChEMBL	CHEMBL434
Chemical data
Formula	C11H17NO3
Molecular 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 ; Key:JWZZKOKVBUJMES-UHFFFAOYSA-N ;
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　　[★]

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)。

動態

注意

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）

副作用

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

「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-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

「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

「sulfate」

　　[★]

n.

(官能基やイオンを表して)硫酸、(化合物)硫酸塩、硫酸エステル、硫酸化する

関: H2SO4、inorganic sulfate、sulfate ester、sulfated、sulfation、sulfuric acid、sulfuric acid ester、sulphate、sulphuric acid

「sulfated」

　　[★]

adj.

硫酸化の

関: sulfate、sulfation、sulphate

「isoproterenol」

　　[★] イソプロテレノール ISP 　

「sulfa」

　　[★]

スルファ、サルファ

[TAAR1_ligands_and_TA_adrenergic_receptor_binding-1] Kleinau G, Pratzka J, Nürnberg D, Grüters A, Führer-Sakel D, Krude H, Köhrle J, Schöneberg T, Biebermann H (October 2011). "Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists". PLoS ONE 6 (10): e27073. doi:10.1371/journal.pone.0027073. PMC 3205048. PMID 22073124.
"Table 1: EC₅₀ values of different agonists at hTAAR1, hADRB1 and hADRB2."

[pharmnemonics-2] Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 5. ISBN 1-59541-101-1.

[3] Medicinal Chemistry of Adrenergics and Cholinergics

[4] Pierce, Neil and Hensley, Michael J. (1998). "Epidemiologic Studies of Beta Agonists and Asthma Deaths" (PDF). Epidemiologic Studies 20 (2).

リンク元	「イソプロテレノール」「isoprenaline sulfate」「dl-isoproterenol hydrochloride」「dl-isoprenaline hydrochloride」「l-isoprenaline hydrochloride」
関連記事	「sulfate」「sulfated」「isoproterenol」「sulfa」

匿名

検索

案内

案内

isoproterenol sulfate

WordNet

Wikipedia preview

wiki en

Contents

Uses

Pharmacology

Warnings and contraindications

Structure-activity relationship

History

References

UpToDate Contents

English Journal

Japanese Journal

Related Links

★リンクテーブル★

「イソプロテレノール」

作用機序

薬理作用

動態

注意

禁忌

副作用

効能又は効果

添付文書

「isoprenaline sulfate」

「dl-isoproterenol hydrochloride」

「dl-isoprenaline hydrochloride」

「l-isoprenaline hydrochloride」

「sulfate」

「sulfated」

「isoproterenol」

「sulfa」