WordNet

beta blocker that can reduce the progression of heart failure in individuals whose disease is not advanced

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/28 02:56:53」(JST)

wiki en

Carvedilol, sold under the brand name Coreg among others, is a nonselective beta blocker/alpha-1 blocker. It is used in the treatment of mild to severe congestive heart failure (CHF), left ventricular dysfunction (LVD) following heart attack in clinically stable patients, and high blood pressure.^[1]

Carvedilol was discovered by Fritz Wiedemann at Boehringer Mannheim and was initially approved in the U.S. in 1995, marketed as Coreg.^[2] On October 20, 2006, the FDA approved an extended-release formulation of carvedilol; it is marketed as Coreg CR.^[3]

Medical use

Carvedilol is indicated in the management of congestive heart failure (CHF), commonly as an adjunct to angiotensin-converting-enzyme inhibitor (ACE inhibitors) and diuretics. It has been clinically shown to reduce mortality and hospitalizations in people with CHF.^[4] The mechanism behind its positive effect when used long-term in clinically stable CHF patients is not fully understood, but is thought to contribute to remodeling of the heart, improving upon its structure and function.^[5]

In addition, carvedilol is indicated in the treatment of hypertension. It can be used alone or with other anti-hypertensive agents. In the 2013 guideline, it is recommended as the drug of choice in people with histories of CHF and/or myocardial infarction.^[6]

Side effects

The most common side effects (>10% incidence) include:^[1]

dizziness
fatigue
low blood pressure
diarrhea
weakness
slowed heart rate
weight gain

Carvedilol is not recommended for people with uncontrolled bronchospastic disease (e.g. current asthma symptoms) as it can block receptors that assist in opening the airways.^[1]

Carvedilol may mask symptoms of low blood sugar.^[1]

Contraindications

According to the FDA, carvedilol should not be used in people with bronchial asthma or bronchospastic conditions. It should not be used in people with second- or third-degree AV block, sick sinus syndrome, severe bradycardia (unless a permanent pacemaker is in place), or a decompensated heart condition. People with severe hepatic impairment are also not advised to take carvedilol.^[7]

Mechanism of action

Carvedilol is both a non-selective beta adrenergic receptor blocker (β1, β2) and an alpha adrenergic receptor blocker (α1). The S(-) enantiomer accounts for the beta blocking activity whereas the S(-) and R(+) enantiomer have alpha blocking activity.^[1]

Carvedilol reversibly binds to beta adrenergic receptors on cardiac myocytes. Inhibition of these receptors prevents a response to the sympathetic nervous system, leading to decreased heart rate and contractility. This action is beneficial in heart failure patients where the sympathetic nervous system is activated as a compensatory mechanism.^[8]

Carvedilol blockade of α1 receptors causes vasodilation of blood vessels. This inhibition leads to decreased peripheral vascular resistance and an antihypertensive effect. There is no reflex tachycardia response due to carvedilol blockade of β1 receptors on the heart.^[9]

Pharmacokinetics

Carvedilol is about 25% to 35% bioavailable following oral administration due to extensive first-pass metabolism. The compound is metabolized by liver enzymes, CYP2D6 and CYP2C9 via aromatic ring oxidation and glucuronidation, then further conjugated by glucuronidation and sulfation. Compared with the parent compound, the three active metabolites exhibits only one-tenth of the vasodilating effect of the parent compound. However, the 4’hydroxyphenyl metabolite is about 13-fold more potent in ß-blockade than the parent compound.^[1]

The mean half-life of carvedilol following oral administration ranges from 7 to 10 hours. Carvedilol has two enantiomers: R(+)-carvedilol and S(-)-carvedilol. R(+)-carvedilol undergoes preferential selection for metabolism, so the mean half-life of the enantiomer is about 5 to 9 hours compared with 7 to 11 hours for the S(-)-enantiomer.^[1]

Majority of carvedilol is bound to plasma proteins (98%), mainly to albumin. Carvedilol is a basic, hydrophobic compound with a steady-state volume of distribution of 115 L. Plasma clearance ranges from 500 to 700 mL/min.^[1]

Absorption is slowed when administered with food, however it does not show significant difference in bioavailability. Taking carvedilol with food decrease the risk of orthostatic hypotension.^[1]

Formulations

•Tablet, Oral ^[1]

•Capsule Extended Release 24 Hour, Oral^[3]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Coreg - Food and Drug Administration" (PDF).
^ U.S. Patent 4503067
^ ^a ^b "Drug Approval Package". www.accessdata.fda.gov. Retrieved 2015-11-05.
^ "2013 AHA Guidelines for the Management of Heart Failure" (PDF).
^ Biaggioni, MD, Italo (2009). Basic and Clinical Pharmacology 11th Edition. New York: McGraw-Hill Medical Publishing Division. p. 189. ISBN 9780071604055.
^ "2013 ASH Guidelines for the Management of Hypertension" (PDF).
^ "Carvedilol Package Insert" (PDF).
^ Manurung, Daulat (2007). "Beta Blockers for Congestive Heart Failure" (PDF). Acta medica Indonesiana.
^ Jr, Dr R. R. Ruffolo; Gellai, M.; Hieble, J. P.; Willette, R. N.; Nichols, A. J. (1990-03-01). "The pharmacology of carvedilol". European Journal of Clinical Pharmacology 38 (2): S82–S88. doi:10.1007/BF01409471. ISSN 0031-6970.

External links

Coreg CR official website
Physicians Desk Reference Info on Carvedilol
Info on carvedilol through rxlist.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. 収縮能障害による心不全におけるβブロッカー使用の理論的根拠および臨床試験 rationale for and clinical trials of beta blockers in heart failure due to systolic dysfunction
2. 収縮能障害による心不全におけるβブロッカーの使用 use of beta blockers in heart failure due to systolic dysfunction
3. 肝硬変患者における静脈瘤出血に対する一次予防および静脈瘤形成予防 primary and pre primary prophylaxis against variceal hemorrhage in patients with cirrhosis
4. 乳児および小児における心不全のマネージメント management of heart failure in infants and children
5. β遮断剤の主な副作用 major side effects of beta blockers

English Journal

Chronic social stress induces cardiomyocyte contractile dysfunction and intracellular Ca(2+) derangement in rats.

Turdi S, Yuan M, Leedy GM, Wu Z, Ren J.SourceDivision of Pharmaceutical Sciences, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.
Physiology & behavior.Physiol Behav.2012 Jan 18;105(2):498-509. Epub 2011 Sep 17.
Chronic psychosocial stress triggers cardiovascular diseases although underlying mechanisms are still elusive. This study examined the effect of social stress on cardiomyocyte contractile function and pathological changes in myocardium using the visible burrow system (VBS) model. Chronic social stre
PMID 21952229

Interdialytic ambulatory blood pressure in patients with intradialytic hypertension.

Van Buren PN, Toto R, Inrig JK.SourceDivision of Nephrology, Department of Internal Medicine, The University of Texas Southwestern Medical Center-Dallas, Dallas, Texas, USA.
Current opinion in nephrology and hypertension.Curr Opin Nephrol Hypertens.2012 Jan;21(1):15-23.
PURPOSE OF REVIEW: Hypertension is common in hemodialysis patients and contributes to this population's high risk for cardiovascular morbidity and mortality. Patients with intradialytic hypertension, or increases in blood pressure during hemodialysis, have been shown to have the highest risk for the
PMID 22123207

Japanese Journal

心不全管理の立場からみた不整脈治療 (特集 2025年を見すえた心不全診療ロードマップ : 突破口はどこにあるのか)

岩崎雄樹,清水渉
内科 113(3), 527-530, 2014-03
NAID 40019987157

急性心不全を契機に診断された心サルコイドーシスの1例

田中絢子,鈴木敦,新井光太郎 [他],鈴木豪,志賀剛,萩原誠久,TANAKA Ayako,SUZUKI Atsushi,ARAI Kotaro,SUZUKI Tsuyoshi,SHIGA Tsuyoshi,HAGIWARA Nobuhisa
東京女子医科大学雑誌 83(4), 261-266, 2013-08-25
症例は54歳男性で、2011年某月に、急性発症した高度呼吸困難により救急搬送された。胸部レントゲンで心拡大を認め、BNP値は2000pg/mLと高値を認め、急性心不全と診断された。カルベジロール3.75mg/日、エナラプリル1.25mg/日、フロセミド20mg/日とアミオダロン100mg/日を投与され退院した。冠動脈CT検査で、冠状動脈に有意狭窄は認めなかった。心臓超音波検査では、左室駆出率21% …
NAID 110009610664

Clinical Status and Outcome of Japanese Heart Failure Patients With Reduced or Preserved Ejection Fraction Treated With Carvedilol

Mori Yoshihiro,Nishikawa Yasuhiro,Kobayashi Fumiaki,Hiramatsu Katsutoshi
International Heart Journal 54(1), 15-22, 2013
… This prospective observational study enrolled 1,682 Japanese HF patients who received carvedilol for the first time. … Carvedilol maintenance dosage was lower in patients with preserved EF (7.9 mg/day versus 6.6 mg/ day). … This study elucidated the characteristics of HF patients given carvedilol in "real world" clinical settings. …
NAID 130003364433

Related Pictures

★リンクテーブル★

リンク元	「カルベジロール」
拡張検索	「carvedilol phosphate」

「カルベジロール」

Carvedilol
Systematic (IUPAC) name
	(±)-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine
Clinical data
Trade names	Coreg
AHFS/Drugs.com	monograph
MedlinePlus	a697042
Pregnancy; category	C;
Legal status	℞ (Prescription only);
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	25–35%
Protein binding	98%
Metabolism	Liver (CYP2D6, CYP2C9)
Biological half-life	7–10 hours
Excretion	Urine (16%), Feces (60%)
Identifiers
CAS Number	72956-09-3
ATC code	C07AG02
PubChem	CID: 2585
IUPHAR/BPS	551
DrugBank	DB01136
ChemSpider	2487
UNII	0K47UL67F2
KEGG	D00255
ChEBI	CHEBI:3441
ChEMBL	CHEMBL723
PDB ligand ID	CVD (PDBe, RCSB PDB)
Chemical data
Formula	C24H26N2O4
Molecular mass	406.474
	SMILES O(c4ccccc4OCCNCC(O)COc3cccc2c3c1c(cccc1)n2)C ;
	InChI InChI=1S/C24H26N2O4/c1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20/h2-12,17,25-27H,13-16H2,1H3 ; Key:OGHNVEJMJSYVRP-UHFFFAOYSA-N ;
(verify)