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beta blocker (trade name Lopressor) used in treating hypertension and angina and arrhythmia and acute myocardial infarction; has adverse side effects (depression and exacerbation of congestive heart failure etc.) (同)Lopressor

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/03 21:54:11」(JST)

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Metoprolol ( /mɛˈtoʊproʊlɑːl/) is a selective β₁ receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate (where 100 mg metoprolol tartrate corresponds to 95 mg metoprolol succinate). The tartrate is an immediate-release and the succinate is an extended-release formulation.^[1]

Medical uses

Metoprolol is used for a number of conditions including: hypertension, angina, acute myocardial infarction, supraventricular tachycardia, ventricular tachycardia, congestive heart failure, and prevention of migraine headaches.^[2]

Treatment of heart failure.^[3]
Vasovagal syncope^[4]
Adjunct in treatment of hyperthyroidism
Long QT syndrome, especially for patients with asthma, as metoprolol's β1 selectivity tends to interfere less with asthma drugs which are often β2-adrenergic receptor-agonist drugs^{[citation needed]}

Due to its selectivity in blocking the beta₁ receptors in the heart, metoprolol is also prescribed for off-label use in performance anxiety, social anxiety disorder, and other anxiety disorders.

Metabolism

Metoprolol undergoes a-hydroxylation and O-demethylation as a substrate of the cytochrome liver enzymes CYP2D6 ^[5] and a small percentage by CYP3A4.

Adverse effects

Side effects, especially with higher dosages, include the following: dizziness, drowsiness, fatigue, diarrhea, unusual dreams, ataxia, trouble sleeping, depression, and vision problems. It may also reduce blood flow to the hands and feet, causing them to feel numb and cold; smoking may worsen this effect.^[6] Due to the high penetration across the blood brain barrier, lipophilic beta blockers such as propranolol and metoprolol are more likely than other less lipophilic beta blockers to cause sleep disturbances such as insomnia and vivid dreams and nightmares.^[7]

Serious side effects which are advised to be reported immediately include, but are not limited to, symptoms of bradycardia (a very slow heartbeat (less than 50 bpm)), persistent symptoms of dizziness, fainting and unusual fatigue, bluish discoloration of the fingers and toes, numbness/tingling/swelling of the hands or feet, sexual dysfunction, erectile dysfunction (impotence), hair loss, mental/mood changes, depression, trouble breathing, cough, dyslipidemia, and increased thirst. Other highly unlikely symptoms include easy bruising or bleeding, persistent sore throat or fever, yellowing skin or eyes, stomach pain, dark urine, and persistent nausea. Symptoms of an allergic reaction include: rash, itching, swelling, and severe dizziness. Taking it with alcohol might cause mild body rashes and therefore is not recommended.^[6]

Precautions

Metoprolol may worsen the symptoms of heart failure in some patients, who may experience chest pain or discomfort; dilated neck veins; extreme fatigue; irregular breathing; an irregular heartbeat; shortness of breath; swelling of the face, fingers, feet, or lower legs; weight gain; or wheezing.^[8]

This medicine may cause changes in blood sugar levels or cover up signs of low blood sugar, such as a rapid pulse rate.^[8]

This medicine may cause some people to become less alert than they are normally, making it dangerous for them to drive, use machines, or do other things.^[8]

Overdosage

Excessive doses of metoprolol can cause severe hypotension, bradycardia, metabolic acidosis, seizures and cardiorespiratory arrest. Blood or plasma concentrations may be measured to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Plasma levels are usually less than 200 μg/L during therapeutic administration, but can range from 1–20 mg/L in overdose victims.^[9]^[10]^[11]

Physical properties

Metoprolol has a very low melting point, tartrate around 120°C, succinate around 136°C. Because of this, metoprolol is always manufactured in a salt-based solution, as drugs with low melting points are difficult to work with in a manufacturing environment. The free base exists as a waxy white solid, and the tartrate salt is finer crystalline material.(Metox-Wockhardt)

Pharmacology

Selective
Moderately lipophilic
Without intrinsic sympathomimetic activity (ISA)
With weak membrane stabilizing activity
Short half-life, therefore must be taken at least twice daily or as a slow-release preparation
Decreases heart rate, contractility and cardiac output, therefore decreasing blood pressure
Metabolized in the liver to inactive metabolite

Chemistry

Metoprolol, 1-(iso-propylamino)-3-[4′(2-methoxyethyl)phenoxy]-2-propanol, is synthesized by reacting 4-(2-methoxyethyl)phenol with epichlorohydrin in the presence of a base, isolating 1,2-epoxy-3-[4′(2-methoxyethyl)phenoxy]propane, the subsequent reaction with isopropylamine, gives an opening of the epoxide ring and leads to the formation of metoprolol.

P. A. E. Carlsson, S. A. I. Carlsson, H. R. Corrodi, L. Ek, B. A. H. Ablad, A. E. Brandstrom, U.S. Patent 3,873,600 (1975).
A. E. Brandstrom, P. A. E. Carlsson, S. A. I. Carlsson, H. R. Corrodi, L. Ek, DE 2106209 (1971).

Brand names

Toprol XL 50 mg

It is marketed under the brand name Lopressor by Novartis, and Toprol-XL (in the USA); Selokeen (in the Netherlands); as Minax by Alphapharm (in Australia), Metrol by Arrow Pharmaceuticals (in Australia), as Betaloc by AstraZeneca, as Bloxan by Krka (company) (in Slovenia), as Neobloc by Unipharm (in Israel), Presolol by Hemofarm (in Serbia) and as Corvitol by Berlin-Chemie AG (in Germany). In India, this drug is available under the brand names of Metxl, Metolar and Starpress,Restopress. A number of generic products are available as well.

References

^ Cupp M (2009). "Alternatives for Metoprolol Succinate" (pdf). Pharmacist's Letter / Prescriber's Letter 25 (250302). http://www.ncbop.org/PDF/MetoprololShortageMarch2009.pdf. Retrieved 2012-07-06.
^ "Metoprolol". The American Society of Health-System Pharmacists. http://www.drugs.com/monograph/metoprolol-succinate.html. Retrieved 3 April 2011.
^ MERIT-HF Study Group (1999). "Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)". Lancet 353 (9169): 2001–2007. doi:10.1016/S0140-6736(99)04440-2. PMID 10376614.
^ Zhang Q, Jin H, Wang L, Chen J, Tang C, Du J (2008). "Randomized comparison of metoprolol versus conventional treatment in preventing recurrence of vasovagal syncope in children and adolescents". Medical Science Monitor 14 (4): CR199–CR203. PMID 18376348. http://www.medscimonit.com/fulltxt.php?ICID=850297.
^ Swaisland HC, Ranson M, Smith RP, Leadbetter J, Laight A, McKillop D, Wild MJ (2005). "Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol". Clinical Pharmacokinetics 44 (10): 1067–1081. PMID 16176119.
^ ^a ^b "Metoprolol". Drugs.com. http://www.drugs.com/metoprolol.html.
^ Cruickshank JM (2010). "Beta-blockers and heart failure". Indian Heart Journal 62 (2): 101–110. PMID 21180298.
^ ^a ^b ^c "Metoprolol (Oral Route) Precautions". Drug Information. Mayo Clinic. http://www.mayoclinic.com/health/drug-information/DR602483/DSECTION=precautions-.
^ Page C, Hacket LP, Isbister GK (2009). "The use of high-dose insulin-glucose euglycemia in beta-blocker overdose: a case report". Journal of Medical Toxicology 5 (3): 139–143. PMID 19655287.
^ Albers S, Elshoff JP, Völker C, Richter A, Läer S (2005). "HPLC quantification of metoprolol with solid-phase extraction for the drug monitoring of pediatric patients". Biomedical Chromatography 19 (3): 202–207. PMID 15484221.
^ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1023–1025.

External links

AstraZeneca's page for Toprol-XL
Novartis's page for Lopressor (PDF)
U.S. National Library of Medicine: Drug Information Portal - Metoprolol

UpToDate Contents

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1. 頸動脈内膜剥離術および頸動脈ステント留置術の麻酔 anesthesia for carotid endarterectomy and carotid stenting
2. 急性冠症候群：β遮断剤の役割 acute myocardial infarction role of beta blocker therapy
3. 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
4. 駆出率低下を伴う心不全におけるβブロッカーおよびイバブラジンの使用 use of beta blockers and ivabradine in heart failure with reduced ejection fraction
5. β遮断剤の主な副作用 major side effects of beta blockers

English Journal

Assessing the reliability of uptake and elimination kinetics modelling approaches for estimating bioconcentration factors in the freshwater invertebrate, Gammarus pulex.

Miller TH1, McEneff GL2, Stott LC3, Owen SF4, Bury NR3, Barron LP5.
The Science of the total environment.Sci Total Environ.2016 Mar 15;547:396-404. doi: 10.1016/j.scitotenv.2015.12.145. Epub 2016 Jan 12.
This study considers whether the current standard toxicokinetic methods are an accurate and applicable assessment of xenobiotic exposure in an aquatic freshwater invertebrate. An in vivo exposure examined the uptake and elimination kinetics for eight pharmaceutical compounds in the amphipod crustace
PMID 26789375

Micropollutant removal in an algal treatment system fed with source separated wastewater streams.

de Wilt A1, Butkovskyi A2, Tuantet K3, Leal LH4, Fernandes TV5, Langenhoff A3, Zeeman G3.
Journal of hazardous materials.J Hazard Mater.2016 Mar 5;304:84-92. doi: 10.1016/j.jhazmat.2015.10.033. Epub 2015 Oct 20.
Micropollutant removal in an algal treatment system fed with source separated wastewater streams was studied. Batch experiments with the microalgae Chlorella sorokiniana grown on urine, anaerobically treated black water and synthetic urine were performed to assess the removal of six spiked pharmaceu
PMID 26546707

Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans.

Gong Y1, Wang Z2, Beitelshees AL2, McDonough CW2, Langaee TY2, Hall K2, Schmidt SO2, Curry RW Jr2, Gums JG2, Bailey KR2, Boerwinkle E2, Chapman AB2, Turner ST2, Cooper-DeHoff RM2, Johnson JA2.
Hypertension.Hypertension.2016 Mar;67(3):556-63. doi: 10.1161/HYPERTENSIONAHA.115.06345. Epub 2016 Jan 4.
African Americans suffer a higher prevalence of hypertension compared with other racial/ethnic groups. In this study, we performed a pharmacogenomic genome-wide association study of blood pressure (BP) response to β-blockers in African Americans with uncomplicated hypertension. Genome-wide meta-ana
PMID 26729753

Super-fine powdered activated carbon (SPAC) for efficient removal of micropollutants from wastewater treatment plant effluent.

Bonvin F1, Jost L2, Randin L2, Bonvin E3, Kohn T2.
Water research.Water Res.2016 Mar 1;90:90-9. doi: 10.1016/j.watres.2015.12.001. Epub 2015 Dec 10.
In an effort to mitigate the discharge of micropollutants to surface waters, adsorption of micropollutants onto powdered activated carbon (PAC) after conventional wastewater treatment has been identified as a promising technology for enhanced removal of pharmaceuticals and pesticides from wastewater
PMID 26724443

Japanese Journal

Variability of Bioavailability and Intestinal Absorption Mechanisms of Metoprolol

FUKAO Miki,ISHIDA Kazuya,HORIE Asuka,TAGUCHI Masato,NOZAWA Takashi,INOUE Hiroshi,HASHIMOTO Yukiya
Drug Metabolism and Pharmacokinetics 29(2), 162-167, 2014
… We previously reported that aging and/or cytochrome P450 2D6 polymorphism are responsible for the interindividual variability in the systemic clearance (CL) and bioavailability (F) of metoprolol. … The aim of the present study was to evaluate the residual variability of F of metoprolol in routinely treated Japanese patients and to investigate the intestinal absorption mechanism of the drug using human intestinal epithelial LS180 cells. …
NAID 130004463366

経口メチルセルロース/アルギン酸液剤の物性に及ぼす薬物の影響

下山哲哉,浦木睦,高橋彩,小林正拓,高畑雅臣,牧野陽佑,伊藤邦彦,小林道也
薬剤学 74(1), 73-83, 2014
… The present study aimed to determine how the addition of drugs (acetaminophen, mexiletine, metoprolol, ambroxol, loxoprofen, theophylline, ketotifen and salbutamol) affects the rheological and in vitro drug release characteristics of a 2% methylcellulose formulation and of a 2% methylcellulose/0.5% alginate formulation. …
NAID 130003398001

SYMPATHETIC AND PARASYMPATHETIC CONTROL OF HEART RATE RESPONSE TO RESTRAINT STRESS DURING THE VULNERABLE PERIOD IN NEWBORN RATS

Tokunaga Jun,Sato Shinichi,Kanbayashi Takashi [他],Imanishi Aya,Sagawa Yohei,Sato Masatoshi,Sakai Noriaki,Nishino Seiji,Shimizu Tetsuo
秋田医学 40(2), 89-103, 2013-11-21
… Autonomic blockade with atropine, metoprolol, and dual atropine/metoprolol blockade (2 mg/kg) at postnatal day (P) 4 and P12 demonstrated predominantly sympathetic effects on baseline HR. …
NAID 110009658221

マウスの実験的動脈硬化に対する3種類のβアドレナリン受容体遮断薬 (プロプラノロール, メトプロロール, カルベジロール) の効果

島田佳奈,平野絵美,木村剛,岸本千晴
Shinzo 45(5), 519-526, 2013
目的 : アポリポプロテインE (アポE) ノックアウトマウスに対して, βアドレナリン受容体遮断薬 (β遮断薬) であるプロプラノロール, メトプロロール, カルベジロールの投与を行い, 動脈硬化に対する効果を検討した. 方法 : 実験的動脈硬化症は, アポEノックアウトマウスに高脂肪食を与えて作成した. 高脂肪食開始と同時の6週の時点で, 飲料水中にプロプラノロール (30mg/kg/日) …
NAID 130004688783

Related Pictures

★リンクテーブル★

リンク元	「メトプロロール」
拡張検索	「metoprolol fumarate」「metoprolol succinate」「metoprolol tartrate」

「メトプロロール」

Metoprolol
Systematic (IUPAC) name
	(RS)-1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
Clinical data
Trade names	Lopressor, Toprol-xl
AHFS/Drugs.com	monograph
MedlinePlus	a682864
Licence data	US FDA:link
Pregnancy cat.	C (AU) C (US)
Legal status	℞ Prescription only
Routes	Oral, IV
Pharmacokinetic data
Bioavailability	12%
Metabolism	Hepatic via CYP2D6, CYP3A4
Half-life	3-7 hours
Excretion	Renal
Identifiers
CAS number	51384-51-1
ATC code	C07AB02
PubChem	CID 4171
IUPHAR ligand	553
DrugBank	DB00264
ChemSpider	4027
UNII	GEB06NHM23
KEGG	D02358
ChEBI	CHEBI:6904
ChEMBL	CHEMBL13
Chemical data
Formula	C15H25NO3
Mol. mass	267.364 g/mol
	SMILES O(c1ccc(cc1)CCOC)CC(O)CNC(C)C;
	InChI InChI=1S/C15H25NO3/c1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3/h4-7,12,14,16-17H,8-11H2,1-3H3 ; Key:IUBSYMUCCVWXPE-UHFFFAOYSA-N ;
Physical data
Melt. point	120 °C (248 °F)
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