塩酸ラベタロール

関: dilevalol、labetalol

WordNet

antihypertensive drug (trade names Trandate and Normodyne) that blocks alpha and beta-adrenergic receptors of the sympathetic nervous system (leading to a decrease in blood pressure) (同)labetalol_hydrochloride, Trandate, Normodyne
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）』「2015/08/06 18:43:24」(JST)

wiki en

Labetalol (INN) (/ləˈbɛtəlɔːl/) (trade names Normodyne and Trandate) is a mixed alpha/beta adrenergic antagonist that is used to treat high blood pressure.^[1]

Medical uses

It has a particular indication in the treatment of pregnancy-induced hypertension which is commonly associated with pre-eclampsia.^[2]

It is also used to treat chronic and acute hypertension of pheochromocytoma and hypertensive crisis.^[3]

Side effects

Side effects may include:

Drowsiness
Fatigue
Weakness
Difficulty sleeping
Diminished sexual function
Orthostatic hypotension (due to alpha receptor blockade)
Scalp tingling
Hyperkalemia
Hepatotoxicity
Drug eruption similar to lichen planus^[4]
A rare but potentially lethal side effect is respiratory distress.

Contraindications

Labetalol has relative contraindications for use in patients with asthma, congestive heart failure, any degree of heart block, bradycardia, hypotension or those in cardiogenic shock.

Chemistry

For adrenergic agents, when the substituent on the amine nitrogen is greater in size than a t-butyl group, then the molecule typically is found to have receptor affinity without intrinsic activity, and is therefore an antagonist.^[5] Labetalol has two chiral carbons and consequently exists as four stereoisomers.^[6] Two of these isomers, the (S,S)- and (R,S)- forms are inactive. The third, the (S,R)-isomer, is a powerful α₁ blocker. The fourth isomer, the (R,R)-isomer which is also known as dilevalol, is a mixed nonselective β blocker and selective α₁ blocker.

Labetalol acts by blocking alpha and beta adrenergic receptors, resulting in decreased peripheral vascular resistance without significant alteration of heart rate or cardiac output. The β:α antagonism of labetalol is approximately 3:1.^[3]^[7]

Mechanism of action

Labetalol combines both selective, competitive, alpha-1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta- blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively. The principal physiologic action of labetalol is to competitively block adrenergic stimulation of β-receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors), and α1-receptors within vascular smooth muscle. This causes a decrease in systemic arterial blood pressure and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently because of its combined α- and β-adrenergic blocking activity.

Labetalol has local anesthetic activity.^[8]

Labetalol, in animal models, was found to cross the blood-brain-barrier in only negligible amounts.^[9]

References

^ Fahed S, Grum DF, Papadimos TJ (2008). "Labetalol infusion for refractory hypertension causing severe hypotension and bradycardia: an issue of patient safety". Patient Saf Surg 2: 13. doi:10.1186/1754-9493-2-13. PMC 2429901. PMID 18505576.
^ http://www.bnf.org/bnf/bnf/56/2488.htm?q=%22labetalol%22
^ ^a ^b Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical. p. 170. ISBN 0-07-145153-6.
^ Shiohara T, Kano Y (2007). "Lichen planus and lichenoid dermatoses". In Bolognia JL. Dermatology. St. Louis: Mosby. p. 161. ISBN 1-4160-2999-0.
^ Medicinal Chemistry of Adrenergics and Cholinergics
^ Riva E, Mennini T, Latini R (December 1991). "The alpha- and beta-adrenoceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers". Br. J. Pharmacol. 104 (4): 823–8. doi:10.1111/j.1476-5381.1991.tb12513.x. PMC 1908821. PMID 1687367.
^ D A Richards, J Tuckman, and B N Prichard (October 1976). "Assessment of alpha- and beta-adrenoceptor blocking actions of labetalol". Br J Clin Pharmacol 3 (5): 849–855. doi:10.1111/j.1365-2125.1976.tb00637.x. PMC 1428931. PMID 9968.
^ Exam Zone (1 January 2009). Elsevier Comprehensive Guide. Elsevier India. pp. 449–. ISBN 978-81-312-1620-0.
^ Detlev Ganten; Patrick J. Mulrow (6 December 2012). Pharmacology of Antihypertensive Therapeutics. Springer Science & Business Media. pp. 147–. ISBN 978-3-642-74209-5.

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. 腹部大動脈瘤ステントグラフト留置術に対する麻酔 anesthesia for endovascular aortic repair
3. 高血圧緊急症の治療に用いる薬物 drugs used for the treatment of hypertensive emergencies
4. 妊婦および出産後女性における高血圧のマネージメント management of hypertension in pregnant and postpartum women
5. 成人における高血圧緊急症の評価および治療 evaluation and treatment of hypertensive emergencies in adults

English Journal

A liposomal fluorescence assay to study permeation kinetics of drug-like weak bases across the lipid bilayer.

Eyer K1, Paech F2, Schuler F1, Kuhn P1, Kissner R3, Belli S2, Dittrich PS4, Krämer SD5.Author information 1Bioanalytics, Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.2Biopharmacy and Radiopharmaceutical Sciences, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.3Bioinorganic and Solution Chemistry, Laboratory of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.4Bioanalytics, Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland. Electronic address: dittrich@org.chem.ethz.ch.5Biopharmacy and Radiopharmaceutical Sciences, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland. Electronic address: stefanie.kraemer@pharma.ethz.c.AbstractLipid bilayer permeation is considered the major route for in vivo barrier passage of drugs. Despite this fact, no technique is currently available to measure the kinetics of permeation across a single lipid bilayer of structurally unrelated drug-like solutes. We developed a liposomal fluorescence assay capable to determine permeation kinetics of basic drug-like solutes across lipid bilayers. The assay is based on the hypothesis that permeation of a weak base along a concentration gradient results in net proton release at the cis-side and net proton capture at the trans-side of the bilayer. The resulting pH changes were monitored with pH-sensitive fluorophores: Test compounds were incubated with liposomes containing a pH-sensitive fluorophore at the bilayer surfaces or in the aqueous lumen and fluorescence changes were monitored with a stopped-flow apparatus in solution or by total internal reflection fluorescence microscopy with surface-captured liposomes on a microfluidic platform. Incubation with lipophilic basic drugs resulted in the expected fluorescence changes while incubation with compounds without basic functionality or high polarity did not affect fluorescence. Kinetics of fluorescence changes followed bi-exponential functions. Logarithmic permeation coefficients (logPermapp) determined in solution and by microfluidics technology showed a good correlation (r(2)=0.94, n=7) and logPermapp increased with increasing lipophilicity. Neither diffusion in the aqueous phase nor partitioning into the bilayer was rate-limiting. PEGylation of 2% of the liposomal lipids reduced Permapp by a factor ~300. In conclusion, the presented liposomal fluorescence assay is capable to determine permeation kinetics of weak basic drug-like solutes across lipid bilayers. The method is adaptable to microfluidics technology for high-throughput measurements and can potentially be modified to work for weak acid solutes.
Journal of controlled release : official journal of the Controlled Release Society.J Control Release.2014 Jan 10;173:102-9. doi: 10.1016/j.jconrel.2013.10.037. Epub 2013 Nov 6.
Lipid bilayer permeation is considered the major route for in vivo barrier passage of drugs. Despite this fact, no technique is currently available to measure the kinetics of permeation across a single lipid bilayer of structurally unrelated drug-like solutes. We developed a liposomal fluorescence a
PMID 24211703

Influence of Gestational Age and Body Weight on the Pharmacokinetics of Labetalol in Pregnancy.

Fischer JH, Sarto GE, Hardman J, Endres L, Jenkins TM, Kilpatrick SJ, Jeong H, Geller S, Deyo K, Fischer PA, Rodvold KA.Author information Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, 833 S Wood Street, Room 164, Chicago, IL, 60612, USA, jfischer@uic.edu.AbstractBACKGROUND AND OBJECTIVES: Labetalol is frequently prescribed for the treatment of hypertension during pregnancy; however, the influence of pregnancy on labetalol pharmacokinetics is uncertain, with inconsistent findings reported by previous studies. This study examined the population pharmacokinetics of oral labetalol during and after pregnancy in women receiving labetalol for hypertension.
Clinical pharmacokinetics.Clin Pharmacokinet.2013 Dec 3. [Epub ahead of print]
BACKGROUND AND OBJECTIVES: Labetalol is frequently prescribed for the treatment of hypertension during pregnancy; however, the influence of pregnancy on labetalol pharmacokinetics is uncertain, with inconsistent findings reported by previous studies. This study examined the population pharmacokineti
PMID 24297680

Perioperative metoprolol and risk of stroke after noncardiac surgery.

Mashour GA, Sharifpour M, Freundlich RE, Tremper KK, Shanks A, Nallamothu BK, Vlisides PE, Weightman A, Matlen L, Merte J, Kheterpal S.Author information * Assistant Professor and Associate Chair for Faculty Affairs, § Robert B. Sweet Professor and Chair, ∥ Director of Statistical Core, Department of Anesthesiology, # Associate Professor, Department of Internal Medicine, ‡ Resident in Anesthesiology, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan. † Resident in Anesthesiology, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. ** Medical Student, Department of Anesthesiology, University of Michigan Medical School. †† Assistant Professor, Director, Center for Perioperative Outcomes Research, Department of Anesthesiology, University of Michigan.AbstractBACKGROUND: Numerous risk factors have been identified for perioperative stroke, but there are conflicting data regarding the role of β adrenergic receptor blockade in general and metoprolol in particular.
Anesthesiology.Anesthesiology.2013 Dec;119(6):1340-6. doi: 10.1097/ALN.0b013e318295a25f.
BACKGROUND: Numerous risk factors have been identified for perioperative stroke, but there are conflicting data regarding the role of β adrenergic receptor blockade in general and metoprolol in particular.METHODS: The authors retrospectively screened 57,218 consecutive patients for radiologic evide
PMID 23612244

Japanese Journal

Umbilical cord blood concentrations of labetalol hydrochloride administered to patients with pregnancy induced hypertension, and subsequent neonatal findings

Hypertension Research in Pregnancy 1(2), 88-92, 2013
NAID 130004638243

妊娠中毒症における塩酸ラベタロールの降圧効果

医療 43(2), 192-196, 1989
NAID 130004314186

活動性ＳＬＥ合併妊娠の臨床経過

産婦人科の進歩 40(6), 711-718, 1988
NAID 130004187987

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リンク元	「ラベタロール」
関連記事	「hydrochloride」

「ラベタロール」

Labetalol
Systematic (IUPAC) name
	(RS)-2-hydroxy-5-{1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl}benzamide
Clinical data
Trade names	Normodyne, Trandate
AHFS/Drugs.com	monograph
MedlinePlus	a685034
Pregnancy; category	C; One of few drugs used for PIH;
Legal status	℞ (Prescription only);
Routes of; administration	oral iv
Pharmacokinetic data
Bioavailability	25%
Protein binding	50%
Metabolism	hepatic pass metabolism,
Biological half-life	Tablet: 6-8 hours; IV: 5.5 hours
Excretion	Excreted in urine, not removed by hemodialysis
Identifiers
CAS Registry Number	36894-69-6
ATC code	C07AG01
PubChem	CID: 3869
IUPHAR/BPS	7207
DrugBank	DB00598
ChemSpider	3734
UNII	R5H8897N95
KEGG	D08106
ChEBI	CHEBI:6343
ChEMBL	CHEMBL429
Chemical data
Formula	C19H24N2O3
Molecular mass	328.406 g/mol
	SMILES O=C(c1cc(ccc1O)C(O)CNC(C)CCc2ccccc2)N ;
	InChI InChI=1S/C19H24N2O3/c1-13(7-8-14-5-3-2-4-6-14)21-12-18(23)15-9-10-17(22)16(11-15)19(20)24/h2-6,9-11,13,18,21-23H,7-8,12H2,1H3,(H2,20,24) ; Key:SGUAFYQXFOLMHL-UHFFFAOYSA-N ;
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　　[★]

英: labetalol
同: 塩酸ラベタロール labetalol hydrochloride
商: トランデート、アスクール、アドブロール、アミタロール、レスポリート、Normodyne
関: アドレナリン受容体、交感神経拮抗薬一覧

α1受容体遮断薬、β受容体遮断薬

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[pmid18505576-1] Fahed S, Grum DF, Papadimos TJ (2008). "Labetalol infusion for refractory hypertension causing severe hypotension and bradycardia: an issue of patient safety". Patient Saf Surg 2: 13. doi:10.1186/1754-9493-2-13. PMC 2429901. PMID 18505576.

[2] ttp://www.bnf.org/bnf/bnf/56/2488.htm?q=%22labetalol%22

[katzung10-3] Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical. p. 170. ISBN 0-07-145153-6.

[bolognia-4] Shiohara T, Kano Y (2007). "Lichen planus and lichenoid dermatoses". In Bolognia JL. Dermatology. St. Louis: Mosby. p. 161. ISBN 1-4160-2999-0.

[5] Medicinal Chemistry of Adrenergics and Cholinergics

[pmid1687367-6] Riva E, Mennini T, Latini R (December 1991). "The alpha- and beta-adrenoceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers". Br. J. Pharmacol. 104 (4): 823–8. doi:10.1111/j.1476-5381.1991.tb12513.x. PMC 1908821. PMID 1687367.

[7] D A Richards, J Tuckman, and B N Prichard (October 1976). "Assessment of alpha- and beta-adrenoceptor blocking actions of labetalol". Br J Clin Pharmacol 3 (5): 849–855. doi:10.1111/j.1365-2125.1976.tb00637.x. PMC 1428931. PMID 9968.

[Zone2009-8] Exam Zone (1 January 2009). Elsevier Comprehensive Guide. Elsevier India. pp. 449–. ISBN 978-81-312-1620-0.

[GantenMulrow2012-9] Detlev Ganten; Patrick J. Mulrow (6 December 2012). Pharmacology of Antihypertensive Therapeutics. Springer Science & Business Media. pp. 147–. ISBN 978-3-642-74209-5.

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案内

labetalol hydrochloride