Norepinephrine (medication)

Norepinephrine
	Skeletal formula of noradrenaline
	Ball-and-stick model of the zwitterionic form of noradrenaline found in the crystal structure
Clinical data
Trade names	Levarterenol, Levophed, Norepin, other
Other names	Noradrenaline; (R)-(–)-Norepinephrine; l-1-(3,4-Dihydroxyphenyl)-2-aminoethanol; 3,4,β-Trihydroxyphenethylamine
AHFS/Drugs.com	Monograph
License data	US DailyMed: Norepinephrine; US FDA: Norepinephrine;
Pregnancy; category	AU: B3; ;
Routes of; administration	Intravenous
Drug class	Adrenergic receptor agonist; Sympathomimetic
ATC code	C01CA03 (WHO) ;
Physiological data
Source tissues	Locus coeruleus; sympathetic nervous system; adrenal medulla
Target tissues	System-wide
Receptors	α1, α2, β1, β3
Agonists	Sympathomimetic drugs, clonidine, isoprenaline
Antagonists	Tricyclic antidepressants, Beta blockers, antipsychotics
Metabolism	MAO-A; COMT
Legal status
Legal status	AU: S4 (Prescription only); CA: OTC; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Metabolism	MAO-A; COMT
Excretion	Urine (84–96%)
Identifiers
	IUPAC name 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol;
CAS Number	51-41-2 ;
PubChem CID	439260;
IUPHAR/BPS	505;
DrugBank	DB00368 ;
ChemSpider	388394 ;
UNII	X4W3ENH1CV;
KEGG	D00076 ; as salt: D05206 ;
ChEBI	CHEBI:18357 ;
ChEMBL	ChEMBL1437 ;
Chemical and physical data
Formula	C8H11NO3
Molar mass	169.180 g·mol−1
3D model (JSmol)	Interactive image;
Density	1.397±0.06 g/cm3
Melting point	217 °C (423 °F) (decomposes)
Boiling point	442.6 °C (828.7 °F) ±40.0°C
	SMILES Oc1ccc(cc1O)[C@@H](O)CN;
	InChI InChI=1S/C8H11NO3/c9-4-8(12)5-1-2-6(10)7(11)3-5/h1-3,8,10-12H,4,9H2/t8-/m0/s1 ; Key:SFLSHLFXELFNJZ-QMMMGPOBSA-N ;
	(verify)

Norepinephrine, also known as noradrenaline and sold under the brand name Levophed among others, is a medication used to treat people with very low blood pressure.^[2] It is the typical medication used in sepsis if low blood pressure does not improve following intravenous fluids.^[3] It is the same molecule as the hormone and neurotransmitter norepinephrine.^[2] It is given by slow injection into a vein.^[2]

Common side effects include headache, slow heart rate, and anxiety.^[2] Other side effects include an irregular heartbeat.^[2] If it leaks out of the vein at the site it is being given, norepinephrine can result in limb ischemia.^[2] If leakage occurs the use of phentolamine in the area affected may improve outcomes.^[2] Norepinephrine works by binding and activating alpha adrenergic receptors.^[2]

Norepinephrine was discovered in 1946 and was approved for medical use in the United States in 1950.^[2]^[4] It is available as a generic medication.^[2]

Medical uses

Norepinephrine is used mainly as a sympathomimetic drug to treat people in vasodilatory shock states such as septic shock and neurogenic shock, while showing fewer adverse side-effects compared to dopamine treatment.^[5]^[6]

Pharmacology

Mechanism of action

It stimulates α₁ and α₂ adrenergic receptors to cause blood vessel contraction, thus increases peripheral vascular resistance and resulted in increased blood pressure. This effect also reduces the blood supply to gastrointestinal tract and kidneys. Norepinephrine acts on beta-1 adrenergic receptors, causing increase in heart rate and cardiac output.^[7] However, the elevation in heart rate is only transient, as baroreceptor response to the rise in blood pressure as well as enhanced vagal tone ultimately result in a sustained decrease in heart rate.^[8] Norepinephrine acts more on alpha receptors than the beta receptors.^[9]

Pharmacokinetics

Norepinephrine does not cross the blood–brain barrier under normal circumstances and hence is a peripherally selective drug.^[10]

Chemistry

Norepinephrine, or noradrenaline, also known as 3,4,β-trihydroxyphenethylamine, is a substituted phenethylamine and catecholamine. It is the N-demethylated analogue of epinephrine (adrenaline; 3,4,β-trihydroxy-N-methylphenethylamine) and the β-hydroxylated analogue of dopamine (3,4-dihydroxyphenethylamine).

Society and culture

Names

Norepinephrine is the generic name of the drug and its INNTooltip International Nonproprietary Name, while noradrenaline is its BANTooltip British Approved Name.^[11]^[12]

References

^ Andersen AM (1975). "Structural studies of metabolic products of dopamine. IV. Crystal and molecular structure of (-)-noradrenaline". Acta Chemica Scandinavica B. 29 (8): 871–876. doi:10.3891/acta.chem.scand.29b-0871. PMID 1202890.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Norepinephrine Bitartrate". The American Society of Health-System Pharmacists. Archived from the original on 26 March 2017. Retrieved 26 March 2017.
^ Latifi R (2016). Surgical Decision Making: Beyond the Evidence Based Surgery. Springer. p. 67. ISBN 9783319298245. Archived from the original on 2017-03-27.
^ Encyclopedia of the Neurological Sciences. Academic Press. 2014. p. 224. ISBN 9780123851581. Archived from the original on 2017-03-27.
^ Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. (March 2017). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016". Critical Care Medicine. 45 (3): 486–552. doi:10.1097/CCM.0000000000002255. hdl:10281/267577. PMID 28098591. S2CID 52827184. We recommend norepinephrine as the first-choice vasopressor (strong recommendation, moderate quality of evidence).
^ De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, et al. (March 2010). "Comparison of dopamine and norepinephrine in the treatment of shock". The New England Journal of Medicine. 362 (9): 779–789. doi:10.1056/nejmoa0907118. PMID 20200382.
^ Moore JI (6 December 2012). Pharmacology (3rd ed.). Springer Science and Business Media. p. 39. ISBN 9781468405248. Retrieved 19 November 2017.
^ Klabunde RE (7 December 2022). "Circulating Catecholamines". CV Physiology. Retrieved 2019-02-27.
^ Pollard S, Edwin SB, Alaniz C (July 2015). "Vasopressor and Inotropic Management Of Patients With Septic Shock". P & T. 40 (7): 438–450. PMC 4495871. PMID 26185405.
^ Froese L, Dian J, Gomez A, Unger B, Zeiler FA (October 2020). "The cerebrovascular response to norepinephrine: A scoping systematic review of the animal and human literature". Pharmacol Res Perspect. 8 (5): e00655. doi:10.1002/prp2.655. PMC 7510331. PMID 32965778.
^ Elks, J. (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 885. ISBN 978-1-4757-2085-3. Retrieved 31 August 2024.
^ Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 874. ISBN 978-3-88763-101-7. Retrieved 31 August 2024.

External links

"Norepinephrine". Drug Information Portal. U.S. National Library of Medicine.
"Norepinephrine bitartrate". Drug Information Portal. U.S. National Library of Medicine.

[1] Andersen AM (1975). "Structural studies of metabolic products of dopamine. IV. Crystal and molecular structure of (-)-noradrenaline". Acta Chemica Scandinavica B. 29 (8): 871–876. doi:10.3891/acta.chem.scand.29b-0871. PMID 1202890.

[AHFS2017-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Norepinephrine Bitartrate". The American Society of Health-System Pharmacists. Archived from the original on 26 March 2017. Retrieved 26 March 2017.

[3] Latifi R (2016). Surgical Decision Making: Beyond the Evidence Based Surgery. Springer. p. 67. ISBN 9783319298245. Archived from the original on 2017-03-27.

[4] Encyclopedia of the Neurological Sciences. Academic Press. 2014. p. 224. ISBN 9780123851581. Archived from the original on 2017-03-27.

[5] Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. (March 2017). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016". Critical Care Medicine. 45 (3): 486–552. doi:10.1097/CCM.0000000000002255. hdl:10281/267577. PMID 28098591. S2CID 52827184. We recommend norepinephrine as the first-choice vasopressor (strong recommendation, moderate quality of evidence).

[6] De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, et al. (March 2010). "Comparison of dopamine and norepinephrine in the treatment of shock". The New England Journal of Medicine. 362 (9): 779–789. doi:10.1056/nejmoa0907118. PMID 20200382.

[7] Moore JI (6 December 2012). Pharmacology (3rd ed.). Springer Science and Business Media. p. 39. ISBN 9781468405248. Retrieved 19 November 2017.

[8] Klabunde RE (7 December 2022). "Circulating Catecholamines". CV Physiology. Retrieved 2019-02-27.

[9] Pollard S, Edwin SB, Alaniz C (July 2015). "Vasopressor and Inotropic Management Of Patients With Septic Shock". P & T. 40 (7): 438–450. PMC 4495871. PMID 26185405.

[FroeseDianGomez2020-10] Froese L, Dian J, Gomez A, Unger B, Zeiler FA (October 2020). "The cerebrovascular response to norepinephrine: A scoping systematic review of the animal and human literature". Pharmacol Res Perspect. 8 (5): e00655. doi:10.1002/prp2.655. PMC 7510331. PMID 32965778.

[Elks2014-11] Elks, J. (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 885. ISBN 978-1-4757-2085-3. Retrieved 31 August 2024.

[IndexNominum2004-12] Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 874. ISBN 978-3-88763-101-7. Retrieved 31 August 2024.

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