Norepinephrine (medication)

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Norepinephrine
Norepinephrine.svg
Skeletal formula of noradrenaline
Noradrenaline-from-xtal-view-1-3D-bs-17.png
Ball-and-stick model of the zwitterionic form of noradrenaline found in the crystal structure [1]
Clinical data
Trade names Levarterenol, Levophed, Norepin, other
Other namesNoradrenaline
(R)-(–)-Norepinephrine
l-1-(3,4-Dihydroxyphenyl)-2-aminoethanol
3,4,β-Trihydroxyphenethylamine
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:B3
Routes of
administration
Intravenous
Drug class Adrenergic receptor agonist; Sympathomimetic
ATC code
Physiological data
Source tissues Locus coeruleus; sympathetic nervous system; adrenal medulla
Target tissuesSystem-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
Pharmacokinetic data
Metabolism MAO-A; COMT
Excretion Urine (84–96%)
Identifiers
  • 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C8H11NO3
Molar mass 169.180 g·mol−1
3D model (JSmol)
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
  • Oc1ccc(cc1O)[C@@H](O)CN
  • 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 Yes check.svgY
  • Key:SFLSHLFXELFNJZ-QMMMGPOBSA-N Yes check.svgY
   (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]

Contents

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 INN Tooltip International Nonproprietary Name, while noradrenaline is its BAN Tooltip British Approved Name. [11] [12]

Related Research Articles

<span class="mw-page-title-main">Catecholamine</span> Class of chemical compounds

A catecholamine is a monoamine neurotransmitter, an organic compound that has a catechol and a side-chain amine.

<span class="mw-page-title-main">Adrenergic receptor</span> Class of G protein-coupled receptors

The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.

<span class="mw-page-title-main">Septic shock</span> Dangerously low blood pressure due to damage from an organ infection

Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defines septic shock as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by requiring a vasopressor to maintain a mean arterial pressure of 65 mm Hg or greater and having serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%.

<span class="mw-page-title-main">Atenolol</span> Beta blocker medication

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality in those with the condition. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Metoprolol</span> Medication of the selective β1 receptor blocker type

Metoprolol, sold under the brand name Lopressor among others, is a medication used to treat angina and a number of conditions involving an abnormally fast heart rate. It is also used to prevent further heart problems after myocardial infarction and to prevent headaches in those with migraines. It is a selectiveβ1 receptor blocker medication. It is taken by mouth or is given intravenously.

<span class="mw-page-title-main">Sympathomimetic drug</span> Substance that mimics effects of catecholamines

Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart rate, force of cardiac contraction, and blood pressure. The primary endogenous agonists of the sympathetic nervous system are the catecholamines, which function as both neurotransmitters and hormones. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.

<span class="mw-page-title-main">Phenylephrine</span> Decongestant medication

Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among numerous others, is a medication used as a decongestant for uncomplicated nasal congestion, used to dilate the pupil, used to increase blood pressure, and used to relieve hemorrhoids. It can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, applied to the skin, or as a rectal suppository.

<span class="mw-page-title-main">Isoprenaline</span> Medication for slow heart rate

Isoprenaline, also known as isoproterenol and sold under the brand name Isuprel among others, is a sympathomimetic medication which is used in the treatment of acute bradycardia, heart block, and rarely for asthma, among other indications. It is used by injection into a vein, muscle, fat, or the heart, by inhalation, and in the past under the tongue or into the rectum.

<span class="mw-page-title-main">Dobutamine</span> Medication which strengthens heart contractions

Dobutamine is a medication used in the treatment of cardiogenic shock and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an injection into a vein or intraosseous as a continuous infusion. The amount of medication needs to be adjusted to the desired effect. Onset of effects is generally seen within 2 minutes. It has a half-life of two minutes. This drug is generally only administered short term, although it may be used for longer periods to relieve symptoms of heart failure in patients awaiting heart transplantation.

<span class="mw-page-title-main">Carvedilol</span> Blood pressure medication

Carvedilol, sold under the brand name Coreg among others, is a beta blocker medication, that may be prescribed for the treatment of high blood pressure (hypertension) and chronic heart failure with reduced ejection fraction. Beta-blockers as a collective medication class are not recommended as routine first-line treatment of high blood pressure for all patients, due to evidence demonstrating less effective cardiovascular protection and a less favourable safety profile when compared to other classes of blood pressure-lowering medications.

<span class="mw-page-title-main">Metaraminol</span> Antihypotensive medication

Metaraminol, also known as metaradrine and sold under the brand names Aramine and Pressonex among others, is a sympathomimetic medication which is used in the prevention and treatment of hypotension, particularly as a complication of anesthesia. It is given by intramuscular or intravenous administration.

<span class="mw-page-title-main">Norepinephrine</span> Catecholamine hormone and neurotransmitter

Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "noradrenaline" is more commonly used in the United Kingdom, whereas "norepinephrine" is usually preferred in the United States. "Norepinephrine" is also the international nonproprietary name given to the drug. Regardless of which name is used for the substance itself, parts of the body that produce or are affected by it are referred to as noradrenergic.

<span class="mw-page-title-main">Dopexamine</span> Chemical compound

Dopexamine is a synthetic analogue of dopamine that is administered intravenously in hospitals to reduce exacerbations of heart failure and to treat heart failure following cardiac surgery. It is not used often, as more established drugs like epinephrine, dopamine, dobutamine, norepinephrine, and levosimendan work as well. It works by stimulating beta-2 adrenergic receptors and peripheral dopamine receptor D1 and dopamine receptor D2. It also inhibits the neuronal re-uptake of norepinephrine.

<span class="mw-page-title-main">Adrenaline</span> Hormone and medication

Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions. It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and by a small number of neurons in the medulla oblongata. It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output by acting on the SA node, pupil dilation response, and blood sugar level. It does this by binding to alpha and beta receptors. It is found in many animals, including humans, and some single-celled organisms. It has also been isolated from the plant Scoparia dulcis found in Northern Vietnam.

<span class="mw-page-title-main">Droxidopa</span> Synthetic amino acid/norepinephrine prodrug

Droxidopa, also known as L-threo-dihydroxyphenylserine (L-DOPS) and sold under the brand names Northera and Dops among others, is sympathomimetic medication which is used in the treatment of hypotension and for other indications. It is taken by mouth.

<span class="mw-page-title-main">History of catecholamine research</span>

The catecholamines are a group of neurotransmitters composed of the endogenous substances dopamine, noradrenaline (norepinephrine), and adrenaline (epinephrine), as well as numerous artificially synthesized compounds such as isoprenaline - an anti-bradycardiac medication. Their investigation constitutes a major chapter in the history of physiology, biochemistry, and pharmacology. Adrenaline was the first hormone extracted from an endocrine gland and obtained in pure form, before the word hormone was coined. Adrenaline was also the first hormone whose structure and biosynthesis was discovered. Second to acetylcholine, adrenaline and noradrenaline were some of the first neurotransmitters discovered, and the first intercellular biochemical signals to be found in intracellular vesicles. The β-adrenoceptor gene was the first G protein-coupled receptor to be cloned.

<span class="mw-page-title-main">Dopamine (medication)</span> Hormone used as a medication

Dopamine, sold under the brand name Intropin among others, is a medication most commonly used in the treatment of very low blood pressure, a slow heart rate that is causing symptoms, and, if epinephrine is not available, cardiac arrest. In newborn babies it continues to be the preferred treatment for very low blood pressure. In children epinephrine or norepinephrine is generally preferred while in adults norepinephrine is generally preferred for very low blood pressure. It is given intravenously or intraosseously as a continuous infusion. Effects typically begin within five minutes. Doses are then increased to effect.

<span class="mw-page-title-main">Epinephrine (medication)</span> Hormone used as a medicine

Epinephrine, also known as adrenaline, is a medication and hormone. As a medication, it is used to treat several conditions, including anaphylaxis, cardiac arrest, asthma, and superficial bleeding. Inhaled epinephrine may be used to improve the symptoms of croup. It may also be used for asthma when other treatments are not effective. It is given intravenously, by injection into a muscle, by inhalation, or by injection just under the skin.

<span class="mw-page-title-main">Vasopressin (medication)</span> Chemical compound

Vasopressin infusions are in use for septic shock patients not responding to fluid resuscitation or infusions of catecholamines to increase the blood pressure while sparing the use of catecholamines. These argipressins have much shorter elimination half-life than synthetic non-arginine vasopresines with much longer elimination half-life of many hours. Further, argipressins act on V1a, V1b, and V2 receptors which consequently lead to higher eGFR and lower vascular resistance in the lungs. A number of injectable arginine vasopressins are in clinical use in the United States and the European Union. Pitressin among others, is a medication most commonly used in the treatment of frequent urination, increased thirst, and dehydration such as that resulting from diabetes insipidus, which causes increased and diluted urine. It is used to treat abdominal distension following some surgeries, and in stomach roentgenography. Vasopressin is a hormone that affects the kidneys and reduces urine flow.

<span class="mw-page-title-main">Angiotensin II (medication)</span> Medication for low blood pressure

Angiotensin II is a medication that is used to treat hypotension resulting from septic shock or other distributive shock. It is a synthetic vasoconstrictor peptide that is identical to human hormone angiotensin II and is marketed under the brand name Giapreza. The Food and Drug Administration approved the use of angiotensin II in December 2017 to treat low blood pressure resulting from septic shock.

References

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  2. 1 2 3 4 5 6 7 8 9 10 "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.
  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.
  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.
  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.