Epinephrine, also known as adrenaline, is a
medication and
hormone.[7][8] As a medication, it is used to treat several conditions, including
anaphylaxis,
cardiac arrest,
asthma, and superficial bleeding.[5]Inhaled epinephrine may be used to improve the symptoms of
croup.[9] It may also be used for
asthma when other treatments are not effective.[5] It is given
intravenously, by injection into a muscle, by inhalation, or by injection just under the skin.[5]
Common side effects include shakiness,
anxiety, and sweating.[5] A fast heart rate and high blood pressure may occur.[5] Occasionally, it may result in an
abnormal heart rhythm.[5] While the safety of its use during
pregnancy and
breastfeeding is unclear, the benefits to the mother must be taken into account.[5]
While epinephrine is often used to treat
cardiac arrest, it has not been shown to improve long-term survival or mental function after recovery.[22][23][24] It does, however, improve
return of spontaneous circulation.[24] When used
intravenously to treat cardiac arrest in adults, epinephrine is typically given at a dose of 1 mg every three to five minutes.[25]
In cases of IV infusion for bradycardia the dose is 1 mg epinephrine is mixed with 500ml of NS or D5W. The infusion should run at 2-10 micrograms/min (titrated to effect). IV infusion for post-cardiac arrest hypotension: The dosing is 2 to 10 micrograms/min.
Endotracheal Tube: 2-2.5 mg epinephrine is diluted in 10cc NS and given directly into the ET tube.[26]
Anaphylaxis
Epinephrine is the drug of choice for treating
allergic reactionanaphylaxis. The commonly used
epinephrine autoinjector delivers a 0.3 mg epinephrine injection (0.3 mL, 1:1000). It is indicated in the emergency treatment of allergic reactions, including anaphylaxis to stings, contrast agents, medicines, or people with a history of anaphylactic reactions to known triggers. A single dose is recommended for people who weigh 30 kg or more, repeated if necessary. A lower-strength product is available for children.[27][28][29][30]
Intramuscular injection can be complicated in that the depth of subcutaneous fat varies and may result in
subcutaneous injection, or may be injected intravenously in error, or the wrong strength used.[31] Intramuscular injection gives a faster and higher
pharmacokinetic profile compared to subcutaneous injection.[32]
Asthma
Epinephrine is also used as a
bronchodilator for
asthma if specific β2 agonists are unavailable or ineffective.[33]
When given by the subcutaneous or intramuscular routes for asthma, an appropriate dose is 0.3 to 0.5 mg.[34][35]
Because of the high intrinsic efficacy (receptor binding ability) of epinephrine, high drug concentrations cause adverse side effects when treating asthma. The value of using nebulized epinephrine in acute asthma is unclear.[36]
Croup
Racemic epinephrine has historically been used for the
treatment of croup.[37][38] Regular epinephrine, however, works equally well[fact or opinion?][medical citation needed].
Racemic adrenaline is a 1:1 mixture of the two
enantiomers of adrenaline.[39] The L-form is the active component.[39] Racemic adrenaline works by stimulating the alpha-adrenergic receptors in the airway, with resultant mucosal vasoconstriction and decreased subglottic edema, and by stimulating the β adrenergic receptors, with resultant relaxation of the bronchial smooth muscle.[38]
Bronchiolitis
There is a lack of consensus as to whether inhaled nebulized epinephrine is beneficial in the treatment of
bronchiolitis, with most guidelines recommending against its use.[40]
Local anesthetics
When epinephrine is mixed with local anesthetics, such as
bupivacaine or
lidocaine, and used for local anesthesia or intrathecal injection, it prolongs the numbing effect and motor block effect of the anesthetic by up to an hour.[41] Epinephrine is frequently combined with local anesthetic and can cause panic attacks.[42]
As a hormone, epinephrine acts on nearly all body tissues. Its actions vary by tissue type and tissue expression of
adrenergic receptors. For example, high epinephrine levels cause
smooth muscle relaxation in the airways but cause contraction of the smooth muscle that lines most
arterioles.[citation needed]
Epinephrine acts by binding to a variety of
adrenergic receptors. Epinephrine is a nonselective
agonist of all adrenergic receptors, including the major subtypes
α1,
α2,
β1,
β2, and
β3.[46] Epinephrine's binding to these receptors triggers several metabolic changes. Binding to α-adrenergic receptors inhibits
insulin secretion by the
pancreas, stimulates
glycogenolysis in the
liver and
muscle,[47] and stimulates
glycolysis and inhibits insulin-mediated
glycogenesis in muscle.[48][49] β adrenergic receptor binding triggers
glucagon secretion in the pancreas, increased
adrenocorticotropic hormone (ACTH) secretion by the
pituitary gland, and increased
lipolysis by
adipose tissue. Together, these effects increase
blood glucose and
fatty acids, providing substrates for energy production within cells throughout the body.[49] In the heart, the coronary arteries have a predominance of β2 receptors, which cause
vasodilation of the coronary arteries in the presence of epinephrine.[50]
Its actions increase peripheral resistance via
α1 receptor-dependent
vasoconstriction and increase
cardiac output via its binding to β1 receptors. The goal of reducing peripheral circulation is to increase coronary and cerebral perfusion pressures and therefore increase oxygen exchange at the cellular level.[51] While epinephrine does increase aortic, cerebral, and carotid circulation pressure, it lowers carotid blood flow and
end-tidal CO2 or ETCO2 levels. It appears that epinephrine may improve macrocirculation at the expense of the capillary beds where perfusion takes place.[52]
Extracts of the
adrenal gland were first obtained by Polish physiologist
Napoleon Cybulski in 1895. These extracts, which he called nadnerczyna, contained adrenaline and other catecholamines.[53] American ophthalmologist
William H. Bates discovered adrenaline's usage for eye surgeries prior to 20 April 1896.[54] Japanese chemist
Jōkichi Takamine and his assistant Keizo Uenaka independently discovered adrenaline in 1900.[55][56] In 1901, Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen.[57] Adrenaline was first synthesized in the laboratory by
Friedrich Stolz and
Henry Drysdale Dakin, independently, in 1904.[56]
Society and culture
Legal status
In June 2024, the
Committee for Medicinal Products for Human Use of the
European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Eurneffy, intended for emergency treatment of allergic reactions (anaphylaxis) due to insect stings or bites, foods, medicinal products and other allergens as well as idiopathic or exercise induced anaphylaxis.[58][59][60] The applicant for this medicinal product is ARS Pharmaceuticals IRL Limited.[58]
Brand names
Common brand names include Asthmanefrin, Micronefrin, Nephron, VapoNefrin, and Primatene Mist.
Delivery forms
Epinephrine is available in an
autoinjector delivery system.
A common concentration for epinephrine is 2.25% w/v epinephrine in solution, which contains 22.5 mg/mL, while a 1% solution is typically used for aerosolization.
Adults: 0.5–0.75 ml of a 2.25% solution in 2.0 ml normal saline.[64]
Pediatrics: 0.25–0.75 ml of a 2.25% solution in 2.0 ml normal saline.[64][65]
^El-Bahr SM, Kahlbacher H, Patzl M, Palme RG (May 2006). "Binding and clearance of radioactive adrenaline and noradrenaline in sheep blood". Veterinary Research Communications. 30 (4). Springer Science and Business Media LLC: 423–32.
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^Franksson G, Anggård E (13 March 2009). "The plasma protein binding of amphetamine, catecholamines and related compounds". Acta Pharmacologica et Toxicologica. 28 (3). Wiley: 209–14.
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10.1111/j.1600-0773.1970.tb00546.x.
PMID5468075.
^Peaston RT, Weinkove C (January 2004). "Measurement of catecholamines and their metabolites". Annals of Clinical Biochemistry. 41 (Pt 1). SAGE Publications: 17–38.
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^Hummel MD (2012).
"Emergency Medications". In Pollak AN (ed.). Nancy Caroline's Emergency Care in the Streets (7th ed.). Burlington: Jones & Bartlett Learning. p. 557.
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^Everard ML (February 2009). "Acute bronchiolitis and croup". Pediatric Clinics of North America. 56 (1): 119–33, x–xi.
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^Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. p. 157.
ISBN9780071481274. Epinephrine occurs in only a small number of central neurons, all located in the medulla. Epinephrine is involved in visceral functions, such as the control of respiration. It is also produced by the adrenal medulla.
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization.
hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^Koninckx M, Buysse C, de Hoog M (June 2013). "Management of status asthmaticus in children". Paediatric Respiratory Reviews. 14 (2): 78–85.
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10.1016/j.prrv.2013.03.003.
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^Soar, Perkins, et al (2010) European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in special circumstances: Electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution. Resuscitation. Oct. pp.1400–1433
^Fisher, Brown, Cooke (Eds) (2006) Joint Royal Colleges Ambulance Liaison Committee. UK Ambulance Clinical Practice Guidelines.
^Abroug F, Dachraoui F, Ouanes-Besbes L (March 2016). "Our paper 20 years later: the unfulfilled promises of nebulised adrenaline in acute severe asthma". Intensive Care Medicine. 42 (3): 429–31.
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abThomas LP, Friedland LR (January 1998). "The cost-effective use of nebulized racemic epinephrine in the treatment of croup". The American Journal of Emergency Medicine. 16 (1): 87–9.
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^Rahn R, Ball B (2001). Local Anesthesia in Dentistry: Articaine and Epinephrine for Dental Anesthesia (1 st ed.). Seefeld, Germany: 3M ESPE. p. 44.
ISBN978-3-00-008562-8.
^Markovchick V (2007). Critical Care Secrets (fourth ed.).
^Nazir S, Lohani S, Tachamo N, Ghimire S, Poudel DR, Donato A (February 2017). "Takotsubo cardiomyopathy associated with epinephrine use: A systematic review and meta-analysis". Int. J. Cardiol. 229: 67–70.
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abShen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 4.
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^Arnall DA, Marker JC, Conlee RK, Winder WW (June 1986). "Effect of infusing epinephrine on liver and muscle glycogenolysis during exercise in rats". The American Journal of Physiology. 250 (6 Pt 1): E641–9.
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ab"European Medicines Agency". Eurneffy EPAR. 27 June 2024. Retrieved 29 June 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^"Frequent Asked Questions". Armstrong Pharmaceuticals. Archived from
the original on 25 September 2011. Retrieved 22 September 2011. Primatene® Mist was launched in 1963. The Primatene® Mist brand has built a long-time heritage for over-the-counter relief of bronchial asthma.