Epinephrine (medication)

{{Short description|Hormone used as a medicine}} {{About|the medication|this substance as a naturally occurring hormone|Adrenaline}} {{Distinguish|ephedrone|ephedrine}} {{Use dmy dates|date=December 2024}} {{cs1 config|name-list-style=vanc|display-authors=6}} <section begin=Drugbox /> {{Infobox drug | drug_name = Epinephrine | image = Epinephrine.svg | image_class = skin-invert-image | width = 250 | alt = Skeletal formula of adrenaline | caption = Skeletal formula of adrenaline | image2 = Adrenaline-from-xtal-3D-bs-17.png | image_class2 = bg-transparent | width2 = 250 | caption2 = Ball-and-stick model of the zwitterionic form of adrenaline found in the crystal structure<ref>{{ cite journal | title = Structural Studies of Metabolic Products of Dopamine. III. Crystal and Molecular Structure of (−)-Adrenaline. | vauthors = Andersen AM | journal = Acta Chem. Scand. | volume = 29b | pages = 239–244 | year = 1975 | issue = 2 | doi = 10.3891/acta.chem.scand.29b-0239 | pmid = 1136652 | doi-access = free | title-link = doi }}</ref> | alt2 = Ball-and-stick model of epinephrine (adrenaline) molecule

| tradename = Epipen, Adrenaclick, others | Drugs.com = {{drugs.com|monograph|epinephrine}} | MedlinePlus = a603002 | DailyMedID = Epinephrine | pregnancy_AU = A | pregnancy_category = | class = Adrenergic receptor agonist; Sympathomimetic | routes_of_administration = Intravenous, intramuscular, endotracheal, intracardiac, intranasal, ophthalmic | ATC_prefix = A01 | ATC_suffix = AD01 | ATC_supplemental = {{ATC|B02|BC09}} {{ATC|C01|CA24}} {{ATC|R01|AA14}} {{ATC|R03|AA01}} {{ATC|S01|EA01}} | legal_AU = S4 | legal_UK = POM | legal_US = Rx-only | legal_US_comment = <ref name="Neffy FDA label">{{cite web | title=Neffy- epinephrine spray | website=DailyMed | date=20 August 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a1758142-a905-401d-8961-05829f51023a | access-date=5 September 2024}}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Eurneffy EPAR" /><ref name="Eurneffy PI">{{cite web | title=Eurneffy Product information | website=Union Register of medicinal products | date=23 August 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1846.htm | access-date=27 August 2024}}</ref> | legal_status =  | bioavailability = {{Ublist|Oral: negligible| Intravenous: {{circa}} 99%|Subcutaneous: high}} | metabolism = Adrenergic synapse (MAO and COMT) | onset = Rapid<ref name=AHFS2015/> | elimination_half-life = 2–3 minutes in plasma | duration_of_action = Few minutes<ref>{{cite book| vauthors = Hummel MD | veditors = Pollak AN |chapter=Emergency Medications|title=Nancy Caroline's Emergency Care in the Streets|date=2012|publisher=Jones & Bartlett Learning|location=Burlington|isbn=978-1-4496-4586-1|page=557|edition=7th|chapter-url=https://books.google.com/books?id=7uk0GJckmy0C&pg=PA557|url-status=live|archive-url= https://web.archive.org/web/20170908140647/https://books.google.com/books?id=7uk0GJckmy0C&pg=PA557|archive-date=8 September 2017}}</ref> | excretion = Urine

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 51-43-4 | PubChem = 5816 | IUPHAR_ligand = 479 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00668 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 5611 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = YKH834O4BH | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00095 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 28918 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 679 | PDB_ligand = ALE | synonyms = Epinephrine, adrenaline, adrenalin; 3,4,β-Trihydroxy-''N''-methylphenethylamine

| IUPAC_name = (''R'')-4-(1-Hydroxy-2-(methylamino)ethyl)benzene-1,2-diol | C = 9 | H = 13 | N = 1 | O = 3 | SMILES = CNC[C@H](O)c1ccc(O)c(O)c1 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C9H13NO3/c1-10-5-9(13)6-2-3-7(11)8(12)4-6/h2-4,9-13H,5H2,1H3/t9-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = UCTWMZQNUQWSLP-VIFPVBQESA-N | density = 1.283±0.06 | density_notes = @ 20 °C, 760 Torr | protein_bound = 15–20%<ref name="El-Bahr Kahlbacher Patzl Palme 2006 pp. 423–432">{{cite journal | vauthors = El-Bahr SM, Kahlbacher H, Patzl M, Palme RG | title = Binding and clearance of radioactive adrenaline and noradrenaline in sheep blood | journal = Veterinary Research Communications | volume = 30 | issue = 4 | pages = 423–32 | date = May 2006 | pmid = 16502110 | doi = 10.1007/s11259-006-3244-1 | publisher = Springer Science and Business Media LLC | s2cid = 9054777 }}</ref><ref name="Franksson Änggård pp. 209–214">{{cite journal | vauthors = Franksson G, Anggård E | title = The plasma protein binding of amphetamine, catecholamines and related compounds | journal = Acta Pharmacologica et Toxicologica | volume = 28 | issue = 3 | pages = 209–14 | date = March 2009 | pmid = 5468075 | doi = 10.1111/j.1600-0773.1970.tb00546.x | publisher = Wiley }}</ref> | metabolites = Metanephrine<ref name="Peaston Weinkove pp. 17–38">{{cite journal | vauthors = Peaston RT, Weinkove C | title = Measurement of catecholamines and their metabolites | journal = Annals of Clinical Biochemistry | volume = 41 | issue = Pt 1 | pages = 17–38 | date = January 2004 | pmid = 14713382 | doi = 10.1258/000456304322664663 | publisher = SAGE Publications | doi-access = free | title-link = doi | s2cid = 2330329 }}</ref> | receptors = Adrenergic receptors }}<section end="Drugbox" />

'''Epinephrine''', also known as '''adrenaline''', is a medication and hormone.<ref name=Chan2013>{{cite book | vauthors = Lieberman M, Marks A, Peet A | title = Marks' Basic Medical Biochemistry: A Clinical Approach | date = 2013 | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | isbn = 978-1-60831-572-7 | page = 175 | edition = 4 | url = https://books.google.com/books?id=3FNYdShrCwIC&pg=PA175 | url-status = live | archive-url = https://web.archive.org/web/20170908140647/https://books.google.com/books?id=3FNYdShrCwIC&pg=PA175 | archive-date = 8 September 2017 }}</ref><ref>{{cite web|url= http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479|title= (-)-adrenaline|website= Guide to Pharmacology|publisher= IUPS/BPS|access-date= 21 August 2015|url-status= live|archive-url= https://web.archive.org/web/20150901050002/http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479|archive-date= 1 September 2015}}</ref> As a medication, it is used to treat several conditions, including anaphylaxis, cardiac arrest, asthma, and superficial bleeding.<ref name=AHFS2015>{{cite web |title= Epinephrine|url=https://www.drugs.com/monograph/epinephrine.html |work=The American Society of Health-System Pharmacists|access-date=15 August 2015 |url-status=live |archive-url= https://web.archive.org/web/20150906030812/http://www.drugs.com/monograph/epinephrine.html|archive-date=6 September 2015 }}</ref> Inhaled epinephrine may be used to improve the symptoms of croup.<ref name=PedN09>{{cite journal | vauthors = Everard ML | title = Acute bronchiolitis and croup | journal = Pediatric Clinics of North America | volume = 56 | issue = 1 | pages = 119–33, x-xi | date = February 2009 | pmid = 19135584 | doi = 10.1016/j.pcl.2008.10.007 }}</ref> It may also be used for asthma when other treatments are not effective.<ref name=AHFS2015/> It is given intravenously, by injection into a muscle, by inhalation, or by injection just under the skin.<ref name=AHFS2015/>

Common side effects include shakiness, anxiety, and sweating.<ref name=AHFS2015/> A fast heart rate and high blood pressure may occur.<ref name=AHFS2015/> Occasionally, it may result in an abnormal heart rhythm.<ref name=AHFS2015/> While the safety of its use during pregnancy and breastfeeding is unclear, the benefits to the mother must be taken into account.<ref name=AHFS2015/>

Epinephrine is normally produced by both the adrenal glands and a small number of neurons in the brain, where it acts as a neurotransmitter.<ref name=Chan2013 /><ref name="NHM Epinephrine">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York, USA | isbn = 978-0-07-148127-4 | page = 157 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote = 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.}}</ref> It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output, pupil dilation, and blood sugar.<ref>{{cite book| vauthors = Bell DR |title=Medical physiology: principles for clinical medicine|date=2009|publisher=Lippincott Williams & Wilkins |location= Philadelphia |isbn=978-0-7817-6852-8 |page=312 |edition=3rd |url=https://books.google.com/books?id=tBeAeYS-vRUC&pg=PA312 |url-status=live |archive-url=https://web.archive.org/web/20170908140647/https://books.google.com/books?id=tBeAeYS-vRUC&pg=PA312|archive-date=8 September 2017}}</ref><ref name=Kh2008/> Epinephrine does this through its effects on alpha and beta receptors.<ref name=Kh2008>{{cite book|last1=Khurana|title=Essentials of Medical Physiology|date=2008|publisher=Elsevier India|isbn=978-81-312-1566-1|page=460|url=https://books.google.com/books?id=Cm_kLhU1AP0C&pg=PA460|url-status=live|archive-url=https://web.archive.org/web/20170908140647/https://books.google.com/books?id=Cm_kLhU1AP0C&pg=PA460|archive-date=8 September 2017}}</ref> It is found in many animals and some single-celled organisms,<ref>{{cite book| vauthors = Buckley E |title=Venomous Animals and Their Venoms: Venomous Vertebrates|date=2013|publisher=Elsevier|isbn=978-1-4832-6288-8|page=478|url=https://books.google.com/books?id=3SrLBAAAQBAJ&pg=PA478|url-status=live|archive-url=https://web.archive.org/web/20170908140647/https://books.google.com/books?id=3SrLBAAAQBAJ&pg=PA478|archive-date=8 September 2017}}</ref><ref>{{cite book|title=Animal Physiology: Adaptation and Environment|date=1997|publisher=Cambridge University Press|isbn=978-1-107-26850-0|page=510|edition=5|url=https://books.google.com/books?id=hcw2AAAAQBAJ&pg=PA510|url-status=live|archive-url=https://web.archive.org/web/20170908140647/https://books.google.com/books?id=hcw2AAAAQBAJ&pg=PA510|archive-date=8 September 2017}}</ref> but the medication is produced synthetically and is not harvested from animals.<ref>{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/Epinephrine|title=Epinephrine|access-date=19 April 2021|archive-date=26 January 2024|archive-url=https://web.archive.org/web/20240126092906/https://pubchem.ncbi.nlm.nih.gov/compound/Epinephrine|url-status=live}}</ref>

Jōkichi Takamine first isolated epinephrine in 1901, and it came into medical use in 1905.<ref>{{cite book| vauthors = Wermuth CG |title=The practice of medicinal chemistry|date=2008|publisher=Elsevier/Academic Press|location=Amsterdam|isbn=978-0-08-056877-5|page=13|edition=3|url=https://books.google.com/books?id=Qmt1_DQkCpEC&pg=PA13|url-status=live|archive-url=https://web.archive.org/web/20170908140647/https://books.google.com/books?id=Qmt1_DQkCpEC&pg=PA13|archive-date=8 September 2017}}</ref><ref name=Fis2006>{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=541 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA541 |language=en |access-date=29 August 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110003625/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA541 |url-status=live }}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available as a generic medication.<ref name=AHFS2015/> In 2023, it was the 247th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Epinephrine Drug Usage Statistics, United States, 2014 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Epinephrine | access-date = 20 August 2025 }}</ref>

== Etymology == The word ''epinephrine'' is formed from the Ancient Greek ''ἐπι-'' (''epi''-, "on") and ''νεφρός'' (''nephros'', "kidney") because the adrenal glands, where it is produced, are located just above the kidneys.<ref>{{cite journal | last1=Arthur | first1=Greer | date=May 2015 | title=Epinephrine: a short history | url=https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(15)00087-9/fulltext | journal=The Lancet Respiratory Medicine | volume=3 | issue=5 | pages=350–351 | doi=10.1016/S2213-2600(15)00087-9 | pmid=25969360 | access-date=9 October 2024}}</ref>

==Medical uses== thumb|Epinephrine vial 1 mg (Adrenalin).

Epinephrine is used to treat a number of conditions, including cardiac arrest, anaphylaxis, and superficial bleeding.<ref name=AHFS>{{cite web|title=Epinephrine|url=https://www.drugs.com/monograph/epinephrine.html|work=The American Society of Health-System Pharmacists|access-date=3 April 2011|url-status=live|archive-url=https://web.archive.org/web/20110307044247/http://www.drugs.com/monograph/epinephrine.html|archive-date=7 March 2011}}</ref> It has been used historically for bronchospasm and low blood sugar, but newer treatments for these that are selective for β2 adrenoceptors, such as salbutamol, are preferred.{{citation needed|date=February 2018}}

===Heart problems=== While epinephrine is often used to treat cardiac arrest, it has not been shown to improve long-term survival or mental function after recovery.<ref>{{cite journal | vauthors = Kempton H, Vlok R, Thang C, Melhuish T, White L | title = Standard dose epinephrine versus placebo in out of hospital cardiac arrest: A systematic review and meta-analysis | journal = The American Journal of Emergency Medicine | volume = 37 | issue = 3 | pages = 511–517 | date = March 2019 | pmid = 30658877 | doi = 10.1016/j.ajem.2018.12.055 | s2cid = 58580872 | hdl = 10072/416506 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Reardon PM, Magee K | title = Epinephrine in out-of-hospital cardiac arrest: A critical review | journal = World Journal of Emergency Medicine | volume = 4 | issue = 2 | pages = 85–91 | date = 2013 | pmid = 25215099 | pmc = 4129833 | doi = 10.5847/wjem.j.issn.1920-8642.2013.02.001 }}</ref><ref name=Lin2014>{{cite journal | vauthors = Lin S, Callaway CW, Shah PS, Wagner JD, Beyene J, Ziegler CP, Morrison LJ | title = Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials | journal = Resuscitation | volume = 85 | issue = 6 | pages = 732–40 | date = June 2014 | pmid = 24642404 | doi = 10.1016/j.resuscitation.2014.03.008 }}</ref> It does, however, improve return of spontaneous circulation.<ref name=Lin2014/><ref>{{cite journal | vauthors = Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, Paxton JH, Silvers SM, White RD, Yannopoulos D, Donnino MW | title = Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care | journal = Circulation | volume = 132 | issue = 18 Suppl 2 | pages = S444-64 | date = November 2015 | pmid = 26472995 | doi = 10.1161/CIR.0000000000000261 | doi-access = free | title-link = doi }}</ref>

===Anaphylaxis=== Epinephrine is the only life-saving treatment for anaphylaxis.<ref name="FDA PR 20240809" /> The commonly used epinephrine autoinjector delivers a 0.3 mg epinephrine injection (0.3 mL, 1:1000).{{cn|date=August 2024}} 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.{{cn|date=August 2024}} A lower-strength product is available for children.<ref>{{cite web|last=Mylan Specialty L.P.|title=Epipen- epinephrine injection, Epipen Jr- epinephrine injection |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019430s053lbl.pdf|publisher=FDA Product Label|access-date=22 January 2014|url-status=live|archive-url=https://web.archive.org/web/20140201150929/http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019430s053lbl.pdf|archive-date=1 February 2014}}</ref><ref>{{cite journal|last=ECC Committee, Subcommittees and Task Forces of the American Heart Association|title=2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 10.6: Anaphylaxis|journal=Circulation|year=2005|volume=112|issue=24 suppl|pages=IV–143–IV–145|doi=10.1161/circulationaha.105.166568| doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callaway CW, Kudenchuk PJ, Ornato JP, McNally B, Silvers SM, Passman RS, White RD, Hess EP, Tang W, Davis D, Sinz E, Morrison LJ | title = Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care | journal = Circulation | volume = 122 | issue = 18 Suppl 3 | pages = S729–67 | date = November 2010 | pmid = 20956224 | doi = 10.1161/CIRCULATIONAHA.110.970988 | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, Bernstein JA, Burks AW, Feldweg AM, Fink JN, Greenberger PA, Golden DB, James JM, Kemp SF, Ledford DK, Lieberman P, Sheffer AL, Bernstein DI, Blessing-Moore J, Cox L, Khan DA, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph C, Schuller DE, Spector SL, Tilles S, Wallace D | title = The diagnosis and management of anaphylaxis practice parameter: 2010 update | journal = The Journal of Allergy and Clinical Immunology | volume = 126 | issue = 3 | pages = 477–80.e1–42 | date = September 2010 | pmid = 20692689 | doi = 10.1016/j.jaci.2010.06.022 | doi-access = free | title-link = doi }}</ref>

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.<ref>{{cite web | title=Let's Stop this "Epi"demic!—Preventing Errors with Epinephrine | website=Pennsylvania Patient Safety Authority |url=https://patientsafety.pa.gov/ADVISORIES/Pages/200609_16.aspx | date=1 September 2006 | access-date=22 January 2014|url-status=live|archive-url=https://web.archive.org/web/20140202172416/http://patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2006/Sep3(3)/Pages/16.aspx|archive-date=2 February 2014}}</ref><ref>{{cite web | title=An Update on the "Epi"demic: Events Involving Epinephrine | website=Pennsylvania Patient Safety Authority | date=1 September 2009 | url=https://patientsafety.pa.gov/ADVISORIES/Pages/200909_102.aspx | access-date=9 August 2024}}</ref> Intramuscular injection gives a faster and higher pharmacokinetic profile compared to subcutaneous injection.<ref>{{cite journal | vauthors = McLean-Tooke AP, Bethune CA, Fay AC, Spickett GP | title = Adrenaline in the treatment of anaphylaxis: what is the evidence? | journal = BMJ | volume = 327 | issue = 7427 | pages = 1332–5 | date = December 2003 | pmid = 14656845 | pmc = 286326 | doi = 10.1136/bmj.327.7427.1332 }}</ref>

In August 2024, an epinephrine nasal spray (brand name Neffy) was approved in the United States for the emergency treatment of allergic reactions (type I), including those that are life-threatening (anaphylaxis), in people who weigh at least {{convert|30|kg|lb}}.<ref name="Neffy FDA label" /><ref name="FDA PR 20240809">{{cite press release | title=FDA Approves First Nasal Spray for Treatment of Anaphylaxis | website=U.S. Food and Drug Administration (FDA) | date=9 August 2024 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-nasal-spray-treatment-anaphylaxis | access-date=10 August 2024}} {{PD-notice}}</ref><ref>{{cite press release | title=ARS Pharmaceuticals Receives FDA Approval of Neffy (epinephrine nasal spray), the First and Only Needle-Free Treatment for Type I Allergic Reactions, Including Anaphylaxis | publisher=ARS Pharmaceuticals | via=GlobeNewswire | date=9 August 2024 | url=https://www.globenewswire.com/en/news-release/2024/08/09/2927866/0/en/ARS-Pharmaceuticals-Receives-FDA-Approval-of-neffy-epinephrine-nasal-spray-the-First-and-Only-Needle-Free-Treatment-for-Type-I-Allergic-Reactions-Including-Anaphylaxis.html | access-date=10 August 2024}}</ref> It is the first nasal spray for the treatment of anaphylaxis approved by the US Food and Drug Administration (FDA).<ref name="FDA PR 20240809" /> In March 2025, the FDA expanded the indication of Neffy to include children aged four years of age and older who weigh {{convert|15|to|30|kg|lb}}.<ref name="FDA PR 20250307">{{cite web | title=FDA Roundup: March 7, 2025 | website=U.S. Food and Drug Administration | date=7 March 2025 | url=https://www.fda.gov/news-events/press-announcements/fda-roundup-march-7-2025 | access-date=7 March 2025}} {{PD-notice}}</ref>

The approval of epinephrine nasal spray is based on four studies in 175 healthy adults, without anaphylaxis, that measured the epinephrine concentrations in the blood following administration of epinephrine nasal spray or approved epinephrine injection products.<ref name="FDA PR 20240809" /> Results from these studies showed comparable epinephrine blood concentrations between epinephrine nasal spray and approved epinephrine injection products.<ref name="FDA PR 20240809" /> Epinephrine nasal spray also demonstrated similar increases in blood pressure and heart rate as epinephrine injection products, two critical effects of epinephrine in the treatment of anaphylaxis.<ref name="FDA PR 20240809" /> A study of epinephrine nasal spray in children weighing more than 66 pounds showed that epinephrine concentrations in children were similar to adults who received epinephrine nasal spray.<ref name="FDA PR 20240809" />

The most common side effects of epinephrine nasal spray include throat irritation, tingling nose (intranasal paresthesia), headache, nasal discomfort, feeling jittery, tingling sensation (paresthesia), fatigue, tremor, runny nose (rhinorrhea), itchiness inside the nose (nasal pruritus), sneezing, abdominal pain, gum (gingival) pain, numbness in the mouth (hypoesthesia oral), nasal congestion, dizziness, nausea and vomiting.<ref name="FDA PR 20240809" /> The FDA granted the application of epinephrine nasal spray fast track designation and granted the approval of Neffy to ARS Pharmaceuticals.<ref name="FDA PR 20240809" />

===Asthma=== Epinephrine is also used as a bronchodilator for asthma if specific β2 agonists are unavailable or ineffective.<ref name="Koninckx2013">{{cite journal | vauthors = Koninckx M, Buysse C, de Hoog M | title = Management of status asthmaticus in children | journal = Paediatric Respiratory Reviews | volume = 14 | issue = 2 | pages = 78–85 | date = June 2013 | pmid = 23578933 | doi = 10.1016/j.prrv.2013.03.003 }}</ref>

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.<ref>{{cite journal | vauthors = Abroug F, Dachraoui F, Ouanes-Besbes L | title = Our paper 20 years later: the unfulfilled promises of nebulised adrenaline in acute severe asthma | journal = Intensive Care Medicine | volume = 42 | issue = 3 | pages = 429–31 | date = March 2016 | pmid = 26825950 | doi = 10.1007/s00134-016-4210-1 | s2cid = 37328426 }}</ref>

===Croup=== Racemic epinephrine has been used for the treatment of croup.<ref>{{cite journal | vauthors = Bjornson CL, Johnson DW | title = Croup | journal = Lancet | volume = 371 | issue = 9609 | pages = 329–39 | date = January 2008 | pmid = 18295000 | doi = 10.1016/S0140-6736(08)60170-1 | pmc = 7138055 }}</ref><ref name="Thomas">{{cite journal | vauthors = Thomas LP, Friedland LR | title = The cost-effective use of nebulized racemic epinephrine in the treatment of croup | journal = The American Journal of Emergency Medicine | volume = 16 | issue = 1 | pages = 87–9 | date = January 1998 | pmid = 9451322 | doi = 10.1016/S0735-6757(98)90073-0 }}</ref> Racemic adrenaline is a 1:1 mixture of the two enantiomers of adrenaline.<ref name="Malhotra">{{cite journal | vauthors = Malhotra A, Krilov LR | title = Viral croup | journal = Pediatrics in Review | volume = 22 | issue = 1 | pages = 5–12 | date = January 2001 | pmid = 11139641 | doi = 10.1542/pir.22-1-5 | s2cid = 41978318 }}</ref> The L-form is the active component.<ref name="Malhotra"/> 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.<ref name="Thomas"/>

===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.<ref>{{cite journal |vauthors=Kirolos A, Manti S, Blacow R, Tse G, Wilson T, Lister M, Cunningham S, Campbell A, Nair H, Reeves RM, Fernandes RM, Campbell H |title=A Systematic Review of Clinical Practice Guidelines for the Diagnosis and Management of Bronchiolitis |journal=J. Infect. Dis. |volume= 222|issue= Supplement_7|pages= S672–S679|date=August 2019 |pmid=31541233 |doi=10.1093/infdis/jiz240 | doi-access = free | title-link = doi |hdl=20.500.11820/7d4708e3-7cdc-49f7-a9b3-a29040f4ff4e |hdl-access=free }}</ref>

===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.<ref>{{cite journal |vauthors=Tschopp C, Tramèr MR, Schneider A, Zaarour M, Elia N |title=Benefit and Harm of Adding Epinephrine to a Local Anesthetic for Neuraxial and Locoregional Anesthesia: A Meta-analysis of Randomized Controlled Trials With Trial Sequential Analyses |journal=Anesth. Analg. |volume=127 |issue=1 |pages=228–239 |date=July 2018 |pmid=29782398 |doi=10.1213/ANE.0000000000003417 |s2cid=29154283 |url=https://www.zora.uzh.ch/id/eprint/159005/1/Benefit_and_Harm_of_Adding_Epinephrine_to_a_Local.39.pdf |access-date=10 December 2019 |archive-date=22 February 2020 |archive-url=https://web.archive.org/web/20200222072319/https://www.zora.uzh.ch/id/eprint/159005/1/Benefit_and_Harm_of_Adding_Epinephrine_to_a_Local.39.pdf |url-status=live }}</ref> Epinephrine is frequently combined with local anesthetic and can cause panic attacks.<ref>{{cite book | vauthors = Rahn R, Ball B | title = Local Anesthesia in Dentistry: Articaine and Epinephrine for Dental Anesthesia | date = 2001 | publisher = 3M ESPE | location = Seefeld, Germany | isbn = 978-3-00-008562-8 | page = 44 | edition = 1 st }}</ref>

Epinephrine is mixed with cocaine to form Moffett's solution, used in nasal surgery.<ref>{{cite journal | vauthors = Benjamin E, Wong DK, Choa D | title = 'Moffett's' solution: a review of the evidence and scientific basis for the topical preparation of the nose | journal = Clinical Otolaryngology and Allied Sciences | volume = 29 | issue = 6 | pages = 582–7 | date = December 2004 | pmid = 15533141 | doi = 10.1111/j.1365-2273.2004.00894.x | doi-access = free | title-link = doi }}</ref>

=== Upper airway obstruction === Upper airway obstruction with edema and stridor can be treated with racemic epinephrine.<ref>{{cite book | vauthors = Markovchick V |title=Critical Care Secrets |year=2007 |edition=fourth}}</ref>

==Adverse effects==

Adverse reactions to adrenaline include palpitations, tachycardia, arrhythmia, anxiety, panic attack, headache, anorexia, tremor, hypertension, and acute pulmonary edema.{{medcn|date=August 2024}} The use of epinephrine based eye-drops, commonly used to treat glaucoma, may also lead to a buildup of adrenochrome pigments in the conjunctiva, iris, lens, and retina.{{medcn|date=August 2024}}

Rarely, exposure to medically administered epinephrine may cause Takotsubo cardiomyopathy.<ref>{{cite journal |vauthors=Nazir S, Lohani S, Tachamo N, Ghimire S, Poudel DR, Donato A |title=Takotsubo cardiomyopathy associated with epinephrine use: A systematic review and meta-analysis |journal=Int. J. Cardiol. |volume=229 |pages=67–70 |date=February 2017 |pmid=27889211 |doi=10.1016/j.ijcard.2016.11.266 }}</ref>

Use is contraindicated in people on nonselective β-blockers because severe hypertension and even cerebral hemorrhage may result.<ref name="pharmnemonics" />

==Mechanism of action== {{See also|Adrenergic receptor}} {| class="wikitable" style="float:right; margin:1em" |+ {{nowrap|Physiologic responses by organ}} |- ! Organ ! Effects |- | Heart | Increases heart rate; contractility; conduction across AV node |- | Lungs | Increases respiratory rate; bronchodilation |- | Liver | Stimulates glycogenolysis |- | Brain | |- | Rowspan=3| Systemic | Vasoconstriction and vasodilation |- | Triggers lipolysis |- | Muscle contraction |}

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.<ref name="pharmnemonics">{{cite book | vauthors = Shen H | title=Illustrated Pharmacology Memory Cards: PharMnemonics | year=2008 | publisher=Minireview | isbn=978-1-59541-101-3 | page=4}}</ref> 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,<ref>{{cite journal | vauthors = Arnall DA, Marker JC, Conlee RK, Winder WW | title = Effect of infusing epinephrine on liver and muscle glycogenolysis during exercise in rats | journal = The American Journal of Physiology | volume = 250 | issue = 6 Pt 1 | pages = E641–9 | date = June 1986 | pmid = 3521311 | doi = 10.1152/ajpendo.1986.250.6.E641 }}</ref> and stimulates glycolysis and inhibits insulin-mediated glycogenesis in muscle.<ref name="pmid1900669">{{cite journal | vauthors = Raz I, Katz A, Spencer MK | title = Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle | journal = The American Journal of Physiology | volume = 260 | issue = 3 Pt 1 | pages = E430–5 | date = March 1991 | pmid = 1900669 | doi = 10.1152/ajpendo.1991.260.3.E430 }}</ref><ref name="sabyasachi">{{cite book | vauthors = Sircar S |title=Medical Physiology |publisher=Thieme Publishing Group |year=2007 |page=536 |isbn=978-3-13-144061-7 }}</ref> 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.<ref name="sabyasachi" /> In the heart, the coronary arteries have a predominance of β2 receptors, which cause vasodilation of the coronary arteries in the presence of epinephrine.<ref name="EpiCoronaryB2">{{cite journal | vauthors = Sun D, Huang A, Mital S, Kichuk MR, Marboe CC, Addonizio LJ, Michler RE, Koller A, Hintze TH, Kaley G | title = Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles | journal = Circulation | volume = 106 | issue = 5 | pages = 550–5 | date = July 2002 | pmid = 12147535 | doi = 10.1161/01.CIR.0000023896.70583.9F | doi-access = free | title-link = doi }}</ref>

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.<ref name="Australian Resuscitation Council Guideline 11.5 - Drugs in Cardiac Arrest">{{cite web|title=Guideline 11.5: Medications in Adult Cardiac Arrest|url=http://resus.org.au/?wpfb_dl=55|format=PDF|work=Australian Resuscitation Council|date=December 2010|access-date=7 March 2015|url-status=live|archive-url=https://web.archive.org/web/20150312105855/http://resus.org.au/?wpfb_dl=55|archive-date=12 March 2015}}</ref> 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.<ref>{{cite journal | vauthors = Burnett AM, Segal N, Salzman JG, McKnite MS, Frascone RJ | title = Potential negative effects of epinephrine on carotid blood flow and ETCO2 during active compression-decompression CPR utilizing an impedance threshold device | journal = Resuscitation | volume = 83 | issue = 8 | pages = 1021–4 | date = August 2012 | pmid = 22445865 | doi = 10.1016/j.resuscitation.2012.03.018 }}</ref>

== Chemistry == Epinephrine, or adrenaline, also known as 3,4,β-trihydroxy-''N''-methylphenethylamine, is a substituted phenethylamine and catecholamine. It is the ''N''-methylated analogue of norepinephrine (noradrenaline; 3,4,β-trihydroxyphenethylamine) and the ''N''-methylated and β-hydroxylated analogue of dopamine (3,4-dihydroxyphenethylamine).

== History == {{Main|History of catecholamine research}}

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.<ref>{{cite journal | vauthors = Skalski JH, Kuch J | title = Polish thread in the history of circulatory physiology | journal = Journal of Physiology and Pharmacology | volume = 57 | issue = Suppl 1 | pages = 5–41 | date = April 2006 | pmid = 16766800 | url = https://www.jpp.krakow.pl/journal/archive/04_06_s1/articles/01_article.html | url-status = live | archive-url = https://web.archive.org/web/20110310020926/http://www.jpp.krakow.pl/journal/archive/04_06_s1/articles/01_article.html | archive-date = 10 March 2011 }}</ref> American ophthalmologist William H. Bates discovered adrenaline's usage for eye surgeries prior to 20 April 1896.<ref>{{cite journal | vauthors = Bates WH |title=The Use of Extract of Suprarenal Capsule in the Eye |journal=New York Medical Journal |date=May 1896 |pages=647–650 |url=http://www.central-fixation.com/bates-medical-articles/use-of-extract-of-suprarenal-capsule.php |access-date=16 March 2015 |url-status=live |archive-url=https://web.archive.org/web/20150403062831/http://www.central-fixation.com/bates-medical-articles/use-of-extract-of-suprarenal-capsule.php |archive-date=3 April 2015 }}</ref> Japanese chemist Jōkichi Takamine and his assistant Keizo Uenaka independently discovered adrenaline in 1900.<ref>{{cite journal | vauthors = Yamashima T | title = Jokichi Takamine (1854-1922), the samurai chemist, and his work on adrenalin | journal = Journal of Medical Biography | volume = 11 | issue = 2 | pages = 95–102 | date = May 2003 | pmid = 12717538 | doi = 10.1177/096777200301100211 | s2cid = 32540165 }}</ref><ref name="pmid10454061">{{cite journal | vauthors = Bennett MR | title = One hundred years of adrenaline: the discovery of autoreceptors | journal = Clinical Autonomic Research | volume = 9 | issue = 3 | pages = 145–59 | date = June 1999 | pmid = 10454061 | doi = 10.1007/BF02281628 | s2cid = 20999106 }}</ref> In 1901, Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen.<ref>{{cite journal | vauthors=Takamine J | title=Proceedings of the Physiological Society: December 14, 1901 | journal=The Journal of Physiology | date=December 1902 | volume=27 | issue=suppl | issn=0022-3751 | doi=10.1113/jphysiol.1902.sp000893 | doi-access=free | title-link=doi | pages=i.2–viii.2 | pmid=16991344 | url=https://books.google.com/books?id=xVEq06Ym6qcC&pg=RA1-PR29 | access-date=29 August 2020 | archive-date=14 January 2023 | archive-url=https://web.archive.org/web/20230114103741/https://books.google.com/books?id=xVEq06Ym6qcC&pg=RA1-PR29 | url-status=live | url-access=subscription | pmc=1484989 }}</ref> Adrenaline was first synthesized in the laboratory by Friedrich Stolz and Henry Drysdale Dakin, independently, in 1904.<ref name="pmid10454061"/>

==Society and culture==

===Names=== ===Brand names=== ''Epinephrine'' is the generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}} and {{Abbrlink|USAN|United States Adopted Name}}, while ''adrenaline'' is its {{Abbrlink|BAN|British Approved Name}}.<ref name="Elks2014">{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA16 | access-date=31 August 2024 | page=16}}</ref><ref name="IndexNominum2004">{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum: International Drug Directory | publisher=Medpharm Scientific Publishers | year=2004 | isbn=978-3-88763-101-7 | url=https://books.google.com/books?id=EgeuA47Ocm4C&pg=PA451 | access-date=31 August 2024 | page=451}}</ref><ref name="MortonHall2012">{{cite book | vauthors = Morton IK, Hall JM | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=2012 | isbn=978-94-011-4439-1 | url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA6 | access-date=31 August 2024 | page=6}}</ref> Epinephrine is sold under various brand names including Asthmanefrin, Micronefrin, Neffy, Nephron, VapoNefrin, and Primatene Mist, among others.<ref name="IndexNominum2004" />

===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.<ref name="Eurneffy EPAR" /><ref>{{cite press release | title=First nasal adrenaline spray for emergency treatment against allergic reactions | website=European Medicines Agency | date=28 June 2024 | url=https://www.ema.europa.eu/en/news/first-nasal-adrenaline-spray-emergency-treatment-against-allergic-reactions | access-date=29 June 2024 | archive-date=29 June 2024 | archive-url=https://web.archive.org/web/20240629061650/https://www.ema.europa.eu/en/news/first-nasal-adrenaline-spray-emergency-treatment-against-allergic-reactions | url-status=live }}</ref><ref>{{cite web | title=Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 June 2024 | website=European Medicines Agency | date=28 June 2024 | url=https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-24-27-june-2024 | access-date=12 July 2024 | archive-date=12 July 2024 | archive-url=https://web.archive.org/web/20240712152232/https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-24-27-june-2024 | url-status=live }}</ref> The applicant for this medicinal product is ARS Pharmaceuticals IRL Limited.<ref name="Eurneffy EPAR">{{cite web | title=European Medicines Agency | website=Eurneffy EPAR | date=27 June 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/eurneffy | access-date=29 June 2024 | archive-date=29 June 2024 | archive-url=https://web.archive.org/web/20240629061650/https://www.ema.europa.eu/en/medicines/human/EPAR/eurneffy | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Eurneffy was authorized for medical use in the European Union in August 2024.<ref name="Eurneffy EPAR" /><ref name="Eurneffy PI" />

===Delivery forms=== Epinephrine is available in an autoinjector delivery system and a nasal spray.

There is an epinephrine metered-dose inhaler sold over the counter in the United States to relieve bronchial asthma.<ref>{{cite web | title=Primatene Mist- epinephrine inhalation aerosol | website=DailyMed | date=5 June 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=95011f7e-51be-4851-80a6-a7e9c6cad82a | access-date=10 August 2024}}</ref><ref>{{cite web | url = https://www.fda.gov/news-events/press-announcements/fda-statement-approval-otc-primatene-mist-treat-mild-asthma | archive-url = https://web.archive.org/web/20191214051955/https://www.fda.gov/news-events/press-announcements/fda-statement-approval-otc-primatene-mist-treat-mild-asthma | archive-date = 14 December 2019 | title = FDA statement on approval of OTC Primatene Mist to treat mild asthma | date = 8 November 2018 | publisher = U.S. Food and Drug Administration (FDA) }}</ref> It was introduced in 1963 by Armstrong Pharmaceuticals.<ref name="mistfaq">{{cite web| url= http://www.primatene.com/faq/answers.asp| title= Frequent Asked Questions| publisher= Armstrong Pharmaceuticals| access-date= 22 September 2011 | archive-url= https://web.archive.org/web/20110925172056/http://www.primatene.com/faq/answers.asp| archive-date= 25 September 2011}}</ref>

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.<ref name="pmid17626698">{{cite journal | vauthors = Wiebe K, Rowe BH | title = Nebulized racemic epinephrine used in the treatment of severe asthmatic exacerbation: a case report and literature review | journal = Canadian Journal of Emergency Medicine | volume = 9 | issue = 4 | pages = 304–8 | date = July 2007 | pmid = 17626698 | doi = 10.1017/s1481803500015220| doi-access = free | title-link = doi }}</ref><ref name="pmid11869578">{{cite journal | vauthors = Davies MW, Davis PG | title = Nebulized racemic epinephrine for extubation of newborn infants | journal = The Cochrane Database of Systematic Reviews | issue = 1 | article-number = CD000506 | year = 2002 | pmid = 11869578 | pmc =7038644 | doi = 10.1002/14651858.CD000506 }}</ref>

==References== {{Reflist}}

{{Antiglaucoma preparations and miotics}} {{Adrenergic receptor modulators}} {{Portal bar | Medicine}} {{Authority control}}

Category:Alpha-adrenergic agonists Category:Antihypotensive agents Category:Beta-adrenergic agonists Category:Cardiac stimulants Category:Catecholamines Category:Chemical substances for emergency medicine Category:Ophthalmology drugs Category:Over-the-counter drugs in the United States Category:Peripherally selective drugs Category:Respiratory therapy Category:Sympathomimetics Category:Vasoconstrictors Category:World Anti-Doping Agency prohibited substances Category:World Health Organization essential medicines Category:Wikipedia medicine articles ready to translate Category:Triols