Epinephrine (medication)

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Epinephrine
Epinephrine.svg
Skeletal formula of adrenaline
Adrenaline-from-xtal-3D-bs-17.png
Ball-and-stick model of the zwitterionic form of adrenaline found in the crystal structure [1]
Clinical data
Trade names Epipen, Adrenaclick, others
Other namesEpinephrine, adrenaline, adrenalin; 3,4,β-Trihydroxy-N-methylphenethylamine
AHFS/Drugs.com Monograph
MedlinePlus a603002
License data
Pregnancy
category
  • AU:A
Routes of
administration 		Intravenous, intramuscular, endotracheal, intracardiac, nasal, eye drop
Drug class Adrenergic receptor agonist; Sympathomimetic
ATC code
Physiological data
Receptors Adrenergic receptors
Metabolism Adrenergic synapse (MAO and COMT)
Legal status
Legal status
Pharmacokinetic data
Bioavailability
  • Oral: negligible
  • Intravenous: c. 99%
  • Subcutaneous: high
Protein binding 15–20% [5] [6]
Metabolism Adrenergic synapse (MAO and COMT)
Metabolites Metanephrine [7]
Onset of action Rapid [8]
Elimination half-life 2–3 minutes in plasma
Duration of action Few minutes [9]
Excretion Urine
Identifiers
  • (R)-4-(1-Hydroxy-2-(methylamino)ethyl)benzene-1,2-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
Chemical and physical data
Formula C9H13NO3
Molar mass 183.207 g·mol−1
3D model (JSmol)
Density 1.283±0.06 g/cm3 @ 20 °C, 760 Torr
  • CNC[C@H](O)c1ccc(O)c(O)c1
  • InChI=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 Yes check.svgY
  • Key:UCTWMZQNUQWSLP-VIFPVBQESA-N Yes check.svgY

Epinephrine, also known as adrenaline, is a medication and hormone. [10] [11] As a medication, it is used to treat several conditions, including anaphylaxis, cardiac arrest, asthma, and superficial bleeding. [8] Inhaled epinephrine may be used to improve the symptoms of croup. [12] It may also be used for asthma when other treatments are not effective. [8] It is given intravenously, by injection into a muscle, by inhalation, or by injection just under the skin. [8]

Contents

Common side effects include shakiness, anxiety, and sweating. [8] A fast heart rate and high blood pressure may occur. [8] Occasionally, it may result in an abnormal heart rhythm. [8] While the safety of its use during pregnancy and breastfeeding is unclear, the benefits to the mother must be taken into account. [8]

Epinephrine is normally produced by both the adrenal glands and a small number of neurons in the brain, where it acts as a neurotransmitter. [10] [13] It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output, pupil dilation, and blood sugar. [14] [15] Epinephrine does this through its effects on alpha and beta receptors. [15] It is found in many animals and some single-celled organisms, [16] [17] but the medication is produced synthetically and is not harvested from animals. [18]

Jōkichi Takamine first isolated epinephrine in 1901, and it came into medical use in 1905. [19] [20] It is on the World Health Organization's List of Essential Medicines. [21] It is available as a generic medication. [8] In 2022, it was the 240th most commonly prescribed medication in the United States, with more than 1 million prescriptions. [22] [23]

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. [24]

Medical uses

Epinephrine vial 1 mg (Adrenalin). Epinephrine-ampule.JPG
Epinephrine vial 1 mg (Adrenalin).

Epinephrine is used to treat a number of conditions, including cardiac arrest, anaphylaxis, and superficial bleeding. [25] 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 ]

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. [26] [27] [28] It does, however, improve return of spontaneous circulation. [28] [29]

Anaphylaxis

Epinephrine is the only life-saving treatment for anaphylaxis. [30] The commonly used epinephrine autoinjector delivers a 0.3 mg epinephrine injection (0.3 mL, 1:1000).[ citation needed ] 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.[ citation needed ] A lower-strength product is available for children. [31] [32] [33] [34]

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. [35] [36] Intramuscular injection gives a faster and higher pharmacokinetic profile compared to subcutaneous injection. [37]

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 30 kilograms (66 lb). [2] [30] [38] It is the first nasal spray for the treatment of anaphylaxis approved by the US Food and Drug Administration (FDA). [30]

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. [30] Results from these studies showed comparable epinephrine blood concentrations between epinephrine nasal spray and approved epinephrine injection products. [30] 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. [30] 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. [30]

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. [30] The FDA granted the application of epinephrine nasal spray fast track designation and granted the approval of Neffy to ARS Pharmaceuticals. [30]

Asthma

Epinephrine is also used as a bronchodilator for asthma if specific β2 agonists are unavailable or ineffective. [39]

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. [40]

Croup

Racemic epinephrine has been used for the treatment of croup. [41] [42] Racemic adrenaline is a 1:1 mixture of the two enantiomers of adrenaline. [43] The L-form is the active component. [43] 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. [42]

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. [44]

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. [45] Epinephrine is frequently combined with local anesthetic and can cause panic attacks. [46]

Epinephrine is mixed with cocaine to form Moffett's solution, used in nasal surgery. [47]

Upper airway obstruction

Upper airway obstruction with edema and stridor can be treated with racemic epinephrine. [48]

Adverse effects

Adverse reactions to adrenaline include palpitations, tachycardia, arrhythmia, anxiety, panic attack, headache, anorexia, tremor, hypertension, and acute pulmonary edema.[ medical citation needed ] 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.[ medical citation needed ]

Rarely, exposure to medically administered epinephrine may cause Takotsubo cardiomyopathy. [49]

Use is contraindicated in people on nonselective β-blockers because severe hypertension and even cerebral hemorrhage may result. [50]

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. [30] The FDA granted the application of epinephrine nasal spray fast track designation and granted the approval of Neffy to ARS Pharmaceuticals. [30]

Mechanism of action

Physiologic responses by organ
OrganEffects
Heart Increases heart rate; contractility; conduction across AV node
Lungs Increases respiratory rate; bronchodilation
Liver Stimulates glycogenolysis
Brain
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. [50] 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, [51] and stimulates glycolysis and inhibits insulin-mediated glycogenesis in muscle. [52] [53] 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. [53] In the heart, the coronary arteries have a predominance of β2 receptors, which cause vasodilation of the coronary arteries in the presence of epinephrine. [54]

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. [55] 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. [56]

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

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. [57] American ophthalmologist William H. Bates discovered adrenaline's usage for eye surgeries prior to 20 April 1896. [58] Japanese chemist Jōkichi Takamine and his assistant Keizo Uenaka independently discovered adrenaline in 1900. [59] [60] In 1901, Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen. [61] Adrenaline was first synthesized in the laboratory by Friedrich Stolz and Henry Drysdale Dakin, independently, in 1904. [60]

Society and culture

Names

Brand names

Epinephrine is the generic name of the drug and its INN Tooltip International Nonproprietary Name and USAN Tooltip United States Adopted Name, while adrenaline is its BAN Tooltip British Approved Name. [62] [63] [64] Epinephrine is sold under various brand names including Asthmanefrin, Micronefrin, Neffy, Nephron, VapoNefrin, and Primatene Mist, among others. [63]

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. [3] [65] [66] The applicant for this medicinal product is ARS Pharmaceuticals IRL Limited. [3] Eurneffy was approved for medical use in the European Union in August 2024. [3] [4]

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. [67] [68] It was introduced in 1963 by Armstrong Pharmaceuticals. [69]

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. [70] [71]

Related Research Articles

Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typically causes more than one of the following: an itchy rash, throat closing due to swelling that can obstruct or stop breathing; severe tongue swelling that can also interfere with or stop breathing; shortness of breath, vomiting, lightheadedness, loss of consciousness, low blood pressure, and medical shock. These symptoms typically start in minutes to hours and then increase very rapidly to life-threatening levels. Urgent medical treatment is required to prevent serious harm and death, even if the patient has used an epipen or has taken other medications in response, and even if symptoms appear to be improving.

<span class="mw-page-title-main">Naloxone</span> Opioid receptor antagonist

Naloxone, sold under the brand name Narcan among others, is an opioid antagonist, a medication used to reverse or reduce the effects of opioids. For example, it is used to restore breathing after an opioid overdose. Effects begin within two minutes when given intravenously, five minutes when injected into a muscle, and ten minutes as a nasal spray. Naloxone blocks the effects of opioids for 30 to 90 minutes.

<span class="mw-page-title-main">Ephedrine</span> Medication and stimulant

Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection, it lasts about an hour, and when taken by mouth, it can last up to four hours.

<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) antagonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.

<span class="mw-page-title-main">Xylometazoline</span> Nasal decongestant

Xylometazoline, also spelled xylomethazoline, is a medication used to reduce symptoms of nasal congestion, allergic rhinitis, and sinusitis. It is used directly in the nose as a spray or drops.

An epinephrine autoinjector is a medical device for injecting a measured dose or doses of epinephrine (adrenaline) by means of autoinjector technology. It is most often used for the treatment of anaphylaxis. The first epinephrine autoinjector was brought to market in 1983.

A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine. Intranasal corticosteroids can also be used as decongestants and antihistamines can be used to alleviate runny nose, nasal itch, and sneezing.

<span class="mw-page-title-main">Ipratropium bromide</span> Type of anticholinergic

Ipratropium bromide, sold under the brand name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.

<span class="mw-page-title-main">Type I hypersensitivity</span> Type of allergic reaction

Type I hypersensitivity, in the Gell and Coombs classification of allergic reactions, is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. Type I is distinct from type II, type III and type IV hypersensitivities. The relevance of the Gell and Coombs classification of allergic reactions has been questioned in the modern-day understanding of allergy, and it has limited utility in clinical practice.

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

Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among others, is a medication used as a decongestant for uncomplicated nasal congestion in the form of a nasal spray or oral tablet, to dilate the pupil, to increase blood pressure given intravenously in cases of low blood pressure, and to relieve hemorrhoids as a suppository. It can also be applied to the skin.

Beta<sub>2</sub>-adrenergic agonist Compounds that bind to and activate adrenergic beta-2 receptors

Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.

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

Aminophylline is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate.

<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">Dihydroergotamine</span> Chemical used to treat migraines

Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an ergot alkaloid used to treat migraines. It is a derivative of ergotamine. It is administered as a nasal spray or injection and has an efficacy similar to that of sumatriptan. Nausea is a common side effect.

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

Levosalbutamol, also known as levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence is inconclusive regarding the efficacy of levosalbutamol versus salbutamol or salbutamol-levosalbutamol combinations, though levosalbutamol is believed to have a better safety profile due to its more selective binding to β2 receptors versus β1.

<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">Beta-adrenergic agonist</span> Medications that relax muscles of the airways

Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. They are a class of sympathomimetic agents, each acting upon the beta adrenoceptors. In general, pure beta-adrenergic agonists have the opposite function of beta blockers: beta-adrenoreceptor agonist ligands mimic the actions of both epinephrine- and norepinephrine- signaling, in the heart and lungs, and in smooth muscle tissue; epinephrine expresses the higher affinity. The activation of β1, β2 and β3 activates the enzyme, adenylate cyclase. This, in turn, leads to the activation of the secondary messenger cyclic adenosine monophosphate (cAMP); cAMP then activates protein kinase A (PKA) which phosphorylates target proteins, ultimately inducing smooth muscle relaxation and contraction of the cardiac tissue.

<span class="mw-page-title-main">Glucagon (medication)</span> Medication that increases blood sugar levels

Glucagon, sold under the brand name Baqsimi among others, is a medication and hormone. As a medication it is used to treat low blood sugar, beta blocker overdose, calcium channel blocker overdose, and those with anaphylaxis who do not improve with epinephrine. It is given by injection into a vein, muscle, or under the skin. A version given in the nose is also available.

<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.

Anti-allergic agents are medications used to treat allergic reactions. Anti-allergic agents have existed since 3000 B.C in countries such as China and Egypt. It was not until 1933 when antihistamines, the first type of anti-allergic agents, were developed. Common allergic diseases include allergic rhinitis, allergic asthma and atopic dermatitis with varying symptoms, including runny nose, watery eyes, itchiness, coughing, and shortness of breath. More than one-third of the world's population is currently being affected by one or more allergic conditions.

References

  1. ↑ Andersen AM (1975). "Structural Studies of Metabolic Products of Dopamine. III. Crystal and Molecular Structure of (−)-Adrenaline". Acta Chem. Scand. 29b (2): 239–244. doi: 10.3891/acta.chem.scand.29b-0239 . PMID   1136652.
  2. 1 2 "Neffy- epinephrine spray". DailyMed. 20 August 2024. Retrieved 5 September 2024.
  3. 1 2 3 4 "European Medicines Agency". Eurneffy EPAR. 27 June 2024. Archived from the original on 29 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.
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  5. ↑ 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. doi:10.1007/s11259-006-3244-1. PMID   16502110. S2CID   9054777.
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  9. ↑ 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. ISBN   9781449645861. Archived from the original on 8 September 2017.
  10. 1 2 Lieberman M, Marks A, Peet A (2013). Marks' Basic Medical Biochemistry: A Clinical Approach (4 ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 175. ISBN   9781608315727. Archived from the original on 8 September 2017.
  11. ↑ "(-)-adrenaline". Guide to Pharmacology. IUPS/BPS. Archived from the original on 1 September 2015. Retrieved 21 August 2015.
  12. ↑ Everard ML (February 2009). "Acute bronchiolitis and croup". Pediatric Clinics of North America. 56 (1): 119–33, x–xi. doi:10.1016/j.pcl.2008.10.007. PMID   19135584.
  13. ↑ 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. ISBN   9780071481274. 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.
  14. ↑ Bell DR (2009). Medical physiology : principles for clinical medicine (3rd ed.). Philadelphia: Lippincott Williams & Wilkins. p. 312. ISBN   9780781768528. Archived from the original on 8 September 2017.
  15. 1 2 Khurana (2008). Essentials of Medical Physiology. Elsevier India. p. 460. ISBN   9788131215661. Archived from the original on 8 September 2017.
  16. ↑ Buckley E (2013). Venomous Animals and Their Venoms: Venomous Vertebrates. Elsevier. p. 478. ISBN   9781483262888. Archived from the original on 8 September 2017.
  17. ↑ Animal Physiology: Adaptation and Environment (5 ed.). Cambridge University Press. 1997. p. 510. ISBN   9781107268500. Archived from the original on 8 September 2017.
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  23. ↑ "Epinephrine Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
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  27. ↑ Reardon PM, Magee K (2013). "Epinephrine in out-of-hospital cardiac arrest: A critical review". World Journal of Emergency Medicine. 4 (2): 85–91. doi:10.5847/wjem.j.issn.1920-8642.2013.02.001. PMC   4129833 . PMID   25215099.
  28. 1 2 Lin S, Callaway CW, Shah PS, Wagner JD, Beyene J, Ziegler CP, et al. (June 2014). "Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials". Resuscitation. 85 (6): 732–40. doi:10.1016/j.resuscitation.2014.03.008. PMID   24642404.
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