Medical uses of adrenaline

Main article: Epinephrine (medication)

As a medication, it is used to treat several conditions, including allergic reaction anaphylaxiscardiac arrest, and superficial bleeding.

  •  “Epinephrine”. The American Society of Health-System Pharmacists. Retrieved 15 August 2015.

Inhaled adrenaline 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.

  • “Epinephrine”. The American Society of Health-System Pharmacists. Retrieved 15 August 2015.

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

  • “Epinephrine”. The American Society of Health-System Pharmacists. Retrieved 15 August 2015.

A case has been made for the use of adrenaline infusion in place of the widely accepted treatment of inotropes for preterm infants with clinical cardiovascular compromise. Although sufficient data strongly recommends adrenaline infusions as a viable treatment, more trials are needed to conclusively determine that these infusions will successfully reduce morbidity and mortality rates among preterm, cardiovascularly compromised infants.

  • Paradisis M, Osborn DA (2004). “Adrenaline for prevention of morbidity and mortality in preterm infants with cardiovascular compromise”. The Cochrane Database of Systematic Reviews (1): CD003958. doi:10.1002/14651858.CD003958.pub2PMID 14974048.

Epinephrine can also be used to treat open-angle glaucoma, as it has been found to lower the outflow of aqueous humor in the eye. This lowers the intraocular pressure in the eye and thus aids in treatment. 

Jōkichi Takamine first isolated epinephrine in 1901, and it came into medical use in 1905. It is on the World Health Organization’s List of Essential Medicines. It is available as a generic medication. In 2020, it was the 251st most commonly prescribed medication in the United States, with more than 1 million prescriptions.

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 currently 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. It does, however, improve return of spontaneous circulation. When used intravenously, epinephrine is typically given every three to five minutes.

Epinephrine infusions may also be used for symptomatic bradycardia.

  • “Part 6: Advanced Cardiovascular Life Support Section 6: Pharmacology II: Agents to Optimize Cardiac Output and Blood Pressure”. Circulation. 102 (Supp 1): I–129–I–135. 2000. doi:10.1161/01.CIR.102.suppl_1.I-129.

Anaphylaxis

Epinephrine is the drug of choice for treating allergic reaction anaphylaxis. 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.

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. Intramuscular injection gives a faster and higher pharmacokinetic profile compared to subcutaneous injection.

Asthma

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

When given by the subcutaneous or intramuscular routes for asthma, an appropriate dose is 0.3 to 0.5 mg.

  • 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.

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.

  • 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. doi:10.1007/s00134-016-4210-1PMID 26825950S2CID 37328426.

Croup

Racemic epinephrine has historically been used for the treatment of croup. Regular epinephrine, however, works equally well. Racemic adrenaline is a 1:1 mixture of the two enantiomers of adrenaline. The L-form is the active component. 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.

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.

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. Epinephrine is frequently combined with local anesthetic and can cause panic attacks.

Epinephrine is mixed with cocaine to form Moffett’s solution, used in nasal surgery.

  • Benjamin E, Wong DK, Choa D (December 2004). “‘Moffett’s’ solution: a review of the evidence and scientific basis for the topical preparation of the nose”. Clinical Otolaryngology and Allied Sciences. 29 (6): 582–7. doi:10.1111/j.1365-2273.2004.00894.xPMID 15533141.

Upper airway obstruction

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

  • Markovchick, Vincent (2007). Critical Care Secrets (fourth ed.).

Adverse effects

Adverse reactions to adrenaline include palpitationstachycardiaarrhythmiaanxietypanic attackheadacheanorexiatremorhypertension, and acute pulmonary edema. 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.

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

  • 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. doi:10.1016/j.ijcard.2016.11.266PMID 27889211.

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

  • Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 4. ISBN 978-1-59541-101-3.

Mechanism of action

See also: Adrenergic receptor

OrganEffects
HeartIncreases heart rate; contractility; conduction across AV node
LungsIncreases respiratory rate; bronchodilation
LiverStimulates glycogenolysis
Brain
SystemicVasoconstriction and vasodilation
Triggers lipolysis
Muscle contraction

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 α1α2β1β2, and β3. 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, and stimulates glycolysis and inhibits insulin-mediated glycogenesis in muscle. 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. In the heart, the coronary arteries have a predominance of β2 receptors, which cause vasodilation of the coronary arteries in the presence of epinephrine.

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. 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.

History

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

Society and culture

Brand names

Common brand names include Asthmanefrin, Micronefrin, Nephron, VapoNefrin, and Primatene Mist.

Delivery forms

Epinephrine is available in an autoinjector delivery system.

There is an epinephrine metered-dose inhaler sold over the counter in the United States to relieve bronchial asthma. It was introduced in 1963 by Armstrong Pharmaceuticals.

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.

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