|Systematic (IUPAC) name|
|Trade names||EpiPen, Adrenaclick, others|
|IV, IM, endotracheal, IC, nasal, eye drop|
|Metabolism||adrenergic synapse (MAO and COMT)|
|Onset of action||Rapid|
|Biological half-life||2 minutes|
|Duration of action||Few minutes|
|ATC code||A01AD01 (WHO) B02BC09 (WHO) C01CA24 (WHO) R01AA14 (WHO) R03AA01 (WHO) S01EA01 (WHO)|
|PDB ligand ID||ALE (PDBe, RCSB PDB)|
|Molar mass||183.204 g/mol|
Epinephrine, also known as adrenalin or adrenaline, is primarily a medication and a hormone. As a medication it is used for a number of conditions including anaphylaxis, cardiac arrest, and superficial bleeding. Inhaled epinephrine may be used to improve the symptoms of croup. It may also be used for asthma when other treatments are not effective. It is given intravenously, by injection into a muscle, by inhalation, or by injection just under the skin.
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 is normally produced by both the adrenal glands and certain neurons. It plays an important role in the fight-or-flight response by increasing blood flow to muscles, output of the heart, pupil dilation, and blood sugar. Epinephrine does this by its effects on alpha and beta receptors. It is found in many animals and some one cell organisms.
Jokichi Takamine first isolated epinephrine in 1901. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. It is available as a generic medication. The wholesale cost in the developing world is between US$0.10 and US$0.95 a vial. In the United States the cost of the most commonly used autoinjector for anaphylaxis was about US$600 for two in 2016, while a generic version was about US$140 for two.
- 1 Medical uses
- 2 Adverse effects
- 3 Physiological effects
- 4 Pathology
- 5 Terminology
- 6 Mechanism of action
- 7 Measurement in biological fluids
- 8 Biosynthesis and regulation
- 9 History
- 10 Society and culture
- 11 References
- 12 External links
Epinephrine is used to treat a number of conditions including: cardiac arrest, anaphylaxis, and superficial bleeding. It has been used historically for bronchospasm and hypoglycemia, but newer treatments for these that are selective for β2 adrenoceptors, such as salbutamol are currently preferred.
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.
Epinephrine is the drug of choice for treating anaphylaxis. Different strengths, doses and routes of administration of epinephrine are used.
The commonly used epinephrine autoinjector delivers a 0.3 mg epinephrine injection (0.3 mL, 1:1000) and 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 does give a faster and higher pharmacokinetic profile when compared to subcutaneous injection.
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 dextrorotatory (D) and levorotatory (L) isomers of adrenaline. The L-form is the active component. Racemic adrenaline works by stimulation of the alpha adrenergic receptors in the airway, with resultant mucosal vasoconstriction and decreased subglottic edema, and by stimulation of the β adrenergic receptors, with resultant relaxation of the bronchial smooth muscle.
Adrenaline is added to injectable forms of a number of local anesthetics, such as bupivacaine and lidocaine, as a vasoconstrictor to slow the absorption and, therefore, prolong the action of the anesthetic agent. Due to epinephrine's vasoconstricting abilities, the use of epinephrine in localized anesthetics also helps to diminish the total blood loss the patient sustains during minor surgical procedures. Some of the adverse effects of local anesthetic use, such as apprehension, tachycardia, and tremor, may be caused by adrenaline. Epinephrine/adrenaline is frequently combined with dental and spinal anesthetics and can cause panic attacks in susceptible patients at a time when they may be unable to move or speak due to twilight anesthesia. Currently the maximum recommended daily dosage for people in a dental setting requiring local anesthesia with a peripheral vasoconstrictor is 10 µg/lb of total body weight.[not in citation given]
Use is contraindicated in people on nonselective β-blockers, because severe hypertension and even cerebral hemorrhage may result. Although it is commonly believed that administration of adrenaline may cause heart failure by constricting coronary arteries, this is not the case. Coronary arteries have only β2 receptors, which cause vasodilation in the presence of adrenaline. Even so, administering high-dose adrenaline has not been definitively proven to improve survival or neurologic outcomes in adult victims of cardiac arrest.
The adrenal medulla is a minor contributor to total circulating catecholamines (L-DOPA is at a higher concentration in the plasma), though it contributes over 90% of circulating epinephrine. Little epinephrine is found in other tissues, mostly in scattered chromaffin cells. Following adrenalectomy, epinephrine disappears below the detection limit in the blood stream.
The adrenals contribute about 7% of circulating norepinephrine, most of which is a spill over from neurotransmission with little activity as a hormone. Pharmacological doses of epinephrine stimulate α1, α2, β1, β2, and β3 adrenoceptors of the sympathetic nervous system. Sympathetic nerve receptors are classified as adrenergic, based on their responsiveness to adrenaline.
The concept of the adrenal medulla and the sympathetic nervous system being involved in the flight, fight and fright response was originally proposed by Cannon. But the adrenal medulla, in contrast to the adrenal cortex, is not required for survival. In adrenalectomized patients haemodynamic and metabolic responses to stimuli such as hypoglycaemia and exercise remain normal.
One physiological stimulus to epinephrine secretion is exercise. This was first demonstrated using the denervated pupil of a cat as an assay, later confirmed using a biological assay on urine samples. Biochemical methods for measuring catecholamines in plasma were published from 1950 onwards. Although much valuable work has been published using fluorimetric assays to measure total catecholamine concentrations, the method is too non-specific and insensitive to accurately determine the very small quantities of epinephrine in plasma. The development of extraction methods and enzyme-isotope derivate radio-enzymatic assays (REA) transformed the analysis down to a sensitivity of 1 pg for epinephrine. Early REA plasma assays indicated that epinephrine and total catecholamines rise late in exercise, mostly when anaerobic metabolism commences.
During exercise the epinephrine blood concentration rises partially from increased secretion from the adrenal medulla and partly from decreased metabolism because of reduced hepatic blood flow. Infusion of epinephrine to reproduce exercise circulating concentrations of epinephrine in subjects at rest has little haemodynamic effect, other than a small β2-mediated fall in diastolic blood pressure. Infusion of epinephrine well within the physiological range suppresses human airway hyper-reactivity sufficiently to antagonize the constrictor effects of inhaled histamine.
A link between what we now know as the sympathetic system and the lung was shown in 1887 when Grossman showed that stimulation of cardiac accelerator nerves reversed muscarine induced airway constriction. In elegant experiments in the dog, where the sympathetic chain was cut at the level of the diaphragm, Jackson showed that there was no direct sympathetic innervation to the lung, but that bronchoconstriction was reversed by release of epinephrine from the adrenal medulla. An increased incidence of asthma has not been reported for adrenalectomized patients; those with a predisposition to asthma will have some protection from airway hyper-reactivity from their corticosteroid replacement therapy. Exercise induces progressive airway dilation in normal subjects that correlates with work load and is not prevented by beta blockade. The progressive dilation of the airway with increasing exercise is mediated by a progressive reduction in resting vagal tone. Beta blockade with propranolol causes a rebound in airway resistance after exercise in normal subjects over the same time course as the bronchoconstriction seen with exercise induced asthma. The reduction in airway resistance during exercise reduces the work of breathing.
Every emotional response has a behavioral component, an autonomic component, and a hormonal component. The hormonal component includes the release of epinephrine, an adrenomedullary response that occurs in response to stress and that is controlled by the sympathetic nervous system. The major emotion studied in relation to epinephrine is fear. In an experiment, subjects who were injected with epinephrine expressed more negative and fewer positive facial expressions to fear films compared to a control group. These subjects also reported a more intense fear from the films and greater mean intensity of negative memories than control subjects. The findings from this study demonstrate that there are learned associations between negative feelings and levels of epinephrine. Overall, the greater amount of epinephrine is positively correlated with an arousal state of negative feelings. These findings can be an effect in part that epinephrine elicits physiological sympathetic responses including an increased heart rate and knee shaking, which can be attributed to the feeling of fear regardless of the actual level of fear elicited from the video. Although studies have found a definite relation between epinephrine and fear, other emotions have not had such results. In the same study, subjects did not express a greater amusement to an amusement film nor greater anger to an anger film. Similar findings were also supported in a study that involved rodent subjects that either were able or unable to produce epinephrine. Findings support the idea that epinephrine does have a role in facilitating the encoding of emotionally arousing events, contributing to higher levels of arousal due to fear.
It has been found that adrenergic hormones, such as epinephrine, can produce retrograde enhancement of long-term memory in humans. The release of epinephrine due to emotionally stressful events, which is endogenous epinephrine, can modulate memory consolidation of the events, ensuring memory strength that is proportional to memory importance. Post-learning epinephrine activity also interacts with the degree of arousal associated with the initial coding. There is evidence that suggests epinephrine does have a role in long-term stress adaptation and emotional memory encoding specifically. Epinephrine may also play a role in elevating arousal and fear memory under particular pathological conditions including post-traumatic stress disorder. Overall, "Extensive evidence indicates that epinephrine (EPI) modulates memory consolidation for emotionally arousing tasks in animals and human subjects.” Studies have also found that recognition memory involving epinephrine depends on a mechanism that depends on β adrenoceptors. Epinephrine does not readily cross the blood–brain barrier, so its effects on memory consolidation are at least partly initiated by β adrenoceptors in the periphery. Studies have found that sotalol, a β adrenoceptor antagonist that also does not readily enter the brain, blocks the enhancing effects of peripherally administered epinephrine on memory. These findings suggest that β adrenoceptors are necessary for epinephrine to have an effect on memory consolidation.
For noradrenaline to be acted upon by PNMT in the cytosol, it must first be shipped out of granules of the chromaffin cells. This may occur via the catecholamine-H+ exchanger VMAT1. VMAT1 is also responsible for transporting newly synthesized adrenaline from the cytosol back into chromaffin granules in preparation for release.
In liver cells, adrenaline binds to the β adrenergic receptor, which changes conformation and helps Gs, a G protein, exchange GDP to GTP. This trimeric G protein dissociates to Gs alpha and Gs beta/gamma subunits. Gs alpha binds to adenyl cyclase, thus converting ATP into cyclic AMP. Cyclic AMP binds to the regulatory subunit of protein kinase A: Protein kinase A phosphorylates phosphorylase kinase. Meanwhile, Gs beta/gamma binds to the calcium channel and allows calcium ions to enter the cytoplasm. Calcium ions bind to calmodulin proteins, a protein present in all eukaryotic cells, which then binds to phosphorylase kinase and finishes its activation. Phosphorylase kinase phosphorylates glycogen phosphorylase, which then phosphorylates glycogen and converts it to glucose-6-phosphate.
Increased epinephrine secretion is observed in phaeochromocytoma, hypoglycaemia, myocardial infarction and to a lesser degree in benign essential familial tremor. A general increase in sympathetic neural activity is usually accompanied by increased adrenaline secretion, but there is selectivity during hypoxia and hypoglycaemia, when the ratio of adrenaline to noradrenaline is considerably increased. Therefore, there must be some autonomy of the adrenal medulla from the rest of the sympathetic system.
Benign familial tremor (BFT) is responsive to peripheral β adrenergic blockers and β2-stimulation is known to cause tremor. Patients with BFT were found to have increased plasma epinephrine, but not norepinephrine.
Low, or absent, concentrations of epinephrine can be seen in autonomic neuropathy or following adrenalectomy. Failure of the adrenal cortex, as with Addisons disease, can suppress epinephrine secretion as the activity of the synthesing enzyme, phenylethanolamine-N-methyltransferase, depends on the high concentration of cortisol that drains from the cortex to the medulla.
Epinephrine is the pharmaceutical's United States Adopted Name and International Nonproprietary Name, though the name adrenaline is frequently used. The term epinephrine was coined by the pharmacologist John Abel (from the Greek for "on top of the kidneys"), who used the name to describe the extracts he prepared from the adrenal glands as early as 1897. In 1901, Jokichi Takamine patented a purified adrenal extract, and called it "adrenalin" (from the Latin for "on top of the kidneys"), which was trademarked by Parke, Davis & Co in the U.S. In the belief that Abel's extract was the same as Takamine's, a belief since disputed, epinephrine became the generic name in the U.S. The British Approved Name and European Pharmacopoeia term for this drug is adrenaline and is indeed now one of the few differences between the INN and BAN systems of names.
Among American health professionals and scientists, the term epinephrine is used over adrenaline. However, pharmaceuticals that mimic the effects of epinephrine are often called adrenergics, and receptors for epinephrine are called adrenergic receptors or adrenoceptors.
Mechanism of action
|Heart||Increases heart rate|
|Lungs||Increases respiratory rate|
|Systemic||Vasoconstriction and vasodilation|
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 levels of epinephrine causes smooth muscle relaxation in the airways but causes contraction of the smooth muscle that lines most arterioles.
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. Epinephrine's binding to these receptors triggers a number of 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 lead to increased blood glucose and fatty acids, providing substrates for energy production within cells throughout the body.
Its actions are to increase peripheral resistance via α1 receptor-dependent vasoconstriction and to 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 be improving macrocirculation at the expense of the capillary beds where actual perfusion is taking place.
Measurement in biological fluids
Epinephrine may be quantified in blood, plasma or serum as a diagnostic aid, to monitor therapeutic administration, or to identify the causative agent in a potential poisoning victim. Endogenous plasma epinephrine concentrations in resting adults are normally less than 10 ng/L, but may increase by 10-fold during exercise and by 50-fold or more during times of stress. Pheochromocytoma patients often have plasma adrenaline levels of 1000–10,000 ng/L. Parenteral administration of epinephrine to acute-care cardiac patients can produce plasma concentrations of 10,000 to 100,000 ng/L.
Biosynthesis and regulation
In chemical terms, epinephrine is one of a group of monoamines called the catecholamines. It is produced in some neurons of the central nervous system, and in the chromaffin cells of the adrenal medulla from the amino acids phenylalanine and tyrosine.
Epinephrine is synthesized in the medulla of the adrenal gland in an enzymatic pathway that converts the amino acid tyrosine into a series of intermediates and, ultimately, epinephrine. Tyrosine is first oxidized to L-DOPA, which is subsequently decarboxylated to give dopamine. Oxidation gives norepinephrine. The final step in epinephrine biosynthesis is the methylation of the primary amine of noradrenaline. This reaction is catalyzed by the enzyme phenylethanolamine N-methyltransferase (PNMT) which utilizes S-adenosyl methionine (SAMe) as the methyl donor. While PNMT is found primarily in the cytosol of the endocrine cells of the adrenal medulla (also known as chromaffin cells), it has been detected at low levels in both the heart and brain.
The major physiologic triggers of adrenaline release center upon stresses, such as physical threat, excitement, noise, bright lights, and high ambient temperature. All of these stimuli are processed in the central nervous system.
Adrenocorticotropic hormone (ACTH) and the sympathetic nervous system stimulate the synthesis of adrenaline precursors by enhancing the activity of tyrosine hydroxylase and dopamine β-hydroxylase, two key enzymes involved in catecholamine synthesis. ACTH also stimulates the adrenal cortex to release cortisol, which increases the expression of PNMT in chromaffin cells, enhancing adrenaline synthesis. This is most often done in response to stress. The sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of adrenaline. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and, thus, the release of adrenaline (and noradrenaline) into the bloodstream.
Unlike many other hormones adrenaline (as with other catecholamines) does not exert negative feedback to down-regulate its own synthesis. Abnormally elevated levels of adrenaline can occur in a variety of conditions, such as surreptitious epinephrine administration, pheochromocytoma, and other tumors of the sympathetic ganglia.
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 Jokichi 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
The wholesale cost of epinephrine in the developing world is between US$0.10 and US$0.95 a vial.
Names for epinephrine include adrenaline, adrenalin, and β,3,4-trihydroxy-N-methylphenethylamine.
Epinephrine is available in an autoinjector delivery system.
There is an epinephrine metered-dose inhaler sold over-the-counter in the United States for the relief of bronchial asthma. It was introduced in 1963 by Armstrong Pharmaceuticals. In 2008, the Food and Drug Administration (FDA) announced that inhalers, which contain chlorofluorocarbons (CFCs), failed to comply with the environmental regulations of the Montreal Protocol and therefore could not be manufactured or sold after December 31, 2011. In April 2013, after completing several years of trials, Armstrong Pharmaceuticals submitted a New Drug Application to the FDA for an HFA version.
An adrenaline junkie is somebody who engages in sensation-seeking behavior through "the pursuit of novel and intense experiences without regard for physical, social, legal or financial risk". Such activities include extreme and risky sports, substance abuse, unsafe sex, and crime. The term relates to the increase in circulating levels of adrenaline during physiological stress. Such an increase in the circulating concentration of adrenaline is secondary to activation of the sympathetic nerves innervating the adrenal medulla, as it is rapid and not present in animals where the adrenal gland has been removed. Although such stress triggers adrenaline release, it also activates many other responses within the central nervous system reward system which drives behavioral responses, so while the circulating adrenaline concentration is present, it may not drive behavior. Nevertheless, adrenaline infusion alone does increase alertness and has roles in the brain including the augmentation of memory consolidation.:147–8
- "Epinephrine". The American Society of Health-System Pharmacists. Retrieved Aug 15, 2015.
- Nancy caroline's emergency care in the streets. (7 ed.). [S.l.]: Jones And Bartlett Learning. 2012. p. 557. ISBN 9781449645861.
- Chansky, Michael Lieberman, Allan Marks, Alisa Peet ; illustrations by Matthew (2013). Marks' basic medical biochemistry : a clinical approach (4 ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 175. ISBN 9781608315727.
- "(-)-adrenaline". Guide to Pharmacology. IUPS/BPS. Retrieved 21 August 2015.
- Everard ML (February 2009). "Acute bronchiolitis and croup". Pediatr. Clin. North Am. 56 (1): 119–33, x–xi. doi:10.1016/j.pcl.2008.10.007. PMID 19135584.
- Bell, David R. (2009). Medical physiology : principles for clinical medicine (3rd ed.). Philadelphia: Lippincott Williams & Wilkins. p. 312. ISBN 9780781768528.
- Khurana (2008). Essentials of Medical Physiology. Elsevier India. p. 460. ISBN 9788131215661.
- Buckley, Eleanor (2013). Venomous Animals and Their Venoms: Venomous Vertebrates. Elsevier. p. 478. ISBN 9781483262888.
- Animal Physiology: Adaptation and Environment (5 ed.). Cambridge University Press. 1997. p. 510. ISBN 9781107268500.
- Wermuth, Camille Georges (2008). The practice of medicinal chemistry (3 ed.). Amsterdam: Elsevier/Academic Press. p. 13. ISBN 9780080568775.
- "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- "Epinephrine". International Drug Price Indicator Guide. Retrieved 15 August 2015.
- Ginger Skinner (August 11, 2016). "Can You Get A Cheaper EpiPen?". Consumer Reports.
- "Epinephrine". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
- 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. PMID 25215099.
- Lin, S; Callaway, CW; Shah, PS; Wagner, JD; Beyene, J; Ziegler, CP; Morrison, LJ (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.
- Mylan Specialty L.P.,. "EPIPEN®- epinephrine injection, EPIPEN Jr®- epinephrine injection" (PDF). FDA Product Label. Retrieved 22 January 2014.
- ECC Committee, Subcommittees and Task Forces of the American Heart Association (2005). "2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 10.6: Anaphylaxis". Circulation. 112 (24 suppl): IV–143–IV–145. doi:10.1161/circulationaha.105.166568.
- Neumar, RW; Otto CW; Link MS; et al. (2010). "Part 8: adult advanced cardiovascular life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care". Circulation. 122 (18 suppl 3): S729–S767. doi:10.1161/CIRCULATIONAHA.110.970988. PMID 20956224.
- Lieberman, P; Nicklas RA, Oppenheimer J; et al. (2010). "The diagnosis and management of anaphylaxis practice parameter: 2010 update". J Allergy Clin Immunol. 126 (3): 477–480. doi:10.1016/j.jaci.2010.06.022. PMID 20692689.
- Pensylvannia Patient Advisory. "Let's Stop this "Epi"demic!—Preventing Errors with Epinephrine". Retrieved 22 January 2014.
- McLean-Tooke, AP; Bethune CA; Fay AC; Spickett GP (2003). "Adrenaline in the treatment of anaphylaxis: what is the evidence?". BMJ. 327 (7427): 1332–5. doi:10.1136/bmj.327.7427.1332. PMC . PMID 14656845.
- Koninckx M, Buysse C, de Hoog M (2013 Jun). "Management of status asthmaticus in children". Paediatr Respir Rev. 14 (2): 78–85. doi:10.1016/j.prrv.2013.03.003. PMID 23578933. Check date values in:
- 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.
- Bjornson CL, Johnson DW; Johnson (2008). "Croup". The Lancet. 371 (9609): 329–339. doi:10.1016/S0140-6736(08)60170-1. PMID 18295000.
- Thomas LP, Friedland LR; Friedland (1998). "The cost-effective use of nebulized racemic adrenaline in the treatment of croup". American Journal of Emergency Medicine. 16 (1): 87–89. doi:10.1016/S0735-6757(98)90073-0. PMID 9451322.
- Malhotra A, Krilov LR; Krilov (2001). "Viral Croup". Pediatrics in Review. 22 (1): 5–12. doi:10.1542/pir.22-1-5. PMID 11139641.
- R. Rahn and B. Ball. Local Anesthesia in Dentistry, 3M ESPE AG, ESPE Platz, Seefeld, Germany, 2001, 44 pp.
- 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.x. PMID 15533141.
- About.com – "The Definition of Epinephrine"
- Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 4. ISBN 1-59541-101-1.
- Sun, D.; Huang, A.; Mital, S.; Kichuk, M. R.; Marboe, C. C.; Addonizio, L. J.; Michler, R. E.; Koller, A.; Hintze, T. H.; Kaley, G. (2002). "Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles". Circulation. 106 (5): 550–555. doi:10.1161/01.CIR.0000023896.70583.9F. PMID 12147535.
- Stiell, I. G.; Hebert, P. C.; Weitzman, B. N.; Wells, G. A.; Raman, S.; Stark, R. M.; Higginson, L. A. J.; Ahuja, J.; Dickinson, G. E. (1992). "High-Dose Epinephrine in Adult Cardiac Arrest". New England Journal of Medicine. 327 (15): 1045–1050. doi:10.1056/NEJM199210083271502. PMID 1522840.
- Rizzo, V; Memmi, M; Moratti, R; Melzi d'Eril, G; Perucca, E (June 1996). "Concentrations of L-dopa in plasma and plasma ultrafiltrates". Journal of Pharmaceutical and Biomedical Analysis. 14 (8–10): 1043–6. doi:10.1016/s0731-7085(96)01753-0. PMID 8818013.
- Cryer, PE; Moore, Mary Jean; Cryer, Philip E. (1980). "Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system". NEJM. 303 (8): 436–444. doi:10.1056/nejm198008213030806. PMID 6248784.
- Cryer, PE (1976). "Isotope-derivative measurements of plasma norepinephrine and epinephrine in man". Diabetes. 25 (11): 1071–1082. doi:10.2337/diab.25.11.1071. PMID 825406.
- "Gerich J, et al. Hormonal mechanisms of recovery from insulin-induced hypoglycaemia in man". Am J Physiol. 236: 380–385. 1979.
- Pacak, Karel (2007). Catecholamines and adrenergic receptors. In: Pheochromocytoma Diagnosis, Localization, and Treatment. Chapter 6: Blackwell Publishing Ltd, Oxford. p. 62.
- Barger, G; Dale HH (1910). "Chemical structure and sympathetic action of amines". J Physiol. 41 (1–2): 19–59. doi:10.1113/jphysiol.1910.sp001392. PMC . PMID 16993040.
- Von Euler, US (1946). "A specific sympathomimetic ergone in adrenergic nerve fibres (sympathin) and its relations to adrenaline and nor adrenaline". Acta Physiol Scand. 12: 73–97. doi:10.1111/j.1748-1716.1946.tb00368.x.
- Von Euler, US; Hillarp NA (1956). "Evidence for the presence of noradrenaline in submicroscopic structures of adrenergic axons". Nature. 177 (4497): 44–45. Bibcode:1956Natur.177...44E. doi:10.1038/177044b0. PMID 13288591.
- Warren, JB. (1986). "The adrenal medulla and the airway". Br J Dis Chest. 80 (1): 1–6. doi:10.1016/0007-0971(86)90002-1. PMID 3004549.
- Twentyman, OP; Disley, A; Gribbin, HR; Alberti, KG; Tattersfield, AE (1981). "Effect of B-blockade on respiratory and metabolic responses to exercise". J Appl Physiol. 51 (4): 788–793. PMID 6795164.
- Richter, EA; Galbo, H; Christensen, NJ (1981). "Richter EA et al. Control of exercise-induced muscular glycogenolysis by adrenomedullary hormones in rats". J Appl Physiol. 50 (1): 21–26. PMID 7009527.
- Canon, WB. (1931). "Studies on the conditions of activity in endocrine organs xxvii. Evidence that medulliadrenal secretion is not continuous". Am J Physiol. 98: 447–453.
- Cryer, PE; Tse TF, Clutter WE, Shah SD ( (1984). "Roles of glucagon and epinephrine in hypoglycemic and nonhypoglycemic glucose counterregulation in humans". Am J Physiol. 247 (2 Pt 1): E198–E205. PMID 6147094.
- Hoelzer, DR; Dalsky GP; Schwartz NS; Clutter WE; Shah SD; Holloszy JO; Cryer PE (1986). "Epinephrine is not critical to prevention of hypoglycemia during exercise in humans". Am J Physiol. 251 (1 Pt 1): E104–E110. PMID 3524257.
- Hartman, FA; Waite RH; McCordock HA. (1922). "The liberation of epinephrine during muscular exercise". Am J Physiol. 62: 225–241.
- Von Euler, US; Hellner S (1952). "Excretion of noradrenaline and adrenaline in muscular work". Acta Phys Scand. 26 (2–3): 183–191. doi:10.1111/j.1748-1716.1952.tb00900.x.
- Lund, A (1950). "Simultaneous fluorimetric determinations of adrenaline and noradrenaline in blood". Acta Pharmac Tox: 137–146.
- Johnson, GA; Kupiecki RM; Baker CA. (1980). "Single isotope derivatice (radioenzymatic) methods in the measurement of catecholamines". Metabolism 1980;29:suppl:. 29suppl (11): 1106–1112. doi:10.1016/0026-0495(80)90018-9.
- Galbo, HJ; Holst, JJ; Christensen, NJ (1975). "Glucagon and catecholamine responses to graded and prolonged exercise in man". J Appl Physiol. 38 (1): 70–76. PMID 1110246.
- Winder, WW; et al. (1978). "Time course of sympathoadrenal adaptation to endurance exercise training in man. J". Apply Physiol. 45: 370–374.
- Kindermann, W; Schmitt, W. M.; Biro, G.; Hippchen, M.; et al. (1982). "Catecholamines, GH, cortisol, glucagon, insulin and sex hormones in exercise and B-1 blockade". Klin Wochenschrift. 60 (10): 505–512. doi:10.1007/bf01756096. Missing
|last2=in Authors list (help)
- Warren, JB; Dalton N; Turner C; Clark TJH; Toseland PA. (1984). "Adrenaline secretion during exercise". Clin Sci. 66 (1): 47–51. PMID 6690194.
- Fitzgerald, GA; Barnes P; Hamilton CA; Dollery CT. (1980). "Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man". Eur J Clin Invest 1980. 10 (5): 401–406. doi:10.1111/j.1365-2362.1980.tb00052.x.
- Warren, JB; Dalton N (1983). "A comparison of the bronchodilator and vassopresser effects of exercise levels of adrenaline in man". Clin Sci. 64 (5): 475–479. PMID 6831836.
- Warren, JB; Dalton N; Turner C; Clark TJH. (1984). "Protective effect of circulating epinephrine within the physiological range on the airway response to inhaled histamine in non-asthmatic subjects". J Allergy Clin Immunol. 74 (5): 683–686. doi:10.1016/0091-6749(84)90230-6. PMID 6389647.
- Grossman, M (1887). "Das muscarin-lungen-odem". Z Klin Med. 12: 550–591.
- Jackson, DE (1912). "The pulmonary action of the adrenal glands". J Pharmac Exp Therap. 4: 59–74.
- Kagawa, J; Kerr HD. (1970). "Effects of brief graded exercise on specific airway conductance in normal subjects". J Appl Physiol. 28 (2): 138–144. PMID 5413299.
- Warren, JB; Jennings SJ; Clark TJH. (1984). "Effect of adrenergic and vagal blockade on the normal human airway response to exercise". Clin Sci. 66 (1): 79–85. PMID 6228370.
- Jennings, SJ; Warren JB; Pride NB (1987). "Airway caliber and the work of breathing in humans". J Appl Physiol. 63 (1): 20–24. PMID 2957350.
- Mezzacappa, E.S.; Katkin, E.S.; Palmer, S.N. (1999). "Epinephrine, arousal, and emotion: A new look at two-factor theory". Cognition and Emotion. 13 (2): 181–199. doi:10.1080/026999399379320.
- Mate, T.; et al. (2013). "Impaired conditioned fear response and startle reactivity in epinephrine-deficient mice". Behavioural Pharmacology. 24 (1): 1–9. doi:10.1097/FBP.0b013e32835cf408. PMC . PMID 23268986.
- Cahill, L.; Alkire, M.T. (2002). "Epinephrine enhancement of human memory consolidation; Interaction with arousal at encoding". Neurobiology of Learning and Memory. 79 (2): 194–198. doi:10.1016/S1074-7427(02)00036-9. PMID 12591227.
- Dornelles, A.; et al. (2007). "Adrenergic enhancement of consolidation of object recognition memory". Neurobiology of Learning and Memory. 88 (1): 137–142. doi:10.1016/j.nlm.2007.01.005. PMID 17368053.
- Roozendaal, B.; James, L.M. (2011). "Theoretical review: Memory Modulation". Behavioral Neuroscience. 125 (6): 797–824. doi:10.1037/a0026187. PMID 22122145.
- "SLC18 family of vesicular amine transporters". Guide to Pharmacology. IUPHAR/BPS. Retrieved 21 August 2015.
- Feldberg, W; Minz B (1934). "The mechanism of the nervous discharge of adrenaline". J Physiol 1934;81:. 81 (3): 286–304. doi:10.1113/jphysiol.1934.sp003136.
- Burn, JH; Hutcheon DE; Parker RHO. (1950). "Adrenaline and noradrenaline in the suprarenal medulla after insulin". Br J Pharmacol Chemotherap. 5 (3): 417–423. doi:10.1111/j.1476-5381.1950.tb00591.x.
- Outshoorn, AS (1952). "The hormones of the adrenal medulla and their release". Br J Pharmacol Chemotherap. 7 (4): 605–615. doi:10.1111/j.1476-5381.1952.tb00728.x.
- Benedict, CR; DG Grahame-Smith (1979). "Plasma adrenaline and noradrenaline and dopamine B-hydroxylase activity in myocardial infarction with or without cardiogenic shock". Br Heart J. 42 (2): 214–220. doi:10.1136/hrt.42.2.214. PMID 486283.
- Nadeau, RA; DeCamplain J (1979). "Plasma catecholamines in acute myocardial infarction". Am Heart J. 98 (5): 548–554. doi:10.1016/0002-8703(79)90278-3. PMID 495400.
- Larsson, S; Svedmyr N (1977). "Tremor caused by sympathomimetics is mediated by beta 2-adrenoceptors". Scand J Resp Dis. 58: 5–10.
- Warren, JB; O'Brien M; Dalton N; Turner CT (1984). "Sympathetic activity in benign familial tremor". Lancet. 1 (8374): 461–2. doi:10.1016/S0140-6736(84)91804-X. PMID 6142198.
- Wurtman, RJ; Pohorecky LA; Baliga BS. (1972). "Adrenocortical control of the biosynthesis of epinephrine and proteins in the adrenal medulla". Pharmacol Rev. 24 (2): 411–426. PMID 4117970.
- Jones, A; Jones IC (1955). "Chromaffin tissue in the lizard adrenal gland". Nature. 175 (4466): 1001–2. Bibcode:1955Natur.175.1001W. doi:10.1038/1751001b0. PMID 14394091.
- Coupland, RE (1953). "On the morphology and adrenaline-noradrenaline content of chromaffin tissue". Journal of Endocrinology. 9 (2): 194–203. doi:10.1677/joe.0.0090194. PMID 13052791.
- Aronson, Jeffrey K (19 February 2000). ""Where name and image meet"—the argument for "adrenaline"". British Medical Journal. 320 (2733): 506–509. doi:10.1136/bmj.320.7233.506. PMC . PMID 10678871.
- Changes to medicines names: BANs to rINNs, Medicines and Healthcare products Regulatory Agency
- 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. PMID 3521311.
- Raz, I; Katz, A; Spencer, MK (March 1991). "Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle.". The American Journal of Physiology. 260 (3 Pt 1): E430–5. PMID 1900669.
- Sabyasachi Sircar (2007). Medical Physiology. Thieme Publishing Group. p. 536. ISBN 3-13-144061-9.
- "Guidline 11.5: Medications in Adult Cardiac Arrest" (PDF). Australian Resuscitation Council. December 2010. Retrieved 7 March 2015.
- Burnett, Aaron M.; Segal, Nicolas; Salzman, Joshua G.; McKnite, M. Scott; Frascone, Ralph J. (August 2012). "Potential negative effects of epinephrine on carotid blood flow and ETCO2 during active compression–decompression CPR utilizing an impedance threshold device". Resuscitation. 83 (8): 1021–1024. doi:10.1016/j.resuscitation.2012.03.018. PMID 22445865.
- Raymondos, K.; Panning, B.; Leuwer, M.; Brechelt, G.; Korte, T.; Niehaus, M.; Tebbenjohanns, J.; Piepenbrock, S. (2000). "Absorption and hemodynamic effects of airway administration of adrenaline in patients with severe cardiac disease". Ann. Intern. Med. 132 (10): 800–803. doi:10.7326/0003-4819-132-10-200005160-00007. PMID 10819703.
- Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 545–547. ISBN 0-9626523-7-7.
- von Bohlen und Halbach, O; Dermietzel, R (2006). Neurotransmitters and neuromodulators: handbook of receptors and biological effects. Wiley-VCH. p. 125. ISBN 978-3-527-31307-5.
- Kirshner, Norman; Goodall, McC. (1957). "The Formation of Adrenaline From Noradrenaline". Biochimica et Biophysica Acta. 24 (3): 658–659. doi:10.1016/0006-3002(57)90271-8. PMID 13436503.
- Axelrod, Julius (May 1962). "Purification and Properties of Phenylethanolamine-N-methyl Transferase". The Journal of Biological Chemistry. 237 (5): 1657–1660.
- Nelson, L.; Cox, M. (2004). Lehninger Principles of Biochemistry (4th ed.). New York: Freeman. p. 908. ISBN 0-7167-4339-6.
- Pharmacology for Anesthetists 5, p52. PediaPress.
- "Adrenaline – Epinephrine". World of Molecules. Retrieved 7 March 2015.
- Skalski, J.H.; Kuch, J. "Polish Thread in the History of Circulatory Physiology". Journal of Physiology and Pharmacology. Retrieved 7 March 2015.
- Bates, William H. (16 May 1896). "The Use of Extract of Suprarenal Capsule in the Eye". New York Medical Journal. Read before the Section in Ophthalmology of the New York Academy of Medicine, 20 April 1896: 647–650. Retrieved 7 March 2015.
- Yamashima T (2003). "Jokichi Takamine (1854–1922), the samurai chemist, and his work on adrenalin". J Med Biogr. 11 (2): 95–102. PMID 12717538.
- Bennett M (1999). "One hundred years of adrenaline: the discovery of autoreceptors". Clin Auton Res. 9 (3): 145–59. doi:10.1007/BF02281628. PMID 10454061.
- Takamine J (1901). The isolation of the active principle of the suprarenal gland. The Journal of Physiology. Great Britain: Cambridge University Press. pp. xxix–xxx.
- Cite error: The named reference
armstrongwas invoked but never defined (see the help page).
- Cite error: The named reference
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- Saundra Young (September 22, 2011). "No more Primatene Mist in the U.S. after this year". The Chart (blog). CNN. Retrieved 2011-09-22.
- Zuckerman, Marvin (2007). Sensation seeking and risky behavior (2. print. ed.). Washington, DC: American Psychological Association. ISBN 1591477387.
- Jänig, Wilfrid (2006). The integrative action of the autonomic nervous system : neurobiology of homeostasis. Cambridge: UK. pp. 143–146. ISBN 9780521845182.
- Deane, W.H.; Rubin, B.L. (1964). "Absence of adrenal meduallary secretions". The Adrenocortical Hormones Their Origin - Chemistry Physiology and Pharmacology. Berlin, Heidelberg: Springer Berlin Heidelberg. p. 105. ISBN 9783662131329.
- FRANKENHAEUSER, M; JARPE, G; MATELL, G (NaN). "Effects of intravenous infusions of adrenaline and noradrenaline on certain psychological and physiological functions". Acta physiologica Scandinavica. 51 (2–3): 175–86. doi:10.1111/j.1748-1716.1961.tb02126.x. PMID 13701421. Check date values in:
- "When Fear Makes Us Superhuman". Scientific American. 28 Dec 2009. Retrieved 25 August 2015.
- Wise, Jeff (2009). Extreme fear : the science of your mind in danger (1st ed.). New York: Palgrave Macmillan. ISBN 0230614396.
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