Epinephrine, also known as adrenaline, is a medication and hormone. [7] [8] As a medication, it is used to treat several conditions, including anaphylaxis, cardiac arrest, asthma, and superficial bleeding. [5] Inhaled epinephrine may be used to improve the symptoms of croup. [9] It may also be used for asthma when other treatments are not effective. [5] It is given intravenously, by injection into a muscle, by inhalation, or by injection just under the skin. [5]
Common side effects include shakiness, anxiety, and sweating. [5] A fast heart rate and high blood pressure may occur. [5] Occasionally, it may result in an abnormal heart rhythm. [5] While the safety of its use during pregnancy and breastfeeding is unclear, the benefits to the mother must be taken into account. [5]
Epinephrine is normally produced by both the adrenal glands and a small number of neurons in the brain, where it acts as a neurotransmitter. [7] [10] It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output, pupil dilation, and blood sugar. [11] [12] Epinephrine does this through its effects on alpha and beta receptors. [12] It is found in many animals and some single-celled organisms, [13] [14] but the medication is produced synthetically and is not harvested from animals. [15]
Jōkichi Takamine first isolated epinephrine in 1901, and it came into medical use in 1905. [16] [17] It is on the World Health Organization's List of Essential Medicines. [18] It is available as a generic medication. [5] In 2021, it was the 221st most commonly prescribed medication in the United States, with more than 1 million prescriptions. [19] [20]
Epinephrine is used to treat a number of conditions, including cardiac arrest, anaphylaxis, and superficial bleeding. [21] 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 ]
While epinephrine is often used to treat cardiac arrest, it has not been shown to improve long-term survival or mental function after recovery. [22] [23] [24] It does, however, improve return of spontaneous circulation. [24] When used intravenously to treat cardiac arrest in adults, epinephrine is typically given at a dose of 1 mg every three to five minutes. [25]
In cases of IV infusion for bradycardia the dose is 1 mg epinephrine is mixed with 500ml of NS or D5W. The infusion should run at 2-10 micrograms/min (titrated to effect). IV infusion for post-cardiac arrest hypotension: The dosing is 2 to 10 micrograms/min.
Endotracheal Tube: 2-2.5 mg epinephrine is diluted in 10cc NS and given directly into the ET tube. [26]
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. [27] [28] [29] [30]
Intramuscular injection can be complicated in that the depth of subcutaneous fat varies and may result in subcutaneous injection, or may be injected intravenously in error, or the wrong strength used. [31] Intramuscular injection gives a faster and higher pharmacokinetic profile compared to subcutaneous injection. [32]
Epinephrine is also used as a bronchodilator for asthma if specific β2 agonists are unavailable or ineffective. [33]
When given by the subcutaneous or intramuscular routes for asthma, an appropriate dose is 0.3 to 0.5 mg. [34] [35]
Because of the high intrinsic efficacy (receptor binding ability) of epinephrine, high drug concentrations cause adverse side effects when treating asthma. The value of using nebulized epinephrine in acute asthma is unclear. [36]
Racemic epinephrine has historically been used for the treatment of croup. [37] [38] Regular epinephrine, however, works equally well [ fact or opinion? ][ citation needed ]. Racemic adrenaline is a 1:1 mixture of the two enantiomers of adrenaline. [39] The L-form is the active component. [39] Racemic adrenaline works by stimulating the alpha-adrenergic receptors in the airway, with resultant mucosal vasoconstriction and decreased subglottic edema, and by stimulating the β adrenergic receptors, with resultant relaxation of the bronchial smooth muscle. [38]
There is a lack of consensus as to whether inhaled nebulized epinephrine is beneficial in the treatment of bronchiolitis, with most guidelines recommending against its use. [40]
When epinephrine is mixed with local anesthetics, such as bupivacaine or lidocaine, and used for local anesthesia or intrathecal injection, it prolongs the numbing effect and motor block effect of the anesthetic by up to an hour. [41] Epinephrine is frequently combined with local anesthetic and can cause panic attacks. [42]
Epinephrine is mixed with cocaine to form Moffett's solution, used in nasal surgery. [43]
Upper airway obstruction with edema and stridor can be treated with racemic epinephrine. [44]
Adverse reactions to adrenaline include palpitations, tachycardia, arrhythmia, anxiety, panic attack, headache, anorexia, tremor, hypertension, 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. [45]
Use is contraindicated in people on nonselective β-blockers because severe hypertension and even cerebral hemorrhage may result. [46]
Organ | Effects |
---|---|
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 |
As a hormone, epinephrine acts on nearly all body tissues. Its actions vary by tissue type and tissue expression of adrenergic receptors. For example, high epinephrine levels cause smooth muscle relaxation in the airways but cause contraction of the smooth muscle that lines most arterioles.[ citation needed ]
Epinephrine acts by binding to a variety of adrenergic receptors. Epinephrine is a nonselective agonist of all adrenergic receptors, including the major subtypes α1, α2, β1, β2, and β3. [46] Epinephrine's binding to these receptors triggers several metabolic changes. Binding to α-adrenergic receptors inhibits insulin secretion by the pancreas, stimulates glycogenolysis in the liver and muscle, [47] and stimulates glycolysis and inhibits insulin-mediated glycogenesis in muscle. [48] [49] β adrenergic receptor binding triggers glucagon secretion in the pancreas, increased adrenocorticotropic hormone (ACTH) secretion by the pituitary gland, and increased lipolysis by adipose tissue. Together, these effects increase blood glucose and fatty acids, providing substrates for energy production within cells throughout the body. [49] In the heart, the coronary arteries have a predominance of β2 receptors, which cause vasodilation of the coronary arteries in the presence of epinephrine. [50]
Its actions increase peripheral resistance via α1 receptor-dependent vasoconstriction and increase cardiac output via its binding to β1 receptors. The goal of reducing peripheral circulation is to increase coronary and cerebral perfusion pressures and therefore increase oxygen exchange at the cellular level. [51] While epinephrine does increase aortic, cerebral, and carotid circulation pressure, it lowers carotid blood flow and end-tidal CO2 or ETCO2 levels. It appears that epinephrine may improve macrocirculation at the expense of the capillary beds where perfusion takes place. [52]
Extracts of the adrenal gland were first obtained by Polish physiologist Napoleon Cybulski in 1895. These extracts, which he called nadnerczyna, contained adrenaline and other catecholamines. [53] American ophthalmologist William H. Bates discovered adrenaline's usage for eye surgeries prior to 20 April 1896. [54] Japanese chemist Jōkichi Takamine and his assistant Keizo Uenaka independently discovered adrenaline in 1900. [55] [56] In 1901, Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen. [57] Adrenaline was first synthesized in the laboratory by Friedrich Stolz and Henry Drysdale Dakin, independently, in 1904. [56]
Common brand names include Asthmanefrin, Micronefrin, Nephron, VapoNefrin, and Primatene Mist.
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. [58] [59] It was introduced in 1963 by Armstrong Pharmaceuticals. [60]
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.
A bronchodilator or broncholytic is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs. Bronchodilators may be originating naturally within the body, or they may be medications administered for the treatment of breathing difficulties, usually in the form of inhalers. They are most useful in obstructive lung diseases, of which asthma and chronic obstructive pulmonary disease are the most common conditions. Although this remains somewhat controversial, they might be useful in bronchiolitis and bronchiectasis. They are often prescribed but of unproven significance in restrictive lung diseases.
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of 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.
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken orally or by intravenous injection. The formulation that is taken orally comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.
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) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.
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.
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.
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.
Isoprenaline, or isoproterenol, is a medication used for the treatment of bradycardia, heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropylamine analog of epinephrine (adrenaline).
Phenoxybenzamine is a non-selective, irreversible alpha blocker.
Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.
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.
The beta-1 adrenergic receptor, also known as ADRB1, can refer to either the protein-encoding gene or one of the four adrenergic receptors. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein that is expressed predominantly in cardiac tissue. In addition to cardiac tissue, beta-1 adrenergic receptors are also expressed in the cerebral cortex.
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.
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.
The catecholamines are a group of neurotransmitters composed of the endogenous substances dopamine, noradrenaline (norepinephrine), and adrenaline (epinephrine), as well as numerous artificially synthesized compounds such as isoprenaline - an anti-bradycardiac medication. Their investigation constitutes a major chapter in the history of physiology, biochemistry, and pharmacology. Adrenaline was the first hormone extracted from an endocrine gland and obtained in pure form, before the word hormone was coined. Adrenaline was also the first hormone whose structure and biosynthesis was discovered. Second to acetylcholine, adrenaline and noradrenaline were some of the first neurotransmitters discovered, and the first intercellular biochemical signals to be found in intracellular vesicles. The β-adrenoceptor gene was the first G protein-coupled receptor to be cloned.
β2-adrenoceptor agonists are a group of drugs that act selectively on β2-receptors in the lungs causing bronchodilation. β2-agonists are used to treat asthma and COPD, diseases that cause obstruction in the airways. Prior to their discovery, the non-selective beta-agonist isoprenaline was used. The aim of the drug development through the years has been to minimise side effects, achieve selectivity and longer duration of action. The mechanism of action is well understood and has facilitated the development. The structure of the binding site and the nature of the binding is also well known, as is the structure activity relationship.
Dopamine, sold under the brand name Intropin among others, is a medication most commonly used in the treatment of very low blood pressure, a slow heart rate that is causing symptoms, and, if epinephrine is not available, cardiac arrest. In newborn babies it continues to be the preferred treatment for very low blood pressure. In children epinephrine or norepinephrine is generally preferred while in adults norepinephrine is generally preferred for very low blood pressure. It is given intravenously or intraosseously as a continuous infusion. Effects typically begin within five minutes. Doses are then increased to effect.
Autonomic drugs can either inhibit or enhance the functions of the parasympathetic and sympathetic nervous systems. This type of drug can be used to treat a wide range of diseases, such as glaucoma, asthma, urinary, gastrointestinal and cardiopulmonary disorders.
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.
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ignored (help)Primatene® Mist was launched in 1963. The Primatene® Mist brand has built a long-time heritage for over-the-counter relief of bronchial asthma.