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Epinephrin

Epinephrine

HCID 5816
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Grundinformationen

CAS
51-43-4
Standard-SMILES
CNC[C@H](O)c1ccc(O)c(O)c1
InChIKey
UCTWMZQNUQWSLP-VIFPVBQESA-N
Summenformel
C9H13NO3
Durchschnittliche Molmasse
183,2 g/mol
Monoisotopische Masse
183,08954328

Überblick

Epinephrine appears as white to nearly-white microcrystalline powder or granules. Odorless. Melting point 211-212 °C. Aqueous solutions are slightly alkaline. Slightly bitter, numbing taste.

Namen und Bezeichner

Bevorzugter Name
Epinephrine
IUPAC
4-[(1R)-1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol
Lokaler Name
Epinephrin
Englischer Name
L(-)-Epinephrine
Summenformel
C9H13NO3
Molmasse
183.2

Namen und Synonyme

epinephrinel-AdrenalineadrenalineAdrenalinLevoepinephrineNephridineEpinefrinaEpipen(-)-AdrenalineAdnephrineChelafrinEpinephran
Weitere Namen anzeigen
(-)-EPINEPHRINEEPINEPHRINEPINEPHERINEEpinefrinL-EPINEPHRINE
EpirenanRenoform(R)-AdrenalineHypernephrinRenostypticinAdrenineHemisineHemostasin

Datenbank-Bezeichner

CAS
51-43-4、840507-49-5
PubChem CID
5816
DTXSID
DTXSID5022986
ChEMBL
CHEMBL42280、CHEMBL679
ChEBI
CHEBI:28918
UNII
YKH834O4BH
EC Number
200-098-7
Nikkaji
J9.224J

Eigenschaften

Berechnete StruktureigenschaftenWird ergänzt

XLogP
-1,4
Polarare Oberfläche (TPSA)
72,7 Ų
H-Brücken-Donoren
4
H-Brücken-Akzeptoren
4
Frei drehbare Bindungen
3
Schwere Atome
13
Formalladung
0
Komplexität
154

Experimentelle und physikochemische Eigenschaften

Drugs · 2 Einträge

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Sympathomimetics

LogP · 2 Einträge

log Kow = -2.59

-1.37

OdorOdorless
Color/Form · 5 Einträge

Brown (in air)

Minute crystals, gradually browning on exposure to liaght and air

Light brown or nearly white crystalline powder

Colorless microcrystals

White to nearly white, microcrystalline powder or granules.

Solubility · 6 Einträge

less than 0.1 mg/mL at 64 °F (NTP, 1992)

less than 0.1 mg/mL at 64° F

Very slightly soluble in alcohol. Readily soluble in aqueous solutions of mineral acids, NaOH, and KOH. Insoluble in aqueous solutions of ammonia and of the alkali carbonates. Insoluble in chloroform, ether, acetone, oils.

Very slightly soluble in alcohol.

Insoluble in ethanol; soluble in acetic acid

In water, 180 mg/L at 20 °C

Human Drugs · 5 Einträge

Breast Feeding; Lactation; Milk, Human; Adrenergic Agonists; Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Antiglaucoma Agents; Bronchodilator Agents; Catecholamines; Mydriatics; Sympathomimetics; Vasoconstrictor Agents

Sicherheit und Regulatorisches

Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.

GHS-Klassifizierung

GHS Classification · 4 Einträge

Danger

H301 (96.1%): Toxic if swallowed [Danger Acute toxicity, oral]

P261, P262, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P316, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 103 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Gefahrenhinweise

Regulatory Information · 2 Einträge

Chemical: 1,2-Benzenediol, 4-[1-hydroxy-2-(methylamino)ethyl]-, (R)-

Epinephrine: Does not have an individual approval but may be used under an appropriate group standard

Other Safety InformationIMAP assessments - 1,2-Benzenediol, 4-[1-hydroxy-2-(methylamino)ethyl]-, (R)-: Human health tier I assessment
DOT LabelPoison
Fire HazardsFlash point data for this chemical are not available. It is probably combustible. (NTP, 1992)
Health Hazards · 1 Eintrag

SYMPTOMS: Symptoms of exposure to this compound may include restlessness, anxiety, fear, throbbing headache, tremor, weakness, dizziness, palpitations, cerebral hemorrhage and cardiac arrhythmias. Other symptoms may include pallor, tenseness and respiratory difficulty. The blood pressure is markedly raised initially but may be below normal later, and may be accompanied by persistent anuria. Exposure may also result in ventricular fibrillation, dyspnea, hyperglycemia, tachycardia, coldness of the extremities and pulmonary edema. Exposure may also result in convulsions, nausea and vomiting, chills, cyanosis, irritability, fever, nervousness, suicidal behavior, mania, blurred vision, opisthotonus, spasms, gasping respiration, coma, respiratory failure and, rarely, death. Contact with this compound may cause irritation. It may also cause contact dermatitis. Inhalation may cause bronchial irritation, sleeplessness and rapid heartbeat. It may also cause epigastric pain. Inhalation or injection of the decomposed chemical will cause a psychosis-like state with hallucinations and morbid fears. Prolonged nasal use leads to chronic nasal congestion. Facial flushing has been reported. Other symptoms of exposure include faintness, trembling, perspiration and extrasystoles. Eye effects include epithelial disturbances such as allergy or contact sensitivity characterized by itching and burning sensation, epiphora and hyperemia of the conjunctiva and lids; reactive hyperemia, tiny black or dark-brown deposits in the conjunctiva, "black cornea", epithelial edema and, rarely, follicular conjunctivitis, white keratinized plaque in the conjunctiva, ocular pemphigoid, loss of eyelashes, excessive tearing and persistent meibomianitis. Other eye effects include corneal endothelial disturbances such as dilated pupils and corneal edema; retinopathy and choroidopathy; lens changes and intraocular pressure. Eye inflammation also occurs.

Chemie und Industrie

Pharmakologische Informationen

ATC Code · 6 Einträge

C01CA24

A - Alimentary tract and metabolism

B - Blood and blood forming organs

S - Sensory organs

C - Cardiovascular system

R - Respiratory system

Pharmacodynamics · 1 Eintrag

Epinephrine is a sympathomimetic drug. It causes an adrenergic receptive mechanism on effector cells and mimics all actions of the sympathetic nervous system except those on the facial arteries and sweat glands. Important effects of epinephrine include increased heart rate, myocardial contractility, and renin release via beta-1 receptors. Beta-2 effects produce bronchodilation which may be useful as an adjunct treatment of asthma exacerbations as well as vasodilation, tocolysis, and increased aqueous humor production. In croup, nebulized epinephrine is associated with both clinically and statistically significant transient reduction of croup symptoms 30 minutes post-treatment. Epinephrine also alleviates pruritus, urticaria, and angioedema and may be helpful in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxing effects on the smooth muscle of the stomach, intestine, uterus, and urinary bladder.

Mechanism of Action · 5 Einträge

Epinephrine acts on alpha and beta-adrenergic receptors. Epinephrine acts on alpha and beta receptors and is the strongest alpha receptor activator. Through its action on alpha-adrenergic receptors, epinephrine minimizes the vasodilation and increased the vascular permeability that occurs during anaphylaxis, which can cause the loss of intravascular fluid volume as well as hypotension. Epinephrine relaxes the smooth muscle of the bronchi and iris and is a histamine antagonist, rendering it useful in treating the manifestations of allergic reactions and associated conditions. This drug also produces an increase in blood sugar and increases glycogenolysis in the liver. Through its action on beta-adrenergic receptors, epinephrine leads to bronchial smooth muscle relaxation that helps to relieve bronchospasm, wheezing, and dyspnea that may occur during anaphylaxis.

The mechanism of rise in blood pressure ... is threefold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), vasoconstriction in many vascular beds, especially in precapillary resistance vessels of skin, mucosa, and kidney, along with marked constriction of veins.

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FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Antiallergics and medicines used in anaphylaxis

Animal Drugs · 2 Einträge

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Pharmaceuticals -> UK Veterinary Medicines Directorate List

DecompositionWhen heated to decomposition it emits toxic fumes of /nitrogen oxides/.
Melting Point · 4 Einträge

412 to 414 °F (NTP, 1992)

211.5 °C

MP: 211-212 °C, approximately 215 °C with decomposition when heated rapidly

211.5 °C

Optical Rotation · 2 Einträge

Specific optical rotation = -50 deg to -53.3 deg at 25 °C/D (in 0.6N HCl)

Specific optical rotation = -53 deg at 20 °C/D (aqueous HCl)

Physical Description · 2 Einträge

Epinephrine appears as white to nearly-white microcrystalline powder or granules. Odorless. Melting point 211-212 °C. Aqueous solutions are slightly alkaline. Slightly bitter, numbing taste.

Solid

Stability/Shelf Life · 1 Eintrag

In some commercially available injections, the air has been replaced with nitrogen to avoid oxidation. Withdrawal of doses from multiple-dose vials introduces air into the vials, subjecting the remaining epinephrine to oxidation. Oxidation of the drug imparts first a pink, then a brown color; epinephrine preparations must not be used if they have a pinkish or darker than slightly yellow color or contain a precipitate.

Physikochemische Eigenschaften

Schmelzpunkt
215 °C · 215 °C (dec.)(lit.)
Siedepunkt
316.88 °C · 316.88°C (rough estimate)
Dichte
1.1967 · 1.1967 (rough estimate)
Brechungsindex
-51.5 ° · -51.5 ° (C=4, 1mol/L HCl)
storage temp.
2 · 2-8°C
Löslichkeit
Practically insoluble in water, in ethanol (96 per cent) and in methylene chloride. It dissolves in hydrochloric acid.
pka
8.66 · 8.66(at 25℃)
Aggregatzustand
Fine Crystalline Powder
Farbe
White to light beige
Wasserlöslichkeit
0.01 g/100 · <0.01 g/100 mL at 18 ºC
Decomposition
212 °C · > 212°C
Merck
14 · 14,3619
BRN
2368277 · 2368277
Henry's Law Constant
1.4 · 1.4×1013 mol/(m3Pa) at 25℃, HSDB (2015)
Stabilität
Stable. Incompatible with acids, acid chlorides, acid anhydrides, oxidizing agents. Light sensitive.
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
InChIKey
UCTWMZQNUQWSLP-VIFPVBQESA-N
SMILES
CNC[C@H](O)c1ccc(O)c(O)c1
CAS Datenbank
51 · 51-43-4(CAS DataBase Reference)
NIST chemische Informationen
L-adrenaline(51-43-4)
EPA chemische Informationen
Epinephrine (51-43-4)
Hazards Summary · 1 Eintrag

The major hazards encountered in the use and handling of epinephrine stem from its toxicologic properties. Exposure to this odorless, white-to-light brown, crystalline substance may occur from its production or medical use as a topical hemostat on bleeding surfaces, a cardiac stimulant, bronchodilator, antiglaucoma agent, and to relieve hypersensitivity reactions. Effects from exposure may include anxiety, headache, nausea, palpitations, tremor, myocardial infarction, pulmonary edema, or renal failure. Because of its instability in the presence of light or air, epinephrine should be stored in tight, light-resistant containers. Epinephrine is a good candidate for disposal by fluidized bed, rotary kiln, or liquid injection forms of incineration.

FDA Requirements · 4 Einträge

Bronchodilator active ingredients. The active ingredients of the product consist of any of the following when used within the dosage limits established for each ingredient: Epinephrine and epinephrine bitartrate are included on this list.

Vasoconstrictor active ingredients. The active ingredient of the product consists of any of the following when used in the concentration or within the concentration range established for each ingredient. Epinephrine and epinephrine hydrochloride are included on this list.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl epinephrine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl epinephrine bitartrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Epinephrine bitartrate/

Reactive GroupAmines, Phosphines, and Pyridines
Special ReportsDHHS/NTP; Toxicology & Carcinogenesis Studies of l-Epinephrine Hydrochloride in F344/N Rats and B6C3F1 Mice Technical Report Series No. 380 (1990) NIH Publication No. 90-2835 /l-Epinephrine hydrochloride/
RCRA Requirements · 1 Eintrag

P042; As stipulated in 40 CFR 261.33, when epinephrine, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

Reactivity ProfileEPINEPHRINE is incompatible with oxidizers, alkalis, copper, iron, silver, zinc and other metals; gum and tannin. It is also incompatible with acids, acid chlorides and acid anhydrides. It reacts with salts of sulfurous acid (NTP, 1992).
Air and Water ReactionsThis chemical darkens slowly on exposure to air and light. Water insoluble. Readily soluble in aqueous solutions of inorganic acids. Solutions undergo oxidation in the presence of oxygen.

Sicherheit und Schutzausrüstung

Fire FightingFires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)
First Aid · 1 Eintrag

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Storage Conditions · 2 Einträge

Epinephrine injection should be stored at room temperature (approximately 25 °C).

Preserve in tight, light-resistant containers.

Nonfire Spill Response · 1 Eintrag

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with 5% acetic acid, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% acetic acid to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% acetic acid followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

Disposal Methods · 3 Einträge

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number p042, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

1. A good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. 2. A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. 3. A good candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds.

Isolation and EvacuationExcerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:
Personal Protective Equipment (PPE) · 1 Eintrag

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

Toxikologische Informationen

Interactions · 5 Einträge

Use in patients taking propranolol and other nonselective beta blockers may produce severe hypertension owing to blockade of beta-2-mediated vasodilation, resulting in unopposed alpha-vasoconstriction.

Epinephrine should not be administered concomitantly with other sympathomimetic agents because of the possibility of additive effects and increased toxicity.

Administration of epinephrine in patients receiving cyclopropane or halogenated hydrocarbon general anesthetics that increase cardiac irritability and seem to sensitize the myocardium to epinephrine may result in arrhythmias including PVCs, tachycardia, or fibrillation. Epinephrine is contraindicated for use with chloroform, trichloroethylene, or cyclopropane and should be used cautiously, if at all, with other halogenated hydrocarbon anesthetics such as halothane. Epinephrine may not be absorbed rapidly enough to cause serious adverse effects when applied topically as a hemostatic in patients undergoing short surgical procedures such as tonsillectomy and adenoidectomy using halothane anesthesia. Prophylactic administration of lidocaine or prophylactic IV administration of propranolol 0.05 mg/kg may protect against ventricular irritability if epinephrine is used during anesthesia with a halogenated hydrocarbon anesthetic. In one study, arrhythmias occurring after parenteral use of epinephrine during general anesthesia responded promptly to IV propranolol 0.05 mg/kg.

The effects of epinephrine 1/200,000 added to mg of epidural morphine were investigated in 3 healthy male volunteers, during 26 hr observation sessions. Cutaneous hypalgesia was intense, faster in onset, and longer in duration after epinephrine-morphine than after plain morphine. Apparently, epinephrine 1/200,000 reduces manifestations of cord and brainstem uptake. The need for the reduction of the customary dose of epidural morphine, while epinephrine is used as an adjuvant, is discussed.

For more Interactions (Complete) data for EPINEPHRINE (20 total), please visit the HSDB record page.

Environmental Fate · 3 Einträge

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 73(SRC), determined from a structure estimation method(2), indicates that epinephrine is expected to have high mobility in soil(SRC). The pKa1 of epinephrine, a catecholamine(7), is 8.28(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because epinephrine partially exists as a cation and cations do not volatilize. Volatilization of the neutral species of epinephrine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.1X10-19 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Epinephrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.4X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Epinephrine deteriorates rapidly on exposure to air or light, turning red from oxidation to adrenochrome(7). Biodegradation data were not available(SRC, 2009); however, the compound was not affected by various strains of Mycobacterium(8).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 73(SRC), determined from a structure estimation method(2), indicates that epinephrine is not expected to adsorb to suspended solids and sediment(SRC). A pKa1 of 8.28(3) indicates epinephrine will exist partially in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(4). According to a classification scheme(5), an estimated BCF of 3.162(SRC), from its log Kow of -2.59(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Epinephrine deteriorates rapidly on exposure to air or light, turning red from oxidation to adrenochrome(8). Biodegradation data were not available(SRC, 2009); however, the compound was not affected by various strains of Mycobacterium(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), epinephrine, which has an estimated vapor pressure of 7.4X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase epinephrine may be removed from the air by wet or dry deposition(SRC). Epinephrine deteriorates rapidly on exposure to air or light, turning red from oxidation to adrenochrome(3).

Adverse EffectsCommon adverse effects of epinephrine include tachycardia, hypertension, headache, anxiety, apprehension, palpitations, diaphoresis, nausea, vomiting, weakness, and tremors. The adverse effects are listed by system as follows:
Milk ConcentrationsEpinephrine is distributed into milk.
Toxicity SummarySigns and Symptoms of Overdose
Ongoing Test Status · 1 Eintrag

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Epinephrine hydrochloride/[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=55-31-2]

Soil Adsorption/Mobility · 1 Eintrag

Using a structure estimation method based on molecular connectivity indices(1), the Koc of epinephrine can be estimated to be 73(SRC). According to a classification scheme(2), this estimated Koc value suggests that epinephrine is expected to have high mobility in soil. The pKa1 of epinephrine is 8.28(3), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

Natural Pollution Sources · 1 Eintrag

Epinephrine is a naturally occurring hormone, which is released from the adrenal medulla and is involved in the regulation of blood pressure and smooth muscle constriction(1). Epinephrine naturally occurs at the ends of sympathetic nerve fibers where they serve as chemical mediators for carrying nerve impulses(2).

Human Toxicity Excerpts · 5 Einträge

/HUMAN EXPOSURE STUDIES/ Normal human beings have shown no significant changes in the a- and b-waves after injection of 1 mg of epinephrine, ... /during/ ERG /electroretinogram/ studies.

/SIGNS AND SYMPTOMS/Pulmonary edema with rales, rhonchi, dyspnea, frothy or bloody sputum, and an atypical chest x-ray picture may occur after an epinephrine overdose. pulmonary edema usually develops within 20 minutes. It is unclear whether this pulmonary edema is cardiogenic or acute lung injury.

/SIGNS AND SYMPTOMS/ Gas gangrene after IM administration of epinephrine has been reported. Three cases of gas gangrene after IM injection of epinephrine have occurred subsequent to administration of the drug into either the buttock or thigh. Two cases have resulted in death and only one case had appropriate treatment with gas gangrene antiserum, steroids, and antibiotics that resulted in survival of the patient. It appears that clostridium organisms become deposited into muscle tissue during penetration of the skin and that the vasoconstrictor properties of adrenaline enhance the effects of the infection.

/SIGNS AND SYMPTOMS/ Syncope has been reported in pediatric patients after administration of 0.05 to 0.2 mL of epinephrine in the treatment of asthma attacks. Syncope is often accompanied with pallor, unconsciousness, weakness, tachycardia, and hypotension.

For more Human Toxicity Excerpts (Complete) data for EPINEPHRINE (20 total), please visit the HSDB record page.

Artificial Pollution SourcesEpinephrine production and medicinal use as a bronchodilator, cardiostimulant, mydriatic, and antiglaucoma agent(1), may result in its release to the environment through various waste streams(SRC).
Environmental BiodegradationPURE CULTURE: Mycobacterium smegmatis, M. vaccae, M. parafortiutum, and M. chitae with known pyrocatechase activity were tested for their activity on epinephrine; the compound was not affected by these bacteria(1).
Drug Induced Liver Injury · 6 Einträge

Drug Induced Liver Injury Rank (DILIrank 2.0)

Epinephrine

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

Regulatorische Informationen

FDA Requirements · 4 Einträge

Bronchodilator active ingredients. The active ingredients of the product consist of any of the following when used within the dosage limits established for each ingredient: Epinephrine and epinephrine bitartrate are included on this list.

Vasoconstrictor active ingredients. The active ingredient of the product consists of any of the following when used in the concentration or within the concentration range established for each ingredient. Epinephrine and epinephrine hydrochloride are included on this list.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl epinephrine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl epinephrine bitartrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Epinephrine bitartrate/

RCRA Requirements · 1 Eintrag

P042; As stipulated in 40 CFR 261.33, when epinephrine, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

CERCLA Reportable Quantities · 1 Eintrag

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1000 lb or 454 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV.D.3.b).

Sicherheitsdaten

F
8-10-23
wgk
3
tsca
TSCA listed
ridadr
UN 2811 6.1/PG 2
hs_code
29373100
RTECS-Nr.
DO2625000
risk_code
23/24/25-52/53-36/37/38-33
Toxizität
LD50 i.p. in mice: 4 mg/kg (Lands)
hazard_code
T
safety_code
36/37/39-45-61-26-23
hazard_class
6.1
packing_group
II
Speicherklasse
6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials
Giftige Stoffe Daten
51-43-4(Hazardous Substances Data)
Hazard Classifications
Acute Tox. 2 DermalAcute Tox. 3 InhalationAcute Tox. 3 Oral

... Epinephrine affects respiration primarily by relaxing bronchial muscle. It has a powerful bronchodilator action, most evident when bronchial muscle is contracted because of disease, as in bronchial asthma, or in response to drugs or various autacoids. In such situations, epinephrine has a striking therapeutic effect as a physiological antagonist to substances that cause bronchoconstriction. The beneficial effects of epinephrine in asthma also may arise from inhibition of antigen-induced release of inflammatory mediators from mast cells, and to a lesser extent from diminution of bronchial secretions and congestion within the mucosa. Inhibition of mast cell secretion is mediated by beta2 receptors, while the effects on the mucosa are mediated by alpha receptors

The electrophysiologic effects of circulating epinephrine in humans were examined in four study groups of 10 subjects each. In 10 subjects without structural heart disease (Group 1) and in 10 patients with coronary disease or dilated cardiomyopathy (Group 2) epinephrine infusion at 25 and 50 ng/kg body weight per min for 14 min resulted in an elevation of the plasma epinephrine concentration in the physiologic range. In both groups it produced a dose-dependent decrease in the effective refractory period of the atrium, atrioventricular node and ventricle and improvement in atrioventricular node conduction. Epinephrine facilitated the induction of sustained ventricular tachycardia in 3 of the 20 subjects. In Group 3, a beta-adrenergic blocking dose of propranolol was added to the infusion of 50 ng/kg per min of epinephrine. Propranolol not only reversed the effects of epinephrine, but also lengthened these variables compared with baseline values. In group 4, propranolol was administered first, followed by 50 ng/kg per min of epinephrine. Propranolol alone slowed atrioventricular node conduction and mildly prolonged the refractory periods. In the presence of beta-blockade, epinephrine had no effect on atrioventricular node properties but resulted in a lengthening of the atrial and ventricular effective refractory periods. In conclusion, epinephrine in physioloic doses shortens the effective refractory period of the atrium, atrioventricular node and ventricle, improves atrioventricular node conduction and may facilitate the induction of sustained ventricular tachycardia. The overall electrophysiologic effects of epinephrine result from stimulation of beta-receptors. Stimulation of alpha-receptors by epinephrine has no effect on the atrioventricular node but prolongs the effective refractory period of the atrium and ventricle, partially offsetting the shortening of refractory periods mediated by beta-receptor stimulation.

Epinephrine plays a key role in the control of vasomotor tone; however, the participation of the NO/cGMP pathway in response to beta-adrenoceptor activation remains controversial. To evaluate the involvement of the endothelium in the vascular response to epinephrine, we assessed NO production, endothelial NO synthase phosphorylation, and tissue accumulation of cGMP in the perfused arterial mesenteric bed of rat. Epinephrine elicited a concentration-dependent increase in NO (EC(50) of 45.7 pM), which was coupled to cGMP tissue accumulation. Both NO and cGMP production were blocked by either endothelium removal (saponin) or NO synthase inhibition (N(omega)-nitro-L-arginine). Blockade of beta(1)- and beta(2)-adrenoceptors with 1 microM propranolol or beta(3)-adrenoceptor with 10 nM SR 59230A displaced rightward the concentration-NO production curve evoked by epinephrine. Selective stimulation of beta(1)-, beta(2)-, or beta(3)-adrenoceptors also resulted in NO and cGMP production. Propranolol (1 microM) inhibited the rise in NO induced by isoproterenol or the beta(2)-adrenoceptor agonists salbutamol, terbutaline, or fenoterol. Likewise, 10 nM SR 59230A reduced the effects of the beta(3)-adrenoceptor agonists BRL 37344, CGP 12177, SR 595611A, or pindolol. The NO production induced by epinephrine and BRL 37344 was associated with the activation of the phosphatidylinositol 3-kinase/Akt pathway and phosphorylation of eNOS in serine 1177. In addition, in anaesthetized rats, bolus administration of isoproterenol, salbutamol, or BRL 37344 produced NO-dependent reductions in systolic blood pressure. These findings indicate that beta(1)-, beta(2)-, and beta(3)-adrenoceptors are coupled to the NO/cGMP pathway, highlighting the role of the endothelium in the vasomotor action elicited by epinephrine and related beta-adrenoceptor agonists.

Biological Half-Life · 2 Einträge

The plasma half-life is approximately 2-3 minutes. However, when administered by subcutaneous or intramuscular injection, local vasoconstriction may delay absorption so that epinephrine's effects may last longer than the half-life suggests.

Elimination half life is 1 minute.

Metabolism/Metabolites · 4 Einträge

Epinephrine is rapidly inactivated mainly by enzymic transformation to metanephrine or normetanephrine, either of which is then conjugated and excreted in the urine in the form of both sulfates and glucuronides. Either sequence results in the formation of 3-methoxy-4- hydroxy-mandelic acid(vanillylmandelic acid, VMA) which is shown to be detectable in the urine. Epinephrine is rapidly inactivated in the body mostly by the enzymes COMT (catechol-O-methyltransferase) and MAO (monoamine oxidase). The liver is abundant in the above enzymes, and is a primary, although not essential, tissue in the degradation process.

The pharmacologic actions of epinephrine are terminated mainly by uptake and metabolism in sympathetic nerve endings. Circulating drug is metabolized in the liver and other tissues by a combination of reactions involving the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). The major metabolites are metanephrine and 3-methoxy-4-hydroxymandelic acid (vanillylmandelic acid, VMA) both of which are inactive. About 40% of a parenteral dose of epinephrine is excreted in urine as metanephrine, 40% as VMA, 7% as 3-methoxy-4-hydroxyphenoglycol, 2% as 3,4-dihydroxymandelic acid, and the remainder as acetylated derivatives. These metabolites are excreted mostly as the sulfate conjugates and, to a lesser extent, the glucuronide conjugates. Only small amounts of the drug are excreted unchanged.

Circulating epinephrine is metabolized in the liver and is taken up into adrenergic neurons and metabolized by MAO and catechol-O-methyltransferase to metadrenaline, sulfate conjugates, and hydroxy derivatives of mandelic acid.

Epinephrine has known human metabolites that include Epinephrine sulfate.

FDA Pharmacological Classification · 6 Einträge

YKH834O4BH

EPINEPHRINE

Mechanisms of Action [MoA] - Adrenergic alpha-Agonists

Mechanisms of Action [MoA] - Adrenergic beta-Agonists

Established Pharmacologic Class [EPC] - alpha-Adrenergic Agonist

Established Pharmacologic Class [EPC] - beta-Adrenergic Agonist

MeSH Pharmacological Classification · 6 Einträge

Drugs that selectively bind to and activate alpha adrenergic receptors.

Drugs that selectively bind to and activate beta-adrenergic receptors.

Agents that cause an increase in the expansion of a bronchus or bronchial tubes.

Agents that dilate the pupil. They may be either sympathomimetics or parasympatholytics.

Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.

Drugs used to cause constriction of the blood vessels.

Absorption, Distribution and Excretion · 6 Einträge

Following I.V. (intravenous) injection, epinephrine disappears rapidly from the blood stream. Subcutaneously or I.M. (intramuscular) administered epinephrine has a rapid onset and short duration of action. Subcutaneous (SC) administration during asthmatic attacks may produce bronchodilation within 5 to 10 minutes, and maximal effects may occur within 20 minutes. The drug becomes fixed in the tissues rapidly,.

The majority of the dose of epinephrine is seen excreted in the urine,. About 40% of a parenteral dose of epinephrine is excreted in urine as metanephrine, 40% as VMA, 7% as 3-methoxy-4-hydroxyphenoglycol, 2% as 3,4-dihydroxymandelic acid, and the rest as acetylated derivatives. These metabolites are excreted mainly as the sulfate conjugates and, to a lesser extent, the glucuronide conjugates. Only small amounts of the drug are excreted completely unchanged.

Intravenous injection produces an immediate and intensified response. Following intravenous injection, epinephrine disappears rapidly from the blood stream.

Following topical application of radiolabeled epinephrine to the eye in rabbits, highest concentrations of the drug in tissues and fluids other than the eye occurred in the pituitary gland, with lower concentrations in the intestine, fat, adrenal gland, kidney, heart, lung, spleen, ovary, pancreas, liver, uterus, muscle, brain, and serum. In humans, systemically absorbed epinephrine crosses the placenta but not the blood-brain barrier. Systemically absorbed epinephrine distributes into milk.

Epinephrine is not effective after oral admin because it is rapidly conjugated and oxidized in GI mucosa and liver. Absorption from sc tissues occurs slowly because of local vasoconstriction ... Absorption is more rapid after im than after sc injection ... Epinephrine is rapidly inactivated in the body.

In a prospective, randomized, five-way crossover study in rabbits, ... plasma epinephrine concentrations /were measured/ before, and at intervals up to 180 min after epinephrine administration by intramuscular or subcutaneous injection, or by inhalation, with intravenous epinephrine and intramuscular saline as the positive and negative controls, respectively. Maximum plasma epinephrine concentrations were higher, and occurred more rapidly, after intramuscular injection than after subcutaneous injection or inhalation, and were 7719+/-3943 (S.E.M.) pg/mL at 32.5+/-6.6 min, 2692+/-863 pg/mL at 111.7+/-30.8 min and 1196+/-369 pg/mL at 45. 8+/-19.2 min, respectively. Intravenous injection of epinephrine resulted in a plasma concentration of 3544+/-422 pg/mL at 5 min, and an elimination half-life (t(1/2)) of 11.0+/-2.5 min. In the saline control study, the endogenous epinephrine concentration peaked at 518+/-142 pg/mL. CONCLUSION: In this model, absorption of epinephrine was significantly faster after intramuscular injection than after subcutaneous injection or inhalation. The extent of absorption was satisfactory after both intramuscular and subcutaneous injections. Neither the rate nor the extent of absorption was satisfactory after administration by inhalation.

Tissue LocationsAdipose Tissue
Cellular LocationsCytoplasm
Metabolite PathwaysAlkaptonuria

Verwendung und Herstellung

Uses · 6 Einträge

Epinephrine may be applied topically to control superficial bleeding from arterioles or capillaries in the skin, mucous membrane, or other tissues. Bleeding from larger vessels is not controllable by topical application of epinephrine.

Epinephrine has been used to relax uterine musculature and inhibit uterine contractions in premature labor; however the cardiovascular effects and other adverse effects limit the usefullness of the drug for this purpose. Some manufacturers state that epinephrine injection is contraindicated during the second stage of labor.

Drug of choice for emergency treatment of severe allergic reactions to insect stings or bites, foods, drugs, and other allergens.

Used in the treatment of idiopathic or exercise-induced anaphylaxis

For more Uses (Complete) data for EPINEPHRINE (9 total), please visit the HSDB record page.

Use (kg; approx.) in Germany (2009): >10

Impurities · 3 Einträge

Adrenalone /SRP: Adrenalone is the keto form of epinephrine/

2-(benzylmethylamino)-1-(3,4-dihydroxyphenyl)ethanone

Noradrenaline

U.S. Imports · 3 Einträge

(1977) 5.58X10+5 g (princpl custms dists)

(1979) 6.45X10+5 g (princpl custms dists

(1983) 5.49X10+7 g

U.S. Production · 2 Einträge

(1975) Probably greater than 4.54x10+5 g

(1979) No Data

Methods of Manufacturing · 3 Einträge

Reaction of pyrocatechol with chloroacetyl chloride, followed by reaction with methylamine, catalytic redn, and separation of racemic mixt with d-tartaric acid.

Isolation from animal adrenal glands.

From the adrenal glands of sheep and cattle or syntehtically from pyrocatechol

Formulations/Preparations · 5 Einträge

EpiPen Auto-Injector

Grade: USP

Adrenalin-medihaler

Adrenamine

For more Formulations/Preparations (Complete) data for EPINEPHRINE (91 total), please visit the HSDB record page.

Use ClassificationPharmaceuticals -> Animal Drugs -> Approved in Taiwan
General Manufacturing Information1,2-Benzenediol, 4-[(1R)-1-hydroxy-2-(methylamino)ethyl]-: ACTIVE
Anwendungen · 2 Einträge

BeschreibungThe combination of the catechol nucleus, the β-hydroxyl group, and the N-methyl give EPI a direct action and a strong affinity for all adrenergic receptors. Epinephrine and all other catechols are chemically susceptible to oxygen and other oxidizing agents, especially in the presence of bases and light, quickly decomposing to inactive quinones. Therefore, all catechol drugs are stabilized with antioxidants and dispensed in air-tight amber containers.

VerwendenEndogenous catcholamine with combined α-and β-agonist activity. Principal sympathomimetic hormone produced by the adrenal medulla. Bronchodilator; cardiostimulant; mydriatic; antiglaucoma.

Vor- und nachgelagerte Produkte

Vorgelagerte Rohstoffe

Ammoniak, wssrige LsungRacepinefrinAcetonD(-)-Tartaric acidMethylamin, gasförmig

Ergänzende Hinweise

DefinitionChEBI: The R-enantiomer of adrenaline. It is a hormone secreted by the adrenal glands resulting in the 'fight-or-flight' response.