General Description
White to nearly-white microcrystalline powder or granules. Odorless. Melting point 211-212°C. Aqueous solutions are slightly alkaline. Slightly bitter, numbing taste.
Reactivity Profile
EPINEPHRINE(51-43-4) is incompatible with oxidizers, alkalis, copper, iron, silver, zinc and other metals; gum and tannin. EPINEPHRINE(51-43-4) is also incompatible with acids, acid chlorides and acid anhydrides. EPINEPHRINE(51-43-4) reacts with salts of sulfurous acid .
Air & Water Reactions
This 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.
Fire Hazard
Flash point data for this chemical are not available. EPINEPHRINE is probably combustible.
Description
The 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.
Chemical Properties
off-white powder
Originator
Adrenalin,Sopharma,Bulgaria
Uses
Endogenous catcholamine with combined α-and β-agonist activity. Principal sympathomimetic hormone produced by the adrenal medulla. Bronchodilator; cardiostimulant; mydriatic; antiglaucoma.
Uses
Gibberellic Acid-3 (GA-3) is a plant growth regulator
Uses
L-Adrenaline (Epinephrine) belongs to a group of the compounds known as catecholamines, which play an important role in the regulation of physiological process in living organisms. The antioxidant activity and antioxidant mechanism of L-adrenaline was cla
Definition
ChEBI: The R-enantiomer of adrenaline. It is a hormone secreted by the adrenal glands resulting in the 'fight-or-flight' response.
Indications
Epinephrine administered subcutaneously is used to
manage severe acute episodes of bronchospasm and
status asthmaticus. In addition to its bronchodilator activity
through β-adrenoceptor stimulation, a portion of
the therapeutic utility of epinephrine in these acute settings
may be due to a reduction in pulmonary edema as
a result of pulmonary vasoconstriction, the latter effect
resulting from α-adrenoceptor stimulation.
Production Methods
Epinephrine is synthesized in the body from the nonessential amino acid tyrosine. Tyrosineundergoes hydroxylation to produce DOPA (3,4-dihydroxyphenylalanine). DOPA decarboxylationproduces dopamine, which is hydroxylated to norepinephrine. Norepinephrine, whichis closely related to epinephrine, performs a number of similar functions in the body. The prefix “nor” associated with a compound is used to denote an alkylated nitrogen in the compoundthat has lost an alkyl group. It comes from the German N-ohne-radical, which means Nitrogenwithout the radical. Therefore norepinephrine is epinephrine minus the methyl, CH3, radicalon the nitrogen. The methylation of norepinephrine gives epinephrine.
Manufacturing Process
1 part by weight of ω-chloro-3,4-dihydroxyacteophenone in 1 part by weight
of ethanol was heated with 60% aqueous solution of methylamine. The crystal
of 3,4-dihydroxy-ω-methylaminoacteophenone obtained was transformed in
hydrochloride by action of diluted hydrochloric acid. The base of (-)-3,4-
dihydroxy-ω-methylaminoacteophenone was prepared by addition of
ammonium hydroxide solution.
Brand name
Bronkaid (Bayer); Epipen (Meridian);
Primatene (Wyeth); Sus-Phrine (Forest); Twinject (Verus);Adrefil;Adrehinal;Adrenalin medihal;Adrenalina ace.p.d.;Adrenalina clorhi;Adrenalina delta;Adrenalina fustery;Adrenalina hormona;Adrenalina p davis;Adrenalina wiener;Bronkaid mistometer;Cetanest;D epinefrin;Dento-caine;Depinefrin;Dysne-inhal;E-caprine;Epiboran ofteno;Epinephrine pediatric;Epineramine;Glaucadrine;Glaucoaicon;Glauconin;Glaucotahil;Isopto epinefrina;Levoreninl-adrenaline;Licothionil;Lidoacton;Lyodrin;Marcaom;Methylaminoethanolcatechol;Neo-rybarex;Niphridine;Orostat;P2e1;Paranephrine;Piladren;Sedo-asmol;Suprarenine;Suprexon 5;Susphrine;Vaponephrine;Xylestesin a.
Therapeutic Function
Vasoconstrictor
World Health Organization (WHO)
Epinephrine, first isolated in 1899, is the main hormone secreted
by the adrenal medulla. It is widely used as a vasoconstrictor substance and in the
treatment of anaphylactic shock. Its use in combination with local anaesthetics to
prolong infiltration anaesthesia has been associated with systemic reactions
including serious cardiovascular and cerebrovascular incidents. Regulations
restricting the concentrations permitted in such preparations have been introduced
in many countries but combination products containing epinephrine or levarterenol
in concentrations of 1:80,000 or less remain widely available. Representative
preparations are included in the WHO Model List of Essential Drugs.
(Reference: (WHTAC1) The Use of Essential Drugs, 2nd Report of the WHO Expert
Committee, 722, , 1985)
Biological Functions
Epinephrine is found only in very low concentrations in
the mammalian CNS, and it is unlikely to play a major
role as a neurotransmitter.
Biochem/physiol Actions
Adrenoceptor agonist.
Mechanism of action
The effects on pulmonary function are quite rapid, with peak effects
occurring within 5 to 15 minutes. Measurable improvement
in pulmonary function is maintained for up
to 4 hours.The characteristic cardiovascular effects seen
at therapeutic doses of epinephrine include increased
heart rate, increased cardiac output, increased stroke
volume, an elevation of systolic pressure and decrease
in diastolic pressure, and a decrease in systemic vascular
resistance. The cardiovascular response to epinephrine
represents the algebraic sum of both α- and β-adrenoceptor
stimulation. A decrease in diastolic blood pressure
and a decrease in systemic vascular resistance are
reflections of vasodilation, a β2-adrenoceptor response.
The increase in heart rate and systolic pressure is the result
of either a direct effect of epinephrine on the myocardium,
primarily a β1 effect, or a reflex action provoked
by a decrease in peripheral resistance, mean
arterial pressure, or both. Overt α-adrenoceptor effects,
such as systemic vasoconstriction, are not obvious unless
large doses are used.
Clinical Use
Epinephrine is used in a variety of clinical situations,
and although concern has been expressed about the use
of epinephrine in asthma, it is still used extensively for
the management of acute attacks.
Clinical Use
The ability of epinephrine to stimulate β2-receptors hasled to its use by injection and by inhalation to relaxbronchial smooth muscle in asthma and in anaphylacticreactions. Several OTC preparations (e.g., Primatene, Bronkaid)used for treating bronchial asthma use E. It is also usedin inhibiting uterine contraction. Because of its α-activity, Eis used to treat hypotensive crises and nasal congestion, toenhance the activity of local anesthetics, and as a constrictorin hemorrhage.
In addition, E is used in the treatment of open-angle glaucoma,where it apparently reduces intraocular pressure byincreasing the rate of outflow of aqueous humor from theanterior chamber of the eye. The irritation often experiencedon instillation of E into the eye has led to the developmentof other preparations of the drug that potentially are not asirritating. One such example is dipivefrin.
Side effects
Patients treated with recommended dosages of epinephrine
will complain of feeling nervous or anxious.
Some will have tremor of the hand or upper extremity
and many will complain of palpitations. Epinephrine is
dangerous if recommended dosages are exceeded or if
the drug is used in patients with coronary artery disease,
arrhythmias, or hypertension. The inappropriate use of
epinephrine has resulted in extreme hypertension and
cerebrovascular accidents, pulmonary edema, angina,
and ventricular arrhythmias, including ventricular fibrillation.
At recommended dosages, adverse effects from inhaled
isoproterenol are infrequent and not serious.
When excessive dosages are used, tachycardia, dizziness,
and nervousness may occur, and some patients
may have arrhythmias.
Synthesis
Epinephrine, L-1-(3,4-dihydroxyphenyl)-2-methylaminoethanol (11.1.2), is
obtained from the adrenal glands tissue of livestock [1,2] as well as in a synthetic manner.
Epinephrine is synthesized from ω-chloro-3,4-dihydroxyacetophenone—chloroacetylpyrocatechine—the reaction of which with excess of methylamine gives ω-methylamino-3,4-
dihydroxyacetophenone (11.1.1). Reduction of this using hydrogen over Raney nickel, or
action of aluminum amalgam, or electrolytic reduction gives D,L-epinephrine (11.1.2) [3–9],
which is separated into isomers using (+) tartaric acid .
Veterinary Drugs and Treatments
Epinephrine is employed primarily in veterinary medicine as a
treatment for anaphylaxis
or cardiac resuscitation. Because of its
vasoconstrictive properties, epinephrine is added to local anesthetics
to retard systemic absorption and prolong effect.
Drug interactions
Potentially hazardous interactions with other drugs
Alpha-blockers: avoid with tolazoline.
Anaesthetics: increased risk of arrhythmias if given
with volatile anaesthetics.
Antidepressants: increased risk of arrhythmias and
hypertension if given with tricyclics; MAOIs and
moclobemide may cause hypertensive crisis.
Beta-blockers: increased risk of severe hypertension
and bradycardia.
Clonidine: possible increased risk of hypertension.
Dopaminergics: effects possibly increased by
entacapone; avoid concomitant use with rasagiline.
Guanethidine: increased risk of hypertension.
Sympathomimetics: effects possibly enhanced by
dopexamine.
Metabolism
Epinephrine is ultimately metabolized by COMT and MAO to 3-methoxy-4-hydroxy-mandelic acid
(vanillylmandelic acid), which is excreted as the sulfate or glucuronide in the urine.
Only a very small amount is excreted unchanged.
Purification Methods
L-Adrenaline has been recrystallised from EtOH/AcOH/NH3 [Jensen J Am Chem Soc 57 1765 1935]. Itis sparingly soluble in H2O, readily in acidic or basic solutions but insoluble in aqueous NH3, alkali carbonate solutions, EtOH, CHCl3, Et2O or Me2CO. It has also been purified by dissolving in dilute aqueous acid, then precipitating it by adding dilute aqueous ammonia or alkali carbonates. It is readily oxidised in air and turns brown on exposure to light and air. (Epinephrine readily oxidises in neutral alkaline solution. This can be diminished if a little sulfite is added). Store it in the dark under N2. [Lewis Br J Pharmacol Chemother 9 488 1954]. The hydrogen oxalate salt has m 191-192o(dec, evacuated capillary) after recrystallisation from H2O or EtOH [Pickholz J Chem Soc 928 1945]. [Beilstein 13 H 830, 13 III/IV 2927.]
Toxicity evaluation
Epinephrine is
available in nebulized racemic dosage form for inhalation.Intoxication from catecholamine usually results from iatrogenic
overdoses, accidental intravenous administration, and the
injection of solution intended for nebulization. High concentrations
of dopamine present inside of a cell than there are
vesicles to store it in, oxidative stress can occur and cause damage
or death to the cell. It is thought that dopamine overload causes
biochemical damage to cellular mitochondria, that provide the
cell with all of the energy it requires to function, resulting in
death of the cell. Catecholamines produced circulatory changes
that reversed propofol anesthesia in animal models.