에핀에피린 C화학적 특성, 용도, 생산
개요
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.
화학적 성질
off-white powder
용도
Endogenous catcholamine with combined α-and β-agonist activity. Principal sympathomimetic hormone produced by the adrenal medulla. Bronchodilator; cardiostimulant; mydriatic; antiglaucoma.
생산 방법
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.
정의
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.
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.
일반 설명
White to nearly-white microcrystalline powder or granules. Odorless. Melting point 211-212°C. Aqueous solutions are slightly alkaline. Slightly bitter, numbing taste.
공기와 물의 반응
L(-)-Epinephrine 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.
반응 프로필
L(-)-Epinephrine is incompatible with oxidizers, alkalis, copper, iron, silver, zinc and other metals; gum and tannin. L(-)-Epinephrine is also incompatible with acids, acid chlorides and acid anhydrides. L(-)-Epinephrine reacts with salts of sulfurous acid .
화재위험
Flash point data for L(-)-Epinephrine are not available. L(-)-Epinephrine is probably combustible.
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
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.
부작용
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.
Safety Profile
Human poison by
subcutaneous route. Experimental poison by
ingestion, skin contact, subcutaneous,
intraperitoneal, intravenous, and
intramuscular routes. Human systemic
effects: cardiomyopathy includmg infarction,
arrhythmias. An experimental teratogen.
Experimental reproductive effects. Mutation
data reported. When heated to
decomposition it emits toxic fumes of NOx.
Used as an adrenergic, sympathomimetic,
vasoconstrictor, bronchodilator, and cardiac
stimulant.
신진 대사
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.]
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