Epinephrine (Epinephrinum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Adreno- and sympathomimetics (alpha-, beta-)

Hypertensive agents

Included in the formulation
  • Adrenalin
    solution for injections 
    MOSCOW ENDOCRINE FACTORY, FSUE     Russia
  • Adrenalin
    solution locally 
    MOSCOW ENDOCRINE FACTORY, FSUE     Russia
  • Adrenalin-SOLOfarm
    solution for injections 
    GROTEKS, LLC     Russia
  • Epinephrine hydrochloride-Vial
    solution for injections 
    VIAL, LLC     Russia
  • EPIDZHECT®
    solution w / m 
    Meda AB     Sweden
    • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    C.01.C.A.24   Epinephrine

    Pharmacodynamics:

    Adrenomimetic, has a direct stimulating effect on α- and β-adrenergic receptors.

    Under the influence of epinephrine (adrenaline) due to stimulation of α-adrenoreceptors, the content of intracellular calcium in smooth muscles increases. Activation of α1β-adrenoreceptors increases the activity of phospholipase C (via stimulation of the G protein) and the formation of inositol triphosphate and diacylglycerol. This facilitates the release of calcium from the sarcoplasmic reticulum depot. Activation of α2-adrenoreceptors leads to the opening of calcium channels and an increase in calcium intake into cells.

    Stimulation of β-adrenergic receptors causes G-protein-induced activation of adenylate cyclase and an increase in cAMP production. This process is the trigger mechanism for the development of reactions from various target organs.As a result of stimulation of β1-adrenoceptors in the heart tissues there is an increase in intracellular calcium. When stimulating β2adrenoreceptors there is a decrease in free intracellular calcium in smooth muscles, caused on the one hand by an increase in its transport from the cell, and on the other hand by its accumulation in the depot of the sarcoplasmic reticulum.

    Has a pronounced effect on the cardiovascular system. Increases the frequency and strength of the heart, stroke and minute volume of the heart. Improves atrioventricular conductivity, increases automatism. Increases myocardial oxygen demand. It causes constriction of the vessels of the abdominal organs, skin, mucous membranes, to a lesser extent - skeletal muscles. Increases blood pressure (mainly systolic), in high doses increases the overall peripheral resistance of blood vessels. The pressor effect can cause a short-term reflex slowing of the heart rate.

    Epinephrine (adrenaline) relaxes the smooth muscles of the bronchi, lowers the tone and motility of the gastrointestinal tract, dilates the pupils, helps lower the intraocular pressure. It causes hyperglycemia and increases the content of free fatty acids in the plasma.

    Pharmacokinetics:

    Metabolized with the participation of MAO and catechol-O-methyltransferase in the liver, kidneys, gastrointestinal tract. Half-life is a few minutes. It is excreted by the kidneys.

    Penetrates through the placental barrier, does not penetrate the blood-brain barrier.

    Excreted in breast milk.

    Indications:

    Allergic reactions of immediate type (including urticaria, angioedema, anaphylactic shock), developing with the use of drugs, serums, blood transfusions, eating foods, insect bites or other allergens.

    Bronchial asthma (arresting an attack), bronchospasm during anesthesia.

    Asystole (including on the background of acute development of atrioventricular blockade of the third degree).

    Bleeding from the superficial vessels of the skin and mucous membranes (including gums).

    Arterial hypotension that does not respond to adequate volumes of replacement fluids (including shock, trauma, bacteremia, open heart surgery, kidney failure, chronic heart failure, drug overdose).

    The need to lengthen the action of local anesthetics.

    Hypoglycemia (due to an overdose of insulin).

    Open angle glaucoma, with surgical operations on the eyes - swelling of the conjunctiva (treatment), for dilated pupils, intraocular hypertension.

    In order to stop bleeding.

    Treatment of priapism.

    ICD-10

    IV.E15-E16.E16.0   Medication hypoglycaemia without coma

    VII.H40-H42.H40.1   Primary open angle glaucoma

    VII.H40-H42.H40.0   Suspicion of glaucoma

    IX.I95-I99.I95   Hypotension

    X.J40-J47.J45   Asthma

    XII.L50-L54.L50   Hives

    XIX.T66-T78.T78.2   Anaphylactic shock, unspecified

    XVIII.R50-R69.R57.8   Other types of shock

    XVIII.R50-R69.R57.1   Hypovolemic shock

    XVIII.R50-R69.R58   Bleeding, not elsewhere classified

    Contraindications:

    Hypertrophic obstructive cardiomyopathy, pheochromocytoma, arterial hypertension, tachyarrhythmia, IHD, ventricular fibrillation, pregnancy, lactation period, hypersensitivity to epinephrine.

    Carefully:

    Metabolic acidosis, hypercapnia, hypoxia, atrial fibrillation, ventricular arrhythmia, pulmonary hypertension, hypovolemia, myocardial infarction, shock of non-allergic genesis (including cardiogenic, traumatic, hemorrhagic), thyrotoxicosis, occlusive vascular diseases (including anamnesis - arterial embolism, atherosclerosis, Buerger's disease,cold trauma, diabetic endarteritis, Raynaud's disease), cerebral atherosclerosis, angle-closure glaucoma, diabetes mellitus, Parkinson's disease, seizure syndrome, prostatic hypertrophy; simultaneous use of inhalational anesthetics (halothane, cyclopropane, chloroform), advanced age, children's age.

    Increases the glycemia, and therefore in diabetes requires higher doses of insulin and sulfonylurea derivatives.

    Pregnancy and lactation:

    Recommendations for FDA - Category C.

    Strictly controlled studies of the use of epinephrine in pregnant women have not been conducted. A statistically consistent relationship between the appearance of malformations and inguinal hernia in children whose mothers were used epinephrine during the first trimester or during the entire pregnancy, there was also reported in one case the occurrence of anoxia in the fetus after intravenous guidance of the epinephrine mother. Epinephrine Do not use in pregnant women with BP above 130/80 mmHg. Experiments on animals have shown that when administered at doses 25 times higher than the recommended dose for a person, it causes a teratogenic effect.

    When used during breastfeeding, risk and benefit should be evaluated because of the high likelihood of side effects in the child.

    Dosing and Administration:

    Subcutaneously, intramuscularly, sometimes intravenously drip.

    Anaphylactic shock: intravenously slowly 0.1-0.25 mg diluted in 10 ml of 0.9% NaCl solution, if necessary continue intravenous drip introduction at a concentration of 0.1 mg / ml. When the patient's condition permits a slow action (3-5 minutes), it is preferable to administer intramuscularly (or subcutaneously) 0.3-0.5 mg in diluted or undiluted form, if necessary repeat administration - 10-20 minutes (up to 3 times).

    Bronchial asthma: subcutaneously 0.3-0.5 mg in diluted or undiluted form, if necessary, repeated doses can be administered every 20 minutes (up to 3 times), or intravenously by 0.1-0.25 mg in diluted concentration of 0 , 1 mg / ml.

    As a vasoconstrictor, intravenously injected at a rate of 1 μg / min (with a possible increase to 2-10 μg / min).

    To lengthen the action of local anesthetics: at a concentration of 5 μg / ml (the dose depends on the type of anesthetic used), for spinal anesthesia 0.2-0.4 mg.

    With asystole: intracardiac 0.5 mg (diluted with 10 ml of a 0.9% solution of NaCl or another solution); during resuscitation - 1 mg (diluted) intravenously every 3-5 minutes. If the patient is intubated, endotracheal instillation is possible-optimal doses are not established, should be 2-2.5 times the dose for intravenous administration.

    Newborns (asystole): intravenously 10-30 mcg / kg every 3-5 min, slowly. Children older than 1 month: intravenously 10 mcg / kg (subsequently, if necessary every 3-5 min, 100 μg / kg is administered (after administration of at least 2 standard doses, higher doses of 200 μg / kg can be used every 5 minutes) Possible use of endotracheal administration.

    Children with anaphylactic shock: subcutaneously or intramuscularly - 10 μg / kg (maximum - to 0.3 mg), if necessary, the administration of these doses is repeated every 15 minutes (up to 3 times).

    Children with bronchospasm: subcutaneously 10 μg / kg (maximum - up to 0.3 mg), doses are repeated if necessary every 15 minutes (up to 3-4 times) or every 4 hours.

    Locally: to stop bleeding in the form of tampons moistened with a solution of the drug.

    With open-angle glaucoma - 1 drop of 1-2% solution 2 times a day.

    Side effects:

    From the side of cardio-vascular system: less often - angina, bradycardia or tachycardia, palpitation, increase or decrease in blood pressure, at high doses - ventricular arrhythmias; rarely - arrhythmia, pain in the chest.

    From the side nervous system: more often - headache, anxiety, tremor; less often - dizziness, nervousness, fatigue, psychoneurotic disorders (psychomotor agitation, disorientation, memory impairment, aggressive or panic behavior, schizophreniform disorders, paranoia), sleep disturbance, muscle twitching.

    From the side digestive system: more often - nausea, vomiting.

    From the side urinary system: rarely - labored and painful urination (with prostatic hyperplasia).

    Local reactions: pain or burning in the place of intramuscular injection.

    Allergic reactions: angioedema, bronchospasm, skin rash, erythema multiforme.

    Other: rarely - hypokalemia; less often - increased sweating.

    Overdose:

    Symptoms: excessive increase in blood pressure, tachycardia, followed by bradycardia, rhythm disturbances (including atrial and ventricular fibrillation),coldness and pallor of the skin, vomiting, headache, metabolic acidosis, myocardial infarction, craniocerebral hemorrhage (especially in elderly patients), pulmonary edema, death.

    Treatment: stop the introduction. Symptomatic therapy: to reduce blood pressure - alpha-adrenoblockers (phentolamine), with arrhythmias - beta-adrenoblockers (propranolol).

    Interaction:

    Antagonists of epinephrine are blockers of alpha and beta-adrenergic receptors.

    Weakens the effects of narcotic analgesics and hypnotic drugs.

    When applied simultaneously with cardiac glycosides, quinidine, tricyclic antidepressants, dopamine, agents for inhalation anesthesia (chloroform, enflurane, halothane, isoflurane, methoxyflurane), the risk of arrhythmias increases with cocaine (together it should be used very carefully or not at all); with other sympathomimetic agents - increased severity of side effects from the cardiovascular system; with antihypertensive agents (including diuretics) - a decrease in their effectiveness.

    Simultaneous administration with MAO inhibitors (including furazolidone, procarbazine, selegiline) can cause a sudden and pronounced increase in blood pressure, hyperpyretic crisis, headache, cardiac arrhythmias, vomiting; with nitrates - weakening of their therapeutic effect; with phenoxybenzamine - increased hypotensive effect and tachycardia; with phenytoin - a sudden decrease in blood pressure and bradycardia (depends on the dose and rate of administration); with preparations of thyroid hormones - mutual reinforcement of action; with drugs that extend the QT-interval (including astemizole, cisapride, terfenadine) - prolongation of the QT-interval; with diatrizoatami, iotalamovoy or yoksaglovoj acids - intensification of neurologic effects; with alkaloids of ergot - increased vasoconstrictor effect (up to pronounced ischemia and development of gangrene).

    Reduces the effect of insulin and other hypoglycemic agents.

    Easily destroyed by alkalis and oxidizing agents.

    Special instructions:

    Infusion should be carried out in a large (better in the central) vein. For infusion, a device with a measuring device should be used to regulate the infusion rate.

    Intra-cardinally administered with asystole, if other methods are not available, since there is a risk of cardiac tamponade and pneumothorax.

    During the treatment period it is recommended to determine the concentration of K+ in blood serum, measurement of blood pressure, diuresis, minute volume of circulation, ECG, central venous pressure, pulmonary artery pressure and wedging pressure in the pulmonary capillaries.

    Excessive doses of myocardial infarction can increase ischemia by increasing myocardial oxygen demand.

    With endotracheal injection, the absorption and final concentration of the drug in the plasma can be unpredictable.

    The introduction of epinephrine in shock states does not replace transfusion of blood, plasma, blood-substituting fluids and / or saline solutions.

    Epinephrine is inexpedient to apply for a long time (narrowing of peripheral vessels, leading to the possible development of necrosis or gangrene).

    Use to correct hypotension during labor is not recommended, since it can delay the second stage of labor; when administered in large doses to reduce uterine contractions, can cause a prolonged atony of the uterus with bleeding.

    It can be used in children with cardiac arrest, but caution is necessary, since two different concentrations of epinephrine are required in the dosing regimen.

    When discontinuing treatment, the dose should be reduced gradually, since sudden withdrawal of therapy can lead to severe hypotension.

    If the solution has become pinkish or brown or contains sediment, it can not be administered. Unused part should be destroyed.

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