Adrenaline, 0.1% 1 ml 5 pcs

Pharmacotherapeutic group: α- and β-adrenomimetic.

ATX code: C01СА24

Pharmacological properties

.Pharmacodynamics

Sympathomimetic acting on α- and β-adrenoreceptors. Its action is caused by activation of receptor-dependent adenylate cyclase on the inner surface of the cell membrane, increase of intracellular concentration of cyclic adenosine monophosphate (cAMP) and calcium ions (Ca²⁺).

In very low doses, at a rate of administration of less than 0.01 µg/kg/min may decrease blood pressure due to dilation of skeletal musculature vessels. At an administration rate of 0.04-0.1 µg/kg/min, it increases heart rate and force, blood stroke volume and minute blood volume, and reduces total peripheral vascular resistance; above 0.02 µg/kg/min, it narrows vessels, increases blood pressure (mainly systolic) and total peripheral vascular resistance. The pressor effect may cause a transient reflex slowing of the heart rate.

The relaxation of bronchial smooth muscles. Doses above 0.3 µg/kg/min decrease renal blood flow, blood flow to internal organs, and gastrointestinal tone and motility.

Dilates the pupils and helps reduce intraocular fluid production and intraocular pressure. Causes hyperglycemia (increases glycogenolysis and gluconeogenesis) and increases plasma free fatty acid content.

Increases myocardial conduction, excitability and automatism. Increases myocardial oxygen demand.

Inhibits induced release of histamine and leukotrienes by antigens, eliminates spasm of bronchioles and prevents development of edema of their mucous membranes.

Acting on α-adrenoreceptors located in the skin, mucous membranes and internal organs it causes vasoconstriction, decrease of absorption rate of local anesthetic agents, increase of duration and decrease of toxic effect of local anesthetic.

Stimulation of β₂-adrenoreceptors is accompanied by increased excretion of potassium ions (K⁺) from the cell and may lead to hypokalemia.

In intracavernous administration, it reduces the blood filling of the cavernous bodies.

The therapeutic effect develops almost immediately with intravenous injection (duration of action 1-2 minutes), 5-10 minutes after subcutaneous injection (maximum effect after 20 minutes), with intramuscular injection the time of onset of effect is variable.

Pharmacokinetics

absorption

In intramuscular or subcutaneous administration, it is well absorbed. When administered parenterally, it breaks down quickly. It is also absorbed by endotracheal and conjunctival administration. Time to reach maximum concentration in blood when administered subcutaneously and intramuscularly is 3-10 minutes. It penetrates through the placenta and into the breast milk; it does not penetrate through the blood-brain barrier.

Metabolism

Metabolized mainly by monoaminoxidase and catechol-O-methyltransferase in sympathetic nerve endings and other tissues, as well as in the liver to form inactive metabolites. The half-life with intravenous administration is 1-2 minutes.

Evacuation

Evacuated by the kidneys mainly as metabolites: vanillylmindalic acid, sulfates, glucuronides, and in small amounts unchanged.

Indications

Active ingredient

Composition

1 ml of the solution contains:

The active ingredient:

epinephrine (adrenaline) – 1.00 mg

Associates:

sodium chloride – 8.00 mg, sodium disulfite (sodium metabisulfite) – 1.00 mg, chlorobutanol hemihydrate (chlorobutanolhydrate), equivalent to 5.00 mg of chlorobutanol, edetate – 0.50 mg, glycerol (glycerin) – 60.00 mg, hydrochloric acid (hydrochloric acid) – to pH 2.5-4.0, water for injection – up to 1 ml.

How to take, the dosage

Subcutaneously, intramuscularly, intravenously drip.

Allergic reactions of immediate type (anaphylactic shock): intravenously slowly 0.1-0.25 mg diluted in 10 ml of 0.9% sodium chloride solution, if necessary continue intravenous drip infusion at a concentration of 1:10000. If there is no immediate threat to life, intramuscular or subcutaneous administration of 0.3-0.5 mg is preferable, if necessary, repeated administration after 10-20 minutes up to 3 times.

Bronchial asthma: subcutaneously 0.3-0.5 mg, if necessary repeated doses can be given every 20 minutes up to 3 times, or intravenously 0.1-0.25 mg with dilution at a concentration of 1:10000.

In asystole: intracardiac 0.5 mg (diluted with 10 ml of 0.9% sodium chloride solution or other solution); during resuscitation, 0.5-1 mg (diluted) intravenously every 3-5 minutes. If the patient is intubated, endotracheal instillation is possible – the doses should be 2-2.5 times the doses for intravenous administration.

Stopping bleeding: locally in the form of swabs moistened with the drug solution.

In case of arterial hypotension: intravenous drip 1 mcg/min, the rate of administration can be increased to 2-10 mcg/min.

To prolong the action of local anesthetics:at a concentration of 0.005 mg/ml (the dose depends on the type of anesthetic used), for spinal anesthesia 0.2-0.4 mg.

Morgany-Adams-Stokes syndrome (bradyarrhythmic form) at a dose of 1 mg in 250 mL of 5% glucose solution intravenously, gradually increasing the infusion rate until a minimum adequate heart rate is achieved.

As a vasoconstrictor: Intravenous drip 1 mcg/min, the infusion rate can be increased to 2-10 mcg/min.

Application in pediatric practice:

Infants (asystole): intravenously, 10-30 mcg/kg every 3-5 minutes, slowly.

Children over 1 month: intravenously, 10 mcg/kg (thereafter, 100 mcg/kg every 3-5 minutes if necessary (after at least 2 standard doses, higher doses of 200 mcg/kg can be used every 5 minutes). Endotracheal administration can be used.

Children in anaphylactic shock: subcutaneously or intramuscularly 0.01 mg/kg (up to 0.3 mg max), if necessary these doses are repeated every 15 minutes (up to 3 times).

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

Interaction

Special Instructions

The determination of serum potassium ion concentration (K+), measurement of blood pressure, diuresis, minute volume of circulation, electrocardiogram, central venous pressure, pulmonary artery pressure and pulmonary capillary wedging pressure are recommended during treatment.

The excessive doses of epinephrine in myocardial infarction may exacerbate ischemia by increasing myocardial oxygen demand.

Epinephrine increases plasma glucose levels, requiring higher doses of insulin and sulfonylurea derivatives in diabetics.

The use of epinephrine is inadvisable for the long term (narrowing of peripheral blood vessels, leading to possible development of necrosis or gangrene).

The use to correct reduced blood pressure during labor is not recommended because it may delay the second period of labor; if administered in high doses to weaken uterine contractions, it may cause prolonged uterine atony with bleeding.

Doses should be reduced gradually when discontinuing treatment, since abrupt withdrawal of therapy can lead to severe arterial hypotension.

It is easily broken down by alkalis and oxidizing agents. Sodium metabisulfite, a component of the drug, may cause an allergic reaction, including symptoms of anaphylaxis and bronchospasm, especially in patients with a history of asthma or allergies. Epinephrine should be used with caution in patients with tetraplegia because of the increased sensitivity of such individuals to epinephrine.

The rapid increase in blood pressure when using epinephrine can lead to hemorrhage, especially in elderly patients with cardiovascular disease.

Patients with Parkinson’s disease may have psychomotor agitation or temporary worsening of symptoms when using adrenaline, and therefore caution should be exercised when using adrenaline in this population.

Do not inject repeatedly into the same areas to avoid development of tissue necrosis. Injection into the gluteal muscles is not recommended.

Epinephrine should be used with caution in elderly patients, patients with coronary heart disease, arterial hypertension, diabetes mellitus, hyperthyroidism, prostatic hyperplasia and urinary disorders.

Particular caution should be exercised when using epinephrine in patients with long-standing bronchial asthma, pulmonary emphysema, and organic heart disease (pulmonary heart disease).

Epinephrine may cause cardiac rhythm disturbances and myocardial ischemia, especially in patients with coronary heart disease or cardiomyopathy.

Epinephrine increases cardiac output and causes peripheral vasoconstriction, which may lead to pulmonary edema.

Epinephrine causes narrowing of the renal arterioles, which can lead to oliguria and renal failure.

Intramuscular injection of epinephrine should be given into the anterolateral surface of the thigh (in the lateral broad muscle of the thigh). Injection into smaller muscles (e.g. deltoid) is not recommended.

Rare cases of severe skin and soft tissue infections, including Clostridia necrotizing fasciitis and muscle necrosis (gas gangrene), at the site of epinephrine administration for anaphylaxis have been described. Patients should be warned to seek medical attention immediately if symptoms of infection, such as persistent redness, increased skin temperature, swelling, or soreness at the site of epinephrine injection occur.

The drug should not be injected into the vessels of the fingers, hands and feet because epinephrine is a powerful vasoconstrictor and can lead to poor blood supply and tissue necrosis (gangrene).

Do not use the drug if there is a discoloration or residue in the solution. The unused portion of the solution should be disposed of.

Influence on the ability to drive vehicles, mechanisms

After using the drug the doctor shall decide on a case-by-case basis whether the patient is allowed to drive vehicles or engage in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Synopsis

Contraindications

The use of epinephrine in combination with local anesthetics is not recommended for local anesthesia in fingers and toes because of the risk of ischemic tissue damage.

In emergency conditions, all contraindications are relative.

With caution

Side effects

The incidence of side effects was determined according to the World Health Organization classification: very common (≥ 1/10), common (≥ 1/100, < 1/10), infrequent (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), including individual reports.

Immune system disorders: infrequent- angioedema, bronchospasm, skin rash, erythema multiforme.

Nervous system disorders: often – headache, anxiety, tremor, tics;not infrequently – dizziness, nervousness, fatigue, nausea, vomiting, personality disorders (psychomotor agitation, disorientation, memory disturbance, psychotic disorders: aggressive or panic behavior, schizophrenic-like disorders, paranoia), sleep disturbance, muscle twitching.

Cardiac disorders: infrequent- angina pectoris, bradycardia or tachycardia, palpitations, increased or decreased blood pressure, at high doses – ventricular arrhythmias (including ventricular fibrillation); frequently- arrhythmias, chest pain, pulmonary edema.

vascular disorders: infrequent increase or decrease in blood pressure; rare – pulmonary edema.

Gastrointestinal tract disorders: frequently – nausea, vomiting.

Skin and subcutaneous tissue disorders: infrequent – increased sweating.

Recreational and urinary tract disorders: rarely – difficulty and painful urination (with prostatic hyperplasia).

General disorders and disorders at the site of injection: infrequent – pain or burning at the site of intramuscular injection.

Laboratory and instrumental findings: rarely – hypokalemia.

Overdose

Pregnancy use