Adrenaline

General characteristics. Structure:

Active ingredient: 1 mg of Epinephrinum (adrenaline) in 1 ml of solution.

Excipients: sodium chloride, sodium disulphite, (sodium metabisulphite) chlorobutanol гемигидрат (хлоробутанолгидрат), equivalent to chlorobutanol, dinatrium эдетат, (disodium salt of ethylene diamine tetraacetic acid) глицерол (glycerin), Acidum hydrochloricum, water for injections.

Pharmacological properties:

Pharmacodynamics. Action is caused by activation of retseptorzavisimy adenylatecyclase on an internal surface cellular, membranes, increase in intracellular concentration of cyclic adenosinemonophosphate (tsAMF) and calcium ions (Sa2+).

In very low doses, at rate of administering arterial pressure, owing to vasodilatation of skeletal muscles can reduce less than 0,01 mkg/kg/min. At rate of administering of 0,04-0,1 mkg/kg/min. increases the frequency and force of cordial reductions, a stroke output of blood and minute volume of blood, reduces the general peripheric vascular resistance; higher than 0,02 mkg/kg/min. narrow vessels, increases arterial pressure (mainly, systolic) and the general peripheric vascular resistance. The pressor effect can cause short-term reflex delay of heart rate.

Weakens unstriated muscles of bronchial tubes. Doses are higher than 0,3 mkg/kg/min., reduce a renal blood stream, blood supply of internals, a tone and, motility of digestive tract. Expands pupils, promotes decrease in products of intraocular liquid and intraocular pressure. Causes a hyperglycemia (strengthens a glycogenolysis, and a gluconeogenesis) and increases the content in plasma of free fatty acids.

Increases conductivity, excitability and automatism of a myocardium. Increases the need of a myocardium for oxygen. Inhibits the release of a histamine and leukotrienes induced by antigens, eliminates a spasm, bronchioles, prevents edematization of their mucous membrane.

Affecting the alpha adrenoceptors located in skin, mucous membranes and internals causes vasoconstriction, reduction in the rate of absorption of mestnoanesteziruyushchy means, increases duration and reduces toxic influence of local anesthesia.

Stimulation of b2-adrenoceptors is followed by strengthening of removal of potassium ions (To +) from a cell and can lead to a hypopotassemia.

At intrakavernozny introduction reduces a krovenapolneniye of cavernous bodies.

The therapeutic effect develops almost instantly at intravenous administration (action duration - 1-2 min.), in 5-10 min. after hypodermic introduction (the maximum effect - in 20 min.), at intramuscular introduction - time of the beginning of effect variable.

Pharmacokinetics. Absorption. At intramuscular or hypodermic introduction it is well soaked up. Entered parenterally, quickly collapses. Also it is absorbed at endotracheal and conjunctival introduction. Time of achievement of the maximum concentration in blood. at hypodermic and. intramuscular introduction - 3-10 min. Gets through a placenta, into breast milk, does not get through a blood-brain barrier.

Metabolism. It is metabolized generally by a monoaminooxidase and katekhol-O-methyltransferase in the terminations of sympathetic nerves and other fabrics, and also in a liver with formation of inactive metabolites. An elimination half-life at intravenous administration - 1-2 min.

Removal. It is removed by kidneys in a main type of metabolites: vanililmindalny acid, sulfates, glucuronides, and also in insignificant quantity - in not changed look.

Indications to use:

· The allergic reactions of immediate type (including a small tortoiseshell, a Quincke's disease, an acute anaphylaxis) developing at use of medicines, serums, hemotransfusion, the use of foodstuff, stings of insects or administration of other allergens; asthma of physical effort;

· Bronchial asthma (stopping of the asthmatic status), a bronchospasm during an anesthesia;

· An asystolia (including against the background of sharply developed atrioventricular block of the III degree);

· Bleeding from superficial vessels of skin and mucous membranes (including from gums);

· The arterial hypotension which is not giving in to influence of adequate volumes of the replacing liquids (including shock, bacteremia, open heart operations, a renal failure);

· Need of lengthening of effect of local anesthetics;

· Episodes, a full atrioventricular block (with development of a syncopal state (Morganyi-Adams-Stokes's syndrome));

· Bleeding stop (as vasoconstrictor).

Route of administration and doses:

Subcutaneously, intramusculary, intravenously kapelno.

Allergic reactions of immediate type (acute anaphylaxis): intravenously slowly 0,1-0,25 mg of 0,9% of solution of sodium of chloride divorced in 10 ml, if necessary continue intravenous drop administration in concentration 1:10000. In the absence of direct, threats of life, introduction intramuscular or hypodermic 0,3-0,5 mg, if necessary repeated introduction in 10-20 min. to 3 times is more preferable.

Bronchial asthma: subcutaneously 0,3-0,5 mg, if necessary it is possible to enter repeated doses every 20 min. to 3 times, or intravenously on 0,1-0,25 mg with cultivation into concentration 1:10000.

At an asystolia: vnutriserdechno 0,5 mg (dilute 10 ml of 0,9% of solution of sodium of chloride or other solution); during the resuscitation actions - on 0,5 - 1 mg (in the diluted look) intravenously each 3-5 min. If the patient is intubated, endotracheal instillation is possible - doses have to exceed by 2-2,5 times doses for intravenous administration.

Stop of bleedings - locally in the form of the tampons moistened with drug solution.

At arterial hypotension: intravenously kapelno 1 mkg/min., rate of administering it is possible to increase to 2-10 mkg/min.

For lengthening of effect of local anesthetics: in concentration of 0,005 mg/ml (the dose depends on a type of the used anesthetic), for spinal anesthesia - 0,2 - 0,4 mg.

Morganyi-Adams-Stokes's syndrome (bradiaoitmichesky Form) in a dose of 1 mg in 250 ml of 5% of solution of glucose intravenously, gradually increasing infusion speed before achievement of minimum sufficient number of cordial reductions.

As vasoconstrictor: intravenously kapelno 1 mkg/min.; it is possible to increase rate of administering to 2-10 mkg/min.:

Use in children's practice:

- newborns (asystolia): intravenously, to 10-30 mkg/kg there are each 3-5 min., slowly.

- to children: is more senior than 1 month: intravenously, 10 mkg/kg (in the subsequent if necessary each 3-5 min. enter 100 mkg/kg (after introduction, at least, 2 standard doses it is possible to use each 5 min. higher doses - 200 mkg/kg). It is possible to use endotracheal introduction.

- to children at an acute anaphylaxis: subcutaneously or intramusculary on 0,01 mg/kg (as much as possible - to 0,3 mg), if necessary introduction of these doses is repeated every 15 min. (to Z times).

- to children at a bronchospasm: subcutaneously 10 mkg/kg (as much as possible - to 0,3 mg), if necessary repeat doses each 15 min.; (to 3-4 times) or each 4 h.

Features of use:

Accidental intravenous administration of Epinephrinum can cause sharp increase in arterial pressure.

Increase in arterial pressure at administration of drug can cause stenocardia attacks. Epinephrinum can cause a konstriktion of capillaries of kidneys, reducing thereby a diuresis.

At infusion it is necessary to use the device with measuring adaptation for the purpose of regulation of speed of infusion.

Infusions should be carried out in large (better in central) a vein.

Vnutriserdechno is entered at an asystolia if other ways are unavailable since there is a risk of a cardiac tamponade and pheumothorax.

During treatment, definition of concentration of potassium ions (To +) in blood serum, measurement of arterial pressure, a diuresis, minute volume of blood circulation, the electrocardiogram, the central venous pressure, pulmonary pressure and pressure of jamming in pulmonary capillaries is recommended. Overdoses at a myocardial infarction, can strengthen ischemia by increase in need of a myocardium for oxygen.

Increases a glycemia, in, bonds with what at a diabetes mellitus higher doses of insulin and derivatives of sulphonylurea are required.

At endotracheal introduction absorption and final concentration of drug in plasma can be unpredictable.

Introduction of Epinephrinum at shock, states does not replace hemotransfusion, plasma, blood-substituting liquids and/or saline solutions.

Epinephrinum is inexpedient to be applied is long (the narrowing of peripheral vessels leading to possible development of a necrosis or gangrene).

Strictly controlled researches of use of Epinephrinum for pregnant women are not conducted. The interrelation of emergence of malformations and inguinal hernia at children whose mothers applied Epinephrinum during the I trimester or throughout all pregnancy is established statistically natural, it was reported also in one case about emergence of an anoxia, at a fruit, after intravenous maintaining - mothers of Epinephrinum.

Use for correction of reduced arterial pressure at the time of delivery is not recommended as can detain the second stage of childbirth; at introduction in high doses for weakening of reduction of a uterus can, cause a long atony of a uterus with bleeding.

It is possible to use at children at a cardiac standstill, however it is necessary to be careful.

At the termination, treatments of a dose follows, to reduce gradually since. Sudden cancellation of therapy can lead to a lowering of arterial pressure.

Easily collapses alkiruyushchy substances and oxidizers, including chlorides, bromides, nitrites, iron salts, peroxides.

If solution gained pinkish or brown color or contains a deposit it it is impossible to enter. An unused part should be destroyed.

Influence on ability to manage vehicles and mechanisms. After drug use the doctor has to individually, resolve in each case issues of the admission of the patient to management of transport or occupation by other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions

Side effects:

Classification of frequency of development of side effects (WHO): very often> 1/10; often from> 1/100 to <1/10; infrequently from> 1/1000 to <1/100; seldom from> 1/10000 to <1/1000; very seldom from <1/10000, including separate messages.

From cardiovascular system: infrequently - stenocardia, bradycardia or tachycardia, a heart consciousness, increase or decrease arterial - pressure, at high doses - ventricular arrhythmias (including fibrillation of ventricles); seldom - arrhythmia, thorax pain, a fluid lungs.

From a nervous system: often - a headache, an alarming state, a tremor; a tic, infrequently - dizziness, nervousness, fatigue, nausea, vomiting, frustration of the personality (psychomotor excitement, a disorientation, memory disturbance, psychotic frustration: agressive or panic behavior, shizofrenopodobny frustration, paranoia), sleep disorder, muscular twitchings.

From the alimentary system: often - nausea, vomiting.

From an urinary system: seldom - - complicated and an urodynia (at a prostate hyperplasia).

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

Allergic reactions: infrequently - a Quincke's disease, a bronchospasm, skin rash, a mnogoformny erythema.

Others: infrequently - the increased sweating; seldom - a hypopotassemia.

If the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Antagonists of Epinephrinum are blockers and - and b - adrenoceptors.

Efficiency of use of Epinephrinum is reduced at the patients with heavy anaphylactic reactions accepting b-adrenoblockers. In this case intravenously apply salbutamol.

Use together with other adrenomimetika can strengthen effect of Epinephrinum.

Weakens effects of narcotic analgetics and somnolent drugs.

At use along with cardiac glycosides, quinidine, tricyclic antidepressants, a dopamine, means for an inhalation anesthesia (энфлуран, a halothane, изофлуран, метоксифлуран), cocaine the risk of development of arrhythmias increases (together it is necessary to apply extremely carefully or at all not to apply); with other adrenomimetika - strengthening of expressiveness of side effects from outside, cardiovascular system; with anti-hypertensive means - decrease in their efficiency.

With diuretics - increase in pressor effect of Epinephrinum is possible. Simultaneous use with the drugs inhibiting a monoaminooxidase (Procarbazinum, селегилин, and also furasolidone) can cause the sudden and expressed increase in arterial pressure, hyperpyrexial crisis, a headache, heart arrhythmias, vomiting; with nitrates - weakening of their therapeutic action; with phenoxybenzamine - strengthening of hypotensive effect and tachycardia; with Phenytoinum - a sudden lowering of arterial pressure and bradycardia (depends on a dose and rate of administering); with drugs of hormones, a thyroid gland - mutual strengthening of action; with the medicines extending a QT interval (including astemizoly, tsizapridy, terfenadiny) - lengthening of a QT interval; with Diatrizoatums, yotalamovy or yoksaglovy acids - strengthening of neurologic effects; with ergot alkaloids - strengthening of vasopressor effect (up to the expressed ischemia and a gangrenosis).

Reduces effect of insulin and other hypoglycemic medicines.

Contraindications:

Hypersensitivity to any of drug components, arterial hypertension, expressed атеросклеррз (including cerebral atherosclerosis), a hypertrophic subaortic stenosis, a tachyarrhythmia, coronary heart disease, fibrillation of ventricles, fibrillation of auricles, ventricular arrhythmias, chronic heart failure 3-4 degrees, a myocardial infarction, a pheochromocytoma, a thyrotoxicosis, a diabetes mellitus, acute and chronic arterial insufficiency (including in the anamnesis - an arterial embolism, atherosclerosis, a Thrombangiitis obliterans, a diabetic endarteritis, a Raynaud's disease), a hypovolemia, a metabolic acidosis, a hypercapnia, a hypoxia, pulmonary hypertensia, shock of not allergic genesis (including cardiogenic, traumatic, hemorrhagic), a cold injury, Parkinson's disease; organic injuries of a brain, closed-angle glaucoma, convulsive syndrome, prostate hyperplasia, age up to 18 years (except states, directly life-threatening), pregnancy, the lactation period, simultaneous use of inhalation means for the general anesthesia (halothane), do not apply Epinephrinum in a combination with local anesthetics to local anesthesia of fingers of hands and legs because of risk of ischemic damage of fabrics.

At medical emergencies all contraindications are relative.

With care. Hyperthyroidism, advanced age. For prevention of arrhythmias against the background of, drug uses, appoint. beta adrenoblockers.

Overdose:

Symptoms: excessive increase. arterial pressure, the tachycardia which is replaced by bradycardia, disturbances of a rhythm (including fibrillation of auricles and ventricles), a cold snap and pallor of integuments, vomiting, a headache, a metabolic acidosis, a myocardial infarction, craniocereberal hemorrhage (especially at elderly patients), a fluid lungs, death.

Treatment: to stop introduction, symptomatic therapy - for a lowering of arterial pressure - alpha adrenoblockers (phentolamine), at arrhythmia - beta adrenoblockers (propranolol).

Storage conditions:

In the place protected from light, at a temperature not above 15 °C. To store in the places unavailable to children. A period of validity - 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for injections of 1 mg/ml. Packaging: in ampoules on 1 ml. On 5 ampoules in a blister strip packaging. On 1 or 2 blister strip packagings with the application instruction of drug, a knife or the scarificator ampoule in a pack from a cardboard. On 20, 50 or 100 blister strip packagings with 20, 50 or 100 application instructions of drug respectively, knives or, scarificators ampoule in boxes from a cardboard or in boxes from corrugated fibreboard (for a hospital). When packaging ampoules with notches, rings and points of a break knives or scarificators ampoule do not put.