Gross formula

Pharmacological group of substance ESMOLOL

Nonological Classification (ICD-10)

CAS code

Characteristics of substance ESMOLOL

Esmolol hydrochloride - white or almost white crystalline powder. It is a relatively hydrophilic compound, well soluble in water and easily soluble in alcohol. The distribution coefficient (octanol / water) at pH 7.0 is 0.42. Molecular weight - 331.8. It has one asymmetric center and exists like enantiomeric steam.

Pharmacology

Cardooselective beta 1 -adrenoblocator, deprived of its own sympathomimetic and membrane-stabilizing activity. It has a negative chrono-, other, dromo and batmostropic effect. Suppresses the automatism of the sinus node, lengthens the refractory period and slows down on the AV node. It slows down the central sympathetic impulsation and reduces the sensitivity of peripheral tissues to the catecholaminams. Reduces heart rate, myocardial reduction, oxygen heart consumption (anti-infanal effect), cardiac ejection and hell. Antianginal I. antihypertensive effect 10-20 min last after the cessation of infusion.

When in / in administration, proteins are binding to 55%, in the erythrocytes, it is quickly hydrolyzed by Esterases to the free sour metabolite (activity is 1/1500 from such esmolol) and methanol. T 1/2 - 9 min, free sour metabolite - 3.7 h (with renal failure Increases 10 times). The equilibrium concentration in the blood is achieved in the range of 5 minutes when using a load dose and after 30 minutes without it. Examined by the kidneys in the form of a metabolite.

In doses exceeding the maximum maintenance-supporting 8 times (rabbits) and 30 times (rats) toxic action The mother's body increases the frequency of resorption and mortality of fruits.

The use of substance Esmolol

Arterial hypertension, sinus tachycardia, suctivaricular tachycardia and tachyarhythmia (including fibrillation and atrial fluttering, incl. during and after operations), myocardial infarction, unstable angina, thyrotoxic crisis, pheochromocytoma.

Contraindications

Hypersensitivity, sinus bradycardia (less than 45 wt. / Min), cardiogenic shock, AV blockade II-III degree, pronounced heart failure, sine node weak syndrome, synoyatrial blockade, arterial hypotension (garden below 90 mm Hg. Art., Dad below 50 mm Hg. Art.), Bleeding, hypovolemia.

Restrictions on application

Bronchial asthma, emphysema, chronic obstructive bronchitis, stagnant heart failure, diabetes mellitus, renal function; Secondary hypertension due to vasoconstriction against the background of hypothermia during or after operations; Pregnancy, breastfeeding, childhood (safety and efficiency in children are not defined), elderly age.

Application in pregnancy and breastfeeding

During pregnancy, it is possible if the expected effect of therapy exceeds the potential risk to the fetus. Although adequate and strictly controlled safety research uses in pregnant women were not conducted, when using esmolol in the last trimester of pregnancy and in the period of birth, the development of bradycardia in the fetus continued after the end of the LAN infusion was reported.

Side effects Esmolol substance

The frequency of side effects with the use of esmolol was estimated in 369 patients with sufficiently valuable tachycardia and more than 600 patients during or after operations included in clinical trials. Most of the marked effects were weakly pronounced and transit. The most significant side effect was hypotension (see "Precautions"). During post-payment research, lethal outcomes were reported on clinical conditions when the esmolol was probably used to control the frequency of ventricular abbreviations (see "Precautions").

From side nervous system and sense organs: dizziness (3%), drowsiness (3%), headache (2%), assessment (2%), confusion of consciousness (2%), feeling of fatigue (1%); Less than 1% is a light dizziness, asthenia, paresthesia, depression, anxiety, convulsions, impaired thinking, taste, vision and speech.

From the side of the cardiovascular system and blood (blood formation, hemostasis): Symptomatic hypotension (accompanied by an abundant sweating, dizziness) - 12% (therapy was discontinued about 11% of patients, half of which was noted symptomatic hypotension), asymptomatic hypotension - 25%, violation of peripheral blood circulation (1%); Less than 1% - pallor, tide of blood to face, bradycardia (less than 50 stroks / min), chest pain, heartbeat, syncope, AV blockade, lung edema. In 2 patients without hydrodynricular tachycardia, but with severe IBS (condition after myocardial infarction or unstable angina) developed reversible (when treatment) severe bradycardia / sinus pause / asistolia.

From the head of the gastrointestinal authorities: nausea (7%), vomiting (1%); Less than 1% is dry mouth, dyspeptic phenomena, anorexia, constipation, discomfort in the stomach.

From side respiratory system: less than 1% - nasal congestion, wheezing in chest, breathing difficulty, shortness of breath, bronchospasm.

From the side of the skin: infusion reactions, including inflammation and induration at the injection site (in 8% of cases); Less than 1% - swelling, erythema, changing the color of the skin, burning at the injection site, skin necrosis (during extravasation).

Others: Less than 1% - fever, sweating, chills, urine delay, pain in the interstopane region, cooling of brushes and stop, cancellation syndrome.

Interaction

Potenties the effect of non-polarizing muscle relats, cardiodepressive effect of chinidine, procainamide, dyspepiramide and verapamil. Increases the risk of developing bradycardia and hypotension against the background of reserpine. Sympathomimetics and xanthin derivatives weaken (mutually) effects; Other hypotensive drugs are enhanced by hypotension. Increases the level of digoxin in plasma; Warfarin, morphine and succinylcholine increase the plasma concentration. Incompatible in one syringe with other means, incl. With 5% sodium hydrocarbonate solution.

Overdose

Symptoms: Excessive decrease in blood pressure, bradycardia, ventricular extrasystoles, heart failure, bronchospasm. Overdose of esmolol can cause a heart stop.

Treatment: giving the patient of the position of trendelenburg, oxygen therapy, in / in the introduction of the liquid (if there is no edema of the lungs); Symptomatic therapy: in bradycardia - the introduction of atropine sulfate, isoproterene or dobutamine (the use of epinephrine or transgeneous electrocardialization is possible); in heart failure - in / in the appointment of heart glycosides and / or diuretics; under hypotension - vasoconductive means (epinephrine, norepinephrine, dopamine, dobutamine) under the control of blood pressure; Vetricular extrasystoles are stopped in / in the introduction of lidocaine or phenytio, bronchospasm - in / in the introduction of beta 2 -adrenomimetics (isoproterenol) or xanthine derivatives. Perhaps in / in the purpose of glucagon to eliminate bradycardia or hypotension.

Ways of administration

Precautionary Precautions Esmolol

When using esmolol, careful and permanent medical monitoring and monitoring ECG, Hell, CSS and other indicators are needed.

Hypotension. IN clinical studies In 25-50% of patients treated by esmolol, hypotension was observed, usually defined as a garden below 90 mm Hg. Art. and / or DD below 50 mm Hg. Art. About 12% of patients had mainly symptomatic hypertension (mainly abundant sweating, dizziness). The hypotension could be observed at any doses, but was a dose-dependent, so doses of over 200 μg / kg / min are not recommended. Especially thorough control of hell is needed in patients with initially low blood pressure before treatment. With a decrease in the dose or end of infusion, hypotension disappears, usually within 30 minutes.

Heart failure. At the first signs or symptoms of heart failure, the esmolol should be canceled and, if necessary, conduct specific therapy. The use of esmolol to control the frequency of ventricular abbreviations in patients with reductant-centricular arrhythmia should be carried out with caution, if the patient is broken by hemodynamics or in the case of taking other substances that reduce the peripheral resistance, heartfelt, heart rate, the distribution of the electrical pulse in myocardium, because Despite the rapid start of action and the development of the effect of esmolol, several deaths have been reported when using esmolol, it is likely to control the frequency of ventricular abbreviations.

Tachycardia and / or hypertension during and after surgery. Esmolol is not recommended to be used in patients with secondary hypertension associated with vasoconstriction due to hypothermia.

Bronchospastic diseases. Since the esmolol is a cardioslelective blocker, it can be used in patients with bronchospast diseases, but with caution, carefully titrating the dose until the smallest efficient is achieved. In the case of bronchospasm, infusion should be terminated immediately; If necessary, beta 2 -stimulating substances can be used, but with very great caution, if the patients already had a rapid ventricular rhythm.

Sugar diabetes and hypoglycemia. The possibility of masking signs of hypoglycemia (tachycardia, hypertension) in patients should be taken into account diabetes. Against the background of burdened allergological history, it is possible a heavier manifestation of hypersensitivity reactions and the absence therapeutic effect From ordinary doses of epinephrine. At a concentration of over 10 mg / ml, tissue irritation is possible. If a local response occurs during infusion, the introduction must be stopped and resumed elsewhere.

Description of the active component

pharmachologic effect

Cardiodelective beta adrenoblocator without internal sympathomimetic and membrane-stabilizing activity. It has antianginal, hypotensive and antiarrhythmic effect. The hypotensive effect is due to a decrease in the formulated Catecholamines of the formation of CAMF from ATP, intracellular calcium current, heart rate and reduced myocardial reductions.

The antianginal effect is due to a decrease in the needs of myocardium in oxygen as a result of the heart rate (lengthening of diastole and improved myocardial perfusion) and reduce the contractility.

Due to the increase in the finite-diastolic pressure in the left ventricle and an increase in the stretching of muscle fibers of the ventricles can increase the need for oxygen, especially in patients with chronic heart failure.

The antiarrhythmic effect is determined by the oppression of the pulses in the antegrade and to a lesser extent retrograde directions through the AV node and for additional paths.

Action occurs from the moment of administration, full therapeutic effect It develops 2 minutes after administration and ends after 10-20 minutes after the cessation of infusion.

Indications

Sinus and supannivicular tachycardia, sugantivaricular tachyarhythmia ( cleaning arrhythmia, atrial flutter), arterial hypertension, incl. During and after operations.

Dosing mode

In / in, in / in drip. The dose is set by introducing a series of load and supporting doses. In the arrhythmias - initially with the help of a dosing device for 1 min, a load dose is introduced - 500 μg / kg, then at a rate of 50 μg / kg / min over the next 4 minutes; When achieving the desired effect is a supporting dose of 25 μg / kg / min. Possible breaks from 5 to 10 minutes between re-administration. With a not enough effect by the end of 5 minutes, the introduction of the load dose should be repeated, then introduced 100 μg / kg / min (with repeated attempts, this dose can be increased to 150 and then 200 μg / kg / min).

During the operating anesthesia - B / in Bolusno, 80 μg for 15-30 s, then infusion at a speed of 150-300 μg / min. Arterial hypertension or arrhythmia during or after operations - V / B, 250-500 μg / kg for 1 min (load dose), then in / in drip for 4 minutes - 50 μg / kg / min (supporting dose). In the absence of effect, it is reused, up to 4 times (load and maintenance dose, increasing each subsequent supportive dose by 50 μg / kg). Maximum supporting dose for adults - 200 μg / kg / min. Children with religious arrhythmia - in / in drip, 50 μg / kg / min, with a subsequent increase in dose (if necessary) every 10 minutes to 300 μg / kg / min.

Side effect

From the side of the cardiovascular system: A pronounced decrease in blood pressure (symptomatic - 12%, asymptomatic - 25%), 1% - disorders of peripheral blood circulation; Less than 1% - lung edema, bradycardia, heartbeat, AV blockade, ventricular asistol, fainting, collapse, thrombophlebitis, "tide" of blood to the skin of the face.

From the CNS and the peripheral nervous system:3% - drowsiness, anxiety; 2% - headache, assessment, confusion of consciousness, feeling of fatigue; Less than 1% - dizziness, paresthesia, asthenia, depression, convulsions, impaired thinking, violation of taste, vision, speech.

From the digestive system:7% - nausea; 1% - vomiting; less than 1% - dry mouth, dyspepsia, decline in appetite, abdominal pain, constipation.

From the respiratory system:less than 1% - nasal congestion, pain and wheezes in the chest, difficulty breathing, bronchospasm, shortness of breath.

From the urinary system:less than 1% - swelling, urination disorder.

From the side of the skin:8% - skin hyperemia; Less than 1% - the pallor or change in the color of the skin, acricyanosis, erythematous rashes, skin necrosis (with random extravasive administration).

Others:plowness at the place of administration, hyperthermia, increased sweating, chills, pain in the inter-opaque region, grinding of brushes and stop, cancellation syndrome.

Contraindications

Bradycardia (heart rate less than 45 / min), AV blockade of the II-III Art., Arterial hypotension (systolic blood pressure below 90 mmT.st., diastolic hell below 50 mm.T.), cardiogenic shock, acute heart failure, SCSU , Sinoatrial blockade, bleeding, hypovolemia, lactation period, increased sensitivity to esmolol.

Pregnancy and lactation

Apply with caution during pregnancy.

In experimental studies when appointing in doses exceeding the maximum supportive for humans 8 times (rabbits) and 30 times (rats), has a toxic effect on the mother's body, increases the frequency of resorption and fetal mortality.

Contraindicated during lactation.

Application with violations of the kidney function

C care should be used in chronic renal failure.

Application in old age

Caution should be used in old age.

Application for children

special instructions

C care should be applied at bronchial asthma, COPD (emphysema, chronic obstructive bronchitis), chronic heart failure, chronic renal failure, in secondary hypertension (due to vasoconstriction, during or after operations, against hypothermia), diabetes, pregnancy, elderly age.

During the treatment period, it is necessary to carry out careful and constant monitoring of ECG, Hell, heart rate. It is not recommended to use for the introduction of a butterfly needle.

Application experience in children is limited.

It is necessary to take into account the possibility of masking signs of hypoglycemia (tachycardia, increased blood pressure) in patients with diabetes.

Against the background of a burdened allergological history, it is possible a more severe manifestation allergic reactions And the absence of therapeutic effect from ordinary epinephrine doses.

At a concentration exceeding 10 mg / ml, irritation of fabrics may be irritated; If a local response occurs during infusion, the introduction must be stopped and then change the place of administration.

Overdose

Symptoms:excessive decrease in blood pressure, bradycardia (pass 10-20 minutes after the termination of administration), ventricular extrasystole, heart failure, bronchospasm.

Treatment:giving the patient of the situation of trendelenburg, oxygen therapy, in bradycardia - in / in atropine sulfate or dobutamine, possibly in / in the introduction of glucagon or epinephrine, carrying out the transgeneous electrocardialism). With a significant decrease in Hell-B / in the introduction of plasma-substituting solutions (in the absence of edema of the lungs) and under the control of the blood pressure (epinephrine, norepinephrine, dopamine or dobutamine). With bronchospasm - isoprenaline or theophylline. With heart failure - cardiac glycosides and / or glucagon and diuretics. With ventricular extrasystole - lidocaine or phenytoin.

Medicinal interaction

Invisible in one syringe with other drugs (including with a 5% sodium hydrocarbonate solution).

Increases the concentration of digoxin in plasma.

Morphine, suucametonium and indirect anticoagulants Increase the concentration of esmolol in the blood. Increases the duration of the neuromuscular blockade caused by sub-mounted 1.5 times.

Allergens used for immunotherapy, or extracts of allergens for skin samples increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving esmolol.

Phenytoin with in / in the introduction, medicinal products For inhalation anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive action and the likelihood of reduction of blood pressure.

Changes the effectiveness of insulin and oral hypoglycemic drugs, masks symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

Reduces lidocaine clearance and xanthines (except for the diffillin) and increases their plasma concentration, especially in patients with initially elevated theophylline clearance under the influence of smoking.

The hypotensive effect weakens the NSAIDs (sodium delay and the blockade of the synthesis of prostaglandins in the kidneys), GKS and estrogens (sodium delay).

Cardiac glycosides, methyldop, reserpine and guangafacin, calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of development or aggravation of bradycardia, AV blockades, heart stops and heart failure.

Nifedipine can lead to a significant decrease in blood pressure.

With simultaneous use with antihypertensive means (incl. With diuretics, clonidine, sympatholitic, hydralazine), an excessive decrease in blood pressure is possible.

Extlifies the effect of non-compolant minelaxants and the anticoagulant effect of Kumarins.

Three and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedative and snow pills Strengthen the oppression of the CNS.

Simultaneous use with Mao inhibitors is not recommended due to a significant increase in hypotensive action, a break in the treatment between the intake of Mao and Esmolol inhibitors should be at least 14 days.

Unhydrated burden alkaloids increase the risk of developing peripheral circulatory disorders.

Selective Blocator β1-adrenoreceptors without ACCs and membrane-stabilizing activity. Hypotensive, antiarrhythmic and antichangal agent. Suppresses the automatism of the sinus node, lengthens the refractory period and slows down on the AV node. It slows down the central sympathetic impulsation and reduces the sensitivity of peripheral tissues to the catecholaminams. Reduces heart rate, myocardial cutness, oxygen myocardial consumption (antianginal effect), cardiac output and blood pressure.
The therapeutic effect develops after 2 minutes from the beginning of the infusion and stops 15-20 minutes after its completion. Half-life - 9 min. Examined by the kidneys in the form of an inactive metabolite.

Indications for the use of the drug ESMOLOL

AG (arterial hypertension), hypertensive crisis, sinus tachycardia, hydrodynivicular tachycardia and tachyarithmia (including fibrillation and atrial fibrillation, including during and after operational interventions), thyrotoxic crisis, myocardial infarction, pheochromocytoma, unstable angina.

Application of the drug esmolol

In / c, at a dose of 500 μg / kg for 1 min (load dose), then 50 μg / kg in 1 min over the next 4 minutes; supporting dose - 25 μg / kg in 1 min (or less); Possible a break between repeated administrations - 5-10 minutes. In case of insufficient effect, the loadal dose of 500 μg / kg for 1 min, then for 4 min - 100 μg / kg per 1 min (with repeated administrations, it is possible to increase the dose to 150 μg / kg. kg in 1 min, then up to 200 μg / kg in 1 min). Upon reaching the desired level of heart rate, propranolol hydrochloride can be used in a dose of 10-20 mg every 4-6 hours inside, verapamil 80 mg every 6 hours inside, digoxin at a dose of 0.125-0.5 mg every 6 hours inside or in / in , County 200 mg every 2 h orally (against the background of the use of their first dose during the first hour, the infusion dose of esmolol is reduced by half). In the case of a stable condition of the patient during hours surveillance after receiving the 1st, or the introduction of the 2nd dose of one of the specified preparations, the system of esmolol can be stopped. During the operating anesthesia, if necessary, introduced B / in a bolus at a dose of 80 mg for 15-30 s, then in the form of infusion at a speed of 150-300 μg / kg in 1 min.

Contraindications for the use of the drug ESMOLOL

Increased sensitivity to esmolol, sinus bradycardia (CSS less than less than 45 ° C / min), cardiogenic shock, AV blockade of II-III degree, acute heart failure, sine node weak syndrome, arterial hypotension (systolic blood pressure below 90 mm Hg, Diastolic blood pressure below 50 mm Hg), hypovolemia, bronchospasm, children's age (the safety of application is not established).

Side Effects of the Preparation of Esmolol

Rarely - increased fatigue, drowsiness, confusion, headache, dizziness, speech disorders and / or vision, excitation; arterial hypotension, signs of peripheral ischemia, bradycardia, feeling of heartbeat, thrombophlebitis; Chills, heat, dnae, bronchospasm, constipation, urine delay, burning, induration, or infiltration of the skin around the place of administration of the drug (during extravasization).

Special instructions for the use of the drug ESMOLOL

the safety of use during pregnancy is not installed. Due to the lack of data on the possibility of esmolol penetration in breast milk It is not recommended to apply during breastfeeding period. Caution is prescribed to patients with bronchospast diseases, diabetes mellitus, renal function. An introduction to concentrations of more than 10 mg / ml should be avoided due to the possible skin necrosis. Caution continues infusion more than 24 hours ( clinical experience insufficient). It is possible to use 48 hours after the cancellation of verapamila and reserpine.

The interaction of the drug Esmolol

Invisible in one syringe with 5% r-rum sodium bicarbonate. Increases the concentration of digoxin in serum, enhances the hypotensive effect of inhalation anestics, the muscle relaxant effect of succinylcholine (1.5 times) is prolonging. Morphine and Warfarin increase the concentration of esmolol in serum.

Overdose of the preparation of esmolol, symptoms and treatment

Manifests hypotension, bradycardia, bronchospasm. Treatment: in bradycardia - in / in the introduction of atropine sulfate or isoprenaline; In the arterial hypotension - in / in the introduction of liquid and vasoconducting agents (epinephrine, norepinephrine, dopamine or dobutamine), with bronchospasm - isoprenaline or xanthine derivatives.

List of pharmacies where you can buy esmolol:

• St. Petersburg

Composition

Active substance: esmolol hydrochloride 10 mg;

Excipients:sodium chloride - 5.9 mg, sodium acetate trihydrate - 2.8 mg, acetic acid Ice - 0.546 mg, hydrochloric acid - to pH 5.0, sodium hydroxide - to pH 5.0, water d / and - up to 1 ml.

Indications for scattering

• supported tachycardia, including atrial flications and atrial flirting, in the perioperative and postoperative period or in any other situations where short-term control of the frequency of ventricular abbreviations with a short-range medicinal preparation;
• tachycardia and arterial hypertension in the peripheral period;
• sine tachycardia noncompensator character.

Contraindications for scattering

• pronounced bradycardia (heart rate less than 50 q / min);
• SCS;
• AV blockade II and III degree;
• cardiogenic shock;
• severe arterial hypotension;
• acute heart failure;
• pulmonary hypertension;
• feochromocytoma without the simultaneous use of alpha adrenoblockers;
• age up to 18 years;
• simultaneous V / in the introduction of block plants of slow calcium channels (verapamila, diltiazem);
• increased sensitivity to the components of the drug.

Carefully:

• AV-block I degree;
• bronchial asthma, COPD;
• impairment of peripheral blood circulation (Reino syndrome, intermittent chromotype);
• chronic heart failure;
• renal impairment;
• hypercalemia;
• thyrotoxicosis;
• psoriasis;
• miasti;
• angina printela;
• hypovolemia;
• diabetes;
• pheochromocytoma (with the simultaneous use of alpha adrenobloclars);
• secondary arterial hypertension (due to vasoconstriction, during or after operations, against the background of hypothermia);
• pregnancy;
• elderly age.

The drug is intended only for in / in administration and only for short-term use.

The loading dose of the drug is 500 μg / kg / min for patients with a body weight of 70 kg is 3.5 ml.

The dose should be chosen individually and adjustable depending on the clinical response. Titration of the dose should be carried out with the ventricular rhythm and, if necessary, hell.

Supported tachycardia, including atrial flications and atrial flutter

The effective dose of the drug for the treatment of suctivativericular tachyarhythmia is 50-200 μg / kg / min. To control the ventricular rhythm, supporting infusion doses over 200 μg / kg / min are not recommended. The drug in doses of more than 200 μg / kg / min provides a slight decrease in the heart rate, while the frequency of adverse reactions increases. Nevertheless, higher doses (250-300 μg / kg / min) may be required for adequate control. The safety of the drug in doses of more than 300 μg / kg / min has not been studied.

If the dose of the drug should be chosen individually by titration, during which each step includes a loading dose, followed by a supporting dose.

Scheme of the beginning and treatment of treatment

1. Introduction of the load dose of 500 μg / kg / min for 1 min, then the introduction of a supporting dose of 50 μg / kg / min for 4 minutes *.

2. With a positive result: the introduction of a supporting dose of 50 μg / kg / min.

3. With a negative result for 5 minutes: repeat the administration of a dose of 500 μg / kg / min for 1 min; Increase maintenance dose to 100 μg / kg / min over the next 4 minutes.

4. With a positive result: the introduction of a supporting dose of 100 μg / kg / min.

5. With a negative result for 5 minutes: repeat the administration of a dose of 500 μg / kg / min for 1 min; Increase maintenance dose to 150 μg / kg / min for 4 minutes.

6. With a positive result: the introduction of a supporting dose of 150 μg / kg / min.

7. With a negative result: repeat the administration of a dose of 500 μg / kg / min for 1 min; Increase maintenance dose to 200 μg / kg / min and leave at this level.

* - If the desired degree of decline in heart rate is achieved, but it decreases the blood pressure, it is necessary to stop the introduction of the load dose and reduce the speed of supporting administration from 50 μg / kg / min to 25 μg / kg / min or lower. If necessary, the time interval between the titration stages can be increased from 5 to 10 minutes.

pharmachologic effect

Cardiodelective blocker β1-adrenoreceptors. Esmolol in its chemical nature refers to the class of phenoxiprophanolamine beta-adrenoblockers. It has an enzymatically labile flight (this is due to its rapid metabolism and short T1 / 2 from plasma).

It is characterized by a rapid start of action, a very small duration of action, in therapeutic doses does not have its own sympathomimetic and membrane-stabilizing activity. It has antianginal, hypotensive and antiarrhythmic effect.

Reduces the formation of cyclic amphs from ATP stimulated by catecholamines, reduces the intracellular current of calcium ions, it reaches the heart rate, slows down the conduction, reduces the reduction of myocardium. The antiarrhythmic effect is determined by the oppression of the pulses in the antegrade and, to a lesser extent, in retrograde directions through the AV node and for additional ways.

Esmolol, as well as other beta-adrenoblastors, has a negative ina, chrono-, butmol and drromotropic effect.

In elderly patients, over 65, there are no differences in hemodynamic effects compared with patients of younger age.

The action occurs from the moment of administration, the complete therapeutic effect develops 2 minutes after the administration and ends 10-20 minutes after the cessation of the infusion.

Pharmacokinetics

Distribution and metabolism

Esmolol is metabolized by erythrocyte eserators to acid metabolite ASL-8123, which has a weak (less than 0.1% of hydrochloride esmolol) beta-adrenoblocking activity.

The binding of esmolol with plasma proteins is 55% (for acid metabolite, this indicator is only 10%).

Election

T1 / 2 of esmolol after in / in administration is about 9 minutes. T1 / 2 of sour metabolite kidneys - about 3.7 hours. Less than 2% of the esmolol is removed by the kidneys unchanged.

Pharmacokinetics in special clinical cases

In chronic renal failure, T1 / 2, sour metabolite with urine increases 10 times.

special instructions

During the treatment period, it is necessary to carry out careful and constant monitoring of ECG, blood pressure, heart rate.

Influence on Hell, heart rate, rhythm and reduction of the heart

Unwanted reactions to beta-adrenoblays, including speakers, from the heart and blood vessels can be severe, especially in patients with impaired hemodynamics and patients receiving drugs that increase the risk of cardiovascular reactions. Heavy reactions may include loss of consciousness, cardiogenic shock, stopping the heart, which can lead to death. The score, in the absence of contraindications, should be used with caution and only after a thorough individual assessment of risks and expected benefits in patients with impaired hemodynamics and patients with increased risk due to possible drug interactions.

Arterial hypotension

When applying the drug, arterial hypotension was observed, incl. Heavy. Arterial hypotension depends on the dose. Careful monitoring of patients should be carried out, especially in the case of low blood pressure, before the start of treatment. In the case of a sharp decline in Hell, the dose of the drug should be reduced or terminated its administration. Arterial hypotension, as a rule, passes within 30 minutes after the discontinuation of the drug. In some cases, additional treatment may be required.

Bradycardia

When using the drug was observed bradycardia, incl. Heavy bradycardia, and a heart stop. The drug should be applied with special caution in patients with low heart rate before treatment and only when potential benefits are superior to the risk. Drug is contraindicated in patients with existing heavy sinus bradycardia. In the case of severe bradycardia, a dose of the drug should be reduced or terminated. In some cases, additional treatment may be required.

Heart failure

Due to the blockade of β-adrenoreceptors, the reduction of myocardial decreases, which can provoke or exacerbate heart failure. With the first sign or symptom of the clinically significant oppression of myocardial activities, you should reduce the dose of the drug or terminate its introduction. In some cases, additional treatment may be required. Care should be exercised when the drug is used in patients with a disruption of myocardial cuts (drug is contraindicated in patients with severe heart failure or cardiogenic shock).

Beta-blockers affect the function of the sinus unit, as well as on synoyatrile and AV conductivity, and can lead to the development of the SSSU, the synoatrial and AV blockade, including full blockadeWhat can lead to a heart stop. This effect is most characteristic of patients with already existing sinus node dysfunction and conductivity impairment (drug is contraindicated in patients with AV blockade II or III degree and in patients with the SCC).

The drug should be used with caution in patients with other heart rate disorders, including AV blockade I degree.

Application in patients with feochromocyt

It should be used with caution in patients with a peochromocytoma and only with the simultaneous use of α-adrenoreceptor blockers.

The scorelial should not be used as a means for the treatment of arterial hypertension, due to the mainly vasoconstriction against the background of hypothermia.

Application in patients with bronchospast syndrome

Patients with bronchospast syndrome should not receive beta adrenoblays. The score, due to its relative beta 1 -selectivity and tab, should be used in patients with bronchospast syndrome. However, since the selectivity for β1-adrenoreceptors is not absolute, the exact titration of doses of the drug is required to achieve the minimum possible efficient dose. In the case of bronchospasm or deterioration of the course of the available bronchospasm, the infusion should be immediately stopped; If the condition allows you to prescribe a beta 2 -adrenomimetics.

Application in patients with diabetes or patients prone to hypoglycemia

The drug should be used with caution in patients subject to or prone to hypoglycemia, as well as in patients with diabetes mellitus, which receive insulin or hypoglycemic agents for intake.

Beta-adrenobloclars can mask tachycardia arising from hypoglycemia, although there may be other manifestations, such as dizziness and increased sweating.

The concomitant use of beta-adrenobloclars and hypoglycemic agents can enhance the hypoglycemic effect of the latter.

Reactions at the place of administration

When the preparation of the scatter, the reaction was observed at the injection site. They included signs and symptoms of irritation and inflammation at the injection site.

Tahcardia control in patients receiving drugs that have vasoconstrictor and positive inotropic effects

Due to the risk of decline in the reduction of the heart against the background of high systemic vascular resistance, the drug should not be used to control tachycardia in patients receiving preparations that have vasoconstrictor and positive inotropic effects, incl. Epinephrine, norepinephrine, dopamine.

Application in patients with angina printelast

Beta-adrenoblockers can increase the number and duration of angina attacks in patients with a wall-induced printedhateal due to unhindered spasm-mediated α-adrenoreceptors coronary arteries. For such patients, non-selective beta adrenoblays should not be used, and selective beta1-adrenoblays - only in compliance special Mer Precautions.

Application in patients with hypovolemia

In patients with hypovolemia, the drug can relax the reflex tachycardia and increase the risk of arterial hypotension. In this regard, in such patients the drug should be applied in compliance with special precautions.

Cancellation of the preparation of scatter

Since it is impossible to exclude cancellation syndrome, as well as for all beta-adrenoblockers, caution should be exercised with a sharp discontinuation of drug administration to patients with IBS. In a clinical electrophysiological study, the increase in the heart rate 30 minutes after the discontinuation of the drug was moderate, but significantly higher than the initial heart rate. Beta-adrenoblocators also increase the risk of recurrent hypertension when canceling Klonidin, Guangfatzin and Moxonidine.

Use of drug in patients with peripheral circulatory disorders

In patients with peripheral circulatory disorders (including the disease or referee syndrome and occlusive damage to peripheral vessels), the drug should be used with caution, because Beta-adrenoblocators can enhance disorders of peripheral blood circulation.

Application in patients with impaired kidney function

Caution should be administered to patients with impaired kidney function. An acidic drug is derived by the kidneys mainly unchanged. Its excretion is significantly reduced in patients with kidney disease. In patients with the terminal stage of renal failure, T1 / 2 increased 10 times, and the concentration in blood plasma increased significantly.

Application in patients with hepatic insufficiency

Since the drug is metabolized by erythrocyte eserases, no special precautions in patients with hepatic insufficiency are not required.

Hypercalemia

The use of beta-adrenoblockers, including the score, was accompanied by an increase in potassium content in blood plasma and hyperkalemia. Risk increases if patients have such factors as renal failure. It was reported that in / in the introduction of beta-adrenoblockers causes potentially life-threatening hyperkalemia in patients on hemodialysis.

Application in patients with metabolic acidosis

It has been reported that beta-adrenobloclars, including scatter, cause or contribute to the development of hypercalemic renal tubular acidosis. In addition, the acidosis can usually be accompanied by a reduced myocardial reduction. The drug should be used with caution in patients with preceding metabolic acidosis.

Application in patients with thyrotoxicosis

Beta adrenergic blockade can mask some clinical signs Hyperthyroidism (for example, tachycardia). A sharp termination of beta-adrenobloca can provoke thyrotoxic crisis. In this regard, patients should be carefully observed, in which, when canceling therapy, thyrotoxicosis is expected to develop beta-adrenoblators.

Patients with high risk of developing severe hypersensitivity reactions

When using beta-adrenobloclars, patients with increased risk of developing anaphylactic reactions can be more actively responding to the effects of allergen (random, diagnostic or therapeutic). Patients using beta-adrenoblays can be immune to conventional doses of epinephrine used to treat anaphylactic or anaphylactoid reactions.

Application in patients with psoriasis in history

When using beta-adrenobloclockers, there was an aggravation of the flow of psoriasis, or the appearance of symptoms of psoriasis or psoriazoforming rashes. In patients with psoriasis, a history of beta-adrenoblockers should be prescribed only after careful analysis of the expected benefits and the risk of therapy.

Application in patients with muscle weakness

Beta-adrenobloclars, including score, caused muscle weakness. The drug should be used with caution in patients with muscle weakness.

Application in elderly patients

Elderly patients should be administered with caution. As a rule, the choice of dose for elderly patients should be carried out with caution, starting usually with low level Dose range, taking into account the greater frequency of reduced renal or cardiac function, concomitant diseases or treatment with other drugs.

Impact on the ability to driving vehicles and control mechanisms

Some side effectsarising from the use of the drug, such as dizziness or drowsiness, can influence the patient's ability to manage vehicles and work with mechanisms. Patients should not control vehicles or mechanisms before the disappearance of such effects.

Overdose

Symptoms: From the side of the cardiovascular system - pronounced bradycardia, AV blockade (I, II and III degrees), nodal rhythm, slowdown in the intraventricular conduct, reduced myocardial reduction, pronounced arterial hypotension, acute heart failure (including cardiogenic shock), stopping heart, Electromechanical dissociation; From the CNS side - the oppression of breathing, convulsions, sleep disorders and mood, fatigue, inhibition, coma is possible. Bronchospasm, mesenteric ischemia, peripheral cyanosis, hypercalemia and hypoglycemia are also possible. Overdose can lead to the development of life-threatening states and fatal outcome.

Treatment: Stop the administration of the drug. In bradycardia is shown in / in the introduction of atropine. Catecholamines that increase the heart rate can be shown, and / or it may be necessary to formulate an artificial rhythm driver. In heart failure, it is shown in / in the introduction of diuretics and / or heart glycosides. Under shock, which developed due to inadequate myocardial contractility, is shown in / in the introduction of the drug with a positive inotropic effect, for example, dopamine, dobutamine, isoprenaline or amrinone. In symptomatic arterial hypotension, it is possible to consider the possibility of using plasma-substituting solutions and / or vasopressors such as dopamine or norepinephrine. With bronchospasm, Beta2-adreminimetics and / or derivatives of theophylline are introduced.

Medicinal interaction

Pharmacokinetic interaction

With simultaneous in / in the administration of digoxin and the preparation of the bar, there is an increase in the concentration in the blood of digoxin by 10-20%. Pharmacokinetics of the drug did not change.

With simultaneously in / in the introduction of morphine and the drug, the concentration of morphine in the blood plasma was not observed. The concentration of esmolol in the blood increased by an average of 46%, while other pharmacokinetic parameters remained unchanged.

Pharmacodynamic interaction and other types of interaction

For sharing With antiarrhythmic preparations I class (for example: County, dyspeciramide) or amiodarone, an influence on the time of intra-sub-certificate and to increase the negative inotropic effect.

With the simultaneous use of the drug with other hypotensive drugs, drugs inhibiting myocardial reductions, or by braking the function of the sinus unit or the electrical pulse pulses in the myocardium, the effect of the drug on blood pressure, the reduction of myocardium and the conducting pulses in myocardium can be enhanced. Pharmacodynamic interaction with such preparations can lead, for example, to pronounced arterial hypotension, heart failure, severe bradycardia, sinus pause, synoyatrial blockade, AV blockade and / or heart stop. In addition, the use of some drugs against the background of beta-adrenoblocades can lead to increased cancellation syndrome. Therefore, the drug should be used with caution and only after a thorough individual risk assessment and expected beneficia of therapy with drugs that can cause such pharmacodynamic interaction, including, but not limited to next drugs: alfuzosin, doxazozin and other alpha adrenoblays; amifostin; amiodaron; anticholinesterase agents; antipsychotic drugs; apomorphine; Baclofen; Verapamil, Diltiazem and other blockers of slow calcium channels, depressing cardiac activities (with the joint use of the drug and verapamil in patients with a reduced myocardial function, there were cases of a death of a deathly outcome); heart glycosides; Dizeciramide, lidocaine, phenytoin, cheating; Inhalation anesthetics; levodopa; Mao inhibitors; MEFLOKHIN; opioid receptor agonists, including fentanyl; Barbiturates short action; tricyclic antidepressants (for example, imipramine, amitriptyline); Klonidin, Guangfatzin, Moxonidine. Beta-adrenoblockers increase the risk of recurrent arterial hypertension when canceling Klonidin, Guangfatsin and Moxonidine. Therefore, you first need to cancel the beta-adrenoblocator, and the abolition must be gradual.

When using beta-adrenobloclars, patients with the risk of anaphylactic reactions can more actively respond to the effect of allergen (random, diagnostic or therapeutic). Patients receiving beta-adrenoblays can be immune to conventional epinephrine doses used to treat anaphylactic reactions.

Beta-adrenoblockers, including brook, caused muscle weakness. Therefore, beta-adrenoblockers are theoretically able to reduce the effectiveness of anticholinesterase drugs in the treatment of muscle weakness.

The simultaneous use of beta-adrenoblockers and hypoglycemic agents for intake or insulin can enhance the hypoglycemic effect of the latter. Beta-adrenobloclars can mask tachycardia arising from hypoglycemia, although there may be other manifestations, such as dizziness and increased sweating.

Reserved and other drugs that deplete catecholamine reserves may have an additive effect when used with beta-adrenoblocking agents. Therefore, patients who, together with the drug, are introduced at the same time inhibitors of catecholamines, should be carefully observed to identify signs of arterial hypotension or pronounced bradycardia, which can lead to dizziness, fainting or orthostatic arterial hypotension.

The simultaneous use of beta-adrenoblockers with alkaloid derivatives of the ardines can lead to severe peripheral vasoconstrictions and arterial hypertension.

It is possible to weaken glucagon effects associated with an increase in blood glucose levels.

NSAIDs can cause a decrease in the antihypertensive effect of beta adrenobloclars.

The effect of the drug may decrease with simultaneous use with sympathomimetic preparations with the activity of beta adrenergic agonists. The doses of each of the drugs may need correction based on the patient's response, or one can consider the use of alternative therapeutic agents.

The drug increases the duration of an induced succinylcholine neuromuscular blockade.

With simultaneous use with sulfinpyrazone, it is possible to weaken the antihypertensive effects of beta-adrenobloclars.

Pharmaceutical interaction

The drug is incompatible with a 5% sodium solution of bicarbonate due to limited stability; With furosemide - due to precipitation.

Storage conditions

The drug should be stored in an inaccessible place at a temperature not higher than 25 ° C. Shelf life: - 2 years.

pharmachologic effect

Cardiodelective beta adrenoblocator without internal sympathomimetic and membrane-stabilizing activity. It has antianginal, hypotensive and antiarrhythmic effect. The hypotensive effect is due to a decrease in the formulated Catecholamines of the formation of CAMF from ATP, intracellular calcium current, heart rate and reduced myocardial reductions.
The antianginal effect is due to a decrease in the needs of myocardium in oxygen as a result of the heart rate (lengthening of diastole and improved myocardial perfusion) and reduce the contractility.
Due to the increase in the finite-diastolic pressure in the left ventricle and an increase in the stretching of muscle fibers of the ventricles can increase the need for oxygen, especially in patients with chronic heart failure.
The antiarrhythmic effect is determined by the oppression of the pulses in the antegrade and to a lesser extent retrograde directions through the AV node and for additional paths.

The action occurs from the moment of administration, the complete therapeutic effect develops 2 minutes after the administration and ends 10-20 minutes after the cessation of the infusion.

Pharmacokinetics

Binding with plasma proteins after in / in administration - 55%. C SS in the blood is achieved within 5 minutes when using a load dose and after 30 minutes without it. It is quickly hydrolyzed by Esterates in erythrocytes to free sour metabolite (its activity is 1/1500 of the activity of esmolol) and methanol. T 1/2 - 9 min, free sour metabolite - 3.7 h (in chronic renal failure increases 10 times). Examined by the kidneys in the form of a metabolite.

Indications for use

Sine and reductantaricular tachycardia, supraventricular tachyarhythmia (flickering arrhythmia, atrial trembles), arterial hypertension, incl. During and after operations.

Dosing mode

In / in, in / in drip. The dose is set by introducing a series of load and supporting doses. In the arrhythmias - initially with the help of a dosing device for 1 min, a load dose is introduced - 500 μg / kg, then at a rate of 50 μg / kg / min over the next 4 minutes; When achieving the desired effect is a supporting dose of 25 μg / kg / min. Possible breaks from 5 to 10 minutes between re-administration. With a not enough effect by the end of 5 minutes, the introduction of the load dose should be repeated, then introduced 100 μg / kg / min (with repeated attempts, this dose can be increased to 150 and then 200 μg / kg / min).
During the operating anesthesia - B / in Bolusno, 80 μg for 15-30 s, then infusion at a speed of 150-300 μg / min. Arterial hypertension or arrhythmia during or after operations - V / B, 250-500 μg / kg for 1 min (load dose), then in / in drip for 4 minutes - 50 μg / kg / min (supporting dose). In the absence of effect, it is reused, up to 4 times (load and maintenance dose, increasing each subsequent supportive dose by 50 μg / kg). Maximum supporting dose for adults - 200 μg / kg / min. Children with rustling arrhythmia - in / in drip, 50 μg / kg / min with a subsequent increase in dose (if necessary) every 10 minutes to 300 μg / kg / min

Side effect

From the side of the cardiovascular system: A pronounced decrease in blood pressure (symptomatic - 12%, asymptomatic - 25%), 1% - disorders of peripheral blood circulation; Less than 1% - lung edema, bradycardia, heartbeat, AV blockade, ventricular asistol, fainting, collapse, thrombophlebitis, "tide" of blood to the skin of the face.
From the CNS and the peripheral nervous system:3% - drowsiness, anxiety; 2% - headache, assessment, confusion of consciousness, feeling of fatigue; Less than 1% - dizziness, paresthesia, asthenia, depression, convulsions, impaired thinking, violation of taste, vision, speech.
From the digestive system:7% - nausea; 1% - vomiting; less than 1% - dry mouth, dyspepsia, decline in appetite, abdominal pain, constipation.
From the respiratory system:less than 1% - nasal congestion, pain and wheezes in the chest, difficulty breathing, bronchospasm, shortness of breath.
From the urinary system:less than 1% - swelling, urination disorder.
From the side of the skin:8% - skin hyperemia; Less than 1% - the pallor or change in the color of the skin, acricyanosis, erythematous rashes, skin necrosis (with random extravasive administration).
Others:plowness at the place of administration, hyperthermia, increased sweating, chills, pain in the inter-opaque region, grinding of brushes and stop, cancellation syndrome.

Contraindications for use

Bradycardia (heart rate less than 45 / min), AV blockade of the II-III Art., Arterial hypotension (systolic blood pressure below 90 mmT.st., diastolic hell below 50 mm.T.), cardiogenic shock, acute heart failure, SCSU , Sinoatrial blockade, bleeding, hypovolemia, lactation period, increased sensitivity to esmolol.

Application in pregnancy and breastfeeding

Apply with caution during pregnancy.
In experimental studies when appointing in doses exceeding the maximum supportive for humans 8 times (rabbits) and 30 times (rats), has a toxic effect on the mother's body, increases the frequency of resorption and fetal mortality.
Contraindicated during lactation.

Application with violations of the kidney function

C care should be used in chronic renal failure.

Application in elderly patients

Caution should be used in old age.

Application in children

special instructions

Caution should be used at bronchial asthma, COPD (emphysema, chronic obstructive bronchitis), chronic heart failure, chronic renal failure, in secondary hypertension (due to vasoconstriction, during or after operations, against hypothermia), diabetes, pregnancy, elderly age .
During the treatment period, it is necessary to carry out careful and constant monitoring of ECG, Hell, heart rate. It is not recommended to use for the introduction of a butterfly needle.
Application experience in children is limited.
It is necessary to take into account the possibility of masking signs of hypoglycemia (tachycardia, increased blood pressure) in patients with diabetes.
Against the background of a burdened allergological history, it is possible a heavily manifestation of allergic reactions and the absence of therapeutic effect from conventional doses of epinephrine.
At a concentration exceeding 10 mg / ml, irritation of fabrics may be irritated; If a local response occurs during infusion, the introduction must be stopped and then change the place of administration.

Overdose

Symptoms:excessive decrease in blood pressure, bradycardia (pass 10-20 minutes after the termination of administration), ventricular extrasystole, heart failure, bronchospasm.
Treatment:giving the patient of the situation of trendelenburg, oxygen therapy, in bradycardia - in / in atropine sulfate or dobutamine, possibly in / in the introduction of glucagon or epinephrine, carrying out the transgeneous electrocardialism). With a significant decrease in Hell-B / in the introduction of plasma-substituting solutions (in the absence of edema of the lungs) and under the control of the blood pressure (epinephrine, norepinephrine, dopamine or dobutamine). With bronchospasm - isoprenaline or theophylline. With heart failure - cardiac glycosides and / or glucagon and diuretics. With ventricular extrasystole - lidocaine or phenytoin.

Medicinal interaction

Invisible in one syringe with other drugs (including with a 5% sodium hydrocarbonate solution).
Increases the concentration of digoxin in plasma.
Morphine, Suxametonium and indirect anticoagulants increase the concentration of esmolol in the blood. Increases the duration of the neuromuscular blockade caused by sub-mounted 1.5 times.
Allergens used for immunotherapy, or extracts of allergens for skin samples increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving esmolol.
Iodine-containing radiocontrase drugs for in / in administration increase the risk of developing anaphylactic reactions.
Phenytoin with in / in administration, drugs for inhalation anesthesia (hydrocarbon derivatives) increase the severity of cardiodepressive action and the likelihood of reduction of blood pressure.
Changes the effectiveness of insulin and oral hypoglycemic drugs, masks symptoms of developing hypoglycemia (tachycardia, increased blood pressure).
Reduces lidocaine clearance and xanthines (except for the diffillin) and increases their plasma concentration, especially in patients with initially elevated theophylline clearance under the influence of smoking.
The hypotensive effect weakens the NSAIDs (sodium delay and the blockade of the synthesis of prostaglandins in the kidneys), GKS and estrogens (sodium delay).
Cardiac glycosides, methyldop, reserpine and guangafacin, calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of development or aggravation of bradycardia, AV blockades, heart stops and heart failure.
Nifedipine can lead to a significant decrease in blood pressure.
With simultaneous use with antihypertensive means (incl. With diuretics, clonidine, sympatholitic, hydralazine), an excessive decrease in blood pressure is possible.
Extlifies the effect of non-compolant minelaxants and the anticoagulant effect of Kumarins.
Three and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedative and sleeping pills increase the oppression of the CNS.
Simultaneous use with Mao inhibitors is not recommended due to a significant increase in hypotensive action, a break in the treatment between the intake of Mao and Esmolol inhibitors should be at least 14 days.
Unhydrated burden alkaloids increase the risk of developing peripheral circulatory disorders.