Corvitolum of the tab. of 100 mg No. 50

Pharmacological properties

Pharmacodynamics. metoprolol — a blocker of β-adrenoceptors without internal sympathomimetic activity. in the specific way blocks action of catecholamines at the level of adrenergic β1-рецепторов. reduces the need of a myocardium for oxygen at loading, has positive effect at long-term treatment of stenocardia (decrease in frequency of painful attacks). lowers systolic arterial blood pressure, especially after tension, and prevents development of reflex orthostatic hypotension. decrease diastolic hell occurs in several weeks of regular use — metoprolol reduces plasma activity of renin. inhibiting β2-адренорецепторы, metoprolol can cause increase in a tone of unstriated muscles.

Pharmacokinetics. Absorption and distribution. After intake metoprolol it is completely absorbed. Concentration of a metoprolol in blood plasma linearly depends on the accepted dose within therapeutic doses. With _max in blood plasma it is reached in 1.5-2 h after use (Tmax). Though concentration in blood plasma is various at different persons, the individual reproducibility is good. As a result of important effect at primary passing through a liver the system bioavailability of a metoprolol after use of one oral dose reaches 50%. After repeated use it raises up to 70%. Use at meal time can increase bioavailability by 30–40%. Indicator of linking of a metoprolol with proteins of blood plasma low (about 5-10%).

Biotransformation. Metoprolol is exposed to almost full oxidizing metabolism in a liver P450 cytochrome enzymes (generally an isoenzyme of CYP 2D6). Significant ethnic differences concerning distribution of persons with slow metabolism are noted. The number of persons with slow metabolism is 7% at Caucasians, but less than 1% — at Mongoloids. At patients with slow metabolism through CYP system 2D6 of concentration of a metoprolol in blood plasma can exceed several times concentration of medicament at persons with a normal speed of metabolism through CYP system 2D6. Nevertheless metabolism of a metoprolol for CYP to a 2D6-dependent way, perhaps, does not influence or affects to a lesser extent safety and shipping of a metoprolol. In cirrhosis it is necessary to expect increase in level of a nemetabolizovanny metoprolol in blood plasma because of reduction in the rate of metabolism.

Metabolism and removal from an organism. Metoprolol is metabolized in a liver, at the same time three metabolites are formed. Two of three metabolites have the mild β-blocking properties, however are not clinically significant.

Usually more than 95% of orally accepted dose of medicament are removed by

with urine. About 5% of this dose are removed with urine in not changed look; in some cases the amount of medicament which is removed with urine in not changed look can reach 30%. T _½ makes 3.5 h (1–9 h). The general clearance rate from blood plasma (clearance) reaches about 1000 ml/min.

At patients of advanced age is noted significant changes in pharmacokinetics of a metoprolol in comparison with patients of young age.

System bioavailability and removal of a metoprolol do not change at patients with a renal failure. But removal of metabolites at such patients is reduced. Patients to the glomerular filtration rate of 5 ml/min. have a considerable accumulation of metabolites. Such accumulation of metabolites does not render the β-blocking effect.

At patients with an abnormal liver function the pharmacokinetics of a metoprolol (in connection with the low level of linking with proteins) changes slightly. However at patients with cirrhosis the bioavailability of a metoprolol can increase, and the general clearance — to decrease.

Indication

Ag. stenocardia (including postinfarction). arrhythmia (including supraventricular tachycardia). emergency treatment of a myocardial infarction and prevention of a repeated heart attack. hyperkinetic cardial syndrome. prevention of attacks of migraine.

Use Metoprolol is intended to

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for daily reception, it is desirable in the morning. the tablet should be swallowed without chewing, washing down with enough drinking water. the tablet can be divided into equal parts. for this purpose it is necessary to take a tablet big and index fingers of both hands a notch for division up, to press thumbs and to break a tablet on two half along a break. during selection of a dose it is necessary to control chss for prevention of bradycardia. the maximum daily dose — 200 mg. if after prolonged use of medicament the treatment termination is required, then it is necessary to do it gradually and slowly because sudden medicament withdrawal can lead to sharp increase hell, cardiac ischemia with exacerbation of stenocardia or to a myocardial infarction.

AG. The recommended dose makes 50–100 mg (once in the morning or with distribution to two receptions — in the morning and in the evening). If at such dosage the therapeutic effect is not reached, the daily dose can be raised to 200 mg (with distribution to two receptions — in the morning and in the evening), or medicament should be combined with other antihypertensive medicines.

Stenocardia (including after a myocardial infarction). The recommended dose makes 50–100 mg/days (1 time a day in the morning or 2 times in the morning and in the evening). If this dose does not give desirable therapeutic effect, it can be raised to 200 mg divided into 2 receptions (in the morning and in the evening). At the same time the ABP should check. If necessary medicament can be combined with other medicaments for treatment of stenocardia.

Arrhythmia (including supraventricular tachycardia). The recommended dose makes 100–200 mg/days (the dose of 100 mg is accepted once in the morning, a dose of 200 mg — 100 mg in the morning and 100 mg in the evening).

Treatment of a sharp phase of a myocardial infarction and prevention of a repeated heart attack

Treatment of a sharp phase. In an acute myocardial infarction the treatment is begun as soon as possible after hospitalization, constantly controlling cardiac performance by means of the ECG and measurement of the ABP level. An initial dose — 5 mg of a metoprolol of tartrate in / century. Depending on shipping, the following doses on 5 mg of a metoprolol of tartrate can be entered in/in at an interval of 2 min. before achievement of the general maximum dose of 15 mg of a metoprolol of tartrate. If the full dose of 15 mg entered in/in is transferred well, in 15 min. after the last in/in introductions once apply 50 mg orally. In the subsequent 48 h 50 mg of a metoprolol each 6 h accept orally. For the patients who were not transferring a dose of 15 mg of a metoprolol of tartrate at in in introduction, further therapy with oral administration should be begun with care with 25 mg.

Maintenance dose. The recommended dose makes 200 mg in 2 receptions (in the morning and in the evening). At decrease in ChSS and/or the ABP or other complications which demand treatment the use of medicament should be stopped immediately.

Hyperkinetic warm syndrome. The recommended dose makes 50–100 mg/days (to apply 1 time in the morning or to divide into 2 receptions — in the morning and in the evening). If this dose does not give desirable therapeutic effect, it can be raised to 200 mg divided into 2 receptions (in the morning and in the evening). At the same time it is necessary to check the ABP level. The dose should be lowered at achievement of therapeutic effect.

Prevention of attacks of migraine. The recommended daily dose makes 100–200 mg/days (the dose of 100 mg is accepted 1 time in the morning, a dose of 200 mg — 100 mg in the morning and 100 mg in the evening).

Patients with a renal failure. There is no need for dose adjustment.

Patients with an abnormal liver function. Dose adjustment (dose decline of a metoprolol) is usually necessary for patients with an abnormal liver function (for example with cirrhosis).

Patients of advanced age. There is no need for dose adjustment.

Contraindication

Hypersensitivity to components of medicament or other blockers of β-adrenoceptors; av-blockade (ii and iii of degree), sinuatrial blockade; syndrome of weakness of a sinus node; dekompensirovanny heart failure (fluid lungs, syndrome of hypoperfusion or arterial hypotension); profound bradycardia (chss ≤50 ud. / mines); shock; heavy disturbances of peripheric circulation with pain or trophic changes; arterial hypotension (systolic hell of 100 mm Hg.); bronchial hyperactivity (for example oh), severe form of chronic obstructive bronchopulmonary diseases; acidosis; not treated pheochromocytoma; long or periodic inotropic therapy by agonists of β-receptors; use of a metoprolol is contraindicated at patients at whom it is carried out in to introduction of antagonists of calcium of type of verapamil and diltiazem or other antiarrhytmic medicaments (Disopyramidum); the accompanying therapy by inhibitors mao-and.

Metoprolol patients should not appoint

with suspicion of an acute myocardial infarction at ChSS 50 ud. / mines, P-Q 0.24 interval with or systolic arterial blood pressure of 100 mm Hg.

Side effects

Frequency of emergence of side reactions is defined by

as follows: very often (1/10); often: (1/100, 1/10); infrequently (1/1000, 1/100); seldom (1/10,000, 1/1000); very seldom (1/10,000); frequency is unknown (it cannot be estimated on the available data).

from blood and lymphatic system: very seldom — thrombocytopenia, a leukopenia.

from the immune system: very seldom — allergic rhinitis.

Metabolic and alimentary disturbances: seldom — diabetes, exacerbation of diabetes; it is unknown — a hypoglycemia (after a long, strict post or heavy physical activity, hypoglycemic states can arise against the background of therapy by drug).

from mentality: infrequently — a sleep disorder, nightmares, a depression, hallucinations; very seldom — problems with memory, change of the personality, differences of mood.

from nervous system: infrequently — dizziness, a headache, confusion of consciousness, unusual dreams, paresthesias; very seldom — disturbance of flavoring feelings.

from an organ of sight: seldom — dryness in an eye or inflammation of a conjunctiva; very seldom — a disorder of vision.

from an organ of hearing and balance: very seldom — feeling of a noise/ring in ears, a hearing disorder.

from heart: seldom — tachycardia, bradycardia, disturbance of conductivity, exacerbation of heart failure; seldom — peripheral hypostases; very seldom — strengthening of stenocardia.

from vessels: infrequently — cold extremities; seldom — arterial hypotension, a syncope; it is unknown — aggravation of a syndrome of Reynaud (it concerns as well other forms of disturbances of perfusion of extremities).

from the respiratory system, bodies of a chest cavity and mediastinum: seldom — an asthma at physical activity; it is unknown — a respiratory distress syndrome (because of increase in resistance of airways the respiratory distress at the patients inclined to bronkhospastichesky reactions is possible, especially in obstructive respiratory diseases).

from a digestive tract: infrequently — nausea, vomiting, an abdominal pain, diarrhea, a constipation; seldom — dryness in a mouth.

from a gepatobiliarny system: very seldom — hepatitis.

from skin and hypodermic cellulose: infrequently — reactions of hypersensitivity, the strengthened sweating; very seldom — psoriasis, strengthening of weight of psoriasis, psoriazopodobny rash, a hair loss; it is unknown — lipometabolism disturbance.

from the musculoskeletal system and connective tissue: seldom — muscular spasms, muscle weakness; very seldom — arthritis.

from a reproductive system and mammary glands: very seldom — impotence / sexual dysfunction, Peyroni's disease.

from kidneys and urinary tract: very seldom — exacerbation of a renal failure.

General disturbances and reactions in the injection site: it is unknown — increased fatigue.

Laboratory indicators: very seldom — increase in body weight, an aberration from indicators of function of a liver; it is unknown — decrease in the LPVP level XC and increase in the TG level at the normal level of the general XC.

Special instructions

, as well as at reception of other blockers of β-adrenoceptors, needs to control

At reception of a metoprolol of tartrate chss and hell (at first daily, then once a month).

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As a rule, at treatment of patients OH as the accompanying therapy it is necessary to appoint β ₂ - agonists (in tablets or aerosol). In cases when these patients begin to take the drug, increase in a dose β ₂ - agonists can be required. The risk of influence of medicament on β - receptors is lower than ₂ , than in case of use of usual non-selective blockers β ₁ - adrenoceptors in tablets.

Especially careful medical control is necessary for

at treatment of patients with diabetes (control of level of glucose in blood), patients with the unstable level of glucose in blood, at observance of a rigid diet with starvation, the patients adhering to a long strict post and at big physical activity — because of a possibility of development of serious hypoglycemic conditions.

Metroprolol can mask some clinical manifestations of a thyrotoxicosis (for example tachycardia). Sharp medicament withdrawal for patients with a thyrotoxicosis is contraindicated because of possible increase in expressiveness of symptomatology.

Patients who undergo treatment concerning heart failure have to receive therapy in this disease prior to use of a metoprolol and also during this treatment. Very seldom already existing easy forms of disturbance of AV conductivity can burden and bring to AV blockade of heavier degree. Patients with AV blockade of the I degree have to undergo treatment by this medicament very carefully. With care metoprolol to apply at patients with a myasthenia gravis. In case of development of bradycardia (ChSS 50-55 ud. / mines) during treatment metoprololy the dose has to be reduced and/or medicament should be cancelled gradually. Thanks to hypotensive action, medicament can strengthen manifestations of symptoms of disturbance of peripheric circulation, such as the alternating lameness.

If to use medicament at patients with a pheochromocytoma, in parallel it is necessary to take the α-sympatholytic drug.

If it is impossible to stop use of the medicament Corvitolum prior to a procedure under the general anesthesia or before use of a peripheral muscular relaxant, the anesthesiologist has to be informed on use by the patient of the medicament Corvitolum. It is not recommended to stop treatment during performing surgical intervention. If administration of medicament needs to be cancelled, cancellation should be carried out not later than 48 h before operation, except for special cases, for example a thyrotoxicosis or a pheochromocytoma.

If needs to stop treatment and in case it is possible, it should be stopped within 10–14 days with a daily dose decline on 25 mg/days during the last 6 days. Throughout this period special attention needs to be paid to patients with an ischemic heart disease. The risk of developing of heart attacks, including a sudden lethal outcome, can increase at the treatment termination by blockers of β-adrenoceptors. Therapy should not be cancelled suddenly because of a possibility of development of a withdrawal (strengthening of attacks of stenocardia, increase in the ABP).

Metoprolol can cause slight increase of the TG level and decrease in content of free fatty acids in blood. Insignificant decrease in the LPVP level was in certain cases observed, and it was significant smaller in comparison with reception of non-selective blockers β ₂ - adrenoceptors. Nevertheless in one long-term research the considerable decrease in level of the general in XC after treatment metoprololy within several years is shown.

Data on efficiency and safety of use of medicament for patients with heavy stable heart failure (the IV degree on NYHA) are limited to

. Doctors with special skills and experience have to carry out treatment of such patients.

At patients with Printsmetal's stenocardia the frequency and weight of attacks of stenocardia can increase as a result of the narrowing of coronary vessels mediated by α-receptors. Therefore such patients should not appoint non-selective blockers of β-adrenoceptors, selection blockers β ₁ - adrenoceptors it is necessary to apply with care.

Acute anaphylaxis hard proceeds at the patients receiving treatment by blockers of β-adrenoceptors.

Patients in the history of whose disease heavy allergic reactions were noted have to undergo therapy metoprololy very carefully. Special attention also should be paid to patients with allergic reactions which receive treatment by vaccines (the desensibilizing therapy). The effect of introduction of usual doses of adrenaline can be absent.

to the Patients using contact lenses should consider

that medicament can reduce secretion of plaintive liquid.

In some cases blockers of β-receptors can provoke developing of psoriasis, strengthening of symptoms of this disease or emergence ekzanty, reminding psoriasis. Patients can appoint blockers of β-receptors with psoriasis in the anamnesis only after careful assessment of advantage/risk.

to Patients with depressive diseases in the history of a disease should appoint by

treatment metoprololy, having only carefully estimated the attitude of positive effect towards risk.

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to Patients with heavy renal failures, with serious acute conditions and to patients who receive the combined treatment by foxglove medicaments it is necessary to pay special attention.

Drug contains lactose therefore it is not necessary to appoint him the patient with hereditary deficiency of lactase, intolerance of a galactose or disturbance of metabolism of a glucose/galactose.

Patients with an acute myocardial infarction or unstable stenocardia in the last 28 days and also patients with an abnormal liver function (see USE), are aged more senior than 80 years or 40 years are younger; patients with hemodynamically profound diseases of valves, a hypertrophic subaortic stenosis, patients in time or within 4 months after surgery on heart have to be treated only under observation of the doctor with specialized skills and experience.

Use during pregnancy and feeding by a breast. Metoprolol, as well as other medicines, it is not necessary to apply during pregnancy and feeding by a breast without emergency. As well as other blockers of β-adrenoceptors, metoprolol can cause side effects, such as bradycardia, hypotension and hypoglycemia, in a fruit and the newborn or in the baby during breastfeeding.

As a rule, blockers of β-adrenoceptors suppress a placentary blood stream that can become the reason of premature births, growth inhibitions and death of a fruit. Metoprolol can cause development of bradycardia, arterial hypotension, a hypoglycemia and respiratory depression in newborns therefore its reception should be stopped for 48–72 h till the expected beginning of childbirth. If it is impossible, it is necessary to control carefully a condition of the baby during 48–72 h after the birth.

on the other hand, quantity of a metoprolol which the baby receives with breast milk for implementation of potential effect of blockade of β-adrenoceptors slightly provided that doses of a metoprolol which are received by mother are in limits of normal therapeutic range (except for slow metabolizator). It is necessary to control carefully a condition of babies on breastfeeding for identification of potential effects of blockade of β-adrenoceptors.

In order that concentration of active active ingredient in breast milk was low, it is not necessary to feed the child during 3–4 h after administration of drug.

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In reproduction researches at rats using a metoprolol of tartrate in the doses, by 55.5 times exceeding the maximum recommended dose for the person revealed no proofs of disturbance of fertility, however seldom metoprolol can vyzyvt Peyroni's disease at men.

Children. Use of medicament is contraindicated to children.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Use of medicament can influence the activity demanding the high speed of mental and physical reactions, adoption of the fast decision (for example control of vehicles, service of machines and mechanisms, work at height) therefore for treatment it is necessary to refrain from control of vehicles, service of machines and mechanisms, work at height. Probability of such influence increases in an initiation of treatment, at increase in a dose or change of medicament and also at alcohol intake.

Interaction

Patients have to be under careful observation if they along with medicament Corvitolum accept ganglioblokator, other blockers of β-adrenoceptors (for example eye drops).

Care is recommended to

in case of the combined use of some antiarrhytmic medicaments of type of quinidine or Amiodaronum and a propafenon as blockers of β-adrenoceptors can enhance negative inotropic and negative dromotropic effects. Co-administration with propafenony should be avoided. Propafenon oppresses metabolism of a metoprolol through P450 2D6 cytochrome. The result of such combination is unpredictable as it propafenon also shows properties of blockers of β-adrenoceptors.

Cardiodepressive effect of the medicament Corvitolum and antiarrhytmic medicaments (Amiodaronum, propafenon and other antiarrhytmic drugs) can be summarized by

. The effect of Amiodaronum (considerable sinus bradycardia) can remain after the termination of administration of medicament for a long time.

At simultaneous use of the medicament Corvitolum and cardiac glycosides, reserpine, α-Methyldopums, a guanfatsina or a clonidine considerable decrease in ChSS or delay of conductivity can happen.

At sudden cancellation of a clonidine against the background of treatment by blockers of β-adrenoceptors the ABP can raise. If it is necessary to cancel the accompanying therapy by a clonidine, the blocker of β-adrenoceptors should stop be applied some days before cancellation of a clonidine.

At patients which along with the medicament Corvitolum are accepted by antagonists of calcium of verapamilovy type or diltiazem and/or medicaments for treatment of arrhythmia (such as Disopyramidum) negative inotropic and chronotropic effects are possible

. Therefore careful control of a condition of such patients is recommended.

At the patients receiving treatment by blockers of β-adrenoceptors, inhalation anesthetics enhance cardiodepressive effect. Inductors or inhibitors of metabolism can affect concentration of a metoprolol in blood plasma. Concentration of a metoprolol in blood plasma decreases at intake of rifampicin or can increase at intake of Cimetidinum, Phenytoinum, alcohol, a gidralazin and inhibitors of the return serotonin reuptake (paroksetin, fluoxetine and sertraline).

Simultaneous use of a metoprolol with lidocaine can delay removal of lidocaine from an organism.

Yodosoderzhashchy X-ray contrast substances for in/in introductions increase risk of anaphylactic reactions.

Simultaneous use of a metoprolol and neuromuscular relaxants (for example succinylcholine, tubocurarine) can strengthen neuromuscular blockade.

Simultaneous use of the medicament Corvitolum with NPVP, such as indometacin, can reduce antihypertensive effect of a metoprolol.

Cardioselective blockers of β-adrenoceptors in much smaller degree influence the ABP at introduction to patients of adrenaline, than non-selective blockers of β-adrenoceptors.

As blockers of β-adrenoceptors can influence peripheric circulation, it is necessary to show care at simultaneous use of medicaments with similar action, for example with ergotamine.

Blockers of β-adrenoceptors can provoke paradoxical hypertensive reactions at the patients applying fenilpropanolamin in high doses.

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At a concomitant use of blockers of β-adrenoceptors with insulin or oral anti-diabetic means their action can amplify or be prolonged. At the same time hypoglycemia symptoms (especially tachycardia and a tremor) can mask or disappear. In such cases it is necessary to carry out regular control of level of glucose to blood with possible dose adjustment of gipoglikemiziruyushchy means in case of need.

Should avoid a concomitant use with barbiturates as barbiturates (it is investigated on pentobarbital) stimulate metabolism of a metoprolol by enzyme induction. Metoprolol is almost completely metabolized in a liver by enzymes of a system of P450 cytochrome (generally an isoenzyme of CYP 2D6). The medicaments inhibiting CYP 2D6, for example quinidine, terbinafin, paroksetin, fluoxetine, bupropion, thioridazine, ritonavir, hydroksikhlorokin, kinin, sertraline, tselekoksib, propafenon and difengidramin can affect concentration of a metoprolol in blood plasma. In an initiation of treatment the need of a dose decline of a metoprolol can arise these drugs.

Simultaneous use of glycosides of a foxglove and blockers of β-adrenoceptors can increase time of AV conductivity and cause bradycardia. Difengidramin reduces (by 2.5 times) clearance of a metoprolol to a α-hydroksimetoprolol through CYP system 2D6 at persons with a fast hydroksilyation. Effects of a metoprolol amplify. Perhaps, difengidramin can inhibit metabolism of other CYP substrates 2D6.

Rifampitsin can stimulate with

metabolism of a metoprolol through CYP 2D6 that leads to decrease in its levels in blood plasma.

Should be careful at a combination with nitrates, tricyclic antidepressants, fenotiazina, diuretics and other vazodilatator because of risk of arterial hypotension and/or bradycardia.

Accompanying therapy by dihydropyridinic blockers of calcium channels (for example nifedipine) with metoprololy, as well as other blockers of β-adrenoceptors, increases risk of arterial hypotension and heart failure at patients with latent heart failure.

Metoprolol counteracts β to ₁ - to effects of sympathomimetic means, but has insignificant influence on bronkhodilatatsionny effect β ₂ - agonists at use of therapeutic doses.

At simultaneous use of the medicament Corvitolum and Norepinephrinum, epinephrine or other sympathomimetics of substances (for example those which contain in cough remedies, drops for a nose and eyes) perhaps substantial increase of the ABP level.

At therapy metoprololy can observe decrease in the answer on adrenaline in doses which are usually applied to treatment of allergic reactions.

Because of a possibility of development of heavy AG MAO inhibitors should not be applied together with drug.

Overdose

Symptoms: depending on intoxication degree, the clinical picture is characterized generally by symptoms from cardiovascular and central nervous system. the overdose of a metoprolol can lead to the significant decrease hell, to sinus bradycardia, av-blockade of i-iii of degree, lengthening of an interval of q-t, an asystolia, insufficient peripheral perfusion, heart failure, cardiogenic shock, cardiac arrest, a bronchospasm, oppression or an apnoea, increased fatigue, disturbance or a loss of consciousness, a tremor, spasms, the increased sweating, paresthesia, a coma, nausea, vomiting, esophagospasms, a hypoglycemia (especially at children), to a hyperglycemia, cyanosis, influence on kidneys and a temporary myasthenic syndrome.

Accompanying alcohol intake, intake of antihypertensive drugs, quinidine or barbiturates can worsen a condition of the patient. The first signs of overdose can arise in 20 min.-2 the h after overdose.

Treatment is carried out by

in the conditions of intensive care unit with monitoring of the vital functions. Intake of activated carbon, if necessary — gastric lavage. In case of severe forms of arterial hypotension, bradycardia or threat of heart failure it is necessary to enter β ₁ - agonist in/in (for example prenalterol) with an interval of 2-5 min., or infusionally to achievement of therapeutic effect. In case of absence selection β ₁ - agonist can be entered in into a dopamine or Atropini sulfas for blockade of vagus nerve. Should enter atropine (0.25-0.5 mg of adult, 10–20 mkg/kg of body weight children) before gastric lavage because of risk of vagal stimulation. The intubation and use of the medical ventilator can be required; adequate restoration of OCK; glucose infusion; monitoring of the ECG; 1–2 mg, repeated in/in administration of atropine (mainly at vagal symptoms). If the therapeutic effect is not reached, it is possible to apply other sympathomimetics, such as Dobutaminum, izoprenalin, ortsiprenalin, epinephrine or Norepinephrinum.

Also should enter a glucagon in a dose of 1-10 mkg/kg of body weight in/in, subsequently it is possible to enter 2-2.5 mg/h in the form of continuous infusion. In the considerable bradycardia which is not giving in to medicamentous therapy it is necessary to apply the artificial driver of a warm rhythm. For stopping of a bronchospasm it is necessary to enter it is inhalation or in/in β ₂ - agonist or Aminophyllinum in / century. It is necessary to consider that the doses of antidotes necessary for elimination of symptoms of overdose of blockers of β-adrenoceptors are much higher therapeutic as β-receptors are tied by blockers of β-adrenoceptors.

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in case of generalized spasms recommends slow administration of diazepam.

Storage conditions

At a temperature not above 25 °C.