Бетакард®

General characteristics. Structure:

Active ingredient: 50 mg or 100 mg of an atenolol.

Vspomogatelna of substance: calcium hydrophosphate, starch, magnesium stearate, a karmelloza of sodium, sodium lauryl sulfate, a gipromelloza (E15 LV of 2910), talc, titanium dioxide, a macrogoal-6000, silicon dioxide colloid (aerosil 200), dye yellow iron oxide (dye an azoruby (кармоизин), dye diamond blue for tablets in 100 mg).

Pharmacological properties:

Pharmacodynamics. Cardioselective beta1-adrenoblocker, has no membrane stabilizing and internal sympathomimetic activity. Has hypotensive, anti-anginal and antiarrhytmic effect. Blocking heart beta1-adrenoceptors in low doses, reduces stimulated catecholamines formation of tsAMF from ATP, reduces intracellular current of calcium ions, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat the heart rate (HR), conductivity and excitability oppresses, reduces contractility of a myocardium).

The general peripheric vascular resistance at the beginning of use of beta adrenoblockers (in the first 24 hours after intake) increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation of beta2-adrenoceptors) which in 1-3 days is returned to initial, and at long appointment decreases.

The hypotensive effect is connected with reduction of minute volume of a blood-groove, decrease of the activity system renin-angiotensin-aldosteronovoy (has bigger value for patients with initial hypersecretion of a renin), sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to a lowering of arterial pressure) and influence on the central nervous system.

Hypotensive action is shown by decrease in both systolic, and diastolic arterial pressure, reduction of stroke and minute output of blood circulation. In average therapeutic doses has no effect on a tone of peripheral arteries. The hypotensive effect proceeds 24 hours, at regular reception 2 weeks of treatment are stabilized by the end.

The anti-anginal effect is defined by decrease in need of a myocardium for oxygen as a result of reduction of ChSS (lengthening of a diastole and improvement of perfusion of a myocardium) and contractility, and also decrease in sensitivity of a myocardium to influence of a sympathetic innervation. Urezhayet ChSS at rest and at an exercise stress. Due to increase in end diastolic pressure in a left ventricle and increases in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with chronic heart failure.

The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of a sympathetic nervous system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of atrioventricular carrying out. Oppression of carrying out impulses is noted preferential in antegrade and to a lesser extent in retrograde the directions through an atrioventricular node and on additional ways.

Increases survival of the patients who had a myocardial infarction (reduces the frequency of development of ventricular arrhythmias and attacks of stenocardia).

Practically does not weaken bronkhodilatiruyushchy action of an izoprenalin. Unlike non-selective beta adrenoblockers at appointment in average therapeutic doses exerts less expressed impact on the bodies containing beta2-adrenoceptors (a pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus), and on carbohydrate metabolism; expressiveness of atherogenous action does not differ from effect of propranolol. To a lesser extent renders negative batmo-, hrono-, other and dromotropic effect. At use in high doses (more than 100 mg/days) renders the blocking effect on both subtypes of beta adrenoceptors.

The negative chronotropic effect is shown in 1 hour after reception, reaches a maximum 2-4 hours later and proceeds till 24 o'clock.

Pharmacokinetics. Absorption from digestive tract - bystry, incomplete (50-60%), bioavailability - 40-50%, solubility in fats very low. Time of achievement of the maximum concentration - 2-4 hours. Badly gets through a blood-brain barrier, passes through a placental barrier and in breast milk. Communication with proteins of a blood plasma - 6-16%. Practically it is not metabolized in a liver. An elimination half-life - 6-9 hours (increases at patients of advanced age). It is removed by kidneys by glomerular filtering (85-100% in not changed look). The renal failure is followed by lengthening of an elimination half-life and cumulation (reduction of doses is necessary): at the clearance of creatinine (CC) lower than 35 ml/min./1.73 sq.m. the elimination half-life makes 16-27 hours, at KK it is lower than 15 ml/min. - more than 27 hours, at an anury is extended till 144 o'clock. It is removed during a hemodialysis.

Indications to use:

• arterial hypertension;
• prevention of attacks of stenocardia, except for Printsmetal's stenocardia;
• disturbances of a cordial rhythm: sinus tachycardia, prevention of supraventricular tachyarrhythmias, ventricular premature ventricular contraction.

Route of administration and doses:

Appoint inside before food, do not chew, wash down with a small amount of liquid.

Arterial hypertension. Treatment is begun with 50 mg of the drug Бетакард® 1 of times a day. Achievement of stable hypotensive effect requires 1-2 weeks of reception. At insufficient expressiveness of hypotensive effect the dose is raised to 100 mg on one reception. Further increase in a dose is not recommended as it is not followed by strengthening of clinical effect.

Stenocardia. The initial dose makes 50 mg a day. If within a week the optimum therapeutic effect is not reached, increase a dose to 100 mg a day. Correction of the mode of dosing is necessary for patients of advanced age and patients with disturbances of secretory function of kidneys. In the presence of a renal failure recommend dose adjustment depending on clearance of creatinine. Patients with a renal failure at values of clearance of creatinine have higher than 35 ml/min. / 1,73 the sq.m (normal values make 100-150 ml/min. / 1,73м2) considerable cumulation of the drug Betakard® does not occur.

The following maximum doses for patients with a renal failure are recommended:

Clearance of creatinine (ml/min. / 1,73 sq.m)	Elimination half-life (w)	Maximum dose
15-35    less than 15	16-27    more than 27	50 mg a day 100 mg every other day 50 mg every other day 100 mg of 1 times in four days

The patient who is on a hemodialysis, Betakard® appoint 25 or 50 mg/days right after holding each session of dialysis that needs to be carried out in stationary conditions as falling of arterial pressure can take place.

Elderly patients have an initial single dose - 25 mg (it can be increased under control of arterial pressure, heart rate).

Increase in a daily dose over 100 mg is not recommended since the therapeutic effect amplifies, and the probability of development of side effects increases.

Features of use:

Control of the patients accepting атенолол has to include heart-rate monitoring (ChSS) and the arterial pressure (AP) (in an initiation of treatment - daily, then 1 time in 3-4 months), the content of glucose of blood at patients with a diabetes mellitus 1 and 2 types (1 time in 4-5 months). At elderly patients it is recommended to monitor function of kidneys (1 times in 4-5 months).

It is necessary to train the patient in a technique of calculation of ChSS and to instruct about need of medical consultation at ChSS less than 50 уд. / min. Approximately at 20% of patients with stenocardia beta adrenoblockers are inefficient.

The main reasons - heavy coronary atherosclerosis with a low threshold of ischemia (ChSS less than 100 beats/min.) and the raised final diastolic. the volume of a left ventricle, breaking a subendocardial blood stream. At "smokers" efficiency of beta adrenoblockers is lower.

The patients using contact lenses have to consider that against the background of treatment reduction of products of the lacrimal liquid is possible.

At a thyrotoxicosis атенолол can mask certain clinical signs of a thyrotoxicosis (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology.

At a diabetes mellitus can mask the tachycardia caused by a hypoglycemia. Unlike non-selective beta adrenoblockers practically does not strengthen the hypoglycemia caused by insulin and recovery of content of glucose in blood to normal concentration does not detain.

At a concomitant use of a clonidine its reception can be stopped only in several days after cancellation of an atenolol

Strengthening of expressiveness of allergic reaction and lack of effect of usual doses of Epinephrinum (adrenaline) against the background of the burdened allergological anamnesis is possible.

Some days before carrying out the general anesthesia chloroform or diethyl ether it is necessary to stop administration of drug. If the patient accepted drug before operation, it should pick up medicines for the general anesthesia with minimum negative inotropic effect.

Reciprocal activation of n.vagus can be eliminated in/in administration of atropine (1-2 mg). The medicines reducing stocks of catecholamines (for example, Reserpinum), can strengthen effect of beta adrenoblockers therefore the patients accepting such combinations of medicines have to be under constant observation of the doctor regarding identification of the expressed decrease in the ABP or bradycardia.

Patients can appoint drug with bronkhospastichesky diseases in case of intolerance and/or inefficiency of other antihypertensives, but at the same time it is necessary to watch a dose strictly. The overdose is dangerous by development of a bronchospasm. In case of emergence in patients of advanced age of the accruing bradycardia (less than 50 уд. / min.), arterial hypotension (systolic the ABP is lower than 100 mm hg), an atrioventricular block, a bronchospasm, ventricular arrhythmias, heavy abnormal liver functions and kidneys it is necessary to reduce a dose or to stop treatment. It is recommended to stop therapy at development of the depression caused by reception of beta adrenoblockers.

It is impossible to interrupt sharply treatment because of danger of development of heavy arrhythmias and a myocardial infarction. Cancellation is carried out gradually, reducing a dose within 2 weeks and more (lower a dose by 25% in 3-4 days).

It is necessary to cancel before a research of content in blood and urine of catecholamines, a normetanefrin and vanililmindalny acid; credits of antinuclear antibodies (in 1-2 days

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From the central nervous system: an adynamy, weakness, dizziness, a headache, drowsiness or sleeplessness, "dreadful" dreams, a depression, concern, confusion of consciousness or short-term loss of memory, a hallucination, decline in the ability to concentration of attention, reduction in the rate of reaction, paresthesia in extremities (at patients with the "alternating" lameness and Reynaud's syndrome), a myasthenia, spasms.

From sense bodys: vision disorder, reduction of secretion of the lacrimal liquid, dryness and morbidity of eyes, conjunctivitis.

From cardiovascular system: bradycardia, heartbeat, disturbance of conductivity of a myocardium, an atrioventricular block (up to a cardiac standstill), arrhythmias, easing of contractility of a myocardium, development (aggravation) of chronic heart failure, orthostatic hypotension, manifestations of a vasomotor spasm (a cold snap of the lower extremities, Reynaud's syndrome), a vasculitis, a stethalgia.

From the alimentary system: dryness of a mucous membrane of an oral cavity, nausea, vomiting, abdominal pain, locks or diarrhea, taste changes.

From respiratory system: a nose congestion, difficulty of breath at appointment in high doses (selectivity loss) and/or at predisposed patients - laringo-and a bronchospasm.

From endocrine system: a hyperglycemia (patients with a diabetes mellitus have 2 types), a hypoglycemia (at the patients receiving insulin), a hypothyroid state.

Allergic reactions: skin itch, rash, small tortoiseshell.

From integuments: sweating strengthening, dermahemia, aggravation of symptoms of psoriasis, psoriazopodobny skin rashes, reversible alopecia. Laboratory indicators: thrombocytopenia (unusual bleedings and hemorrhages), agranulocytosis, leukopenia, increase in activity of "hepatic" enzymes, hyperbilirubinemia. Influence on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia.

Others: dorsodynia, arthralgia, weakening of a libido, decrease in a potentiality, syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in arterial pressure).

Frequency of by-effects increases at increase in a dose of drug.

Interaction with other medicines:

The allergens used for an immunotherapy or extracts of allergens for skin tests increase risk of emergence of heavy system allergic reactions or an anaphylaxis at the patients receiving атенолол.

Iodinated X-ray contrast means for in/in introductions increase risk of development of anaphylactic reactions.

Phenytoinum at in introduction, medicines for inhalation anesthesia (derivatives of hydrocarbons) increase expressiveness of cardiodepressive action and probability of a lowering of arterial pressure.

At co-administration with insulin and hypoglycemic means for intake masks symptoms of the developing hypoglycemia.

Reduces clearance of lidocaine and xanthines and increases their concentration in a blood plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.

Hypotensive effect non-steroidal anti-inflammatory drugs (a delay of ions of sodium and blockade of synthesis of prostaglandins kidneys) weaken, glucocorticosteroids and estrogen (a sodium delay).

Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, blockers of "slow" calcium channels (verapamil, diltiazem), Amiodaronum and other antiarrhytmic means increase risk of development or aggravation of heart failure, bradycardia, an atrioventricular block and cardiac standstill. Diuretics, a clonidine, sympatholytics, гидралазин, can lead blockers of "slow" calcium channels and other antihypertensives to excessive decrease in the ABP.

Extends action of not depolarizing muscle relaxants and anticoagulating effect of coumarins.

Rub - and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedative and hypnagogues strengthen oppression of the central nervous system.

Simultaneous use with MAO inhibitors owing to considerable strengthening of hypotensive action is not recommended, having rummaged in treatment between reception of MAO inhibitors and an atenolola has to make not less than 14 days.

Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation.

Contraindications:

Hypersensitivity to drug, cardiogenic shock, an atrioventricular block of P-PG of degree, the expressed bradycardia (ChSS less than 40 уд. / min.), a sick sinus syndrome, sinuatrial blockade, an acute heart failure or dekompensirovanny chronic heart failure, a cardiomegaly without symptoms of chronic heart failure, Printsmetal's stenocardia, arterial hypotension (in case of use at a myocardial infarction, the systolic arterial pressure (AP) less than 100 mm hg), the lactation period, a concomitant use of monoamine oxidase inhibitors (MAO), age up to 18 years (efficiency and safety are not established).

With care. A diabetes mellitus 1 and 2 types, a metabolic acidosis, a hypoglycemia, allergic reactions in the anamnesis, a chronic obstructive pulmonary disease (including bronchial asthma, emphysema of lungs), the chronic heart failure (compensated), obliterating diseases of peripheral vessels (the "alternating" lameness, Reynaud's syndrome); a pheochromocytoma, a liver failure, a chronic renal failure, a myasthenia, a thyrotoxicosis, a depression (including in the anamnesis), psoriasis, pregnancy, advanced age.

Overdose:

Symptoms: the expressed bradycardia, dizziness, an excessive lowering of arterial pressure, unconscious states, arrhythmia, ventricular premature ventricular contraction, an atrioventricular block of the II-III degree, chronic heart failure, cyanosis of nails or palms, spasms, breath difficulty, a bronchospasm.

Treatment: a gastric lavage and purpose of the adsorbing medicines; at disturbance of atrioventricular conductivity and/or bradycardia - in/in introduction of 1-2 mg of atropine, Epinephrinum (adrenaline) or statement of a temporary pacemaker; at ventricular premature ventricular contraction - lidocaine (the drugs IA of a class are not used); at a lowering of arterial pressure - the patient has to be in the provision of Trendelenburga. If there are no fluid lungs signs - in/in plasma substituting solutions, at inefficiency - introduction of Epinephrinum, dopamine, Dobutaminum; at chronic heart failure - cardiac glycosides, diuretics, a glucagon; at spasms - in/in diazepam; at a bronchospasm - it is inhalation or parenterally - beta адреностимуляторы. Carrying out dialysis is possible.

Storage conditions:

List B. To store at a temperature not above 30 °C. To store in the place, unavailable to children. A period of validity - 4 years from the date of production. Not to use after the term specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 50 mg, 100 mg. 10 tablets in the blister from aluminum foil and PVC of a film; 3 blisters or 10 blisters with the application instruction in a cardboard pack. A sample not for sale: 10 tablets in the blister from aluminum foil and PVC of a film; 1 blister together with the application instruction is packed into a cardboard pack.