Bisoprolol

General characteristics. Structure:

Active ingredient: 5 mg or 10 mg of a bisoprolol of a fumarat.

Excipients: croscarmellose sodium (primelloza), povidone (polyvinylpirrolidone middlemolecular), starch prezhelatinizirovanny (starch 1500), silicon dioxide colloid (aerosil), talc, cellulose microcrystallic, lactose (sugar milk), magnesium stearate.

Structure of a film cover: опадрай II (the polyvinyl alcohol which is partially hydrolyzed titanium dioxide, talc, a macrogoal (polyethyleneglycol 3350), dye ferrous oxide (II)).

Pharmacological properties:

Pharmacodynamics. The selection beta1-adrenoblocker, without own sympathomimetic activity, does not possess membrane stabilizing action. Reduces activity of a renin of a blood plasma, reduces the need of a myocardium for oxygen, reduces ChSS (at rest and at loading).

Has hypotensive, antiarrhytmic and anti-anginal 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, oppresses conductivity and excitability of a myocardium, reduces AV conductivity.

At increase in a dose is higher than therapeutic has beta2-adrenoceptor blocking effect.

OPSS at the beginning of drug use, in the first 24 h, 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 blood, sympathetic stimulation of peripheral vessels, decrease of the activity a system renin-angiotenzinovoy (is of great importance for patients with initial hypersecretion of a renin), recovery of sensitivity in response to decrease in the ABP and influence on TsNS. At arterial hypertension the effect occurs in 2-5 days, stable action - in 1-2 months.

The anti-anginal effect is caused by reduction of need of a myocardium for oxygen as a result of reduction of ChSS and decrease in contractility, lengthening of a diastole, improvement of perfusion of a myocardium. 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 AV carrying out (it is preferential in antegrade and, to a lesser extent, in retrograde the directions through an AV node) and on additional ways.

At use in average therapeutic doses, unlike non-selective beta adrenoblockers, 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, does not cause a delay of ions of sodium (Na+) in an organism; expressiveness of atherogenous action does not differ from effect of propranolol.

Pharmacokinetics. Absorption and distribution. Absorption - 80-90%, meal does not influence absorption. Cmax in a blood plasma is observed in 1-3 h.

Communication with proteins of a blood plasma - about 30%. Passes through GEB and a placental barrier in insignificant degree, in insignificant quantities it is allocated with breast milk.

Metabolism and removal. 50% of a dose are metabolized in a liver with formation of inactive metabolites.

T1/2 is 10-12 h. About 98% are removed with urine - 50% in an invariable look, less than 2% - with bile.

Indications to use:

— arterial hypertension;

— Ischemic heart disease: prevention of attacks of stenocardia.

Route of administration and doses:

Drug is accepted inside, in the morning, on an empty stomach, without chewing, in an initial dose of 5 mg of 1 times/days. If necessary the dose is increased to 10 mg of 1 times/days. The maximum daily dose - 20 mg/days.

Patients with a renal failure at KK have less than 20 ml/min. or with the expressed abnormal liver functions the maximum daily dose has to make 10 mg.

Dose adjustment is not required from elderly patients.

Features of use:

Use at pregnancy and feeding by a breast. Use at pregnancy and in the period of a lactation perhaps if the advantage for mother exceeds risk of development of side effects in a fruit and the child.

Special instructions. Control of the patients accepting Bisoprolol has to include measurement of ChSS and the ABP (in an initiation of treatment - daily, then - 1 time in 3-4 months), carrying out an ECG, determination of level of glucose in blood at patients with a diabetes mellitus (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.

Before an initiation of treatment it is recommended to conduct a research of function of external respiration at patients with the burdened bronchopulmonary anamnesis.

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 уд. / mines) and the increased final diastolic volume of a left ventricle breaking a subendocardial blood stream.

At the smoking patients 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.

When using patients with a pheochromocytoma have a risk of development of paradoxical arterial hypertension (if it is previously not reached effective alpha адреноблокада).

At a thyrotoxicosis Bisoprolol 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 concentration of glucose in blood to normal level does not detain.

At a concomitant use of a clonidine its reception can be stopped only in several days after Bisoprolol's cancellation.

Strengthening of expressiveness of hypersensitivity reaction and lack of effect of usual doses of a zpinefrin against the background of the burdened allergologicheeky anamnesis is possible. In case of need performing planned surgical treatment carry out drug withdrawal for 48 h prior to the beginning of the general anesthesia. If the patient accepted drug before operation, it should pick up medicine for the general anesthesia with minimum negative inotropic effect.

Reciprocal activation of a vagus nerve can be eliminated in/in administration of atropine (1-2 mg).

The medicines reducing stocks of catecholamines (including 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 with bronkhospastichesky diseases can appoint cardioselective adrenoblockers in case of intolerance and/or inefficiency of other hypotensive medicines. The overdose is dangerous by development of a bronchospasm.

In case of identification at patients of advanced age of the accruing bradycardia (less than 50 уд. / min.), the expressed decrease in the ABP (systolic the ABP is lower than 100 mm hg), AV - blockade, it is necessary to reduce a dose or to stop treatment.

It is recommended to stop therapy at development of a depression.

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 vanilinmindalny acid, credits of antinuclear antibodies.

Influence on ability to driving of motor transport and to control of mechanisms. 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 TsNS: increased fatigue, weakness, dizziness, a headache, frustration of a dream, a depression, concern, confusion of consciousness or short-term loss of memory, a hallucination, an adynamy, a myasthenia, paresthesias in extremities (at patients with the alternating lameness and Reynaud's syndrome), a tremor.

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

From cardiovascular system: a sinus bradycardia, heartbeat, disturbance of conductivity of a myocardium, AV - blockade (up to development of total cross block and a cardiac standstill), arrhythmias, easing of contractility of a myocardium, development (aggravation) of chronic heart failure (puffiness of anklebones, feet, an asthma), decrease in the ABP, orthostatic hypotension, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation, a cold snap of the lower extremities, Reynaud's syndrome), a stethalgia.

From the alimentary system: dryness of a mucous membrane of an oral cavity, nausea, vomiting, abdominal pain, lock or diarrhea, abnormal liver functions (dark urine, yellowness of scleras or skin, cholestasia), 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 (at patients with a non-insulin-dependent diabetes mellitus), a hypoglycemia (at the patients receiving insulin), a hypothyroid state.

Allergic reactions: skin itch, rash, small tortoiseshell.

Dermatological reactions: sweating strengthening, dermahemia, dieback, psoriazopodobny skin reactions, aggravation of symptoms of psoriasis.

From laboratory indicators: thrombocytopenia (unusual bleedings and hemorrhages), agranulocytosis, leukopenia, change of activity of enzymes of a liver (increase in ALT, ACT), level of bilirubin, triglycerides.

Influence on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia.

Others: dorsodynia, arthralgia, weakening of a libido, decrease in a potentiality, withdrawal (strengthening of attacks of stenocardia, increase in the ABP).

Interaction with other medicines:

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

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

Phenytoinum at in introduction, medicines for inhalation general anesthesia (derivatives of hydrocarbons) increase expressiveness of cardiodepressive action and probability of decrease in the ABP.

Changes efficiency of insulin and peroral hypoglycemic medicines, masks symptoms of the developing hypoglycemia (tachycardia, increase in the ABP).

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

Hypotensive effect NPVS (Na delay + and prostaglandin synthesis blockade by kidneys) weaken, GKS and estrogen (a delay of ions of Na+).

Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, blockers of slow calcium channels (verapamil, diltiazem), Amiodaronum and other antiarrhytmic medicines increase risk of development or aggravation of bradycardia, AV blockade, a cardiac standstill and heart failure.

Nifedipine can lead to considerable decrease in the ABP.

Diuretics, clonidine, sympatholytics, гидралазин and other hypotensive medicines can lead to excessive decrease in the ABP.

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

Rub - and tetracyclic antidepressants, antipsychotic medicines (neuroleptics), ethanol, sedative and somnolent medicines strengthen oppression of TsNS.

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 a bisoprolola has to make not less than 14 days.

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

Ergotamine increases risk of development of disturbance of peripheric circulation; Sulfasalazinum increases concentration of a bisoprolol in plasma; rifampicin shortens an elimination half-life.

Contraindications:

— shock (including cardiogenic);

— collapse;

— fluid lungs;

— acute heart failure;

— chronic heart failure in a decompensation stage;

— AV blockade of II and III degrees;

— sinuatrial blockade;

— SSSU;

— the expressed bradycardia;

— Printsmetal's stenocardia;

— a cardiomegaly (without symptoms of heart failure);

— arterial hypotension (systolic the ABP less than 100 mm hg, especially at a myocardial infarction);

— severe forms of bronchial asthma and a chronic obstructive pulmonary disease in the anamnesis;

— a concomitant use of MAO inhibitors (except for MAO-B);

— late stages of disturbance of peripheric circulation, Raynaud's disease;

— a pheochromocytoma (without simultaneous use of alpha adrenoblockers);

— metabolic acidosis;

— age up to 18 years (efficiency and safety are not established);

— hypersensitivity to components of drug and other beta adrenoblockers.

With care it is necessary to appoint drug at a liver failure, a chronic renal failure, a myasthenia, a thyrotoxicosis, a diabetes mellitus, AV blockade of the I degree, a depression (including in the anamnesis), psoriasis, and also to patients of advanced age.

Overdose:

Symptoms: arrhythmia, ventricular premature ventricular contraction, the expressed bradycardia, AV blockade, the expressed decrease in the ABP, chronic heart failure, cyanosis of nails of fingers or palms, breath difficulty, a bronchospasm, dizziness, unconscious states, spasms.

Treatment: gastric lavage and purpose of adsorbents; symptomatic therapy: at the developed AV to blockade - in/in introduction of 1-2 mg of atropine, Epinephrinum or statement of a temporary pacemaker; at ventricular premature ventricular contraction - lidocaine (the drugs IA of a class are not used); at decrease in the ABP - 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 (for maintenance of chronotropic and inotropic action and elimination of the expressed decrease in the ABP); at heart failure - cardiac glycosides, diuretics, a glucagon; at spasms - in/in diazepam; at a bronchospasm beta адреностимуляторы it is inhalation.

Storage conditions:

List B. Drug should be stored in dry, protected from light, the place, unavailable to children, at a temperature not above 25 °C. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

On 30 tablets in strip packagings and cardboard packs.