Bisoprolol

General characteristics. Structure:

Active ingredient: 5 mg or 10 mg of a bisoprolol in 1 tablet.

The drug rendering the expressed anti-anginal, antiarrhytmic, hypotensive action.

Pharmacological properties:

Pharmacodynamics. Selectively blocks beta1-adrenoceptors. In doses of 20 mg and more blocks beta2-adrenoceptors of bronchial tubes, vessels, etc. Oppresses all functions of heart: reduces ChSS, minute volume, etc. Reduces a tone of sympathetic department of a vasomotor center, cordial emission, secretion of a renin, OPSS (at long reception), the GARDEN and DAD. Anti-anginal action is implemented due to decrease in contractility and other functions of a myocardium, cardiac performance and the need of a myocardium for oxygen (at rest and at an exercise stress).

Increases the effective refractory period sinus and AV nodes, slows down conductivity on AV connection. Practically does not influence lipidic exchange. Hypotension is shown in 3–4 h after reception, more than 24 p proceed and it is stabilized in 2 weeks of regular reception. Prolonged use after a myocardial infarction is followed by decline in mortality for 20–50%. Anti-hypertensive efficiency makes 95% (up to 60 years) — 91% (60 years are more senior).

Pharmacokinetics. After intake it is soaked up for 80%. At "the first passing" through a liver 20% are metabolized. Cmax  is reached in 2–4 h. Linkng with proteins of plasma — 30%. T1/2  is 9–12 h, it is extended at a renal failure (at creatinine Cl less than 40 ml/min. — by 3 times), at advanced age, at liver diseases (at cirrhosis increases to 21,7 h). More than 98% are excreted by kidneys (50% — in not changed look, the rest — inactive metabolites), 2% — with excrements.

Carcinogenicity, mutagenicity, influence on fertility. In pilot studies on mice and rats when using a bisoprolol in the doses exceeding MRDCh in 625 and 312 times respectively signs of carcinogenicity are not revealed. In a number of in vitro tests and in vivo of mutagen action it is not revealed. When using in doses, by 375 times of the exceeding MRDCh, adverse influence on fertility at rats is noted. At the rats and rabbits receiving the doses exceeding MRDCh in 375 and 31 times respectively of teratogenic action it is not revealed. However at rats at doses, by 125 times of the exceeding MRDCh (when calculating on body weight) бисопролол showed fetotoksichesky properties (increase of a late resorption of fruits was noted), and at doses, by 375 times of the exceeding MRDCh, exerted toxic impact on pregnant rats (decrease in consumption of food and a degrowth of a body).

Indications to use:

Arterial hypertension, stenocardia, the postinfarction period, the arrhythmias, chronic heart failure (which is moderately expressed, stable without aggravation during the last 6 weeks).

Route of administration and doses:

Symptoms: bradycardia, arrhythmia, hypotension, heart failure (breath difficulty, a Crocq's disease, hypostases), a hypoglycemia, in hard cases — a collapse.

Treatment: a gastric lavage and purpose of the adsorbing means, symptomatic therapy: atropine, beta-adrenergic agonists (изопреналин), sedative (diazepam, lorazepam) and cardiotonic (Dobutaminum, dopamine, Epinephrinum, Norepinephrinum) drugs, cardiac glycosides, diuretics, glucagon, etc. At a heart block — transvenous stimulation, connection of an artificial pacemaker.

Features of use:

Use at pregnancy and feeding by a breast. It is possible if the expected effect of therapy at mother exceeds potential risk for a fruit and the child (adequate and strictly controlled researches of safety of use for pregnant women and the feeding women did not carry out). As there is a risk of development of bradycardia, hypotension, a hypoglycemia and disorders of breath (neonatal asphyxia) at newborns, treatment of a bisoprolol fumaraty has to be stopped for 48–72 h before childbirth. If it cannot be made, the newborn has to be under careful medical observation during 48–72 h after the birth. Allocation of a bisoprolol of a fumarat with maternal milk, but as it cosecretes in breast milk at rats (less than 2%) was not studied, babies have to be under medical control.

Category of action on a fruit on FDA — C.

It is necessary to consider a possibility of masking of symptoms of a hypoglycemia and a thyrotoxicosis during treatment. Strengthening of expressiveness of reactions of hypersensitivity and lack of effect of usual doses of adrenaline against the background of the burdened allergological anamnesis is possible. At heavy abnormal liver functions, an acute renal failure (creatinine Cl less than 20 ml/min.), the patient who is on haemo - or peritoneal dialysis, it is necessary to reduce a dose. At a pheochromocytoma it is not necessary to appoint without additional administration of alpha adrenoblockers. Bisoprolol reduces compensatory cardiovascular reactions in response to use of the general anesthetics and iodinated contrast agents. It is necessary to cancel drug for 48 h before carrying out an anesthesia or to choose anesthetic with the smallest negative inotropic effect. Treatment should be stopped gradually, during about 2 weeks (the withdrawal is possible). With care to apply in operating time to drivers of vehicles and people whose profession is connected with the increased concentration of attention. It is necessary to exclude the use of alcoholic beverages during treatment (risk of orthostatic hypotension).

Special instructions. Change of results of tests when carrying out laboratory researches is possible.

Side effects:

Frequency of side effects is specified at purpose of the doses which are not exceeding 40 mg.

From a nervous system and sense bodys: dizziness (3,5%), an insomniya (2,5%), an adynamy (1,5%), hypesthesias (1,5%), a depression (0,2%), drowsiness, concern, paresthesias (a cryesthesia in extremities), hallucinations, disturbance of thinking, concentration of attention, orientation in time and space, balances, emotional lability, a sonitus, conjunctivitis, visual disturbances, reduction of secretion of the lacrimal liquid, a spasm.

From cardiovascular system and blood (a hemopoiesis, a hemostasis): bradycardia (0,5%), arrhythmia, heartbeat, AV blockade, hypotension, heart failure, disturbance of microcirculation in a myocardium and extremities, the alternating lameness, a vasculitis, an agranulocytosis, thrombocytopenia, a Werlhof's disease.

From bodies of a GIT: diarrhea (3,5%), nausea (2,2%), vomiting (1,5%), dryness in a mouth (1,3%), the dispeptic phenomena, a lock, ischemic colitis, thrombosis of a mezenterialny artery.

From respiratory system: cough (2,5%), asthma (1,5%), bronkho-and laryngospasm, pharyngitis (2,2%), rhinitis (4%), sinusitis (2,2%), respiratory infections (5%), respiratory distress syndrome.

From urinogenital system: peripheral hypostases (3%), decrease libido, impotence, Peyroni's disease, cystitis, renal colic.

From integuments: rash, acne, ekzemopodobny reactions, пруриго, reddening of integuments, hyperhidrosis, dermatitis, alopecia.

From a metabolism: increase in concentration of liver enzymes (nuclear heating plant, ALT), a hyperglycemia or increase in tolerance to glucose, a hyperuricemia, change of potassium concentration in blood.

Others: a pain syndrome (a headache — 10,9%, an arthralgia — 2,7%, a mialgiya, an abdominal pain, a thorax — 1,5%, eyes, ears), increase in body weight.

Interaction with other medicines:

The probability of disturbances of automatism, conductivity and contractility of heart increases (mutually) against the background of Amiodaronum, diltiazem, verapamil, hinidinovy drugs, cardiac glycosides, Reserpinum, alpha Methyldopa. Co-administration of dihydropyridinic antagonists of calcium, especially at patients with latent heart failure, increases risk of hypotension and a decompensation of cordial activity. Efficiency is lowered by xanthines and sympathomimetics, rifampicin reduces T1/2, derivatives of ergotamine exponentiate disturbance of peripheric circulation. It is incompatible with MAO inhibitors.

Contraindications:

Hypersensitivity, sinus bradycardia (less than 45-50 уд. / mines), syndrome of weakness of a sinus node, sinuatrial and AV blockade of the II-III degree, cardiogenic shock, heavy heart failure, acute myocardial infarction, arterial hypotension, acute and refractory to treatment (GARDEN nizhe90 ммрт. Art.), heavy obstructive respiratory insufficiency, pregnancy, feeding by a breast.

Restrictions to use. Chronic obstructive diseases of lungs, bronchial asthma of a heavy current, alternative stenocardia (Printsmetala), tendency to bradycardia, AV blockade of the I degree, disturbance of peripheric circulation (including Reynaud's syndrome), a diabetes mellitus, a hypoglycemia, a thyrotoxicosis, psoriasis, an abnormal liver function and kidneys, acidosis, children's age (safety and efficiency of use for children are not defined).

Overdose:

Symptoms: bradycardia, arrhythmia, hypotension, heart failure (breath difficulty, a Crocq's disease, hypostases), a hypoglycemia, in hard cases — a collapse.

Treatment: a gastric lavage and purpose of the adsorbing means, symptomatic therapy: atropine, beta-adrenergic agonists (изопреналин), sedative (diazepam, lorazepam) and cardiotonic (Dobutaminum, dopamine, Epinephrinum, Norepinephrinum) drugs, cardiac glycosides, diuretics, glucagon, etc. At a heart block — transvenous stimulation, connection of an artificial pacemaker.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 5 and 10 mg, 20 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.