Atenolol

General characteristics. Structure:

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

Excipients: magnesium hydroxycarbonate, potato starch, gelatin, magnesium stearate, stearic acid.

Pharmacological properties:

Pharmacodynamics. Has anti-anginal, anti-hypertensive and antiarrhytmic effect. Has no membrane stabilizing and internal sympathomimetic activity. Reduces stimulated catecholamines formation of tsAMF from ATP. In the first 24 h after oral administration against the background of decrease in cordial emission reativny increase in the general peripheric resistance of vessels which expressiveness within 1-3 days gradually decreases is noted. The hypotensive effect is connected with reduction of cordial emission, decrease of the activity a renin-angiotenzinovoy of system, sensitivity of baroreceptors and influence on the central nervous system. Hypotensive action is shown as decrease in the systolic, and diastolic arterial pressure (AP), reduction of shock and minute volumes.

In average therapeutic doses does not exert impact on a tone of peripheral arteries. The hypotensive effect proceeds 24 h, at regular use is stabilized by the end of the second week of treatment. The anti-anginal effect is defined by decrease in need of a myocardium for oxygen as a result of reduction of heart rate (lengthening of a diastole and improvement of perfusion of a myocardium) and contractility, and also decrease in sensitivity of a myocardium to impact of sympathetic stimulation. Urezhayet the heart rate (HR) 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.

Antiarrhytmic action is shown by suppression of sinus tachycardia and is connected with elimination of aritmogenny sympathetic influences on the carrying-out system of heart, reduction of speed of spread of activation through a sinuatrial node and lengthening of the refractory period. Carrying out impulses in antegrade and to a lesser extent in retrograde the directions through AV (atrioventricular) node and on additional ways of carrying out oppresses.

The negative chronotropic effect is shown in 1 h after reception, reaches a maximum later 2-4 h, proceeds 24 h.

Reduces automatism of a sinus node, uryazhat ChSS, conductivity slows down AV, reduces contractility of a myocardium, reduces the need of a myocardium for oxygen. Reduces excitability of a myocardium. At use in average therapeutic doses exerts less expressed impact on smooth muscles of bronchial tubes and peripheral arteries, than non-selective beta adrenoblockers.

Pharmacokinetics. Absorption from digestive tract bystry, incomplete (50-60%), bioavailability of 40-50%, time of achievement of the maximum concentration in a blood plasma of 2-4 h Badly gets through a blood-brain barrier, takes place in insignificant quantities through a placental barrier and in breast milk. Communication with proteins of a blood plasma of 6-16%. Practically it is not metabolized in a liver. An elimination half-life of 6-9 h (increases at patients of advanced age).

It is removed by kidneys by glomerular filtering (85-100% in an invariable look). The renal failure is followed by lengthening of an elimination half-life and cumulation: at clearance of creatinine it is lower than 35 ml/min. / 1,73 of sq.m an elimination half-life makes 16-27 h, at clearance of creatinine it is lower than 15 ml/min. / 1,73 of sq.m more than 27 h (reduction of doses is necessary). 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 ektrasistoliya.

Route of administration and doses:

Appoint inside before food, without chewing, washing down with a small amount of liquid.

Arterial hypertension. Treatment is begun with 50 mg of Atenolol of 1 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 in one step. 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. Increase in a dose up to 200 mg is sometimes possible once 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. / 1,73 sq.m) considerable cumulation of Atenolol does not occur.

The following maximum doses for patients with a renal failure are recommended: for providing the following mode of dosing Atenolol's use in a dosage form of a tablet of 25 mg is possible.

The patient who is on a hemodialysis, Atenolol appoint 25 or 50 mg/days right after carrying out each dialysis that needs to be carried out in stationary conditions as decrease in the ABP can take place.

Elderly patients have an initial single dose of 25 mg (it can be increased under control of the ABP, ChSS).

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

Features of use:

Control of the patients accepting Atenolol has to include observation of ChSS and the ABP (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 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.

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.

With the coronary heart disease (CHD) sharp cancellation of beta adrenoblockers can cause increase in frequency or weight of anginal attacks therefore the termination of reception of an atenolol at ischemic heart disease patients needs to be carried out gradually in patients.

In comparison with non-selective beta adrenoblockers, cardioselective beta adrenoblockers possess smaller impact on function of lungs, nevertheless, at obstuktivny respiratory diseases атенолол appoint only in case of absolute indications. In need of their appointment in certain cases it is possible to recommend use of beta2-adrenomimetik.

Patients with bronkhospastichesky diseases can appoint cardioselective adrenoblockers in case of intolerance and/or inefficiency of other hypotensive medicines, but at the same time it is necessary to watch a dosage strictly. The overdose is dangerous by development of a bronchospasm.

The special attention is necessary in cases if surgical intervention under anesthetic is required from the patients accepting атенолол. Administration of drug should be stopped in 48 hours prior to intervention. As anesthetic it is necessary to choose drug with perhaps minimum negative inotropic effect.

At simultaneous use of an atenolol and clonidine reception of an atenolol is stopped for several days before a clonidine for the purpose of avoidance of a symptom of cancellation of the last.

Strengthening of expressiveness of hypersensitivity reaction and lack of effect of usual doses of Epinephrinum against the background of the burdened allergological anamnesis is possible.

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.

In case of emergence in patients of advanced age of the accruing bradycardia (less than 50 уд. / mines), 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.

In case of need intravenous administration of verapamil it should be done in not less than 48 hours after reception of an atenolol.

At use of an atenolol reduction of products of the lacrimal liquid is possible that matters at the patients using contact lenses.

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 during 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.

At smokers efficiency of beta adrenoblockers is lower.

Pregnancy and period of feeding by a breast. Pregnant women should appoint атенолол only when the advantage for mother exceeds potential risk for a fruit. Atenolol is allocated with breast milk therefore during feeding it should be accepted only in exceptional cases and carefully.

Influence on ability to drive the car and to work with the equipment. During treatment it is necessary to refrain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psikhomotory reactions.

Side effects:

Cardiovascular system: development (aggravation) of symptoms of chronic heart failure (puffiness of anklebones, feet; an asthma), disturbance of atrioventricular conductivity, arrhythmia, bradycardia, the expressed decrease in the ABP, orthostatic hypotension, heartbeat.

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

Digestive tract: dryness in a mouth, nausea, vomiting, a diarrhea, pain in a stomach, a lock, taste change.

Respiratory system: диспноэ, bronchospasm, apnoea, nose congestion.

Hematologic reactions: platelet purpura, anemia (aplastic), thrombosis; Endocrine system: a gynecomastia, decrease in a potentiality, decrease in a libido, a hyperglycemia (at patients with a non-insulin-dependent diabetes mellitus), a hypoglycemia (at the patients receiving insulin), a hypothyroid state.

Metabolic reactions: lipidemia.

Skin reactions: urticaria, dermatitis, itch, photosensitivity, sweating strengthening, dermahemia, aggravation of a course of psoriasis, reversible alopecia.

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

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

Laboratory indicators: agranulocytosis, leukopenia, increase in activity of "hepatic" enzymes, hyperbilirubinemia.

Others: dorsodynia, arthralgia, syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in the ABP).

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

Interaction with other medicines:

At simultaneous use of an atenolol with insulin, peroral hypoglycemic medicines their gipoglikemiziruyushchy action amplifies. At combined use to anti-hypertensive means of different groups or nitrates there is strengthening of hypotensive action. Simultaneous use of an atenolol and verapamil (or diltiazem) can cause mutual strengthening of cardiodepressive action.

The hypotensive effect is weakened by estrogen (a sodium delay) and non-steroidal anti-inflammatory drugs, glucocorticosteroids. At simultaneous use of an atenolol and cardiac glycosides increases risk of development of bradycardia and disturbance of atrioventricular conductivity.

At co-administration of an atenolol with Reserpinum, metildopy, a clonidine, verapamil developing of the expressed bradycardia is possible.

Simultaneous in/in administration of verapamil and diltiazem can provoke a cardiac standstill; nifedipine can lead to considerable decrease in the ABP.

At a concomitant use of an atenolol with prozvodny ergotamine, xanthine, its efficiency decreases.

At the termination of the combined use of an atenolol and a clonidine treatment by a clonidine is continued by some more days after cancellation of an atenolol.

Simultaneous use with lidocaine, can reduce its removal and increase risk of toxic effect of lidocaine.

Use together with derivatives of a fenotiazin, promotes increase in concentration of each of drugs in blood serum.

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

At combined use with an Euphyllinum and theophylline, perhaps mutual suppression of therapeutic effects.

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.

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.

Means for an inhalation anesthesia (derivatives of hydrocarbons) increase risk of oppression of function of a myocardium and development of arterial hypertension.

Amiodaronum increases risk of development of bradycardia and oppression of AV of conductivity.

Cimetidinum increases concentration in a blood plasma (slows down metabolism). Iodinated X-ray contrast medicines for in/in introductions increase risk of development of anaphylactic reactions.

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 the central nervous system.

Contraindications:

Hypersensitivity to drug, cardiogenic shock, atrioventricular (AV) blockade of the II-III St, the expressed bradycardia (ChSS less than 45-50 уд. / mines), a sick sinus syndrome, a sinoauricular block, acute or chronic heart failure (in a decompensation stage), a cardiomegaly without symptoms of heart failure, Printsmetal's stenocardia, arterial hypotension (in case of use at a myocardial infarction, systolic the ABP less than 100 mm hg), the lactation period, a concomitant use of inhibitors of a monoaminooxidase (MAO), age up to 18 years (efficiency and safety are not established). The patient who is on a hemodialysis, to elderly patients.

With care: a diabetes mellitus, a metabolic acidosis, a hypoglycemia, allergic reactions in the anamnesis, a chronic obstructive pulmonary disease (including emphysema of lungs), AV the blockade of the I degree, 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, AV blockade of the II-III degree, increase of symptoms of heart failure, excessive decrease in the ABP, breath difficulty, a bronchospasm, dizziness, a syncope, arrhythmia, ventricular premature ventricular contraction, cyanosis of nails of fingers or palms, spasms.

Treatment: a gastric lavage and purpose of the adsorbing medicines; at emergence of a bronchospasm inhalation or intravenous administration of a beta2-adrenomimetik of salbutamol is shown. At disturbance of AV of conductivity, bradycardia in/in introduction of 1-2 mg of atropine, Epinephrinum or statement of a temporary pacemaker; at ventricular premature ventricular contraction lidocaine (drugs 1A of a class are not used); at decrease in the ABP in 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. Carrying out dialysis is possible.

Storage conditions:

List B. To store in the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children. A period of validity - 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of 50 mg and 100 mg. On 10 tablets in a blister strip packaging. On 30, 50 tablets in glass jars. Each can or 3, 5 blister strip packagings with the application instruction in a pack from a cardboard.