Atenolol

General characteristics. Structure:

Active ingredient: 0,025 g, 0,05 g or 0,1 g of an atenolol in 1 tablet.

Excipients: potato starch; кросповидон; povidone; cellulose microcrystallic; silicon dioxide colloid (aerosil); magnesium stearate; polysorbate (twin 80); stearic acid].

Excipients for a cover: Опадрай II (series 85 F) [polyvinyl alcohol; talc; titanium dioxide; macrogoal (dosage of 25 mg) or polyvinyl alcohol; talc; macrogoal; titanium dioxide; an aluminum varnish on the basis of dye of quinolinic yellow; an aluminum varnish on the basis of indigo carmine (a dosage of 50 mg), or polyvinyl alcohol; talc; titanium dioxide; macrogoal; an aluminum varnish on the basis of dye of a sunset yellow; an aluminum varnish on the basis of dye charming red (a dosage of 100 mg)].

Effective treatment and prevention of cardiovascular diseases. Renders anti-hypertensive, anti-anginal, and antiarrhytmic action.

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 Ca2+, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat the heart rate (HR), conductivity and excitability oppresses, reduces contractility of a myocardium).

The General Perefirichesky Vascular Resistance (GPVR) at the beginning of use of beta adrenoblockers (in the first 24 h after oral administration) 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 the minute volume of blood (MVB), 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 (ABP) and influence on the central nervous system (CNS). Hypotensive action is shown by decrease in both the systolic, and diastolic ABP, reduction of the stroke output of blood (SOB) and the IOC. In average therapeutic doses has no effect on a tone of peripheral arteries. The hypotensive effect proceeds 24 h, 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 the left ventricle (LV) and increases in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with the chronic heart failure (CHF).

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

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

Practically does not weaken bronkhodilatiruyushchy action of Isoproterenolum.

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 h after reception, reaches a maximum later 2-4 h and proceeds to 24 h.

Pharmacokinetics. Absorption from the digestive tract (DT) - bystry, incomplete (50-60%), bioavailability - 40-50%, solubility in fats very low. Time of achievement of the maximum concentration of drug in a blood plasma (TCmax) - 2-4 h Badly gets through a blood-brain barrier (GEB), passes through a placental barrier and in breast milk. Communication with proteins of plasma - 6-16%.

Practically it is not metabolized in a liver. An elimination half-life (T1/2) - 6-9 h (increases at patients of advanced age). It is brought by kidneys by glomerular filtering, to 85-100% in not changed look.

The renal failure is followed by lengthening of T1/2 and cumulation (reduction of doses is necessary): at the clearance of creatinine (CC) it is lower than 35 ml/min. / 1,73 of sq.m of T1/2 makes 16-27 h, at KK it is lower than 15 ml/min. - more than 27 h, at an anury - it is extended to 144 h. It is removed during a hemodialysis.

Indications to use:

Arterial hypertension; prevention of attacks of stable stenocardia (except for Printsmetal's stenocardia); disturbances of a cordial rhythm: sinus tachycardia, prevention of supraventricular tachyarrhythmias.

Route of administration and doses:

Inside, before meal, without chewing and washing down with a small amount of liquid. An initial dose - 25-50 mg/days; if necessary the dose is raised in 1 week on 50 mg and further if necessary to 200 mg, an average dose - 100 mg/days.

For prevention of attacks of stenocardia, takhisistolichesky disturbances of a cordial rhythm – 50 mg of 1 times a day.

At KK of 15-35 ml/min. appoint 100 mg every other day or 50 mg/days; at KK less than 15 ml/min. - 50 mg every other day, or 100 mg of 1 times in 4 days, or against the background of a hemodialysis on 50 mg after each dialysis.
 
Elderly patients have an initial single dose - 25 mg (it can be increased under control of the ABP, ChSS).

Appointment more than 1 time a day is inexpedient as атенолол works during 24 h. 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. The maximum daily dose makes 200 mg.

The dose decline in case of the planned cancellation is made gradually.

At an ischemic heart disease, takhisistolichesky disturbances of a cordial rhythm – 50 mg of 1 times a day.

At acute to THEM with stable hemodynamic indicators: inside, in 10 min. after the last in/in introductions, in a dose of 50 mg, then repeatedly 50 mg in 12 h; further - on 50 mg 2 times a day or 100 mg once within 6-9 days (under control of the ABP, the electrocardiogram, content of glucose in blood).

At a hyperkinetic cardial syndrome appoint 25 mg/days.

Features of use:

1) Pregnant and feeding. Purpose of an atenolol to pregnant women is possible only in cases when the advantage for mother exceeds potential risk for a fruit. Breastfeeding is contraindicated during treatment atenololy.

2) To children. Drug is contraindicated for use to children and teenagers up to 18 years.

Data on possible influence of medicine for a medical use on ability to manage vehicles, 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.

Control of the patients accepting атенолол 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/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/mines) and the increased final diastolic volume of LZh, 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, атенолол 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 against the background of the burdened allergological anamnesis is possible.

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

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

It is possible to appoint drug the patient with bronkhospastichesky diseases in case of intolerance and/or inefficiency of other hypotensive HP, but at the same time it is necessary to watch a dosage 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/mines), arterial hypotension (systolic the ABP is lower than 100 mm hg), AV of blockade, 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).

Patients with coronary heart disease have to be during drug withdrawal under careful observation.

Atenolol it is necessary to cancel for 48 h before performing surgery with use of the general anesthesia (chloroform or ether) or to choose anesthetic with the smallest negative inotropic effect.

Use at pregnancy and a lactation is possible if the advantage for mother exceeds risk of development of side effects in a fruit and the child.

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.

Side effects:

From the central nervous system (CNS): 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, the strengthened heartbeat, disturbance of conductivity of a myocardium, AV blockade (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 (at patients with a diabetes mellitus Ι type), a hypoglycemia (at the patients receiving insulin), a hypothyroid state.

Allergic reactions: itch, rash, urticaria.

From integuments: sweating strengthening, dermahemia, aggravation of symptoms of psoriasis, psoriazopodobny skin rashes, skin itch, 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 the ABP).

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. The iodinated X-ray contrast medicines (M) for in/in introductions increase risk of development of anaphylactic reactions.

Phenytoinum at in introduction, HP for inhalation general anesthesia (derivatives of hydrocarbons) is raised by expressiveness of cardiodepressive action and probability of decrease in the ABP.

At co-administration with insulin and peroral hypoglycemic HP masks symptoms of the developing hypoglycemia.

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

Hypotensive effect non-steroidal anti-inflammatory drugs (NPVP) (Na delay + and blockade of synthesis of prostaglandins kidneys) weaken, glucocorticosteroids and estrogen (Na+ delay).

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

Diuretics, clonidine, sympatholytics, гидралазин, can lead blockers of slow calcium channels and other hypotensive HP to excessive decrease in the ABP.

Extends action of not depolarizing muscle relaxants and anticoagulating effect of coumarins.
Rub - and tetracyclic antidepressants, antipsychotic HP (neuroleptics), ethanol, sedative and HP hypnotic drugs strengthen oppression of TsNS.

Simultaneous use with monoaminooxidase inhibitors owing to considerable strengthening of hypotensive action is not recommended, having rummaged in treatment between reception of inhibitors of a monoaminooxidase and atenolol 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 components, cardiogenic shock, AV blockade of the II-III Art., bradycardia about ChSS less than 40/mines, 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, bradycardia, arterial hypotension (in case of use at a myocardial infarction, systolic the ABP less than 100 mm hg), a pheochromocytoma, the lactation period, children's age up to 18 years, a concomitant use of inhibitors of a monoaminooxidase.

With care to use drug at the following states and diseases: diabetes mellitus Ι type, metabolic acidosis, hypoglycemia; allergic reactions in the anamnesis, a chronic obstructive pulmonary disease, bronchial asthma, emphysema of lungs; the chronic heart failure (compensated), obliterating diseases of peripheral vessels (the "alternating" lameness, Reynaud's syndrome); a pheochromocytoma at simultaneous use of alpha adrenoblockers, a liver failure, a chronic renal failure, a myasthenia, a thyrotoxicosis, a depression (including in the anamnesis), psoriasis, pregnancy, advanced age, AV blockade Ι degrees.

Overdose:

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

Treatment: a gastric lavage and purpose of the adsorbing drugs; at disturbance of AV of conductivity and/or bradycardia - 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; 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:

In the dry place protected from light at a temperature not above 25 °C. The instruction on need of storage of medicine for the places unavailable to children. To store in the place, unavailable to children. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 25 mg, 50 mg and 100 mg. On 7, 10, 15, 20 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2, 3, 4, 5 or 10 blister strip packagings together with the application instruction place in a pack from a cardboard.