Atenolol

General characteristics. Structure:

Active ingredient: 50 mg or 100 mg of an atenolol in 1 tablet.

Excipients: (starch corn (EP, USP, GOST P 51985-2002 (premium)), sodium carboxymethylstarch (ND 42-11282-00, ER), gelatin (BP, GOST 23058-89), magnesium hydroxycarbonate (FSP 42-0474-3989-03), cellulose microcrystallic (USP, EP, FS 42-3728-99), magnesium stearate (EP, USP, BP).

Pharmacological properties:

Pharmacodynamics. Has anti-anginal, hypotensive and antiarrhytmic effect. Has no membrane stabilizing and internal sympathomimetic activity. Reduces stimulated catecholamines formation of tsAMF from ATP, reduces intracellular current ^{of Sa2+}. In the first 24 h after oral administration against the background of decrease in cordial emission reactive 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 systolic, and diastolic arterial pressure, reduction of shock and minute volumes. 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 heart rate (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 heart rate at rest and at an exercise stress. Due to increase in a tension of muscle fibers of ventricles and end diastolic pressure in a left ventricle can raise an oxygen request, 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, braking of heterogeneous automatism, reduction of speed of spread of activation through a sinoarikulyarny node and lengthening of the refractory period. Carrying out impulses in antegrade and, to a lesser extent, in retrograde the directions through Avuzel and on additional ways oppresses.

Increases survival of the patients who had a myocardial infarction (lowers the frequency of ventricular arrhythmias and attacks of stenocardia). Slightly reduces a vital sign of lungs, practically does not weaken bronkhodilatiruyushchy action of Isoproterenolum.

In therapeutic concentration does not influence beta2-adrenoceptors, unlike non-selective beta adrenoblockers exerts less expressed impact on smooth muscles of bronchial tubes and peripheral arteries and on lipidic exchange. At reception more than 100 mg a day can have beta2-adrenoceptor blocking effect. The negative chronotropic effect is shown in 1 h after reception, reaches a maximum later 2-4 h, proceeds to 24 h.
 
Pharmacokinetics. Absorption from digestive tract - bystry, incomplete (50%), биодоступносгь - 40-50%, time of achievement of the maximum concentration in plasma - 2-4 h Badly gets through a blood-brain barrier, passes through a placental barrier and in breast milk. Permeability through a blood-brain barrier and a placental barrier - low. Communication with proteins of a blood plasma - 6 - 16%.

Practically it is not metabolized in a liver. Semi-removal time - 6-9 h (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 time of semi-removal and cumulation: at clearance of creatinine it is lower than 35 mg/min. / 1,73 ^{of sq.m}, time of semi-removal makes 16-27 h at clearance of creatinine lower than 15 mg/min. - 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.

Route of administration and doses:

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

Arterial hypertension. Treatment is begun with 50 mg of an 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 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. 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 an atenolol 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 atenolol (h)	Maximum dose
10-30	16-27	50 mg a day or 100 mg every other day
less than 10	more than 27	50 mg every other day

The patient who is on a hemodialysis атенолол appoint 50 mg/days right after carrying out each 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 the ABP, ChSS).

Features of use:

Monitoring 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.

At a thyrotoxicosis атенолол can disguise certain clinical signs of a hyperthyroidism (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology. Unlike non-selective beta adrenoblockers practically does not strengthen the hypoglycemia caused by insulin and recovery of concentration of glucose of blood to normal level does not detain.

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

The special attention is also required by selection of doses at patients with a decompensation of cordial activity. In comparison with non-selective beta adrenoblockers, cardioselective beta adrenoblockers possess smaller impact on function of lungs, nevertheless at obstructive respiratory diseases Atenolol it is necessary to appoint only in case of absolute indications. In need of their appointment in certain cases it is possible to recommend use a beta of 2-adrenomimetik. Patients with bronkhospastichesky diseases can appoint cardioselective adrenoblockers in case of intolerance and/or inefficiency of other hypotensive drugs, 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 Atenolol. Administration of drug should be stopped in 48 hours prior to surgical intervention. As anesthetic it is necessary to choose drug with perhaps minimum negative inotropic effect.

At simultaneous use of Atenolol and a clonidine, Atenolol's reception 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 reaction of hypersensitivity and lack of effect of usual doses of Epinephrinum against the background of the burdened allergological anamnesis is possible.

The drugs reducing stocks of catecholamines (for example, Reserpinum), can strengthen effect of beta adrenoblockers therefore the patients accepting such combinations of drugs have to be under constant observation of the doctor regarding detection of arterial hypotension or bradycardia.

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 by beta adrenoblockers.

In case of need intravenous administration of verapamil, it should be done not less than in 48 hours after Atenolol's reception.

At Atenolol's use reduction of products of the lacrimal liquid is possible that matters for 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 drug 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 Atenolol 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 carefully.

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

Side effects:

The most often found by-effects are connected with the main pharmacological effect of drug and are expressed as follows:

Cardiovascular system: emergence of symptoms of heart failure, disturbance of atrioventricular conductivity, bradycardia, the expressed lowering of arterial pressure, a cryesthesia and paresthesias in extremities.

Central nervous system: dizziness, a sleep disorder, decline in the ability to concentration of attention, drowsiness, a depression, hallucinations, slackness, feeling of fatigue, a headache.

Digestive tract: dryness in a mouth, nausea, vomiting, a diarrhea, abdominal pains, a lock.

Respiratory system: диспноэ, bronchospasm, apnoea.

Hematologic reactions: platelet purpura, anemia (aplastic), thrombosis.

Endocrine system: gynecomastia, decrease in a potentiality, decrease in a libido.

Metabolic reactions: lipidemia, hypoglycemia.

Skin reactions: urticaria, dermatitis, itch, photosensitivity.

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

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

Others: Peyroni's disease, syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in the ABP).

Frequency of side effects increases at increase in a dose of drug.

Interaction with other medicines:

At simultaneous use of Atenolol with insulin, antidiabetic means - their gipoglikemiziruyushchy action amplifies.

At combined use with anti-hypertensive means of different groups or nitrates, diuretics, simptatolitik, there is strengthening of hypotensive action. Simultaneous use of Atenolol and verapamil (or diltiazem) can cause mutual strengthening of cardiodepressive action.

At simultaneous use of Atenolol and cardiac glycosides the risk of development of bradycardia and disturbance of atrioventricular conductivity increases.

At co-administration of 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 Atenolol with derivatives of ergotamine, xanthine, non-steroidal anti-inflammatory drugs its efficiency decreases.

At the termination of the combined Atenolol's use and a clonidine treatment by a clonidine is continued by some more days after Atenolol's cancellation.
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, means for the general anesthesia increases expressiveness of cardiodepressive action.

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

Simultaneous use with MAO inhibitors is not recommended.

The allergens used for an immunotherapy or extracts of allergens for skin tests, are raised by 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 hypotension.

Amiodaronum increases risk of development of bradycardia and oppression Avprovodimosti.

Cimetidinum increases concentration in a blood plasma (slows down metabolism).

Iodinated radiopaque substances for in/in introductions increase risk of development of anaphylactic reactions.

Prolongs action of not depolarizing muscle relaxants, anti-coagulative effect of coumarins.

Rub - and tetracyclic antidepressants, antipsychotic, sedative, hypnagogues and ethanol strengthen oppression of TsNS.

Contraindications:

Hypersensitivity to drug, cardiogenic shock, an atrioventricular block of II-IIIST, the expressed bradycardia, 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, the lowered arterial pressure (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, age up to 18 years.

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

Overdose:

Symptoms: bradycardia. an atrioventricular block of II and III degrees, increase of symptoms of heart failure, the expressed lowering of arterial pressure, a bronchospasm. hypoglycemia.

Treatment: at the expressed bradycardia intravenous administration of 1 ml of 0,1% of solution of Atropini sulfas is shown. At Avblokade II and III degrees purpose of an izoprenalin in tablets (5 mg under language with repetition in 2-4 hours) either intravenous drop or slow jet administration of solution in a dose of 0,5-1 mg is possible. At emergence of a bronchospasm inhalation or intravenous administration of a beta2-adrenomimetik of salbutamol is shown.

Storage conditions:

List B. To store in the dry, unavailable to children and protected from light place. At ^{a temperature not higher than 25 ° C}. Period of validity-2 years. Not to use drug after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 50 mg and 100 mg. On 10 tablets in a blister strip packaging. On 30 or 50 tablets in bankepolimerny. Each can, 1, 3 or 5 blister strip packagings with the application instruction in a pack cardboard.