Atenolol

General characteristics. Structure:

Active agent: atenolola of 50 mg or 100 mg;

Auxiliary components: 

cellulose microcrystallic, sodium-kroskarmeloza, sodium-lauryl sulfate, polyethyleneglycol 6000, silicon dioxide, talc, magnesium stearate.

Description: 

tablets of 50 mg - tablets of color, white or white with a yellowish shade, with an insignificant mramornost, a round form with slanted edge, with risky on one party and the squeezed-out designation of the trademark of firm - on another.

tablets of 100 mg - tablets of color, white or white with a yellowish shade, with an insignificant mramornost, a round form with slanted edge, with risky on one party and the squeezed-out designation PLIVA on another.

Pharmacological properties:

Pharmacodynamics. Has anti-anginal, hypotensive and antiarrhytmic effect. Has no membrane stabilizing and internal sympathomimetic activity. Reduces stimulation by catecholamines formation of tsAMF and ATP, reduces intracellular current of Sa 2 +. In the first 24 hours 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 barotsereptor and influence on the central nervous system. Hypotensive action is shown by 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 hours, 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 increase the need of a myocardium for oxygen, 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 sinoaurikulyarny node.и lengthening of the refractory period. Carrying out impulses in antegrade and, to a lesser extent, in retrograde the directions through an atrioventricular node and on additional ways oppresses. Increases survival of the patients who had a myocardial infarction (reduces the frequency of ventricular arrhythmias and attacks of stenocardia).

Slightly reduces the vital capacity of lungs, practically does not weaken bronkhodilatiruyushchy action of Isoproterenolum. In therapeutic concentration does not influence on beta-2 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 a day beta 2-adrenoceptor blocking action can render more than 100 mg.

The negative chronotropic effect is shown in 1 hour after reception, reaches a maximum 2-4 hours later and proceeds till 24 o'clock.

Pharmacokinetics. After intake drug is quickly soaked up from digestive tract - about 50% of the dose accepted inside. Solubility in fats bad, bioavailability - 40-50%, time of achievement of the maximum concentration in a blood plasma after intake - 2-4 hours. 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 - 6-16%. Practically it is not metabolized in a liver. Time of semi-removal of 6-9 hours (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 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 hours, at clearance it is lower than 15 mg/min. - more than 27 hours (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;

Disturbance of a cordial rhythm: sinus tachycardia, prevention of supraventricular tachyarrhythmias, ventricular premature ventricular contraction, ventricular tachycardia.

Route of administration and doses:

Drug is accepted inside before food, without chewing, washing down with a small amount of liquid.

Arterial hypertension.

Treatment begin with reception 50 mg of an atenolol of 1 times a day. Achievement of stable hypotensive action requires 1-2 weeks of reception. At insufficient expressiveness of hypotensive effect the dose of drug is raised to 100 mg on one reception. Further increase in a dose is not recommended since it is not followed by strengthening of clinical effect.

Stenocardia.

Initial dose of 50 mg a day. If within a week the optimum therapeutic effect is not reached, the dose is increased to 100 mg a day. Increase in a dose up to 200 mg, is sometimes possible once a day. Patients of advanced age and patients with a renal failure need to carry out dose adjustment depending on clearance of creatinine. Patients with a renal failure at values of clearance of creatinine have higher than 35 ml/min. / 1,73м (normal value 100-150 ml/min. / 1,73 make 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     Concentration of creatinine           Dose of an atenolol
(ml/min. / 1,73)                 in blood serum
                                          (µ¼«½ý/l)
 
                                15-35 300-600                                      50 mg a day

                                15-35 300-600                                      50 mg a day

The patient who is on a hemodialysis атенолол appoint 50 mg a day right after carrying out each dialysis in stationary conditions under careful medical control as there is a risk of development of arterial hypotension. Elderly patients have an initial single dose - 25 mg (it can be increased under control of the ABP, ChSS).

Increase in a daily dose over 100 mg is not recommended since the therapeutic effect amplifies, and the probability of side effects increases. The maximum daily dose makes 200 mg. The dose decline in case of the planned cancellation is made on 1/4 doses by each 3-4 days.

Features of use:

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 majority of the side effects connected using an atenolol are slight and tranzitorny.

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

from cardiovascular system: emergence of symptoms of heart failure, disturbance of atrioventricular conductivity, bradycardia, the expressed lowering of arterial pressure, heartbeat.

from the 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, weakness, a headache, insomnia, nightmares, concern, confusion of consciousness or short-term loss of memory, easing of reactionary ability, a parasthesia in extremities (at patients with the "alternating" lameness and Reynaud's syndrome), muscular weakness, spasms;

from digestive tract: dryness in a mouth, nausea, vomiting, a diarrhea, an abdominal pain, a lock;

from respiratory system: диспноэ, apnoea, bronchospasm; hematologic reactions: Werlhof's disease, anemia (aplastic); thrombosis;

from endocrine system: 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;

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;

laboratory indicators: agranulocytosis, leukopenia, change of activity of "hepatic" enzymes, bilirubin level;

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

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

Interaction with other medicines:

At simultaneous use of ATENOLOLA and insulin (or other peroral antidiabetic means) strengthening of their gipoglikemiziruyushchy action is possible.

The concomitant use of an atenolol with anti-hypertensive means of other groups leads to strengthening of hypotensive effect. At reception of an atenolol to verapamil (or mutual strengthening of cardiodepressive action happens diltiazem).

The hypotensive effect is weakened by estrogen (a sodium delay)

At joint appointment with cardiac glycosides the risk of development of bradycardia and disturbance of atrioventricular conductivity increases.

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

The patient accepting at the same time атенолол and the clonidine, a clonidine cancel only on the expiration of several days after the treatment termination atenololy.

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 derivatives of ergotamine, xanthine, non-steroidal anti-inflammatory drugs efficiency of an atenolol decreases.

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

Combined use of an atenolol 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 a concomitant use with an Euphyllinum and theophylline perhaps mutual suppression of therapeutic effect.

Simultaneous use with MAO inhibitors is not recommended.

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 hypotension.

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

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

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

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

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

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 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 expressed bradycardia (less than 50 уд. / 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.

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.

Contraindications:

Hypersensitivity to drug, cardiogenic shock, an atrioventricular block of II or III degrees, the expressed bradycardia, a sick sinus syndrome, a sinoauricular block, an acute heart failure, 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), bronchial asthma, the lactation period, simultaneous prniy MAO inhibitors, age up to 18 years (efficiency and safety are not defined).

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

Overdose:

Symptoms:
bradycardia, atrioventricular block of II and III degrees, the expressed lowering of arterial pressure, increase of symptoms of heart failure, bronchospasm, hypoglycemia, dizziness, faint, arrhythmia, ventricular premature ventricular contraction, cyanosis of nails of fingers or palms, spasms.

Treatment:
gastric lavage and purpose of the adsorbing means. At emergence of a bronchospasm inhalation or intravenous administration a beta of a 2-adrenomimetik of salbutamol is shown. At disturbance of AV of conductivity, bradycardia - intravenous administration of 1-2 mg of atropine, Epinephrinum or statement of a temporary pacemaker. At ventricular premature ventricular contraction - lidocaine (not to use the drugs IA of a class), at arterial hypotension - 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 heart failure - cardiac glycosides, diuretics, a glucagon, at spasms - in/in diazepam. Carrying out dialysis is possible.

Storage conditions:

List B. At the room temperature of 15-25 °C in the place, unavailable to children! A period of validity of 5 years (it is specified on packaging). Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 50 and 100 mg.
10 tablets in a strip (50 mg). On 3 strips together with the application instruction in a cardboard pack.
14 tablets in a strip (100 mg). On 1 strip together with the application instruction in a cardboard pack.