Atenolol

General characteristics. Structure:

Active ingredient: 50 mg of an atenolol.

Excipients: starch corn, calcium phosphate double-base, Natrium benzoicum, talc, magnesium stearate, sodium lauryl sulfate, sodium glikolit starch, silicon colloid oxide.

The cardiological drug having anti-anginal, anti-hypertensive and antiarrhytmic effect.

Pharmacological properties:

Pharmacodynamics. Selectively blocks _{beta1-adrenoceptors}, has no membrane stabilizing and internal sympathomimetic activity. Brakes the central sympathetic impulsation, weakens sensitivity of peripheral fabrics to catecholamines, inhibits secretion of a renin. Urezhayet ChSS at rest and at an exercise stress. The negative chronotropic effect is shown in 1 h, reaches a maximum later 2–4 h proceeds to 24 h. Reduces cordial emission, the GARDEN and DAD, reduces orthostatic tachycardia. Anti-hypertensive action continues 24 h, is stabilized at regular reception by the end 2 weeks. Reduces the need of a myocardium for oxygen, however 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. Suppresses automatism of a sinus node, extends the refractory period, slows down carrying out on an AV node. Increases survival of the patients who had a myocardial infarction (lowers the frequency of ventricular arrhythmias and attacks of stenocardia).

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. Atenolol is soaked up quickly, though not completely (for 50%) from digestive tract. The maximum concentration of blood preparation is reached in 2-4 hours after intake. Atenolol slightly (6-16%) contacts proteins of plasma. A drug elimination half-life - 6-7 hours. The renal failure is followed by lengthening of an elimination half-life and cumulation: at the clearance of creatinine (CC) from 15 to 35 mg/min. / 1,73 ^sq.m the elimination half-life makes 16-27 hours, at KK lower than 15 ml/min. more than 27 h, to 144 h at severe forms (reduction of doses is necessary). It is removed during a hemodialysis.

Atenolol is almost completely brought from an organism in an invariable (nemetabolizirovanny) view with urine (85%). Very badly gets through a blood-brain barrier. Gets through a placental barrier and it is allocated with breast milk.

Indications to use:

- arterial hypertension;
- an angina of exertion, rest and unstable stenocardia (except for Printsmetal's stenocardia);
- a myocardial infarction (except for the acute period and at stable indicators of a hemodynamics), secondary prevention of a myocardial infarction;
- disturbances of a rhythm: sinus, Bouveret's, atrial disease, ventricular arrhythmia, trembling and atrial fibrillation.

Route of administration and doses:

Atenolol accept inside before food, washing down with a small amount of water. A pill is taken, without chewing.

Stenocardia. The initial dose makes 25-50 mg a day. If within a week the optimum therapeutic effect is not reached, the dose is gradually raised to 100 mg a day.

Arterial hypertension. The initial dose makes 25-50 mg of an atenolol once, if necessary on 100–200 mg in 1 or 2 receptions. Maximum daily dose of 200 mg.

Achievement of stable hypotensive effect requires 1-2 weeks of reception.

Myocardial infarction with stable hemodynamic indicators. To 50 mg of 1 times a day, in 12 h - repeatedly 50 mg; further - on 50 mg 2 times a day within 6–9 days (under control of the ABP, an ECG, glucose level).

Disturbances of a rhythm - 50 mg of 1 times a day; if necessary and good tolerance the dose can be increased within a week to 100-200 mg/days.

Correction of the mode of a drug dosing is necessary for patients of advanced age and patients with disturbances of secretory function of kidneys.

At elderly patients the initial single dose makes 25 mg, if necessary it can be increased under control of the ABP and ChSS.

At a renal failure the dose korregirutsya depending on clearance of creatinine. At value of clearance of creatinine of 15-30 ml/min. appoint 50 mg of an atenolol a day or  100 mg every other day; at clearance of creatinine lower than 15 ml/min. the dose of an atenolol should not exceed 50 mg every other day or 100 mg once in 4 days.

The patient who is on a hemodialysis атенолол appoint 25-50 mg a day right after carrying out each dialysis in stationary conditions as the lowering of arterial pressure is possible.

The maximum daily dose of an atenolol makes 200 mg. At a dose more than 100 mg/days атенолол block as beta-1 and beta-2 adrenoceptors.

Features of use:

Treatment is carried out at regular medical observation (ChSS, the ABP, glucose level to blood).

• Sharp cancellation of beta adrenoblockers can cause increase in frequency or weight of anginal attacks therefore treatment cancellation atenololy is carried out gradually in patients with coronary heart disease. It is recommended to reduce a drug dose by 25 mg each 5-6 days.

• The special attention is also required by selection of doses at patients with a decompensation of cordial activity. Before therapy it is necessary to compensate heart failure

• Patients with a diabetes mellitus have to be under special observation as атенолол masks the tachycardia arising at a hypoglycemia and increases duration of hypoglycemic reaction to insulin. With care it is necessary to appoint a sick diabetes mellitus with manifestation of a metabolic acidosis. It is necessary to show care at simultaneous use of an atenolol and hypoglycemic drugs for patients with a diabetes mellitus.

• The special attention is necessary in cases if surgical intervention when carrying out an inhalation anesthesia is required from the patients receiving атенолол. It is necessary to stop administration of drug not less than in 48 hours prior to surgical intervention. As anesthetic it is necessary to choose drug with perhaps minimum negative inotropic effect.

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

• With care it is necessary to appoint sick psoriasis; a pheochromocytoma, a hyperthyroidism and a heavy myasthenia, various obliterating diseases of peripheral arteries (the alternating lameness, Reynaud's syndrome), to patients with the expressed disturbances of secretory function of kidneys, a liver failure, a thyrotoxicosis, at a depression (including in the anamnesis), at advanced age.

• Combined use of an atenolol and clonidine is not recommended. 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, otherwise developing of the expressed arterial hypertension is possible.

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

• When conducting laboratory tests and other functional researches against the background of reception of an atenolol it must be kept in mind possible changes of some results: increase in level of serumal lipoproteins and triglycerides, and also potassium; false increase in level of catecholamines and products of their metabolism in urine and blood; increase in level of antinuclear antibodies; in a false manner negative takes of a radio isotope ventrikulografiya; negative screening test on glaucoma.

• Patients with a heavy allergy in the anamnesis to foodstuff, medicines or poisons of insects should appoint атенолол with care because of a possible exacerbation of an allergy. At emergence of any allergic symptoms during treatment consultation of the doctor is necessary.

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

Pregnancy and feeding by a breast. Pregnant women should appoint атенолол only in cases 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 of driving of motor transport and work with the equipment. As drug can influence concentration of attention, it is recommended to appoint with care it to drivers of vehicles and operators of cars.

Alcohol influence. Alcohol exponentiates oppression of TsNS therefore for the period of therapy it is recommended to exclude alcohol intake.

Side effects:

By-effects are usually expressed poorly and usually quickly pass. They appear in an initiation of treatment and seldom demand reduction of a dose or full drug withdrawal. Emergence of undesirable reactions from various bodies and systems is possible:

• cardiovascular - emergence of symptoms of heart failure, bradycardia, disturbance of atrioventricular conductivity, arterial hypotension, cryesthesias and paresthesias in extremities;

• digestive tract - dryness in a mouth, nausea, vomiting, abdominal pains, a diarrhea, a lock;

• skin reactions - urticaria, dermatitis, an itch, photosensitivity;

• the central nervous system - slackness, fatigue, a headache, dizziness, a sleep disorder, a depression, hallucinations;

• organ of sight - reduction of a slezootdeleniye, conjunctivitis;

• metabolism - deterioration in glucosic tolerance and masking of symptoms of a hypoglycemia at patients with a diabetes mellitus; lipidemia;

• respiratory system - a bronchospasm, диспноэ;

• endocrine system - decrease in a potentiality, a gynecomastia, decrease in a libido;

• hematologic reactions – a leukopenia, thrombocytopenia, a platelet purpura, anemia (aplastic);

• withdrawal – increase of attacks of stenocardia, increase in the ABP.

Interaction with other medicines:

• At simultaneous use of an atenolol with insulin or drugs of sulphonylurea - strengthening of gipoglikemiziruyushchy action of the last.

• At combined use with other anti-hypertensive means and nitrates - strengthening of hypotensive action of an atenolol.

• At co-administration of an atenolol with Reserpinum, metildopy, a clonidine, guanfatsiny developing of the expressed bradycardia, hypotensions, conductivity disturbance is possible.

• At co-administration with cardiac glycosides, verapamil, diltiazem cardiodepressive action of an atenolol amplifies, also the bathmotropic effect amplifies negative hrono-, dromo-.

• Combined use with Amiodaronum has the additive effect on conductivity, especially at patients with dysfunction of a sinus or atrioventricular node.

• Simultaneous use with fenotiazinovy derivatives somewhat increases plasma levels of both drugs.

• Three/tetracyclic antidepressants, neuroleptics, sedative, hypnagogues and alcohol exponentiate oppression of TsNS.

• It is incompatible with MAO inhibitors.

• At simultaneous use of an atenolol with blockers of neuromuscular transfer prolongation of effect of muscle relaxation is possible.

• At simultaneous use with inhalation narcotic means the risk of development of bradycardia, arrhythmia, hypotension, heart failure, oppression of function of a myocardium increases.

• At simultaneous use with lidocaine the risk of its toxic action increases.

• Cimetidinum reduces hepatic clearance of an atenolol and leads to increase in its level in a blood plasma.

• Non-steroidal anti-inflammatory drugs and, in particular indometacin, reduce hypotensive effect of an atenolol.

• At a combination with contrast iodinated connections the risk of development of anaphylactic reaction increases.

• Use with estrogen reduces hypotensive effect of an atenolol as estrogen detains liquid in an organism.

• At an immunotherapy allergens or use of allergens for skin tests атенолол can increase risk of serious allergic reactions

• At simultaneous use with Aminophyllinum, theophylline or caffeine perhaps mutual suppression of therapeutic effects, and also increase in plasma level of theophylline.

• Prolongs anti-coagulative effect of coumarins.

• The refusal of smoking can strengthen therapeutic effect of an atenolol as his metabolism decreases and level in a blood plasma increases. In these cases dose adjustment is necessary.

Contraindications:

Hypersensitivity.

Atrioventricular block of II and III degrees, sick sinus syndrome cardiogenic shock, acute heart failure, sinus bradycardia (ChSS is less than 50 blows in min.), arterial hypotension (systolic pressure is lower than 100 mm hg), acute or chronic heart failure in a decompensation stage, a sinoauricular block, a metabolic acidosis, bronchial asthma, a cardiomegaly without symptoms of heart failure, disturbance of peripheric circulation, the lactation period, a concomitant use of MAO inhibitors.

Overdose:

Symptoms: bronchospasm, breath disturbance, pant, rattle, disturbance of a cordial rhythm, bradycardia, atrioventricular block of II and III degrees, increase of symptoms of heart failure, arterial hypotension, hypoglycemia, dizziness, cold snap of extremities. At emergence of symptoms of overdose immediately to see a doctor.

Treatment: Removal of not absorbed drug by a call of vomiting, a gastric lavage, purpose of absorbent carbon.

Overdose treatment: at the expressed bradycardia - introduction of 1 ml of 0,1% of solution of Atropini sulfas, at heavy arterial hypotension - introduction of Dobutaminum or dopamine. At AV to blockade of 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.

Depending on symptomatology also apply cardiac glycosides or a glucagon. If necessary - installation of an artificial pacemaker.

Atenolol can be removed from general circulation by a hemodialysis.

Storage conditions:

List B. In the place protected from moisture and light at a temperature not over +25 ºС. To store in the place, unavailable to children. Period of validity of 5 years.

Issue conditions:

According to the recipe

Packaging:

On 20 or 30 tablets in banks polymeric. 10 tablets in a blister strip packaging. 2 or 3 blister strip packagings in an individual pack from a cardboard.