Anaprilin

General characteristics. Structure:

Active ingredient: 0,01 g or 0,04 g of an anaprilin (hydrochloride propranolol).

Excipients: sugar (sucrose), calcium stearate, potato starch, talc.

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

Pharmacological properties:

Pharmacodynamics. Non-selective beta adrenoblocker. Not selectively blocking beta adrenoceptors (75% beta1-and 25% beta2-adrenoceptors), reduces stimulated catecholamines formation of tsAMF from ATP therefore reduces intracellular intake of calcium, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat heart rate, conductivity and excitability oppresses, reduces contractility of a myocardium).

At the beginning of use of beta adrenoblockers the general peripheric vascular resistance in the first 24 h increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation of beta2-adrenoceptors of vessels of skeletal muscles), but in 1-3 days is returned to initial, and at long appointment decreases.

The hypotensive effect is connected with reduction of minute volume of heart, sympathetic stimulation of peripheral vessels, decrease of the activity of reninangiotenzinovy system (matters at patients with initial hypersecretion of a renin), sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to decrease in the ABP) and influence on the central nervous system. The hypotensive effect is stabilized by the end of 2 weeks of course appointment.

Anti-anginal action is caused by decrease in need of a myocardium for oxygen (at the expense of a negative chronotropic and inotropic effect). Reduction of heart rate leads to lengthening of a diastole and improvement of perfusion of a myocardium. 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.

The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of a sympathetic nervous system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of atrioventricular carrying out. Oppression of carrying out impulses is noted preferential in antegrade and to a lesser extent in retrograde the directions through an atrioventricular node and on additional ways. On classification of antiarrhytmic medicines treats group II drugs. Reduction of expressiveness of ischemia of a myocardium due to decrease in need of a myocardium for oxygen, a postinfarction lethality can also decrease thanks to antiarrhytmic action.

Ability to prevent development of a headache of vascular genesis is caused by reduction of expressiveness of expansion of cerebral arteries owing to a beta adrenoblokady of vascular receptors, inhibition of the thrombocytes caused by catecholamines of aggregation and a lipolysis, decrease in a platelet stickness, prevention of activation of blood-coagulation factors during adrenaline release, stimulation of intake of oxygen in fabric and reduction of secretion of a renin.

Reduction of a tremor against the background of use of propranolol can be caused by blockade of beta2-adrenoceptors. Increases atherogenous properties of blood. Strengthens reductions of a uterus (spontaneous and vyznanny the medicines stimulating a myometrium). Raises a tone of bronchial tubes.

Pharmacokinetics. Quickly and rather fully (90%) it is soaked up at intake and rather quickly brought out of an organism. Bioavailability after oral administration - 30-40% (effect of "the first passing" through a liver, a microsomal oxidation), at long reception increases (the metabolites inhibiting liver enzymes are formed), its size depends on character of food and intensity of a hepatic blood-groove. It is metabolized by a glyukuronirovaniye in a liver. The maximum concentration in a blood plasma is reached in 1-1,5 h. Has high lipophilicity, collects in tissue of lungs, a brain, kidneys, heart. Gets through hematoencephalic and placental barriers, into breast milk. Communication with proteins of a blood plasma - 90-95%. Distribution volume - 3-5 l/kg.

Gets with bile into intestines, it deglyukuronizirutsya and reabsorbirutsya. The elimination half-life - 3-5 h, against the background of course introduction can be extended to 12 h. It is removed by kidneys - 90%, in not changed look - less than 1%. Is not removed at a hemodialysis.

Indications to use:

Arterial hypertension, angina of exertion, unstable stenocardia, sinus tachycardia (including at a hyperthyroidism), supraventricular tachycardia, a ciliary tachyarrhythmia, supraventricular and ventricular premature ventricular contraction, prevention of a myocardial infarction (systolic the ABP more than 100 mm hg), a pheochromocytoma, an essential tremor, migraine (prevention of attacks), as supportive application in therapy of a thyrotoxicosis and thyrocardiac crisis (at intolerance of thyreostatic medicines), sympathoadrenal crises against the background of a diencephalic syndrome.

Route of administration and doses:

At arterial hypertension: inside, on 40 mg 2 times a day. At insufficient expressiveness of hypotensive effect the dose is increased to 40 mg by 3 times or on 80 mg 2 times a day. The maximum daily dose - 320 mg.

At stenocardia, disturbances of a cordial rhythm: in an initial dose of 20 mg 3 times a day, then increase a dose to 80-120 mg for 2-3 receptions. The maximum daily dose - 240 mg.

For prevention of migraine, and also at an essential tremor: in an initial dose of 40 mg 2-3 times a day, if necessary a dose gradually increase up to 160 mg/days.

At an abnormal liver function the drug dose decline is necessary.

At an impaired renal function it is necessary to lower an initial dose or to increase an interval between administrations of drug.

Prevention of a repeated myocardial infarction: to begin therapy between the 5th and 21st day after the postponed myocardial infarction in a dose 40 mg 4 times a day, within 2-3 days. Then in a dose of 80 mg 2 times a day.

At a pheochromocytoma: to apply only with blockers of alpha adrenoceptors. Before operation appoint 60 mg a day, within 3 days.

Features of use:

Control of the patients accepting Anaprilin has to include observation of ChSS and the ABP (in an initiation of treatment - daily, then 1 time in 3-4 months), an ECG. At elderly patients it is recommended to monitor function of kidneys (1 times in 4-5 months).

In case of emergence in patients of advanced age of the accruing bradycardia (less than 50 уд. / mines), arterial hypotension (systolic the ABP less than 100 mm hg), atriventrikulyarny blockade, a bronchospasm, ventricular arrhythmias, heavy abnormal liver functions and/or kidneys, it is necessary to reduce a dose of drug or to stop treatment.

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.

It is recommended to stop therapy at development of the depression caused by reception of beta adrenoblockers.

The patients using contact lenses have to consider that against the background of treatment reduction of products of the lacrimal liquid is possible.

Before Anaprilin's appointment patients with heart failure (early stages) need to apply a digitalis and/or diuretics.

Treatment of coronary heart disease and persistent arterial hypertension has to be long: Anaprilin's reception is possible within several years.

The termination of treatment is carried out gradually, under observation of the doctor: sharp cancellation can sharply strengthen myocardium ischemia, an anginous syndrome, worsen tolerance to an exercise stress.

Cancellation is carried out gradually, reducing a dose within 2 weeks and more (lower a dose by 25% each 3-4 days).

At patients with a diabetes mellitus use of drug is carried out under control of content of glucose to blood (1 time in 4-5 months).

At a thyrotoxicosis Anaprilin can mask 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. At purpose of beta adrenoblockers the patients receiving hypoglycemic drugs should be careful as during long breaks in meal the hypoglycemia can develop. And its such symptoms as tachycardia or a tremor, will mask due to effect of drug. Patients should be instructed as regards the main symptom of a hypoglycemia during treatment by beta adrenoblockers is the increased sweating.

With care to appoint together with hypoglycemic means (danger of emergence of a hypoglycemia against the background of therapy by insulin and a hyperglycemia - against the background of reception of peroral hypoglycemic means).

At a concomitant use of a clonidine its reception can be stopped only in several days after Anaprilin's cancellation.

At a pheochromocytoma appoint only in combination with alpha adrenoblockers.

In need of inclusion in pregnancy time which is possible only if the advantage for mother exceeds risk of development of side effects in a fruit and the child. In need of inclusion in pregnancy time - careful observation of a condition of a fruit, for 48-72 h before childbirth it is necessary to cancel.

It is impossible to apply at the same time with antipsychotic drugs (neuroleptics) and tranquilizers.

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

Against the background of treatment by Anaprilin it is necessary to avoid intravenous administration of verapamil, diltiazem.

It is careful to apply together with psychotropic drugs, for example, MAO inhibitors, at their course use more than 2 weeks.

For several days before carrying out the general anesthesia chloroform or ether, it is necessary to stop administration of drug (increase in risk of oppression of function of a myocardium and development of arterial hypotension).

During treatment it is necessary to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

At "smokers" efficiency of beta adrenoblockers is lower. During treatment it is not recommended to accept ethanol (perhaps sharp decrease in the ABP).

It is necessary to cancel drug before a research of content in blood and urine of catecholamines, a normetanefrin and vanilinmindalny acid; credits of antinuclear antibodies.

During treatment to avoid uses of a natural liquorice: the food rich with protein is capable to increase bioavailability.

Side effects:

From cardiovascular system: sinus bradycardia, atrioventricular block, heart failure, heartbeat, disturbance of conductivity of a myocardium, arrhythmia, decrease in the ABP, orthostatic hypotension, stethalgia, spasm of peripheral arteries, cold snap of extremities.

From a digestive tract: dryness in a mouth, nausea, vomiting, diarrhea, a lock, pains in epigastric area, an abnormal liver function, taste change.

From a nervous system: seldom - a headache, sleeplessness, "dreadful" dreams, an asthenic syndrome, decline in the ability to bystry mental and motor reactions, excitement, a depression, paresthesias, increased fatigue, weakness, dizziness, drowsiness, confusion of consciousness or short-term loss of memory, a hallucination, a tremor.

From respiratory system: rhinitis, nose congestion, asthma, bronchospasm, laryngospasm.

From a metabolism: a hypoglycemia (at patients with a diabetes mellitus of the I type), a hyperglycemia (at patients with a diabetes mellitus of the II type).

From sense bodys: dryness mucous eye (reduction of secretion of the lacrimal liquid), visual acuity disturbance, keratoconjunctivitis.

From reproductive system: decrease in a libido, decrease in a potentiality.

From integuments: alopecia, aggravation of a course of psoriasis, sweating strengthening, dermahemia, dieback, psoriazopodobny skin reactions.

From endocrine system: depression of function of a thyroid gland.

Allergic reactions: skin rash, itch.

Laboratory indicators: agranulocytosis, increase in activity of "hepatic" transaminases and level of bilirubin.

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

Others: muscular weakness, dorsodynia or joints, thorax pain, leukopenia, thrombocytopenia and syndrome of "cancellation".

Interaction with other medicines:

The hypotensive effect of propranolol amplifies at a combination to diuretics, Reserpinum, gidralaziny and other antihypertensives, and also ethanol.

Hypotensive effect non-steroidal anti-inflammatory drugs (a delay of sodium and blocking of synthesis of prostaglandin kidneys) weaken, estrogen (a sodium delay) and MAO inhibitors.

Cimetidinum increases bioavailability.

Increases concentration of lidocaine in a blood plasma, reduces clearance of theophylline.
Co-administration with derivatives of a fenotiazin increases concentration of both drugs in a blood plasma.

Strengthens effect of thyreostatic and uterotoniziruyushchy drugs; reduces effect of antihistamines.

Increases probability of development of heavy system reactions (anaphylaxis) against the background of administration of allergens, used for an immunotherapy or for skin tests.
Amiodaronum, verapamil and diltiazem - strengthening of expressiveness negative hrono-, other and dromotropic effect of propranolol.

Iodinated X-ray contrast medicines for intravenous administration increase risk of development of anaphylactic reactions.

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

Changes efficiency of insulin and peroral hypoglycemic medicines, masks symptoms of the developing hypoglycemia (tachycardia, increase in the ABP).

Reduces clearance of xanthines (except Diphyllinum).

The hypotensive effect is weakened by glucocorticosteroids.

Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, antiarrhytmic medicines increase risk of development or aggravation of bradycardia, an atrioventricular block, cardiac standstill and heart failure.

Nifedipine can lead to considerable decrease in the ABP.

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 TsNS.

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 propranolol has to make not less than 14 days.

Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation.

Sulfasalazinum increases concentration of propranolol in a blood plasma (slows down metabolism), rifampicin shortens an elimination half-life.

Contraindications:

Hypersensitivity to drug, an atrioventricular block of the II-III degree, a sinoauricular block, a sinus bradycardia, arterial hypotension, uncontrollable chronic heart failure of IIB-III of degree, an acute heart failure, an acute myocardial infarction (systolic arterial pressure - less than 100 mm hg), cardiogenic shock, a fluid lungs, a sick sinus syndrome, Printsmetal's stenocardia, a cardiomegaly (without symptoms of heart failure), vasculomotor rhinitis, occlusal diseases of peripheral vessels, a diabetes mellitus, a metabolic acidosis (in t. h diabetic ketoacidosis), bronchial asthma, tendency to bronkhospastichesky reactions, a chronic obstructive pulmonary disease (including in the anamnesis), a pheochromocytoma (without simultaneous use of alpha adrenoblockers), a spastic colitis, a concomitant use with antipsychotic means and anxiolytics (Chlorpromazinum, Trioxazinum, etc.), MAO inhibitors, the lactation period, age up to 18 years (efficiency and safety are not established).

With care: a liver and/or renal failure, a hyperthyroidism, a myasthenia, heart failure, a pheochromocytoma, psoriasis, pregnancy, allergic reactions in the anamnesis, Reynaud's syndrome, advanced age.

Overdose:

Symptoms: bradycardia, dizziness or faint, decrease in the ABP, arrhythmia, breath difficulty, cyanosis of nails of fingers or palms or spasm.

Treatment: the gastric lavage, purpose of absorbent carbon, at disturbance of atrioventricular conductivity - in/in enter 1-2 mg of atropine, Epinephrinum, at a low performance carry out statement of a temporary pacemaker; at ventricular premature ventricular contraction - lidocaine (the drugs IA of a class are not used); at arterial hypotension of the patient has to be in the provision of Trendelenburga. If there are no fluid lungs signs, in/in enter plasma substituting solutions, at inefficiency - Epinephrinum, a dopamine, Dobutaminum; at spasms - in/in diazepam; at a bronchospasm it is inhalation or parenterally - beta адреностимуляторы.

Storage conditions:

List B. To store in dry, protected from light and the place, unavailable to children. A period of validity - 4 years. Not to apply after expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets on 10 and 40 mg. On 10, 50 tablets in a blister strip packaging. On 50, 100 tablets in glass jars. Each can or 5, 10 blister strip packagings on 10 tablets together with the application instruction are placed in a pack. Or 1, 2 blister strip packagings on 50 tablets together with the application instruction place in a pack.