Anaprilin - instructions for use, doses, side effects, contraindications

Non-selective beta-blocker. Has antianginal, antihypertensive and antiarrhythmic action.Not selectively blocking beta-adrenergic receptors (75% of beta1 and 25% of beta2-adrenoreceptors) reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), which reduces the intracellular intake of calcium ions, has a negative chrono-, Batmo- and inotropic action (urezhaet heart rate (heart rate)), inhibits conduction and excitability, reduces myocardial contractility).

At the beginning of beta-blockers application, the total peripheral vascular resistance increases in the first 24 hours (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and elimination of stimulation of beta2-adrenoreceptors of the vessels of skeletal muscles), but after 1-3 days it returns to the initial one, .

Antihypertensive action is associated with a decrease in the minute volume of blood flow, sympathetic stimulation of the peripheral vessels, a decrease in the activity of the renin-angiotensin-aldosterone system (important in patients with initial hypersecretion of renin), sensitivity of the aortic baroreceptors (there is no increase in their activity in response to a decrease in blood pressure (BP) ) and influence on the central nervous system.Antihypertensive effect is stabilized by the end of the 2-week course appointment.

Antianginal action is caused by a decrease in myocardial oxygen demand (due to a negative chronotropic and inotropic effect). The decrease in heart rate leads to diastole lengthening and improvement of myocardial perfusion. By increasing the end diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers of the ventricles can increase the need for oxygen, especially in patients with chronic heart failure.

Antiarrhythmic effect is caused by the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing of atrioventricular conduction. Oppression of impulses is noted predominantly in the antegrade and to a lesser extent in the retrograde direction through the atrioventricular node and along additional pathways. According to the classification of antiarrhythmic drugs (drugs) belongs to the drugs of the II group.

Reducing the severity of myocardial ischemia - due to the decrease in myocardial oxygen demand, postinfarction lethality may also decrease due to antiarrhythmic action.

Ability to prevent the development of headache of vascular genesis is caused by a decrease in the expansion of the cerebral arteries due to beta-adrenoblockade of the vascular receptors, inhibition of catecholamine-induced platelet aggregation and lipolysis, a decrease in platelet adhesiveness, prevention of activation of clotting factors during the release of epinephrine, stimulation of oxygen supply to the tissue and a decrease in renin secretion.

Decreased tremor on the background of the use of anaprilin is due primarily to the blockade of peripheral beta2-adrenergic receptors. Increases atherogenic properties of blood.

Increases contractions of the uterus (spontaneous and caused by drugs that stimulate the myometrium).

Increases the tone of the bronchi, in large doses causes a sedative effect.

Pharmacokinetics:

Quickly and fairly fully (90%) is absorbed when taken orally and is relatively quickly eliminated from the body.Bioavailability after oral administration - 30-40% (the effect of "first passage" through the liver, microsomal oxidation), with prolonged intake increases (metabolites that inhibit liver enzymes are formed), its magnitude depends on the nature of food and the intensity of hepatic blood flow. The time to reach the maximum concentration is 1-1.5 hours. It has high lipophilicity, accumulates in lung tissue, brain, kidneys, heart. Penetrates through the blood-brain barrier, the placental barrier, into breast milk. The volume of distribution is 3-5 l / kg. The connection with plasma proteins is 90-95%.

Metabolized by glucuronidation in the biscuits It comes with bile in the intestines, deglucuronizes and reabsorbs, resulting in a half-life on the background of the course of administration may extend to 12 hours. The half-life period is 3-5 hours. It is excreted by the kidneys - 90%, unchanged - less than 1% . It is not removed during hemodialysis.

Indications:

- Arterial hypertension;

- Stenocardia of tension;

- unstable angina;

- Sinus tachycardia (including with thyrotoxicosis);

- supraventricular tachycardia;

atrial tachyarrhythmia;

- supraventricular and ventricular extrasystole;

- Myocardial infarction (systolic blood pressure more than 100 mm Hg);

- Essential tremor;

- Migraine (prevention of seizures);

- diffuse-toxic goiter;

- sympathoadrenal crises against the background of the diencephalic syndrome.

Contraindications:

- Hypersensitivity to the components of the drug;

- acute heart failure;

- cardiogenic shock;

- atrioventricular block II-III st;

- sinus bradycardia (heart rate less than 50 / min);

- arterial hypotension (systolic blood pressure less than 90 mm Hg, especially with myocardial infarction);

- Sinoatrial blockade;

- syndrome of weakness of the sinus node;

- Prinzmetal angina;

- cardiomegaly;

- peripheral vascular disease;

metabolic acidosis;

- bronchial asthma;

- propensity to bronchial obstruction;

- COPD;

- simultaneous administration of MAO inhibitors;

- lactation period;

- CHF with the indication of a functional class;

- acute heart failure;

- cardiogenic shock;

- pulmonary edema;

- diabetes;

- age to 18 years.

Carefully:

Diabetes, renal and / or liver failure, hyperthyroidism, depressed, myasthenia gravis, pheochromocytoma (while the use of alpha blockers), psoriasis, occlusive peripheral vascular disease, pregnancy,old age, allergic reactions in the anamnesis, atrioventricular blockade of the 1st degree, CHF I of the functional class according to NYHA.

Pregnancy and lactation:

Use during pregnancy is possible if the benefit to the mother exceeds the risk of side effects in the fetus.

Influence on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

If you need to take during pregnancy - careful monitoring of the fetus, for 48-72 h before delivery should be canceled.

During the period of breastfeeding is contraindicated.

Dosing and Administration:

Inside; regardless of the time of ingestion.

With arterial hypertension - 40 mg twice a day. If the hypotensive effect is insufficient, the dose is increased to 40 mg three times or 80 mg twice a day. The maximum daily dose is 320 mg (in exceptional cases - 640 mg).

With angina pectoris, heart rhythm disturbances - in an initial dose of 20 mg 3 times a day, then gradually increase the dose to 80-120 mg for 2-3 doses. The maximum daily dose is 240 mg.

For the prevention of migraine, as well as with essential tremor - in an initial dose of 40 mg 2-3 times a day, if necessary, the dose is gradually increased to 160 mg / day.

With myocardial infarction - in the period from the 5th to the 21st day after the infarction in the initial dose of 40 mg 4 times a day for 2 or 3 days, then - 80 mg twice a day.

With pheochromocytoma apply only with alpha-adrenoblocker.

In the preoperative period: it is recommended to take 30-60 mg daily for three days.

In inoperable cases of malignant disease: 30 mg per day.

If the liver function is impaired, lower doses are necessary.

Dysregulation of renal dosing does not require correction.

Side effects:

From the nervous system: increased fatigue, weakness, dizziness, headache, drowsiness or insomnia, bright dreams, depression, anxiety, confusion, hallucinations, tremors, nervousness.

From the sense organs: decrease in secretion of tear fluid (dryness and soreness of the eyes).

From the cardiovascular system: sinus bradycardia, atrioventricular block (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, development of chronic heart failure, lowering of blood pressure, orthostatic hypotension, manifestation of angiospasm (increased peripheral circulatory disturbance, cooling of the lower limbs, Raynaud's syndrome), pain in the chest.

From the digestive system: nausea, vomiting, discomfort in the epigastric region, constipation or diarrhea, impaired liver function (dark urine, icteric sclera or skin, cholestasis), changes in taste, dryness of the oral mucosa.

From the respiratory system: congestion of the nose, bronchospasm.

From the endocrine system: change in the concentration of blood glucose (hypo- or hyperglycemia).

Allergic reactions: itching, skin rash, hives.

From the skin: increased sweating, psoriasis-like skin reactions, exacerbation of psoriasis symptoms.

Laboratory indicators: thrombocytopenia; (unusual bleeding and hemorrhage), leukopenia, increased activity of "liver" transaminases, lactate dehydrogenase.

Other: pain in the back, arthralgia, decreased potency, withdrawal syndrome (increased angina attacks, myocardial infarction, increased blood pressure), an increase in the titer of antinuclear antibodies.

Overdose:

Symptoms: severe bradycardia, dizziness, atrioventricular block, marked decrease in blood pressure, syncope, arrhythmia, ventricular extrasystole, heart failure, cyanosis of the fingernails or palms, convulsions, difficulty breathing, bronchospasm.

Treatment: gastric lavage, the appointment of activated charcoal, with violation of atrioventricular conduction - intravenously injected 1-2 mg of atropine, at a low efficiency, a temporary pacemaker is performed; with ventricular extrasystole - lidocaine (preparations of the IA class do not apply); with a decrease in blood pressure the patient should be in the Trendelenburg position. If there are no signs of pulmonary edema, IV injection of plasma-substituting solutions, if ineffective - epinephrine, dopamine, dobutamine; with heart failure cardiac glycosides, diuretics, glucagon; with convulsions - in / in diazepam; with bronhospazme - inhalation or parenteral beta-adrenostimulyatory.

Interaction:

With simultaneous use, allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving anaprilin.

Iodine-containing radiopaque drugs for intravenous administration increase the risk of anaphylactic reactions.

When combined phenytoin with intravenous administration, drugs for inhalation of general anesthesia (derivatives of hydrocarbons) increase the severity of cardiodepressive action and the likelihood of lowering blood pressure.

With simultaneous application changes the effectiveness of insulin and oral hypoglycemic agents for oral administration, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

When combined, reduces the clearance of lidocaine and xanthines (except diphylline) and increases their concentration in the plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

With the simultaneous use of antihypertensive effect weaken non-steroidal anti-inflammatory drugs (sodium ion delay and blockade of prostaglandin synthesis by the kidneys), glucocorticoid agents and estrogens (sodium ion delay).

When combined, cardiac glycosides, methyldopa, reserpine and guanfacine, slow calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, atrioventricular blockade, cardiac arrest and heart failure.

With simultaneous application nifedipine can lead to a significant decrease in blood pressure.

With the joint use of diuretics, clonidine, sympatholytics, hydralazine and etc.hypotensive drugs can lead to excessive blood pressure lowering.

With simultaneous application, it prolongs the effect of nondepolarizing muscle relaxants and the anticoagulant effect of coumarins.

When combined, tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedative and hypnotic drugs increase the depression of the central nervous system.

It is not recommended simultaneous use of anaprilin with monoamine oxidase inhibitors due to a significant increase in antihypertensive action, a break in the treatment between taking monoamine oxidase inhibitors and anaprilin should be at least 14 days.

With simultaneous application of unhydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.

When combined, increases the effect of thyroid and uterotonizing drugs; reduces the effect of antihistamines.

Simultaneous administration with Phenothiazine derivatives increases the concentrations of both drugs in plasma.

With simultaneous application sulfasalazine and cimetidine increase the concentration of anaprilin in plasma (inhibit metabolism).

When combined rifampicin shortens the half-life of anaprilin.

Special instructions:

Control of patients taking anaprilin should include monitoring heart rate and blood pressure (at the beginning of treatment - every day, then once every 3-4 months), an electrocardiogram, a glucose concentration in the blood of patients with diabetes mellitus (1 every 4-5 months) . In elderly patients it is recommended to follow the function of the kidneys (once every 4-5 months).

You should teach the patient how to calculate heart rate and instruct you about the need for medical consultation at a heart rate of less than 50 / min.

Before the appointment of anaprilina, patients with chronic heart failure (early stages) should use cardiac glycosides and / or diuretics.

In "smokers" the effectiveness of beta-blockers is lower.

Patients who use contact lenses should take into account that, on the background of treatment, tear fluid production can be reduced.

Patients with pheochromocytoma are prescribed only after taking an alpha-blocker. In thyrotoxicosis, anaprilin may mask certain clinical signs of thyrotoxicosis (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms.

When prescribing beta-blockers, patients receiving hypoglycemic drugs should be careful, because during prolonged interruptions in eating, hypoglycemia may develop. And such her symptoms, like tachycardia or tremor, will be masked by the action of the drug. Patients should be instructed that the main symptom of hypoglycemia during treatment with beta-blockers is increased sweating.

With the simultaneous administration of clonidine, his reception can be stopped only a few days after the withdrawal of anaprilin.

It is possible to increase the severity of the hypersensitivity reaction and the lack of effect from the usual doses of epinephrine against the background of a burdened allergic anamnesis.

A few days before the general anesthesia with chloroform or ether should stop taking the drug. If the patient took the drug before the operation, he should choose drugs for general anesthesia with a minimum negative inotropic effect.

Reciprocal activation of the vagus nerve can be eliminated by intravenous injection of atropine (1-2 mg).

Drugs that reduce catecholamine stocks (for example, reserpine), can enhance the action of beta-blockers, so patients who take such combinations of drugs should be under constant observation of the doctor for the diagnosis of arterial hypotension or bradycardia.

It can not be used simultaneously with antipsychotic drugs (neuroleptics) and anxiolytic drugs (tranquilizers).

Carefully apply in conjunction with psychoactive drugs, such as monoamine oxidase inhibitors, with their course use for more than 2 weeks.

In the case of an increased bradycardia (less than 50 / min), arterial hypotension (systolic blood pressure below 100 mm Hg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, severe violations of the liver and kidney function, it is necessary to reduce the dose or stop treatment . It is recommended to stop therapy with the development of depression caused by the use of beta-blockers.

Do not abruptly interrupt treatment because of the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose for 2 weeks or more (by 25% in 3-4 days).

It should be canceled before the study in the blood and urine of catecholamines,normetanephrine and vanillylmandelic acid; titers of antinuclear antibodies.

Avoid intravenous administration of verapamil and diltiazem against the background of therapy with Anaprilin.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 40 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 50 or 100 tablets in cans of polymeric.

1, 2, 5, 10 contour mesh packages or each jar with instructions for use is placed in a pack.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

After the expiry date, the drug should not be used.

Terms of leave from pharmacies:On prescription

Registration number:P N003958 / 01

Date of registration:12.03.2010

Expiration Date:Unlimited

The owner of the registration certificate:MEDISORB, CJSC MEDISORB, CJSC Russia

Manufacturer: & nbsp

MEDISORB, CJSC Russia

Information update date: & nbsp28.08.2017

Illustrated instructions

Instructions

Anaprilin (Anaprilin)