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

Non-selective beta-blocker. Has antianginal, hypotensive and antiarrhythmic effect. Nonselectively blocking beta-adrenergic receptors (75% of beta1 and 25% of beta2-adrenoreceptors) reduces the catecholamine-stimulated formation of cAMP from ATP,as a result of which it reduces the intracellular intake of calcium, has a negative chrono-, dromo-, batmo- and inotropic action (it cuts down the 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, .

The hypotensive effect is associated with a decrease in the minute volume of the heart, sympathetic stimulation of the peripheral vessels, a decrease in the activity of the renin-angiotensin 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) and influence on the central nervous system. The hypotensive effect is stabilized by the end of 2 weeks of the course appointment.

Antianginal effect is due to a decrease in myocardial oxygen demand (due to a negative chronotropic and inotropic effect).Reducing the 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 due to 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 belongs to the drugs group II. Reducing the severity of myocardial ischemia - by reducing myocardial oxygen demand, postinfarction mortality may also decrease due to antiarrhythmic action.

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

Reduction of tremor on the background of the use of propranolol may be due to blockade of beta2-adrenergic receptors.

Increases atherogenic properties of blood.

Strengthens uterine contractions (spontaneous and drug-induced, stimulating myometrium).

Increases bronchial tone.

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 admission - increases (metabolites that inhibit liver enzymes are formed), its magnitude depends on the nature of food and intensity of hepatic blood flow.Metabolized by glucuronation in the liver. The maximum concentration in blood plasma is reached after 1-1.5 hours. It has high lipophilicity, accumulates in lung tissue, brain, kidneys, heart. Penetrates through the blood-brain and placental barriers, into breast milk. Connection with blood plasma proteins - 90-95%. The volume of distribution is 3-5 l / kg.

It comes with bile in the intestines, deglukuroniziruetsya and reabsorbed. The half-life is 3-5 hours, against the background of the course administration, it can be extended to 12 hours. It is excreted by the kidneys - 90%, unchanged - less than 1%. It is not removed during hemodialysis.

Indications:

Arterial hypertension, angina pectoris, unstable angina, sinus tachycardia (including hyperthyroidism), supraventricular tachycardia, ciliary tachyarrhythmia, supraventricular and ventricular extrasystole, prevention of myocardial infarction (systolic blood pressure more than 100 mm Hg), pheochromocytoma, essential tremor, migraine (prevention of seizures), as an aid in the therapy of thyrotoxicosis and thyrotoxic crisis (with intolerance of thyreostatic drugs), sympathetic adrenal Riza on the background of diencephalic syndrome.

Contraindications:

Hypersensitivity to the drug, atrioventricular blockade II-III degree, sinoauric blockade, sinus bradycardia, arterial hypotension, uncontrolled chronic heart failure IIB-III degree, acute heart failure, acute myocardial infarction (systolic blood pressure - less than 100 mm Hg), cardiogenic shock, pulmonary edema, sinus node weakness syndrome, Prinzmetal angina, cardiomegaly (no signs of heart failure), vasomotor rhinitis, occlusive diseases peripheral vascular diseases, diabetes mellitus, metabolic acidosis (including diabetic ketoacidosis), bronchial asthma, propensity to bronchospastic reactions, chronic obstructive pulmonary disease (including anamn ze), pheochromocytoma (without the simultaneous use of alpha blockers), spastic colitis, simultaneous with antipsychotics and anxiolytics (chlorpromazine, trioxazine, etc.), MAO inhibitors, lactation period, age under 18 years (efficacy and safety not established).

Carefully:

Hepatic and / or renal insufficiency, hyperthyroidism, myasthenia gravis, heart failure, pheochromocytoma, psoriasis, pregnancy, allergic reactions in the anamnesis, Raynaud's syndrome, elderly age.

Dosing and Administration:

With arterial hypertension - Inward, 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.

With angina pectoris, heart rhythm disturbances - in an initial dose of 20 mg 3 times a day, then 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.

If the liver function is impaired, a dose reduction is necessary.

With impaired renal function, it is necessary to reduce the initial dose or increase the interval between doses of the drug

Prevention of recurrent myocardial infarction - therapy should be started between the 5th and 21st day after a myocardial infarction in a dose of 40 mg 4 times a day for 2 to 3 days. Then in a dose of 80 mg 2 times a day.

With pheochromocytoma - use only with alpha-adrenoreceptor blockers.

Before operation prescribe 60 mg per day, for 3 days.

Side effects:

From the side of the cardiovascular system: sinus bradycardia, atrioventricular blockade, heart failure, palpitation, myocardial conduction disturbance, arrhythmias, lowering of blood pressure, orthostatic hypotension, chest pain, spasm of peripheral arteries, cold extremities.

From the digestive tract: dry mouth, nausea, vomiting, diarrhea, constipation, epigastric pain, liver dysfunction, taste change.

From the nervous system: rarely - headache, insomnia, nightmarish dreams, asthenic syndrome, decreased ability to rapid mental and motor reactions, agitation, depression, paresthesia, fatigue, weakness, dizziness, drowsiness, confusion or short-term memory loss, hallucinations, tremor.

From the respiratory system: rhinitis, nasal congestion, dyspnea, bronchospasm, laryngospasm.

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

From the sense organs: dryness of the mucous eye (decreased secretion of tear fluid), visual acuity, keratoconjunctivitis.

From the side of the reproductive system: decreased libido, decreased potency.

From the skin: alopecia, exacerbation of psoriasis, increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions.

From the endocrine system: decreased thyroid function.

Allergic reactions: skin rash, itching.

Laboratory indicators: agranulocytosis, increased activity of "hepatic" transaminases and bilirubin levels.

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

Other: muscle weakness, pain in the back or joints, chest pain, leukopenia, thrombocytopenia and withdrawal syndrome.

Overdose:

Symptoms: bradycardia, dizziness or fainting, decreased blood pressure, arrhythmias, difficulty breathing, cyanosis of the fingernails or palms, or convulsions.

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

Interaction:

The hypotensive effect of propranolol is enhanced when combined with diuretics, reserpine, hydralazine and other antihypertensive agents, as well as ethanol.

The hypotensive effect weakens non-steroidal anti-inflammatory drugs (sodium retention and blockage of prostaglandin synthesis by the kidneys), estrogens (sodium retention) and MAO inhibitors.

Cimetidine increases bioavailability.

Increases the concentration of lidocaine in the blood plasma, reduces the clearance of theophylline.

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

Strengthens the action of thyreostatic and uterotonizing drugs; reduces the effect of antihistamines.

Increases the likelihood of developing severe systemic reactions (anaphylaxis) against the background of the administration of allergens, used for immunotherapy or for skin tests.

Amiodarone, verapamil and diltiazem - increased severity of negative chrono, foreign and dromotropic effects of propranolol.

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

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.

Changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

Reduces the clearance of xanthines (except diphylline).

The hypotensive effect weakens the glucocorticosteroids.

Cardiac glycosides, methyldopa, reserpine and guanfacine, antiarrhythmic drugs increase the risk of developing or aggravating bradycardia, atrioventricular blockade, cardiac arrest and heart failure.

Nifedipine can lead to a significant reduction in blood pressure.

Lengthens the action of nondepolarizing muscle relaxants and anticoagulant effect of coumarins.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedative and hypnotic drugs increase oppression of the central nervous system.

It is not recommended simultaneous use with MAO inhibitors due to a significant increase in antihypertensive effect, a break in treatment between the intake of MAO inhibitors and propranolol should be at least 14 days.

Unhydrated ergot alkaloids increase the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of propranolol in the blood plasma (inhibits metabolism), rifampicin shortens the half-life.

Special instructions:

Control of patients taking Anaprilin, should include monitoring of heart rate and blood pressure (at the beginning of treatment - every day, then once every 3-4 months), ECG.

In elderly patients it is recommended to monitor the kidney function (1 time in 4-5 months).

In the case of an increasing bradycardia (less than 50 beats per minute), arterial hypotension (systolic blood pressure less than 100 mmHg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, severe liver and / or kidney dysfunction in elderly patients, it is necessary to reduce dose of the drug or discontinue treatment.

It is necessary to teach the patient how to calculate heart rate and instruct about the need for medical consultation at a heart rate of less than 50 beats per minute.

It is recommended to stop therapy with the development of depression caused by the use of beta-blockers.

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

Before the appointment of Anaprilin, patients with heart failure (early stages) should use digitalis and / or diuretics.

Treatment of coronary heart disease and persistent arterial hypertension should be long - anaprilin is possible for several years.

Termination of treatment is carried out gradually, under the supervision of a doctor: a sharp cancellation can dramatically increase myocardial ischemia, anginal syndrome, worsen tolerance to physical exertion.

Cancellation is carried out gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% every 3-4 days).

In patients with diabetes, the drug is administered under the control of blood glucose (1 time in 4-5 months).

In thyrotoxicosis, anaprilin can mask certain clinical signs of hyperthyroidism (for example,tachycardia). Sharp abolition in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms. With the appointment of beta-blockers, patients receiving hypoglycemic drugs should be careful, because during prolonged interruptions in eating can develop hypoglycemia. 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 caution, appoint together with hypoglycemic agents (the risk of hypoglycemia in the background of insulin therapy and hyperglycemia - against oral hypoglycemic agents).

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

When pheochromocytoma is prescribed only in combination with alpha-blockers.

If necessary, taking during pregnancy, which is only possible if the benefit to the mother exceeds the risk of side effects in the fetus and the baby.If you need to take during pregnancy - careful monitoring of the fetus, 48-72 h before delivery - should be canceled.

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

Drugs that reduce catecholamine stocks (for example, reserpine) can enhance the action of beta-blockers, so patients taking a combination of drugs should be under constant observation of the doctor for the diagnosis of arterial hypotension and bradycardia.

Against the background of Anaprilin treatment, intravenous administration of verapamil, diltiazem should be avoided.

Carefully apply together with psychotropic drugs, for example, MAO inhibitors, with their course use for more than 2 weeks.

A few days before the general anesthesia with chloroform or ether, it is necessary to stop taking the drug (increased risk of oppression of myocardial function and development of arterial hypotension).

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

During treatment it is not recommended to take ethanol (possibly a sharp decrease in blood pressure).

It is necessary to cancel the drug before examining the content in the blood and urine of catecholamines, normetanephrine and vanillin-mandelic acid; titers of antinuclear antibodies.

During treatment, avoid using natural licorice; food rich in protein, can increase bioavailability.

Effect on the ability to drive transp. cf. and fur:During the treatment period it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 10 and 40 mg.

Packaging:

10 or 20 tablets in a contour mesh box made of a polyvinylchloride film and aluminum foil or paper with a polyethylene coating.

50, 100 tablets in a jar of orange glass, ukuporennuyu plastic taut cover with a sealing element.

50, 100 tablets in a can of polymer. Each jar or 2, 3, 5 or 10 contour squares with instructions for use is placed in a pack of cardboard.

Storage conditions:

In a dry place, protected from light, out of reach of children, at a temperature above 25 ° C.

Shelf life:

4 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-001384

Date of registration:11.07.2011

Expiration Date:Unlimited

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Representation: & nbspBIOSINTEZ JSC BIOSINTEZ JSC Russia

Information update date: & nbsp27.08.2017

Illustrated instructions

Instructions

Anaprilin (Anaprilin)