Anaprilin, tablets 40 mg 50 pcs

Pharmacotherapeutic group

Beta-adrenoblocker

ATX code: C07AA

Pharmacodynamics:

A nonselective beta-adrenoblocker. It has antianginal hypotensive and antiarrhythmic effect. By nonselective blocking beta-adrenoceptors (75% beta1- and 25% beta2-adrenoceptors) it decreases catecholamine-induced cAMP formation from ATP, which decreases intracellular calcium influx it has negative chrono-dromo-batmo- and inotropic effect (decreases heart rate, inhibits conduction and excitability and reduces myocardial contractility).

In the beginning of administration of beta-adrenoblockers general peripheral vascular resistance increases during the first 24 h (as a result of reciprocal increase of activity of alpha-adrenoreceptors and elimination of stimulation of beta2-adrenoreceptors of skeletal muscle vessels) but in 1-3 days it returns to baseline and with long-term administration it decreases.

Hypotensive effect is related to the decrease of cardiac output by sympathetic stimulation of peripheral vessels, decrease of renin-angiotensin system activity (it is important in patients with initial renin hypersecretion) sensitivity of aortic arch baroreceptors (their activity in response to BP decrease is not increased) and influence on the central nervous system. Hypotensive effect is stabilized by the end of 2 weeks of prescription.

The antianginal action is caused by decrease of myocardial oxygen demand (due to negative chronotropic and inotropic effect). The decrease of heart rate leads to prolongation of diastole and improvement of myocardial perfusion. By increasing left ventricular end-diastolic pressure and increasing ventricular muscle fiber stretch may increase oxygen demand especially in patients with chronic heart failure.

The antiarrhythmic effect is caused by the elimination of arrhythmogenic factors (tachycardia increased activity of the sympathetic nervous system increased cAMP content arterial hypertension) reduction of the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing of atrioventricular conduction. Inhibition of impulse conduction is noted mainly in antegrade and to a lesser extent in retrograde direction through the atrioventricular node and along additional pathways. According to the classification of antiarrhythmic drugs, it belongs to group II drugs. Reduced severity of myocardial ischemia – by reducing myocardial oxygen demand, postinfarction mortality may also be reduced due to antiarrhythmic action.

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

The reduction of tremor with propranololol may be due to blockade of beta2-adrenoreceptors.

Enhances atherogenic blood properties.

Enhances uterine contractions (spontaneous and induced by drugs stimulating the myometrium).

Enhances bronchial tone.

Pharmacokinetics:

It is rapidly and fairly completely (90%) absorbed when ingested and relatively quickly excreted. Bioavailability after oral administration – 30-40% (effect of “first passage” through the liver microsomal oxidation) with prolonged administration – increases (metabolites are formed inhibiting liver enzymes) its value depends on the nature of food and the intensity of hepatic blood flow. It is metabolized by glucuronidation in the liver. Maximal concentration in plasma is reached after 1-15 hours. It is highly lipophilic and accumulates in lung tissue, brain, kidney and heart. It penetrates through the blood-brain barrier and the placental barrier into breast milk. Binding with blood plasma proteins is 90-95%. Volume of distribution is 3-5 l/kg.

It gets into the intestine with bile and is deglucuronized and reabsorbed. Period of half-life – 3-5 hours against the background of a course of administration can be prolonged up to 12 hours. Excreted by the kidneys – 90% in unchanged form – less than 1%. It is not eliminated by hemodialysis.

Indications

Arterial hypertension angina pectoris unstable angina sinus tachycardia (including with hyperthyroidism) supraventricular tachycardia atrial fibrillation tachyarrhythmia supraventricular and ventricular extrasystole prevention of myocardial infarction (systolic blood pressure – more than 100 mm Hg) pheochromocytoma essential tremor migraine (prevention of attacks) as an adjuvant in the treatment of thyrotoxicosis and thyrotoxic crisis (in case of intolerance to thyreostatic drugs); sympatho-adrenal crises against the background of diencephalic syndrome.

Pharmacological effect

Pharmacotherapeutic group

Beta blocker

ATX code: C07AA

Pharmacodynamics:

Non-selective beta blocker. Has antianginal hypotensive and antiarrhythmic effect. By non-selectively blocking beta-adrenergic receptors (75% beta1- and 25% beta2-adrenergic receptors), it reduces the catecholamine-stimulated formation of cAMP from ATP, resulting in a reduction in the intracellular supply of calcium, and has a negative chronodromo-batmo- and inotropic effect (reduces the heart rate, inhibits conductivity and excitability, reduces myocardial contractility).

At the beginning of the use of beta-adrenergic blockers, the total peripheral vascular resistance increases in the first 24 hours (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors in the vessels of skeletal muscles), but after 1-3 days it returns to the original level and decreases with long-term administration.

The hypotensive effect is associated with a decrease in cardiac output, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin system (important in patients with initial hypersecretion of renin), the sensitivity of the baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease in blood pressure) and an effect on the central nervous system. The hypotensive effect stabilizes by the end of 2 weeks of the course.

The antianginal effect is due to a decrease in myocardial oxygen demand (due to the negative chronotropic and inotropic effect). A decrease in heart rate leads to prolongation of diastole and improved myocardial perfusion. By increasing end-diastolic pressure in the left ventricle and increasing the stretch of ventricular muscle fibers, it can increase oxygen demand, especially in patients with chronic heart failure.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown of atrioventricular conduction. Inhibition of impulse conduction is observed predominantly in the antegrade and to a lesser extent in the retrograde directions through the atrioventricular node and along additional pathways. According to the classification of antiarrhythmic drugs, it belongs to group II drugs. Reducing the severity of myocardial ischemia – by reducing myocardial oxygen demand, post-infarction mortality can also be reduced due to the antiarrhythmic effect.

The ability to prevent the development of headaches of vascular origin is due to a decrease in the severity of dilation of cerebral arteries due to beta-blockade of vascular receptors, inhibition of platelet aggregation and lipolysis caused by catecholamines, a decrease in platelet adhesiveness, prevention of activation of blood coagulation factors during the release of adrenaline, stimulation of oxygen supply to tissues and a decrease in renin secretion.

The reduction in tremor with the use of propranolol may be due to the blockade of beta2-adrenergic receptors.

Increases the atherogenic properties of blood.

Strengthens uterine contractions (spontaneous and caused by drugs that stimulate the myometrium).

Increases bronchial tone.

Pharmacokinetics:

It is quickly and fairly completely (90%) absorbed when taken orally and is relatively quickly eliminated from the body. Bioavailability after oral administration is 30-40% (the “first pass” effect through the liver, microsomal oxidation); with long-term use, it increases (metabolites that inhibit liver enzymes are formed); its value depends on the nature of the food and the intensity of hepatic blood flow. Metabolized by glucuronidation in the liver. The maximum concentration in blood plasma is achieved after 1-15 hours. It is highly lipophilic and accumulates in the tissue of the lungs, brain, kidneys, heart. Penetrates through the blood-brain and placental barriers into breast milk. Communication with blood plasma proteins is 90-95%. Volume of distribution – 3-5 l/kg.

It enters the intestine with bile, is deglucuronidated and reabsorbed. The half-life is 3-5 hours against the background of a course of administration and can be extended to 12 hours. Excreted by the kidneys – 90% unchanged – less than 1%. It is not removed by hemodialysis.

Special instructions

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

In elderly patients, it is recommended to monitor kidney function (once every 4-5 months).

If elderly patients develop increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure less than 100 mm Hg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, severe liver and/or kidney dysfunction, it is necessary to reduce the dose of the drug or stop treatment.

The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

It is recommended to discontinue therapy if depression caused by taking beta-blockers develops.

Patients using contact lenses should take into account that during treatment the production of tear fluid may decrease.

Before prescribing Anaprilin, patients with heart failure (early stages) must use digitalis and/or diuretics.

Treatment of coronary heart disease and persistent arterial hypertension should be long-term – taking Anaprilin is possible for several years.

Discontinuation of treatment is carried out gradually under the supervision of a physician: abrupt withdrawal can dramatically increase myocardial ischemia, angina syndrome, and worsen exercise tolerance.

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

In patients with diabetes mellitus, the drug is used under the control of blood glucose levels (once every 4-5 months).

In case of thyrotoxicosis, Anaprilin can mask certain clinical signs of hyperthyroidism (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it can intensify symptoms. When prescribing beta-blockers to patients receiving hypoglycemic drugs, caution should be exercised since hypoglycemia may develop during prolonged breaks in food intake. Moreover, its symptoms such as tachycardia or tremor will be masked due to the action of the drug. Patients should be instructed that the main symptom of hypoglycemia during treatment with beta-blockers is increased sweating.

Prescribe with caution in combination with hypoglycemic agents (the risk of hypoglycemia during insulin therapy and hyperglycemia during oral hypoglycemic agents).

When taking clonidine simultaneously, it can be discontinued only a few days after Anaprilin is discontinued.

For pheochromocytoma, it is prescribed only in combination with alpha-blockers.

If necessary, use during pregnancy, which is possible only if the benefit to the mother outweighs the risk of side effects in the fetus and child. If it is necessary to take it during pregnancy, careful monitoring of the condition of the fetus 48-72 hours before birth should be discontinued.

Do not use simultaneously with antipsychotic drugs (neuroleptics) and tranquilizers.

Drugs that reduce catecholamine reserves (for example, reserpine) can enhance the effect of beta-blockers, so patients taking combinations of drugs should be under constant medical supervision to detect arterial hypotension and bradycardia.

During treatment with Anaprilin, intravenous administration of verapamil diltiazem should be avoided.

Use with caution in combination with psychotropic drugs, such as MAO inhibitors, when used on a course for more than 2 weeks.

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

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

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

The drug should be discontinued before testing the levels of catecholamines normetanephrine and vanillinmandelic acid in the blood and urine; antinuclear antibody titers.

Avoid using natural licorice during treatment; Protein-rich foods can increase bioavailability.

Impact on the ability to drive vehicles. Wed and fur.:
During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Propranolol

Composition

1 tablet contains:

active substance: anaprilin (propranolol hydrochloride) 40 mg;

excipients: refined sugar (sucrose), calcium stearate, potato starch.

Contraindications

Hypersensitivity to the drug atrioventricular block II-III degree sinoauricular block 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 sick sinus syndrome Prinzmetal’s angina cardiomegaly (without signs of heart failure) vasomotor rhinitis occlusive diseases of peripheral vessels diabetes mellitus metabolic acidosis (including diabetic ketoacidosis) bronchial asthma tendency to bronchospastic reactions chronic obstructive pulmonary disease (including a history) pheochromocytoma (without simultaneous use alpha-blockers) spastic colitis simultaneous use with antipsychotics and anxiolytics (chlorpromazine trioxazine, etc.) MAO inhibitors lactation period age up to 18 years (efficacy and safety have not been established).

With caution:

Liver and/or renal failure hyperthyroidism myasthenia gravis heart failure pheochromocytoma psoriasis pregnancy history of allergic reactions Raynaud’s syndrome old age.

Side Effects

From the cardiovascular system: sinus bradycardia, atrioventricular block, heart failure, palpitations, myocardial conduction disturbances, arrhythmias, decreased blood pressure, orthostatic hypotension, chest pain, spasm of peripheral arteries, cold extremities.

From the digestive tract: dry mouth nausea vomiting diarrhea constipation pain in the epigastric region impaired liver function changes in taste.

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

From the respiratory system: rhinitis, nasal congestion, shortness of breath, bronchospasm, laryngospasm.

Metabolism: hypoglycemia (in patients with type I diabetes mellitus) hyperglycemia (in patients with type II diabetes mellitus).

From the senses: dryness of the mucous membrane of the eyes (decreased secretion of tear fluid), impaired visual acuity, keratoconjunctivitis.

From 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 liver transaminases and bilirubin levels.

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

Other: muscle weakness, back or joint pain, chest pain, leukopenia, thrombocytopenia and withdrawal syndrome.

Interaction

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

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

Cimetidine increases bioavailability.

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

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

Enhances the effect of thyreostatic and uterotonic drugs; reduces the effect of antihistamines.

Increases the likelihood of developing severe systemic reactions (anaphylaxis) due to the introduction of allergens used for immunotherapy or for skin tests.

Amiodarone verapamil and diltiazem – increased severity of the negative chrono-ino- and dromotropic effects of propranolol.

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

Phenytoin, when administered intravenously, drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of a decrease in blood pressure.

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

Reduces the clearance of xanthines (except difillin).

The hypotensive effect is weakened by glucocorticosteroids.

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

Nifedipine can lead to a significant decrease in blood pressure.

Prolongs the action of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedative and hypnotic drugs increase CNS depression.

Concomitant use with MAO inhibitors is not recommended due to a significant increase in the hypotensive effect; the break in treatment between taking MAO inhibitors and propranolol should be at least 14 days.

Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.

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

Overdose

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

Treatment: gastric lavage, administration of activated charcoal in case of atrioventricular conduction disturbance – 1-2 mg of atropine epinephrine is administered intravenously; if efficiency is low, a temporary pacemaker is installed; for ventricular extrasystole – lidocaine (class IA drugs are not used); in case of arterial hypotension, the patient should be in the Trendelenburg position. If there are no signs of pulmonary edema, plasma-substituting solutions are administered intravenously if ineffective – epinephrine dopamine dobutamine; for convulsions – intravenous diazepam; for bronchospasm, beta-agonists are inhaled or parenterally.

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 expiration date.

Manufacturer

Biosynthesis, Russia