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

Active ingredient

Composition

1 tablet contains:

the active ingredient: anapriline (propranololol hydrochloride) 40 mg;

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

How to take, the dosage

In case of arterial hypertension, the oral dose is 40 mg 2 times a day. If the hypotensive effect is not sufficiently pronounced, the dose is increased to 40 mg 3 times or 80 mg 2 times a day. Maximum daily dose is 320 mg.

In angina pectoris, the initial dose is 20 mg 3 times daily and then the dose is increased to 80-120 mg in 2 to 3 doses. The maximum daily dose is 240 mg.

For migraine prophylaxis as well as in 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.

In case of liver dysfunction it is necessary to reduce the dose of the drug.

In case of impaired renal function, the initial dose should be reduced or the interval between doses should be increased

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

In pheochromocytoma, use only with alpha-adrenoreceptor blockers.

Before surgery, 60 mg daily for 3 days.

Interaction

The hypotensive effect of propranolol is enhanced when combined with the diuretics reserpine hydralazine and other hypotensive agents and with ethanol.

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

Cimetidine increases bioavailability.

Enhances plasma concentrations of lidocaine decreases clearance of theophylline.

Concomitant administration with phenothiazine derivatives increases plasma concentrations of both drugs.

It potentiates the effects of thyrotropic and uterotonergic drugs; reduces the effect of antihistamines.

It increases the likelihood of severe systemic reactions (anaphylaxis) against the introduction of allergens used for immunotherapy or for skin tests.

Amiodarone verapamil and diltiazem – increase the severity of the negative chrono- and dromotropic effects of propranololol.

Iodine-containing radiopaque 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 cardiodepressant effects and the likelihood of BP reduction.

Alter the effectiveness of insulin and oral hypoglycemic drugs masks the symptoms of developing hypoglycemia (tachycardia increase BP).

Limits the clearance of xanthines (except diphylline).

The hypotensive effect is weakened by glucocorticosteroids.

The 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 BP.

It prolongs the effects of nondepolarizing myorelaxants and the anticoagulant effect of coumarins.

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

The concomitant use with MAO inhibitors is not recommended due to the significant increase in the hypotensive effect; a treatment break of at least 14 days between MAO inhibitors and propranololol should be taken.

Unhydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.

Sulfasalazine increases plasma concentrations of propranololol (inhibits metabolism) rifampicin shortens the elimination half-life.

Special Instructions

Monitoring of patients taking Anaprilin should include monitoring of HR and BP (at the beginning of treatment daily then once every 3-4 months) ECG.

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

In elderly patients with increasing bradycardia (less than 50 bpm) arterial hypotension (systolic BP less than 100 mm Hg) atrioventricular block bronchospasm ventricular arrhythmias severe liver function and/or renal disorders, the drug dose should be reduced or treatment should be stopped.

The patient should be instructed on how to calculate heart rate and instructed to consult a physician if the heart rate is less than 50 bpm.

It is recommended that therapy be discontinued if beta-adrenoblocker-induced depression develops.

Patients who wear contact lenses should be aware that there may be a decrease in tear production during treatment.

Patients with heart failure (early stages) should use digitalis and/or diuretics before prescribing Anaprilin.

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

Stop treatment gradually under a physician’s care: abrupt withdrawal may sharply increase myocardial ischemia and myocardial angina, worsening exercise tolerance.

Cancel the dose gradually over 2 weeks or more (25% reduction every 3 to 4 days).

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

In thyrotoxicosis patients, Anapriline may mask certain clinical signs of hyperthyroidism (e.g., tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it may exacerbate the symptoms. Caution should be exercised when prescribing beta-adrenoblockers to patients receiving hypoglycemic drugs, because hypoglycemia may develop during prolonged interruptions in food intake. Moreover, its symptoms such as 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-adrenoblockers is excessive sweating.

With caution, use with hypoglycemic agents (risk of hypoglycemia with insulin therapy and hyperglycemia with oral hypoglycemic agents).

If clonidine is taken at the same time, its administration can be discontinued only after several days of stopping Anapriline.

In pheochromocytoma, it is prescribed only in combination with alpha-adrenoblockers.

If it is necessary to take during pregnancy, which is possible only if the benefit to the mother outweighs the risk of side effects in the fetus and the baby. If it is necessary to take during pregnancy – close monitoring of the fetus 48-72 h before delivery – should be canceled.

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

Catecholamine-lowering medications (e.g., reserpine) can increase the effects of beta-adrenoblockers, so patients taking combinations of medications should be under constant medical supervision for arterial hypotension and bradycardia.

Verapamil diltiazem intravenous administration should be avoided during treatment with Anaprilin.

Precaution should be taken with psychotropic medications such as MAO inhibitors when used for more than 2 weeks.

A few days before general anesthesia with chloroform or ether the drug should be discontinued (increased risk of myocardial depression and arterial hypotension).

The effectiveness of beta-adrenoblockers is lower in “smokers”.

It is not recommended to take ethanol during treatment (this can cause a sharp decrease in BP).

The drug should be discontinued before testing blood and urine catecholamine levels of normetanephrine and vanillylmindalic acid; antinuclear antibody titers.

Avoid natural licorice during treatment; foods rich in protein may increase bioavailability.

Contraindications

Hypersensitivity to the drug atrioventricular block of II-III degree sinoauricular block sinus bradycardia arterial hypotension uncontrolled chronic heart failure of 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’s angina pectoris (without signs of heart failure) vasomotor rhinitis occlusive peripheral vascular disease diabetes mellitus metabolic acidosis (incl. including diabetic ketoacidosis) bronchial asthma susceptibility to bronchospastic reactions chronic obstructive pulmonary disease (including in anamnesis) pheochromocytoma (without simultaneous use of alpha-adrenoblockers) spastic colitis simultaneous use with antipsychotics and anxiolytics (chlorpromazine trioxazine, etc.) MAO inhibitors lactation age under 18 years (effectiveness and safety are not established).

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

Side effects

Cardiovascular system: sinus bradycardia atrioventricular block heart failure palpitations myocardial conduction disorders arrhythmias decreased BP orthostatic hypotension chest pain peripheral artery spasm cold extremities.

Gastrointestinal disorders: dry mouth nausea vomiting diarrhea constipation epigastric pain liver function disorders change in taste.

Nervous system disorders: rare – headache insomnia “nightmares” dreams asthenic syndrome decreased ability to quick mental and motor reactions agitation depression paresthesia increased fatigability weakness dizziness sleepiness confusion or short term memory loss hallucinations tremor.

Respiratory system: rhinitis nasal congestion dyspnea bronchospasm laryngospasm.

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

Senses: dry eyes (decreased secretion of lacrimal fluid) visual acuity disorders keratoconjunctivitis.

Reproductive system: decreased libido decreased potency.

Skin disorders: alopecia exacerbation of psoriasis increased sweating skin hyperemia exanthema psoriasis-like skin reactions.

Endocrine system disorders: decreased thyroid function.

Allergic reactions: skin rash itching.

Laboratory measures: agranulocytosis increase of “liver” transaminases activity and bilirubin level.

Fetal effects: intrauterine growth retardation hypoglycemia bradycardia.

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

Overdose

Symptoms: bradycardia dizziness or fainting decrease BP arrhythmia difficulty breathing cyanosis finger nails or palms or seizures.

Treatment: gastric lavage administration of activated charcoal if atrioventricular conduction disorder – IV inject 1-2 mg of atropine epinephrine if not effective, place a temporary pacemaker; if ventricular extrasystole – lidocaine (Class IA drugs are not used); if hypotension – the patient should be in Trendelenburg position. If there are no signs of pulmonary edema, plasma-substituting solutions are administered intravenously if ineffective – epinephrine dopamine dobutamine; in convulsions – intravenous diazepam; in bronchospasm inhaled or parenterally – beta-adrenergic stimulants.

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