Azoprol n retard

Azoprole n retard is a drug that selectively blocks the activity of β-adrenergic receptors.

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Indications Azoprola n retard

It is used to treat tachyarrhythmia, angina pectoris, compensated CHF (combination therapy with ACE inhibitors, diuretics and CG), and also to reduce elevated blood pressure.

The drug is also used to prevent coronary death and recurrence of myocardial infarction after its acute phase.

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Release form

The product is produced in tablets, 10 pieces per blister pack. The box contains 3 blister strips.

Pharmacodynamics

Metoprolol selectively blocks β1 elements, is a racemic combination of S- and R-isomers. The ability to selectively block β1-endings is provided by the S(-) isomer of levorotatory nature, but the R(+) isomer does not have a positive therapeutic effect. The activity of the S:R isomer ratio is 33 to 1, because the S-form of metoprolol has a higher affinity for β1-endings than its R-forms. A double clinical randomized blind test demonstrated that the S(-) element in a 50 mg dose has an activity similar to the action of 100 mg of racemic metoprolol.

The hypotensive effect is achieved by weakening cardiac output, as well as renin binding, as well as suppression of RAS activity and restoration of baroreceptor sensitization, resulting in a decrease in sympathetic manifestations of a peripheral nature.

The antianginal effect occurs due to a decrease in the force, and thus the frequency of heart contractions, energy expenditure, and in addition to this, the myocardium's need for oxygen. The drug reduces the frequency and severity of angina attacks and the mortality rate in people diagnosed with myocardial infarction, and at the same time increases the tolerance of various loads. Long-term use of metoprolol increases survival rates and reduces the frequency of hospitalizations of people with CHF, because the drug improves the work of the left ventricle.

Metoprolol succinate helps reduce the risk of death (including sudden death), the development of a recurrent infarction (also in people with diabetes), and in addition, improves the condition of people with myocardial infarction in the acute phase, as well as with idiopathic DCM.

The antiarrhythmic effect manifests itself in the form of eliminating the arrhythmogenic effect of a sympathetic nature in relation to the cardiac conduction system, inhibiting the rate of excitation transmission via the AV node and sinus rhythm, and at the same time slowing down the automatism and prolonging the refractory stage. The active element has a weak membrane-stabilizing effect and does not have the activity of a partial agonist substance.

Metoprolol slows down or weakens the agonistic effect on cardiac activity of catecholamines, which are released under the influence of physical and nervous stress. The substance has the ability to prevent an increase in heart rate, an increase in cardiac contractility and the frequency of the minute volume, and along with this, an increase in blood pressure, which occurs under the influence of a sharp release of catecholamines.

The prolonged activity of the drug allows for a constant concentration of the substance in the plasma for 24 hours, due to which a stable therapeutic effect develops and the likelihood of side effects that are observed at peak plasma values of the drug (for example, weakness in the lower limbs during walking or bradycardia) is reduced. Stable effect, as in the case of therapy using other β-blockers, is noted after 2-3 weeks of the course.

Metoprolol has a weaker effect on carbohydrate metabolism and insulin production than non-selective β-blockers.

Pharmacokinetics

The S(-) component is well absorbed after administration of the drug. Peak values in plasma are 55.98 ng/ml, and they are achieved 6.83±1.52 hours after administration. The bioavailability level of one portion is approximately 94.54%. Bioavailability values may increase if the drug is taken with food.

Only a small part of metoprolol is synthesized with protein. The active element passes through the placenta, and also penetrates into mother's milk. Most of the substance undergoes metabolism with the participation of enzymes of the hemoprotein P450 system inside the liver.

Excretion is mainly carried out by hepatic metabolism, the average values of the half-life are 6.83±1.52 hours. The age of the patients does not affect the pharmacokinetic parameters of the drug. Usually, more than 95% of the dose taken orally is excreted in the urine. About 5% of this dose is in the form of an unchanged component.

Systemic bioavailability parameters, as well as metoprolol excretion, do not change in individuals with impaired renal function.

Dosing and administration

To reduce elevated blood pressure: take 25 mg of the drug once a day. The dose can also be increased to 50-100 mg (single dose per day).

For angina: the initial dose is 25 mg (single dose per day). If the desired result is not observed after taking this dose, it is allowed to increase the daily dose to 50-100 mg or additionally prescribe other antianginal drugs.

In case of heart failure: patients should be at a stable stage of CHF without cases of exacerbation over the last 1.5 months, and without changes in the main treatment regimen over the last 14 days. Treatment of this disease with drugs that block β-adrenergic receptors can sometimes cause a transient deterioration in the condition. Sometimes it may be necessary to reduce the dosage or discontinue the drug. Treatment should be started under the supervision of a doctor. The recommended size of the initial dose is 6.25 mg. This dosage is then gradually increased taking into account the patient's condition every 14 days.

To eliminate bradycardia or at low blood pressure, it may be necessary to reduce the dosage of the drug.

For cardiac arrhythmia: it is recommended to take a single dose per day, ranging from 25 to 100 mg.

The drug can be used as a supportive measure after myocardial infarction: a long-term therapeutic course is carried out with a single daily dose of up to 100 mg.

Use Azoprola n retard during pregnancy

It is prohibited to prescribe Azoprole N retard to pregnant or nursing mothers. The only exceptions are those situations when the use of the drug is absolutely necessary for vital indications.

Like other antihypertensive drugs, β-blockers can provoke the appearance of side effects (for example, bradycardia) in a breastfed baby, fetus or newborn.

Contraindications

Main contraindications:

• the presence of intolerance to the active element of the drug or its other components;
• AV block of the 2nd or 3rd degree, sinoatrial block, heart failure in the chronic or acute stage;
• Short's syndrome;
• severe sinus bradycardia (heart rate less than 55 beats/minute);
• cardiogenic shock or decreased blood pressure (systolic blood pressure is less than 100 mmHg);
• severe disorders of peripheral blood flow function.

Side effects Azoprola n retard

The use of drugs can provoke the appearance of the following drug-induced symptoms:

• reactions affecting the central nervous system: headaches, decreased concentration, increased fatigue and dizziness. Rarely, convulsions with paresthesia, depression, insomnia, nightmares, a feeling of confusion or drowsiness, decreased attention, as well as hallucinations, memory disorders and sexual dysfunction are observed;
• manifestations from the sense organs: occasionally, visual disturbances develop, weakening of the excretory function of the lacrimal gland, tinnitus and hearing loss, and in addition, conjunctivitis;
• dysfunction of the cardiovascular system: development of orthostatic collapse, sinus bradycardia, and in addition, a decrease in blood pressure. Occasionally, there is a potentiation of signs of heart failure, a decrease in myocardial contractility, and in addition, cardialgia, first-degree AV block, problems with heart rhythm and conduction. In people with Raynaud's disease, problems with peripheral blood flow increase;
• digestive disorders: vomiting, constipation, abdominal pain, diarrhea, nausea and dry mouth. Deviations in liver enzyme values, problems with liver function, and taste bud disorders are occasionally observed;
• skin lesions: sometimes hyperemia, photodermatitis, skin manifestations similar to psoriasis, and in addition to this, rashes occur. Alopecia develops occasionally. An exacerbation of the course of psoriasis is noted sporadically;
• respiratory dysfunction: bronchial spasms, nasal congestion and dyspnea;
• problems with the endocrine system: development of hyperglycemia (in people with non-insulin-dependent diabetes) or hypoglycemia (in people who take insulin);
• allergy symptoms: the appearance of rashes or itching, and also the development of hives;
• disorders of hematopoietic function: development of thrombocytopenia;
• disorders of the musculoskeletal system: the appearance of myalgia or arthralgia;
• development of sexual dysfunction.

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Overdose

Signs of poisoning: acute cardiac failure, as well as cardiac arrest, development of bradycardia or AV block, decreased blood pressure. In addition, bronchial spasms, vomiting, cardiogenic shock, generalized convulsions, nausea, impaired consciousness and respiratory function, as well as coma and cyanosis may develop.

To eliminate these disorders, gastric lavage and the following symptomatic procedures are required:

• in case of problems with AV patency or bradycardia, atropine sulfate is administered;
• if myocardial contractility worsens, dobutamine with glucagon is administered;
• to increase decreased blood pressure values, epinephrine with norepinephrine is administered;
• to relieve cramps, diazepam is administered;
• to eliminate manifestations of a bronchospastic nature, an intravenous jet injection of euphyllin is performed, and in addition, inhalation of β-adrenergic agonists;
• A cardiac pacing procedure is also performed.

Interactions with other drugs

It is necessary to carefully monitor the condition of people who combine Azoprole N retard with ganglion blockers and other drugs that block the activity of β-adrenergic receptors (such as eye drops), as well as with MAOIs and antiarrhythmic drugs.

In individuals using the drug together with diltiazem, amiodarone, verapamil, and quinidine analogues, negative chronotropic and inotropic manifestations may develop.

Plasma metoprolol levels decrease when the drug is combined with rifampicin. The opposite effect (increase in levels) is observed when combined with SSRIs, hydralazine, cimetidine, and alcoholic beverages.

When used simultaneously with hypoglycemic drugs for oral administration, their dosage must be changed.

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Storage conditions

Azoprole n retard must be stored in places closed to children. Temperature marks - no more than 25 ° C.

Shelf life

Azoprole N retard is allowed to be used for 2 years from the date of manufacture of the drug.