Azoprol and retard

Azoprol and retard - a drug that selectively blocks the activity of β-adrenergic receptors.

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Indications of the azoprol and retard

It is used for the treatment of tachyarrhythmia, angina pectoris, CHF of compensated type (combined therapy with ACE inhibitors, diuretics and hypertension), and in addition to reducing elevated blood pressure values.

Also, the drug is used to prevent coronary death and recurrence of myocardial infarction after its acute phase.

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Release form

The release is made in tablets, 10 pieces each inside a blister pack. In the box there are 3 blister plates.

Pharmacodynamics

Metoprolol selectively blocks the elements of β1, is a racemic combination of S-, as well as R-isomers. The ability to selectively block β1-terminations provides the S (-) isomer of the left-handed character, but the R (+) isomer does not have a positive therapeutic effect. The activity of the ratio of isomers of S: R is equal to 33k1, because the S-form of metoprolol has a greater affinity for β1-termini than its R-forms. A double clinical trial of a randomized, blinded character demonstrated that the S (-) element in a 50 mg dose had similar activity to 100 mg of racemic metoprolol.

The hypotensive effect is provided by the weakening of the cardiac output, and besides the binding of renin, as well as suppression of the activity of the RAS and restoration of the sensitization of the baroreceptors, as a result of which sympathetic manifestations of the peripheral character decrease.

Anti-anginal effect arises due to a decrease in strength, and at the same time, the frequency of cardiac contractions, energy consumption, and in addition the need for myocardium in obtaining oxygen. The drug reduces the incidence and severity of angina attacks and the death rate in people who have been diagnosed with myocardial infarction, and at the same time increases the tolerance of various loads. Prolonged use of metoprolol increases survival rates and reduces the incidence of hospitalization of people with CHF, because the drug improves left ventricular function.

Metoprolol succinate helps to reduce the likelihood of death (also sudden death), the development of recurrence of the infarction (also in people with diabetes), and in addition, it improves the condition of people with myocardial infarction in the phase of exacerbation, and with idiopathic DCMP.

The antiarrhythmic effect is manifested in the form of elimination of arrhythmogenic effect of sympathetic nature with respect to the conducting cardiac system, inhibition of the transmission rate of excitation by means of the AV node and sinus rhythm, and at the same time, slowing down of automatism and prolongation of 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 or weakens the agonist effect on the cardiac activity of catecholamines, which are released under the influence of physical and nervous stresses. The substance has the ability to prevent the increase in heart rate, increased heart rate and the frequency of minute volume, and with it the increase in blood pressure, which occurs under the action of a sharp release of catecholamines.

Prolonged activity of the drug allows for a constant concentration of the substance within the plasma for 24 hours, due to which a stable therapeutic effect develops and the likelihood of the appearance of side symptoms that occur at peak plasma values of drugs (for example, weakness in the lower extremities during walking or bradycardia ). Stable exposure, as in the case of therapy with 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 using the drug. Peak values inside the plasma are 55.98 ng / ml, and they occur after 6.83 ± 1.52 hours after ingestion. The bioavailability level of one serving is approximately 94.54%. The bioavailability values may increase in the case of drug taking along with food.

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

Excretion is mostly carried out by hepatic metabolism, the mean values of the half-life are 6.83 ± 1.52 hours. The age of the treated does not affect the pharmacokinetic parameters of drugs. Usually, more than 95% of the ingested portion of the drug is excreted in the urine. About 5% of this dosage is in the form of an unchanged component.

Systemic indicators of bioavailability, as well as excretion of metoprolol in persons with impaired renal function, do not change.

Dosing and administration

To reduce the elevated values of blood pressure: taking once a day, 25 mg of the drug. The portion is also allowed to increase to 50-100 mg (single dose per day).

With angina pectoris: the size of the initial portion - 25 mg (one-time reception per day). If the desired result after taking such a dose is not observed, it is allowed to increase the daily dose to 50-100 mg or to prescribe additional other antianginal drugs.

In case of heart failure: patients should stay in stable stage of CHF without cases of exacerbation during the last 1.5 months, and also without changes in the main treatment scheme during the last 14 days. Treatment of this disease with drugs that block β-adrenergic receptors, sometimes can cause a transient deterioration of the condition. Sometimes it may be necessary to reduce the dosage or cancel the medication. To begin treatment it is necessary under the control of the doctor. The recommended size of the initial portion is 6.25 mg. This dosage in the future is gradually increased taking into account the patient's condition every 14 days.

To reduce bradycardia or at a lowered level of pressure, you may need to reduce the dosage of drugs.

When arrhythmia of the heart: it is recommended to take a single dose per day, amounting to 25-100 mg.

The medicine can be used as a supporting agent after a heart attack. A long therapeutic course with a one-time intake per day of a dose of up to 100 mg is carried out.

Use of the azoprol and retard during pregnancy

It is forbidden to appoint Azoprol and retard to pregnant or lactating mothers. Exceptions are only those situations in which the use of a medicine is extremely necessary in terms of vital signs.

Like other antihypertensives, β-blockers are capable of provoking the emergence of side-effects (for example, bradycardia) in the infant, fetus or newborn.

Contraindications

The main contraindications:

• the presence of intolerance with regard to the active element of drugs or other components thereof;
• AV blockade of 2nd or 3rd degree, blockade of sinoatrial character, heart failure in chronic or acute stage;
• Short's syndrome;
• sinus bradycardia in a marked degree (heart rate less than 55 beats / minute);
• cardiogenic shock or a decrease in blood pressure (systolic BP is less than 100 mm Hg);
• disorders of peripheral blood flow function in pronounced form.

Side effects of the azoprol and retard

The use of drugs can provoke the appearance of the following medicamental symptoms:

• reactions affecting the functioning of the central nervous system: headaches, worsening of concentration, increased fatigue and dizziness. Occasionally there are seizures with paresthesia, depression, insomnia, nightmares, sensation of confusion or drowsiness, worsening of attention, as well as hallucinations, memory disorders and violation of sexual function;
• manifestations of the senses: occasionally develop visual disorders, weakening of the excretory function of the lacrimal gland, ear noise and hearing impairment, and besides this, conjunctivitis;
• disturbances of the function of SSS: the development of orthostatic collapse, sinus form of bradycardia, and in addition, a decrease in the values of blood pressure. Occasionally there is a potentiation of signs of heart failure, a decrease in contractile activity of the myocardium, and in addition cardialgia, AV blockade of the 1st degree, problems with heart rhythm and conduction. People with Raynaud's disease have worse peripheral blood flow problems;
• disorders of digestive activity: the appearance of vomiting, constipation, abdominal pain, diarrhea, nausea and the development of dryness of the oral mucosa. The deviation of the values of liver enzymes, problems in the work of the liver, and also the violation of taste receptors are noted singly;
• skin lesions: sometimes there is hyperemia, photodermatitis, cutaneous manifestations similar to psoriasis, and besides this rash. Occasionally, alopecia develops. The exacerbation of psoriasis is noted;
• violations of respiratory function: bronchial spasms, nasal congestion and dyspnea;
• problems with the endocrine system: the development of hyperglycemia (in individuals with insulin-dependent diabetes mellitus) or hypoglycemia (in people who take insulin);
• allergy symptoms: the appearance of rashes or itching, and besides the development of urticaria;
• disorders of hematopoietic function: development of thrombocytopenia;
• violations of the ODA: the appearance of myalgia or arthralgia;
• development of sexual dysfunction.

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Overdose

Signs of poisoning: heart failure in the acute phase, and in addition, cardiac arrest, bradycardia or AV blockade, a decrease in blood pressure. In addition, bronchial spasms, vomiting, cardiogenic shock, generalized convulsions, nausea, mental and respiratory distress, as well as coma and cyanosis may develop.

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

• in case of problems with AV-permeability or bradycardia - atropine sulfate is administered;
• with worsening contractile activity of the myocardium - dobutamine is introduced with glucagon;
• to increase the decreased values of AD - epinephrine with noradrenaline is administered;
• To remove cramps - inject diazepam;
• to eliminate manifestations of bronchospastic character - an intravenous jet injection of euphyllin is made, and in addition, inhalation of β-adrenomimetics;
• the pacemaker procedure is also performed.

Interactions with other drugs

It is necessary to carefully monitor the condition of people who combine Azoprol and Retard with ganglion blockers and other drugs that block the activity of β-adrenergic receptors (such as eye drops), and in addition to MAOI and antiarrhythmic drugs.

People who use the drug along with diltiazem, amiodarone, verapamil, and also quinidine analogs, can develop negative chronotropic and inotropic manifestations.

Plasma metoprolol decreases in the case of a combination of medication with rifampicin. The reverse effect (increase in values) is observed when combined with SSRIs, hydralazine, cimetidine, and also alcoholic beverages.

When used simultaneously with hypoglycemic drugs for ingestion, the size of their dosage should be changed.

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Storage conditions

Azoprol and retard are required to be kept out of the reach of children. Temperature marks - no more than 25 ° С.

Shelf life

Azoprol and retard are allowed to be used for 2 years from the date of manufacture of the medicament.