Metoprolol

Pharmacological properties

betalok. iv treatment with metoprolol for myocardial infarction can reduce the severity of pain in the chest, reduce the incidence of fibrillation and atrial flutter. early initiation of therapy (within 24 hours after the onset of the first symptoms) allows you to limit the development and spread of the zone of myocardial infarction. early initiation of therapy increases the benefits of treatment.

With paroxysmal atrial tachycardia and atrial fibrillation / flutter, a decrease in the frequency of contraction of the ventricles of the heart is observed.

Metoprolol - selective β blocker₁receptors, that is, it affects β₁heart receptors at lower doses compared to those necessary for influencing β₂- receptors of peripheral vessels and bronchi. With increasing doses of the drug β₁-selectivity may decrease.

Metoprolol reduces the effect of catecholamines during physical and psycho-emotional stress, reduces heart rate, reduces cardiac output, and also lowers high blood pressure. In stressful situations, accompanied by an increased adrenaline rush from the adrenal glands, metoprolol does not interfere with the normal physiological expansion of blood vessels. In therapeutic doses, metoprolol has a less contractile effect on the muscles of the bronchi than non-selective β-adrenergic blockers. This property allows metoprolol treatment in combination with β stimulants.₂-adrenoreceptors in patients with AD or other severe obstructive pulmonary diseases. Metoprolol affects insulin release and carbohydrate metabolism to a lesser extent than non-selective β blockers₂-adrenoreceptors, and therefore it can also be used in patients with diabetes mellitus. Cardiovascular reactions with hypoglycemia, such as tachycardia, are less pronounced with metoprolol, and the return of blood glucose levels to normal values ​​is faster than with non-selective β blockers₂-adrenoreceptors.

Betalok Zok. Metoprolol - selective β blocker₁-adrenoreceptors. Metoprolol affects β₁heart receptors at lower doses than doses necessary to influence β₂- receptors of peripheral vessels and bronchi. Betalok Zok selectivity is dose-dependent, since the maximum concentration in blood plasma when using a dosage form with delayed release is significantly lower than when taking the same dose in the form of a regular tablet. Higher β₁-selectivity is achieved through dosage in the dosage form Zok.

Metoprolol has no beta-stimulating effect and exhibits a slight membrane-stimulating effect. Β-receptor blockers have a negative inotropic and chronotropic effect.

Metoprolol treatment reduces the effect of catecholamines on the heart during physical and psycho-emotional stress and leads to a decrease in heart rate, cardiac output, and also reduces high blood pressure. In stressful situations, accompanied by an increased release of adrenaline from the adrenal glands, metoprolol does not interfere with the normal physiological expansion of blood vessels. In therapeutic doses, metoprolol has less effect on the muscles of the bronchi than non-selective β-blockers. This property provides conditions for the treatment of patients with AD or other severe obstructive pulmonary diseases with metoprolol in combination with β stimulants.₂receptors. Metoprolol has a lesser effect on insulin release and carbohydrate metabolism than non-selective β-adrenergic receptor blockers, so it can also be prescribed to patients with diabetes mellitus. Metoprolol has a lesser effect on the cardiovascular response in hypoglycemia, for example, tachycardia, and the return of blood glucose to normal values ​​is faster than when non-selective β-receptor blockers are used.

In hypertension Betalok Zok significantly reduces blood pressure for more than 24 hours both in the supine position and in the standing position, as well as during exercise. At the beginning of treatment with metoprolol, an increase in total peripheral vascular resistance (OPSS) is observed. However, with long-term treatment, a decrease in blood pressure can occur by reducing OPSS against the background of unchanged cardiac output.

In a 4-week study involving 144 patients aged 6 to 16 years with essential hypertension Betalok Zok at a dose of 1 and 2 mg / kg reduced the systolic BP corrected relative to placebo by 4–6 mm Hg. Art. Diastolic blood pressure showed a 5 mm Hg correction relative to placebo. Art. when using the drug in higher doses, as well as a dose-dependent decrease in blood pressure when using the drug in doses of 0.2; 1 and 2 mg / kg. There were no significant differences between age, Tanner scale indicators (adolescent physical development scale) or race.

Metoprolol reduces the risk of cardiovascular death in men with moderate / severe hypertension. Violations from the electrolyte balance were not noted.

Effect in chronic heart failure: in the MERIT-HF study (a survival study in which 3991 patients with chronic heart failure (NYHA class II – IV functional class) and a reduced ejection fraction (≤40) took part) Betalok Zock showed an increase in survival rates and reduction in the number of hospitalizations. With prolonged treatment, patients achieved an overall improvement in symptoms (according to the NYHA classification and the general treatment rating scale).

In addition, it was shown that treatment with Betalok Zok increases the ejection fraction and reduces end-systolic and end-diastolic volumes of the left ventricle.

With tachyarrhythmias, the effect of increased sympatholytic activity is blocked, and this leads to a lower heart rate, primarily due to a decrease in the automatic function in the pacemaker cells, as well as due to the extended time of supraventricular conduction. Metoprolol reduces the risk of recurrent heart attack and death, especially sudden, after myocardial infarction.

Pharmacokinetics Betalok. Metoprolol is metabolized in the liver, mainly with the participation of CYP 2D6. Three major metabolites were identified, and each of them does not have any clinically significant beta-blocking effect. T_½ from blood plasma is 3-5 hours. About 5% of metoprolol is excreted by the kidneys unchanged, the rest - in the form of metabolites.

Betalok Zok.

Betalok Zok sustained release tablet consists of microcapsules containing metoprolol succinate granules, and each capsule is a separate unit of content. Each capsule is coated with a polymer membrane that controls the rate of release of the drug. The tablet quickly breaks down in contact with the liquid, and after that the capsules are distributed over a significant surface of the digestive tract. The release is independent of the pH of the surrounding fluid and continues at an almost constant rate for 20 hours. This dosage form provides a uniform concentration of metoprolol succinate in the blood plasma and the duration of action for 24 hours.

Betalok Zok is completely absorbed after oral administration, and the substance is absorbed throughout the digestive tract, as well as in the colon. The bioavailability of Betaloc Zok is 30–40%. Metoprolol is metabolized in the liver, mainly with the participation of CYP 2D6. 3 main metabolites were identified, while none of them exerts any clinically significant β-blocking effect. About 5% of metoprolol is excreted by the kidneys unchanged, the rest - in the form of metabolites.

The pharmacokinetics of metoprolol in children and adolescents (6-17 years old) resembles the pharmacokinetics in adults.The clearance with oral administration of metoprolol increases with a linear dependence on body weight.

Indications

Betalok injection. treatment of tachyarrhythmias, in particular supraventricular tachyarrhythmias. acute myocardial infarction. early use of betalok in order to reduce the infarction zone and reduce the incidence of ventricular fibrillation. reduction in the severity of pain symptoms, which may also reduce the need for opioid analgesics. mortality reduction in patients with acute myocardial infarction.

Betalok Zok. AH. Angina pectoris. Stable symptomatic chronic heart failure with impaired systolic function of the left ventricle. Prevention of cardiac death and re-infarction after the acute phase of myocardial infarction. Cardiac arrhythmias, including supraventricular tachycardia, a decrease in the frequency of ventricular contraction during atrial fibrillation and ventricular extrasystoles. Functional disorders of cardiac activity, accompanied by palpitations. Migraine Prevention

Application

Betalok injection

Parenteral administration of Betaloc should be carried out under the supervision of specially trained personnel in places where you can measure blood pressure, conduct ECG and resuscitation.

Supraventricular tachyarrhythmia. At the initial stage, 5 mg (5 ml) must be administered intravenously at a rate of 1–2 mg / min. The introduction of the drug in this dose can be repeated every 5 minutes until the desired effect is achieved. Usually a total dose of 10-15 mg (10-15 ml) is sufficient. The recommended maximum dose for iv administration is 20 mg (20 ml).

Prevention and treatment of myocardial ischemia, tachyarrhythmia and pain in case of a suspected or diagnosed myocardial infarction. Acute condition: the drug should be administered iv in a dose of 5 mg (5 ml). The introduction of a dose of the drug can be repeated every 2 min; the maximum dose is 15 mg (15 ml). 15 minutes after the last injection, 50 mg of metoprolol tartrate should be administered orally every 6 hours for 48 hours. For prolonged oral administration, Betalok tablets or tablets with a slow release of Betalok Zok should be prescribed.

The diluted injection solution should be used within 12 hours.

Betalok Zok

Betalok Zok is used 1 time per day, preferably in the morning. Slow-release tablets can be divided, but should not be chewed or crushed. Tablets are washed down with at least 0.5 cups of liquid. Simultaneous eating does not affect the bioavailability of the drug.

The dose is selected individually. To avoid the development of bradycardia, the dose of the drug should be adjusted. The following dosage is recommended.

AH. 50-100 mg once a day. If a dose of 100 mg is insufficient to achieve a therapeutic effect, the drug can be combined with other antihypertensive drugs, preferably diuretics and calcium antagonists of the dihydropyridine type, or you can increase the dose of the drug.

Angina pectoris. 100-200 mg once a day. If necessary Betalok Zok can be combined with nitrates or increase the dose.

Complementary therapy in the treatment of an ACE inhibitor, diuretic and, possibly, digitalis preparations in case of stability of symptomatic heart failure. Patients should be in a stage of stable chronic heart failure without episodes of decompensation for at least 6 weeks and without significant changes in basic therapy over the past 2 weeks.

Treatment of heart failure with β-adrenoreceptor blockers can lead to a temporary worsening of symptoms. In some cases, it is possible to continue therapy or reduce the dose of the drug, sometimes it may be necessary to cancel the drug.In patients with severe heart failure (IV functional class according to NYHA classification), only an experienced specialist should start therapy with Betalok Zok.

Stable heart failure, II functional class. The recommended initial dose of Betaloc Zok in the first 2 weeks is 25 mg once a day. After 2 weeks, the dose can be increased to 50 mg once a day, and then the dose can be doubled every 2 weeks. The target dose of Betaloc Zock for long-term treatment is 200 mg once a day.

Stable heart failure, III – IV functional class. The recommended starting dose is 12.5 mg (half a 25 mg tablet) once a day. The dose of the drug is adjusted individually. During the period of increasing the dose, the patient should be under close medical supervision, as in some patients the symptoms of heart failure may worsen. After 1-2 weeks of taking Betalok Zok, the dose can be increased to 25 mg once a day. After 2 weeks, the dose can be increased to 50 mg once a day. Patients who tolerate high doses can be doubled every 2 weeks until a maximum dose of 200 mg / day is reached.

In case of arterial hypotension and / or bradycardia, it may be necessary to reduce the dose of the concomitant drug or Betalok Zok. Arterial hypotension at the beginning of therapy does not necessarily indicate that the dose of Betalok Zok should be reduced. However, the dose should not be increased until the patients condition is stabilized. It may also be necessary to carefully monitor kidney function.

Cardiac arrhythmia. 100-200 mg once a day. If necessary, the dose can be increased.

Supportive care after myocardial infarction. The recommended maintenance dose is 200 mg once daily.

Functional disorders of cardiac activity, accompanied by palpitations. 100 mg once a day. If necessary, the dose can be increased.

Migraine Prevention 100-200 mg once a day.

Impaired renal function. Renal function only slightly affects the rate of elimination of the drug, so there is no need for dose adjustment in patients with impaired renal function.

Impaired liver function. Typically, patients with cirrhosis can be given the same dose as patients with normal liver function. Only if there are signs of very severe liver dysfunction (for example, in patients with a history of bypass surgery), it is necessary to consider the possibility of reducing the dose of the drug.

Elderly patients. No dose adjustment is required.

Contraindications

Cardiogenic shock. sick sinus syndrome. av blockade of the II and III degrees. heart failure in the decompensation stage (pulmonary edema, hypoperfusion or arterial hypotension); prolonged or periodic inotropic therapy aimed at stimulating β-adrenergic receptors. symptomatic bradycardia or arterial hypotension. untreated pheochromocytoma.

Metabolic acidosis. Metoprolol should not be prescribed to patients with suspected acute myocardial infarction with a heart rate of 45 beats / min, a P – Q interval of 0.24 s, a systolic blood pressure of 100 mmHg, AV blockade of degree I and / or severe heart failure. Serious peripheral vascular disease with the threat of gangrene. Hypersensitivity to the components of the drug or other β-adrenergic blockers.

Betalok. In supraventricular tachyarrhythmia Betalok should not be prescribed to patients whose systolic blood pressure is 110 mm Hg. Art.

Betalok Zok. In the case of symptoms of heart failure, the patients condition with recurring blood pressure values ​​of 100 mm Hg. Art. lying down before treatment should be re-evaluated.

Side effects

Adverse reactions, usually dose-dependent, are noted in approximately 10% of patients.adverse reactions associated with the use of metoprolol are given below depending on the class of organ systems and frequency. the frequency is determined as follows: very often (≥1 / 10); often (≥1 / 100, 1/10); infrequently (≥1 / 1000, 1/100); rarely (≥1 / 10,000, 1/1000); very rarely (1/10 000); frequency is unknown (cannot be estimated based on available data).

Betalok with iv administration can in rare cases cause a clinically significant decrease in blood pressure.

Also, when using metoprolol, insomnia, drowsiness, amnesia, degree I AV block, worsening of existing AV block, postural disorders (very rare with syncope), Raynauds phenomenon, worsening symptoms of intermittent claudication, rash (in the form of psoriatiform urticaria and dystrophic lesions can be observed). skin), impotence / sexual dysfunction, precardial pain, the appearance of antinuclear antibodies (not associated with systemic lupus erythematosus), reactions at the injection site.

special instructions

Patients receiving treatment with β-adrenergic blockers should not be given iv verapamil.

Metoprolol can cause peripheral arterial circulatory disorders, such as intermittent claudication. Particular attention should be paid to patients with severe impaired renal function, serious acute conditions, and patients who receive combination therapy with digitalis preparations.

In patients with Prinzmetal angina, the frequency and severity of angina attacks may increase as a result of alpha receptor-mediated narrowing of the coronary vessels. Therefore, such patients should not be prescribed non-selective β-adrenergic receptor blockers. Selective β blockers₁-adrenoreceptors should be used with caution.

In the treatment of patients with AD or other obstructive pulmonary diseases, adequate bronchodilator therapy should be prescribed at the same time. It may be necessary to increase the dose of stimulants β₂-adrenoreceptors.

Metoprolol treatment can affect carbohydrate metabolism or mask the development of hypoglycemia, although this risk is lower than with non-selective β-adrenergic receptor blockers.

Very rarely, patients with moderate AV severity can worsen (possibly before AV block).

Therapy with β-adrenergic blockers can reduce the effectiveness of stopping the anaphylactic reaction. Treatment with epinephrine in usual doses does not always lead to the expected therapeutic effect.

Patients with pheochromocytoma during treatment with Betalok / Betalok Zok should be simultaneously prescribed α-adrenergic receptor blockers.

Patients with symptomatic heart failure accompanied by acute myocardial infarction and unstable angina were excluded from the study, which established the possibility of using the drug in heart failure. So, the effectiveness and safety of treatment in acute myocardial infarction, which is accompanied by heart failure, has no documented evidence. Betalok / Betalok Zok is contraindicated in case of unstable, uncompensated heart failure.

Sudden withdrawal of β-adrenergic blockers is dangerous, especially in high-risk patients, and can worsen the course of chronic heart failure, as well as increase the risk of myocardial infarction and sudden death. Therefore, stopping treatment with Betalok / Betalok Zok for any reason should, if possible, gradually, for at least 2 weeks, when the dose at each stage is halved to the last dose of 12.5 mg (half a tablet of 25 mg). The last dose should be taken for at least 4 days until the drug is completely discontinued. In case of resumption of symptoms, it is recommended to slow down the dose reduction.

In case of surgical intervention, it is necessary to warn the anesthetist that the patient is taking Betalok / Betalok Zok. It is not recommended to discontinue treatment with β-adrenergic receptor blockers in patients for whom surgery is planned. If the abolition of metoprolol is considered necessary, then, if possible, it should occur at least 48 hours before general anesthesia. Urgent initiation of the use of metoprolol in high doses in patients who have undergone non-cardiac surgery should be avoided, since this is associated with the development of bradycardia, arterial hypotension and stroke, including death in patients with cardiovascular risk factors.

However, some patients have