Metoprolol succinate: a white crystalline powder, readily soluble in water, soluble in methanol, sparingly soluble in ethanol, slightly soluble in dichloromethane and 2-propanol, practically insoluble in ethyl acetate, acetone, diethyl ether and heptane.
Metoprolol tartrate: white, practically odorless crystalline powder, soluble in water, methylene chloride, chloroform and alcohol, slightly soluble in acetone, insoluble in ether.
Pharmacological action Metoprolol Succinate
Pharmacological action – anti-hypertensive, antianginal, antiarrhythmic. Blocks mainly beta_1-adrenoceptors of the heart, has no intrinsic sympathomimetic and membrane stabilizing activity. Reduces cardiac output and Garden, slows the heart rate, decreases the stimulating effect of catecholamines on the myocardium during physical exercise and mental overexertion, warns reflex orthostatic tachycardia. Antihypertensive effect is due to a decrease in cardiac output and renin synthesis, inhibition of renin-angiotensin system and the CNS, the restoration of baroreceptor sensitivity and, ultimately, a decrease in peripheral sympathetic effects. Hypotensive effect develops quickly (SBP decreases after 15 minutes, maximum – 2 hours) and lasts for 6 hours, while taking metoprolol succinate – clinical effect of the blockade beta_1-adrenoceptor saved 24 hours diastolic blood pressure changes slowly: the steady decrease is observed after several weeks of regular admission. Antianginal effect is a consequence of reducing the frequency and severity of heart rate, energy consumption and myocardial oxygen demand. Reduces the frequency and severity of attacks of coronary heart disease, the mortality rate in patients diagnosed with myocardial infarction, improves tolerability loads. Metoprolol succinate reduces the risk of death (including sudden death) of another heart attack (including patients with diabetes) and improves quality of life of patients with acute myocardial infarction and idiopathic dilated cardiomyopathy. Antiarrhythmic effect is manifested in the elimination of arrhythmogenic sympathetic effects on the conducting system of the heart, slowing of sinus rhythm and rate of spread of excitation through the AV node, automaticity, and inhibition of elongation of the refractory period. Has a moderate negative inotropic effect. Cardioselective saved by using daily doses not exceeding 200 mg. Due to selective action on beta_1-Adrenergic theoretically decreases the risk of bronchospasm (in patients with asthma decreased less vital function of the lungs), hypoglycemia, and narrowing of peripheral sosudov.V experiments on dogs (up to 105 mg / kg / day for 1 year), rats (up to 800 mg / kg / day for 2 years) and mice (up to 750 mg / kg / day for 21 months) evidence of carcinogenicity was found, but revealed histological changes such as hyperplasia of the liver cells and macrophages induration of lung tissue. When administered to mice, albinos in doses up to 750 mg / kg / day for 21 months increased in females the incidence of benign lung adenomas, but the repetition of the experience an increase in the incidence of any tumors were noted. The test results of dominant lethal mutations in mice, studies of chromosomes of somatic cells, test for abnormalities of somatic cell nuclear in interphase and others showed no mutagenic properties. In rats treated with doses of 55.5 times the maximum daily dose for humans (450 mg) had no effect on fertility, increased rates postimplantation loss and reduced survival of newborn animals (features of teratogenicity was absent). Metoprolol tartrate is rapidly and almost completely ( 95%) absorbed by ingestion, undergoes intensive presystemic metabolism. Bioavailability of approximately 50% during the first admission, and increases to 70% when reapplying. About 12% bound to plasma albumin. Rapidly distributed in tissues, penetrates through the BBB (the level in the CNS is 78% of plasma concentration), placenta, breast milk (concentrations higher than plasma). The volume of distribution – 5,5 l / kg. C_max achieved within 1-2 h after administration, blood level varies considerably. T_1 / 2 – 3 to 7 hours biotransformed in the liver to form two active metabolites. Excreted mainly by the kidneys as metabolites, Cl – 1 l /
Statement Metoprolol Succinate
Hypertension mild to moderate severity (monotherapy or in combination with other antihypertensive drugs), coronary artery disease, hyperkinetic cardiac syndrome, cardiac arrhythmias (sinus tachycardia, ventricular and supraventricular arrhythmias, including paroxysmal tachycardia, supraventricular tachycardia, extrasystoles, atrial flutter and atrial fibrillation atrial tachycardia), hypertrophic cardiomyopathy, mitral valve prolapse, myocardial infarction (prophylaxis and treatment), migraine (prevention), thyrotoxicosis (combined therapy) treatment for akathisia caused by antipsychotic drugs.
Restrictions apply Metoprolol Succinate
Diabetes, hypoglycemia, compromised allergenic history, metabolic acidosis, asthma, emphysema, non-allergic bronchitis, hyperthyroidism, psoriasis, pheochromocytoma, liver function and / or kidneys, myasthenia gravis, depression, general anesthesia, the elderly and children’s age.
Pregnancy and lactation Metoprolol Succinate
Perhaps, if the effect of therapy outweighs the potential risk to the fetus. At the time of treatment should stop breastfeeding.
Contraindications Metoprolol Succinate
Hypersensitivity, AV block II and III degree sinoatrial block, acute or chronic (in decompensated) heart failure, sick sinus syndrome, severe sinus bradycardia (heart rate <60 beats / min), cardiogenic shock, hypotension (SBP less than 100 mm Hg), expressed in peripheral blood circulation disorders, pregnancy, breast-feeding.
Side effect Metoprolol Succinate
The nervous system and sensory organs: at least 10% – weakness; 1-9,9% – dizziness and headache; 0,1-0,9% – reduction of concentration, sleepiness / insomnia, nightmares, depression, muscle convulsions, paresthesia, 0,01-0,09% – nervousness, anxiety, weakening of libido, impaired vision, xerophthalmia, conjunctivitis, less than 0.01% – weakness, fatigue, anxiety, confusion, amnesia / short-term memory loss, hallucinations , tinnitus, impaired taste oschuscheniy.So the cardiovascular system and blood (hematopoiesis, hemostasis): 1-9,9% – bradycardia, palpitations, hypotension, cold extremities, and in 0,1-0,9% – heart failure, AV block, edematous syndrome, chest pain at 0,01-0,09% – reduction of myocardial contractility, arrhythmias, less than 0,01% – gangrene (in patients with severe peripheral circulation), myocardial conduction disturbances, syncope , thrombocytopenia, leukopenia, agranulotsitoz.So the digestive tract: 1-9,9% – nausea, abdominal pain, diarrhea or constipation; 0,1-0,9% – vomiting 0,01-0,09% – dry in the mouth, liver function, bloating, indigestion, heartburn, gepatit.So the respiratory system: dyspnea (1-9,9%), bronchospasm (0,1-0,9%), vasomotor rhinitis (0,01 – 0,09%), dispnoe.So the skin: 0,1-0,9% – rash, dystrophic skin changes, 0,01-0,09% – reversible alopecia; less than 0,01% – photosensitivity, exacerbation of psoriasis , itching, erythema, urticaria, gipergidroz.Prochie: reduction in body weight (0,1-0,9%), arthralgia, arthritis, myalgia, muscle weakness, Peyronie’s disease.
Cautions Metoprolol Succinate
During treatment, you can change the test results for laboratory studies (increase of urea, transaminases, phosphatases, LDH).
Drug Interactions Metoprolol Succinate
Sympatholytic potentiate hypotension, nifedipine, nitroglycerin, diuretics, etc. apressin antihypertensive drugs. Antiarrhythmic and anesthetic facilities increase the risk of bradycardia, arrhythmia, hypotension. Digitalis drugs potentiate slowing AV conduction. Simultaneously, intravenous verapamil and diltiazem may cause cardiac arrest. Beta-adrenoceptor agonists, aminophylline, cocaine, estrogens, indomethacin and other NSAIDs impair antihypertensive effect. Enhances and prolongs the action antidepolyarizuyuschih muscle relaxants. Combination with alcohol leads to mutual reinforcement of inhibitory effects on the CNS. Allergens increased the risk of severe systemic allergic reactions or anaphylaxis. Alter the effectiveness of insulin and oral antidiabetic drugs and increases the risk of hypoglycemia. Antacids, hydralazine, oral contraceptives, cimetidine, ranitidine, phenothiazines – raise the level of metoprolol in the blood, Rifampicin – reduces. Lowers the Cl of lidocaine, the effectiveness of beta_2-agonists (to increase the dose of the latter). Incompatible with MAO inhibitors of type A.
Overdose Metoprolol Succinate
Symptoms: hypotension, acute heart failure, bradycardia, heart block, AV block, cardiogenic shock, bronchospasm, respiratory failure, and consciousness / coma, nausea, vomiting, generalized convulsions, cyanosis (manifest in 20 minutes – 2 hours after admission). Treatment : gastric lavage, symptomatic treatment: atropine sulfate (w / fast 0,5-2 mg) – at a bradycardia and a violation of AV conduction, glucagon (1-10 mg IV, then IV infusion 2-2,5 mg / h) and dobutamine – in the case of reduction of myocardial contractility; agonists (noradrenaline, adrenaline, etc.) – with arterial hypotension, diazepam (IV slowly) – to eliminate seizures; inhaled beta-agonists or IV jet introduction of aminophylline for relief bronhospasticheskih reactions pacing.
Precautionary measures Metoprolol Succinate
In patients with chronic heart failure may notice a decrease of myocardial contractility, necessitating the use of cardiac glycosides and / or diuretics, with careful monitoring of hemodynamic status. In the case of increasing bradycardia or AV block should reduce the dose or IV atropine to enter. Diabetes mellitus and hyperthyroidism Metoprolol may mask tachycardia caused by hypoglycemia, or hyperthyroidism. Patients with diabetes require dosage adjustment of antidiabetic drugs, and tight control of blood glucose. When carrying out against the treatment of surgical intervention, the treatment of choice should be an anesthetic with minimal negative inotropic effects. Perhaps a more marked development of hypersensitivity reactions and lack of therapeutic effect of conventional doses of adrenaline on the background of aggravated allergy history. Upon the termination of concurrent treatment clonidine, metoprolol cancel gradually, a few days before the abolition of clonidine, because of the danger of severe hypertensive crisis. In patients with pheochromocytoma application is possible only in conjunction with alpha-adrenolitikami. Receiving metoprolol stop for 2-3 days before delivery (risk of bradycardia, hypotension and hypoglycemia in the newborn), in exceptional cases, newborns after delivery should be within 48-72 hours to be under medical supervision. Should refrain from the use in pediatric patients because the safety and efficacy of its use in children is not defined. If you cancel the treatment to reduce the dosage should be gradually within 10-14 days. Patients with CHD should be in this period to be under close medical supervision. Be wary of during the drivers of vehicles and people, a profession which is associated with increased concentration.
Dosing and Administration Metoprolol Succinate
Inside (during or after eating, not chewing and drinking the liquid, once in the morning or morning and evening (when dvurazovom admission), iv. As an antianginal, antihypertensive and anti-arrhythmic means, with the hyperkinetic syndrome of metoprolol tartrate prescribed oral dose of 100 – 200 mg in 2-3 doses, if necessary, increase the dose at weekly intervals up to 450 mg / day. In the acute phase of myocardial infarction under the monitoring of blood pressure, heart rate and ECG spend three bolus intravenous injection of 5 mg of a two-minute intervals (total dose of 15 mg), with good endurance 15 minutes after the last injection designate the interior of 25-50 mg every 6 h for 48 h, and then – at 50-100 mg 2 times a day (morning and evening) for 3 months – 3 years. When you go to the use of metoprolol succinate dose remains the same. For the prevention of migraine attacks – the inside of 50-100 mg 2-4 times a day. Metoprolol succinate in ischemic heart disease, hypertension, arrhythmia, functional disorders of cardiac activity, accompanied by palpitations designate oral dose of 50-100 mg 1 time per day for prophylaxis of migraine – 200 mg 1 time per day. increase the dose no earlier than 1 week, ie after the onset of maximum effect.
