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Pharmacy of Betapace
A non-selective beta-blocker, has a hypotensive, antianginal, antiarrhythmic effect. By blocking beta-adrenergic receptors (75% beta1- and 25% beta2-adrenergic receptors), it reduces the formation of cAMP from ATP stimulated by catecholamines, as a result of which intracellular Ca2 + flow decreases. It has a negative chrono-, dromo-, batmo- and inotropic effect (reduces heart rate, inhibits conductivity and excitability, reduces myocardial contractility). OPSS at the beginning of the use of a beta-blocker (in the first 24 hours) increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors of the vessels of skeletal muscle), which returns to the initial one after 1-3 days, and decreases with prolonged administration.
The antihypertensive effect is associated with a decrease in IOC, sympathetic stimulation of peripheral vessels, a decrease in the RAAS activity (it is of greater importance in patients with initial renin hypersecretion), restoration of the sensitivity of the aortic arch baroreceptors (there is no increase in their activity in response to a decrease in blood pressure) and an effect on the central nervous system.
The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (lengthening of diastole and an improvement in myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity to the effects of sympathetic innervation. Due to an increase in EDV in the LV and an increase in stretching of the muscle fibers of the ventricles, it can increase the demand for oxygen, especially in patients with CHF.
The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased concentration of cAMP, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown in AV conduction.
The suppression of impulse conduction is observed mainly in the antegrade and to a lesser extent in the retrograde directions through the AV node and along additional pathways. The time of the onset of a decrease in heart rate after oral administration is 1-2 hours, the duration of the effect is 12 hours. When administered intravenously in a dose of 40 mg, the effect occurs after 5 minutes and lasts 90-120 minutes. In arterial hypertension, the initial hypotensive effect occurs after 2-5 days, a stable effect is observed after 1-2 months.
Absorption - more than 80%, bioavailability - 90-100%. The simultaneous intake of food (especially milk and dairy products) reduces the absorption of sotalol. Low fat solubility. Practically does not bind to plasma proteins. TCmax when taken orally - 2-3 hours. Permeability through the BBB and the placental barrier is low. Metabolized in the liver. T1 / 2 - 7-18 hours, with chronic renal failure it increases. It is excreted by the kidneys - 75% unchanged. It is excreted during hemodialysis.
Indications for use Betapace
- Ventricular premature beats,
- spontaneous and induced ventricular tachyarrhythmias,
- supraventricular tachycardia (including WPW syndrome),
- paroxysmal atrial fibrillation.
Contraindications for use Betapaca
Hypersensitivity, acute HF or decompensated CHF, cardiogenic shock, grade II-III AV block, SA block, SSS, sinus bradycardia (heart rate less than 55 / min), Prinzmetal angina, cardiomegaly (without signs of heart failure), arterial hypotension (systolic less than 90 mm Hg, especially with myocardial infarction); COPD, bronchial asthma (severe course); peripheral vascular occlusive disease (complicated by gangrene, "intermittent" claudication or pain at rest), diabetes mellitus with ketoacidosis, metabolic acidosis, concomitant use of MAO inhibitors, lactation period.
Carefully. History of allergic reactions, CHF, pheochromocytoma, liver failure, chronic renal failure, Raynaud's syndrome, myasthenia gravis, thyrotoxicosis, depression (including a history), psoriasis, hypokalemia, prolongation of the QT interval, pregnancy, advanced age, childhood (effectiveness and security not defined).
Allergens used for immunotherapy or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving sotalol. Iodine-containing X-ray contrast drugs for intravenous administration increase the risk of developing anaphylactic reactions. Phenytoin when administered intravenously, drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressant effect and the likelihood of lowering blood pressure.
Changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).
Reduces the clearance of lidocaine and xanthines (except diphylline) and increases their plasma concentration, especially in patients with an initially increased clearance of theophylline under the influence of smoking.
The antihypertensive effect is weakened by NSAIDs (Na + delay and blockade of Pg synthesis by the kidneys), corticosteroids and estrogens (Na + delay).
Cardiac glycosides, methyldopa, reserpine and guanfacine, BMCC (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV blockade, cardiac arrest and heart failure. Nifedipine can lead to a significant decrease in blood pressure. Diuretics, clonidine, sympatholytics, hydralazine, and other antihypertensive drugs can lead to an excessive decrease in blood pressure.
Prolongs the action of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.
Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedative and hypnotic drugs increase central nervous system depression.
Simultaneous use with MAO inhibitors is not recommended due to a significant increase in the hypotensive effect, the break in treatment between taking MAO inhibitors and sotalol should be at least 14 days.
Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.
Strengthens the effect of thyrostatic and uterotonizing drugs; reduces the effect of antihistamine drugs.
Concomitant use of norepinephrine or MAO inhibitors, as well as sudden withdrawal of clonidine while taking sotalol, can cause a sharp rise in blood pressure.
Drugs that inhibit the deposition of catecholamines (reserpine) increase the risk of hypotension and / or bradycardia. Co-administration with antiarrhythmic drugs I (especially quinidine type) or class III can cause a pronounced prolongation of the QT interval and severe ventricular arrhythmias.
Concomitant administration with phenothiazine derivatives increases plasma concentrations of both drugs.
Sulfasalazine and cimetidine increase the concentration of sotalol in plasma (inhibit metabolism), rifampicin shortens T1 / 2.
Control over patients taking sotalol should include monitoring heart rate and blood pressure (at the beginning of treatment - daily, then once every 3-4 months), ECG, blood glucose concentration in patients with diabetes mellitus (1 time in 4-5 months). In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months). Due to the presence of the properties of class III antiarrhythmics in the drug, the possibility of prolonging the QT interval should be monitored and, if necessary, individual dose selection should be carried out.
In case of stable exertional angina, exercise tolerance, the number of angina attacks per day, the number of nitroglycerin tablets to relieve an angina attack are assessed. The dose of the drug is adequate if the heart rate at rest decreases to 55-60 / min, with a load - no more than 110 / min. It is recommended to use the paired loading test method.
The patient should be trained in the method of calculating the heart rate and instructed on the need for medical advice if the heart rate is less than 50 / min. In smokers, the effectiveness of beta-blockers is lower. Patients using contact lenses should take into account that during treatment, it is possible to reduce the production of tear fluid. Patients with pheochromocytoma are prescribed only after taking an alpha-blocker.
Intravenous administration is possible in the presence of life-threatening tachyarrhythmia heart rhythm disturbances.
IV injection should be carried out slowly under constant control of ECG parameters, respiratory function and blood pressure. With a pronounced decrease in blood pressure or a decrease in heart rate, the daily dose should be reduced. Patients with renal insufficiency require dosage adjustment. With thyrotoxicosis, sotalol can mask certain clinical signs of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it can aggravate the symptoms.
When prescribing beta-blockers to patients receiving hypoglycemic drugs, care should be taken, since hypoglycemia may develop during long breaks in food intake. Moreover, her 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-blockers is increased sweating. With the simultaneous administration of clonidine, its reception can be stopped only a few days after the withdrawal of sotalol. It is possible that the severity of the hypersensitivity reaction and the lack of effect from the usual doses of epinephrine against the background of a burdened allergic history are possible.
A few days before the general anesthesia with chloroform or ether, you must stop taking the drug. If the patient has taken the drug before the operation, he should choose drugs for general anesthesia with minimal negative inotropic effect. Reciprocal activation of n.vagus can be eliminated by intravenous administration of atropine (1-2 mg).
Drugs that reduce the supply of catecholamines (for example, reserpine) can enhance the action of beta-blockers, therefore, patients taking such drug combinations should be under constant medical supervision for detecting arterial hypotension or bradycardia. Caution should be used in conjunction with psychoactive drugs, such as MAO inhibitors, with their course use for more than 2 weeks. If elderly patients develop bradycardia (less than 50 / min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV blockade, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction, it is necessary to reduce the dose or stop treatment. ... It is recommended to discontinue therapy with the development of depression caused by the intake of beta-blockers. It is impossible to abruptly interrupt treatment due to the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 days). Use during pregnancy and lactation is possible if the benefits to the mother outweigh the risk of side effects in the fetus and child. Sotalol should be canceled 48-72 hours before the expected due date.
For the duration of treatment, exclude the intake of ethanol.
Should be canceled before testing in the blood and urine of catecholamines, normetanephrine and vanilla-mandelic acid; antinuclear antibody titers.
During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions (individual selection of doses is required for persons whose profession requires these qualities).
From the side of the central nervous system and peripheral nervous system: increased fatigue, weakness, dizziness, headache, drowsiness or insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia gravis, paresthesia in the extremities (in patients with intermittent claudication syndrome and Raynaud's syndrome), tremor.
From the side of the cardiovascular system: sinus bradycardia, palpitations, myocardial conduction disturbance, AV block (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, weakening of myocardial contractility, development (worsening) of chronic heart failure, lowering blood pressure, orthostatic hypotension , manifestation of angiospasm (increased impairment of peripheral circulation, cooling of the lower extremities, Raynaud's syndrome), chest pain; in rare cases - increased attacks of angina pectoris, ventricular paroxysmal tachycardia of the "pirouette" type (the risk of developing is higher with the combined use of drugs that prolong the QT interval, or hypokalemia).
From the senses: in some cases - impaired visual acuity, decreased secretion of tear fluid, dry and sore eyes, keratoconjunctivitis.
From the digestive system: dryness of the oral mucosa, nausea, vomiting, pain in the epigastric region, flatulence, constipation or diarrhea, liver dysfunction (dark urine, yellowness of the sclera or skin, cholestasis), taste changes, changes in the activity of liver enzymes, concentration bilirubin.
From the respiratory system: nasal congestion, rhinitis, difficulty breathing, laryngo- and bronchospasm.
From the endocrine system: hyperglycemia (in patients with non-insulin dependent diabetes mellitus), hypoglycemia (in patients receiving insulin or with strict adherence to a diet), hypothyroid state.
Allergic reactions: itching, skin rash, urticaria.
Dermatological reactions: increased sweating, skin flushing, exanthema, alopecia, psoriasis-like skin reactions, exacerbation of psoriasis symptoms.
From the hematopoietic system: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia.
Others: back pain, arthralgia, weakening of libido, decreased potency, withdrawal syndrome (increased angina attacks, increased blood pressure).
Contraindications for use Betapace
Acute heart failure or decompensated chronic heart failure, cardiogenic shock, AV block II or III degree, sinoatrial block, SSSU, sinus bradycardia (heart rate less than 55 beats / min), Prinzmetal angina, cardiomegaly (without signs of heart failure) , arterial hypotension (systolic blood pressure less than 90 mm Hg, especially with myocardial infarction); COPD, bronchial asthma (severe course); peripheral vascular occlusive disease (complicated by gangrene, intermittent claudication or pain at rest), diabetes mellitus with ketoacidosis, metabolic acidosis, concomitant use of MAO inhibitors, lactation period, hypersensitivity to sotalol and sulfonamides.