2010/06/14

Sotalol

International name:
Sotalol (Sotalol)

Group Affiliation:
Beta-blocker

Description of the active substance (INN):
Sotalol

Dosage form:
injection, tablets

Mode of action:
Nonselective beta-blocker, has hypotensive, antianginal, antiarrhythmic action. By blocking beta-adrenergic receptors (beta1-75% and 25% beta 2-adrenergic receptors), decreases catecholamines stimulated formation of cAMP from ATP, resulting in reduced intracellular current of Ca2 +. Has a negative chrono-, Drome, BATM-and inotropic effects (slows heart rate, depresses conduction and excitability, reduces myocardial contractility). TPVR early use of beta-blockers (in the first 24 h) increases (as a result of reciprocal increase in activity of alpha-adrenergic and removal of beta2-adrenergic stimulation of skeletal muscle blood vessels), which after 1-3 days, returning to the original, but with long-term assignment is reduced. Hypotensive effect associated with a decrease in the IOC, sympathetic stimulation of peripheral blood vessels, decreased activity of the renin-angiotensin system (it has a greater significance in patients with initial hypersecretion of renin), restoring the sensitivity of baroreceptors of the aortic arch (not going to enhance their activity in response to BP decrease), and the influence of the central nervous system. antianginal effect is determined by the decrease in myocardial oxygen demand by decreasing heart rate (lengthening of diastole, and improved myocardial perfusion) and contractility, and decreased sensitivity to the effects of myocardial sympathetic innervation. Due to the increase in LV EDV and an increase in tension of muscle fibers of the ventricles can increase oxygen demand, especially in patients with CHF. Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased concentration of cAMP, hypertension), decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing of AV. Inhibition of the pulses observed mainly in the antegrade and to a lesser extent in the retrograde direction through the AV node and on additional routes. Time of onset of shortening of heart rate after ingestion - 1-2 hours, duration of effect - 12 h. In / a dose of 40 mg effect after 5 minutes and lasts for 90-120 minutes. When hypertension initial hypotensive effect after 2-5 days, stable operation is noted in 1-2 months.

Indications:
Ventricular premature beats, spontaneous and induced ventricular tachyarrhythmias, supraventricular tachycardia (including Syndrome WPW), paroxysmal form of atrial.

Contraindications:
Hypersensitivity, acute decompensated HF or CHF, cardiogenic shock, AV block II-III century., SA block, SSS, sinus bradycardia (HR less than 55/min), Prinzmetal angina, cardiomegaly (with no signs of CHF), hypotension (systolic blood pressure less than 90 mm Hg, especially in myocardial infarction), COPD, asthma (heavy flow); occlusive peripheral vascular disease (complicated by gangrene, "intermittent" claudication or pain at rest), diabetes with ketoacidosis, metabolic acidosis, simultaneous reception MAO inhibitors, period laktatsii.C caution. Allergic reactions in the anamnesis, CHF, pheochromocytoma, liver failure, chronic renal failure, Raynaud syndrome, myasthenia gravis, hyperthyroidism, depression (including history), psoriasis, hypokalemia, prolongation of the interval QT, pregnancy, old age, children's age (efficiency and security is not defined).

Adverse effects:
On the part of the nervous system: fatigue, weakness, dizziness, headache, drowsiness or insomnia, nightmares, dreams, depression, anxiety, confusion, or short-term memory loss, hallucinations, asthenia, myasthenia gravis, paresthesia in the extremities (in patients with intermittent "claudication and Raynaud's syndrome), tremor. On the part of the sense organs: very rarely - a violation of visual acuity, reduced secretion of tears, dryness and soreness of eyes, keratoconjunctivitis. On the part of the SSA: sinus bradycardia, palpitations, conduction disturbances infarction, AV block (up to the development of complete transverse blockade and heart failure), arrhythmia, myocardial relaxation, development (widening) of CHF, decrease blood pressure, orthostatic hypotension, a manifestation of Angiospasm (abnormalities of the peripheral circulation, cooling of the lower extremities, Raynaud syndrome), chest pain, and in rare cases - increased angina attacks, ventricular paroxysmal tachycardia of the type "pirouette" (higher risk of admission to the combined drugs prolong the QT interval and hypokalemia). On the part of the digestive system: dryness of the oral mucosa, nausea, vomiting, pain in the epigastrium, flatulence , constipation or diarrhea, liver problems (dark urine, yellow skin or sclera, cholestasis), changes in taste. the respiratory system: nasal congestion, rhinitis, shortness of breath, laryngitis, and bronchospasm. On the part of the endocrine system: hyperglycemia (in patients insulin-dependent diabetes), hypoglycemia (in patients receiving insulin or when strict adherence to the diet), hypothyroid state. Allergic reactions: itching, skin rash, urticaria. On the part of the skin: increased sweating, flushing of the skin, rash, alopecia, cutaneous psoriazopodobnye reactions, exacerbation of symptoms of psoriasis. Laboratory parameters: thrombocytopenia (unusual bleeding and bleeding), agranulocytosis, leukopenia, changes in enzyme activity, bilirubin concentration. Effect on the fetus: Fetal growth retardation, hypoglycemia, bradycardia. Other: back pain, arthralgia, weakening of libido , reducing the potency syndrome "cancel" (increasing angina episodes, increase blood pressure). Overdosage. Symptoms: marked bradycardia, vertigo, AV block, marked reduction of blood pressure, fainting, arrhythmia, ventricular extrasystoles, cyanosis of nails of fingers or hands, cramps, difficulty breathing, bronchospasm. Treatment: gastric lavage, the appointment of activated carbon in violation of AV conduction - in / to introduce 1-2 mg of atropine, the low efficiency of implementing staging temporary pacemaker with ventricular arrhythmia - lidocaine (class Ia drugs do not apply) with a decrease in blood pressure, the patient should be in the Trendelenburg position. If there are no signs of pulmonary edema in / injected plazmozameschayuschie solutions for inefficiency - epinephrine, dopamine, dobutamine, with CH - cardiac glycosides, diuretics, glucagon, with convulsions - in / diazepam, with bronchospasm - inhaled or parenteral beta-adrenostimulyatorov.

Dosage and administration:
Inside, in / in. Inside, tablets should be taken without chewing, drinking plenty of fluids. As antianginal drug - 80 mg 2 times a day. When hypertension the initial dose - 80 mg / day if necessary increase the dose to 80 mg 1 times per week at a dose of 320 mg and above the drug can be taken only once. In the treatment of ventricular tachyarrhythmias - 80 mg 2 times a day. With the lack of effective dose is increased to 80 mg 3 times daily or 160 mg 2 times a day. In severe arrhythmia maximum daily dose - 480 mg (up to 640 mg), divided into 2-3 reception. Typically, the minimum effective dose is 320 mg / day. V / a - the initial dose for adults is 20 mg (2 ml solution for injection). The introduction should be done slowly, over 5 minutes, under the control of heart rate, blood pressure and ECG parameters. After 20 minutes, depending on the patient's condition and the therapeutic effect, slowly (1 mg / min) injected with 20 mg of the drug. The total maximum dose of 1.5 mg / kg and can be given for 5-15 min. Selection of doses for patients with impaired renal function should be carried out taking into account the value of glomerular filtration (CC). When the value of QC 10-30 ml / min (serum creatinine 5.2 mg / dL), the dose should be reduced in 2 times, but when CC <10 ml / min (serum creatinine more than 5 mg / dL) - 4 times.

Cautions:
Monitoring of patients taking sotalol should include monitoring of heart rate and blood pressure (at the beginning of treatment - every day, then 1 every 3-4 months), ECG, blood glucose concentration in diabetic patients (1 every 4-5 months) . In elderly patients are encouraged to monitor renal function (1 every 4-5 months). In connection with the presence of the drug properties of class III antiarrhythmic drugs should monitor the possibility of long QT interval, and if necessary, to conduct individual selection of doses. In stable angina evaluated exercise tolerance, number of angina attacks per day, number of nitroglycerin tablets for relief of attacks of angina. Dose is adequate, if the heart rate at rest decreased to 55-60/min, with a load - no more than 110/min. It is recommended to use the method of paired stress tests. It should teach the patient methods of calculating heart rate and instructed on the need of medical advice in the heart rate less than 50/min. Smokers effectiveness of beta-blockers lower. Patients who use contact lenses must bear in mind that during the treatment may decrease production tear fluid. Patients with pheochromocytoma appointed only after taking alpha-blockers. In / in is possible with the introduction of life-threatening cardiac arrhythmias tahiaritmicheskih. In / in injection should be done slowly under constant control parameters of ECG, respiratory function and blood pressure values. In marked decrease in blood pressure or heart rate, eg, decreased daily dose should be reduced. Patients with renal insufficiency require correction dosing regimen. When thyrotoxicosis sotalol may mask certain clinical signs of thyrotoxicosis (eg tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since symptoms can increase. In appointing the beta-blocker patients receiving hypoglycemic drugs should be careful, because during long breaks in food intake can develop hypoglycemia. And its such symptoms as tachycardia or tremor, are blacked out due to the drug. Patients should be instructed on what the main symptom of hypoglycemia during treatment with beta-blockers is increased sweating. At the same time taking clonidine its reception can be terminated only in a few days after discontinuation of sotalol. Perhaps increased severity of hypersensitivity reactions and the lack of effect of conventional doses of epinephrine against the burdened allergic history. A few days before the general anesthesia with chloroform or ether must stop taking the drug. If the patient received the drug before surgery, he should pick up drugs for general anesthesia, with minimal negative inotropic effects. N.vagus reciprocal activation can be resolved in / atropine (1-2 mg.) Drugs that reduce the reserves of catecholamines (eg reserpine), may strengthen the action of beta-blockers, so patients taking these combinations of drugs should be kept under medical observation for detection of arterial hypotension or bradycardia. Gently used in conjunction with psychoactive drugs, such as MAO inhibitors, with their exchange application is more than 2 weeks. In the case of elderly patients increasing bradycardia (less than 50/min), hypotension (systolic blood pressure below 100 mm Hg), AV blockade, bronchospasm, ventricular arrhythmia, severe violations of liver and kidney function should reduce the dose or stop treatment. It is recommended to stop therapy in the development of depression, caused by taking beta-blockers. You can not abruptly interrupt treatment because of the risk of severe arrhythmias and myocardial infarction. The lifting of the hold gradually reducing the dose within 2 weeks or more (lower the dose by 25% in 3-4 days). Use during pregnancy and lactation may be the case if the benefit to the mother outweigh the risks of adverse effects in the fetus and child. Acceptance of sotalol should be abolished for 48-72 h before the expected date of birth. At the time of treatment to exclude admission of ethanol. Should be lifted before the test in blood and urine catecholamines, normetanephrine and vanillylmandelic acid, antinuclear antibody titers. During the period of treatment must be careful when driving and lesson, etc. potentially dangerous activities that require high concentration and quickness of psychomotor reactions (requires individual selection of doses to persons whose profession requires these qualities).

Interaction:
The allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving sotalol. Iodinated radiopaque drugs for i / v administration increase the risk of anaphylactic reactions. Phenytoin in in / in the Introduction, the drug for inhalation general anesthesia (derivatives of hydrocarbons) increase the severity of cardiodepressive action and the likelihood of BP reduction. Modifies the effectiveness of insulin and oral hypoglycemic drugs mask the symptoms of a developing hypoglycemia (tachycardia, increased blood pressure). Reduces clearance of lidocaine and xanthine (except difillina) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking. Hypotensive effect of weakening the NSAID (delay of Na + and blockade of the synthesis of Pg by the kidneys) SCS and estrogens (delay Na +). Cardiac glycosides, methyldopa, reserpine, and guanfatsin, BCCI (verapamil, diltiazem), amiodarone, and others antiarrhythmic drugs increase the risk of development or worsening of bradycardia, AV blockade, cardiac arrest and heart failure. Nifedipine can cause a significant reduction in blood pressure. Diuretics, clonidine, sympatholytic, hydralazine and other antihypertensive drugs may lead to excessive blood pressure decrease. Lengthens action nondepolarizing muscle relaxants and the anticoagulant effect of coumarins. Tri-and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, Sedatives and hypnotics drugs increase CNS depression. We do not recommend the simultaneous use of MAO inhibitors due to a significant increase in antihypertensive action, a break in treatment between the intake of MAO inhibitors and sotalol should be at least 14 days. Negidrirovannye ergot alkaloids increase the risk of disorders of peripheral circulation. intensifies the effect thyreostatic and uterotoniziruyuschih drugs, decreases the effect of antihistamine drugs. Simultaneous reception of norepinephrine or MAO inhibitors, as well as the sudden cancellation of clonidine on the intake of sotalol may cause a sharp rise in blood pressure. drugs, which suppress the deposit of catecholamines (reserpine), increase the risk of hypotension and / or bradycardia. Joint appointment with antiarrhythmic drugs I (especially hinidinovogo type) or class III may cause marked prolongation of the QT interval and severe ventricular arrhythmias. Simultaneous with the appointment of phenothiazine derivatives increases the concentration of both drugs in plasma. Sulfasalazine and cimetidine increase the concentration of sotalol in plasma (inhibit metabolism) rifampicin shortens T1 / 2.