Bretilia tosylate (Bretylii tosilas)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Antiarrhythmics

Included in the formulation
АТХ:

C.01.B.D.02   Bretilia tosylate

Pharmacodynamics:

Antiarrhythmic remedy class III.It exerts a biphasic action: direct output after administration stimulates norepinephrine from presynaptic nerve endings, which leads to rapid (but slight) increase in blood pressure and heart rate in some cases to the arrhythmogenic effect. In the second phase, there is a persistent decrease in the output of the mediator in the synaptic cleft in response to neuron stimulation, leading to a chemical sympathectomy of the heart and peripheral adrenergic blockade, which is characterized by a decrease total peripheral resistance of blood vessels, blood pressure (orthostatic hypotension) and heart rate. Hemodynamic effect does not correlate with its antiarrhythmic effect. Antiarrhythmic effect is caused by an increase in the threshold of occurrence of ventricular fibrillation activity, an increase in the duration of the action potential and an effective refractory period. Bretilia tosylate contributes to the normalization of the amplitude of the action potential (phase 0) and the membrane resting potential (phase IV) in case of their pathological changes, slightly affecting the normal cardiomyocyte.The increase in the duration of the action potential and the effective refractory period occurs without changing their ratio. Eliminates aberrant and re-entry impulses, and also reduces differences in the level of excitability of the myocardium.

With myocardial infarction reduces the severity of differences in the duration of the action potential between intact and ischemic myocardium; increases the rate of spontaneous depolarization of the sinus node (in some cases, after administration, there may be a slight and unstable increase in heart rate) and the rate of intraventricular conduction. Has some positive inotropic effect.

Antiarrhythmic effect is more correlated with tissue concentration than with serum, and therefore its concentration in plasma can not be a reliable criterion for the effectiveness of treatment of urgent states. After intramuscular injection, the maximum severity of hemodynamic (by changes in arterial pressure) is observed in 20-60 minutes, the greatest antiarrhythmic activity: elimination of ventricular fibrillation after 20-60 minutes, elimination of ventricular tachycardia after 20-120 minutes.After intravenous administration, suppression of ventricular fibrillation develops after 5-10 minutes, suppression of ventricular arrhythmias (including ventricular tachycardia) in 20-120 minutes; duration of action - 6-24 hours.

Pharmacokinetics:

It is well absorbed after intramuscular injection. Time to reach Cmax is 1 hour. After a single intravenous injection the elimination half-life is 10 hours. It is mainly excreted by the kidneys in the unchanged form - 90% in the first 24 hours, another 10% is excreted within the next 3 days. In chronic renal failure, the half-life is prolonged to 16-31.5 hours. It is excreted in hemodialysis.

Indications:

Ventricular fibrillation (including refractory to electropulse therapy and lidocaine, which arose against a background of deep hypothermia). Heart failure due to ventricular fibrillation (early stages of resuscitation), ventricular paroxysmal tachycardia. Ventricular arrhythmias caused by surgical intervention on the heart, ventricular arrhythmia such as "pirouette" (ventricular flutter associated with prolongation of the QT interval on the ECG, after treatment with quinidine).

ICD-10

IX.I30-I52.I47.2   Ventricular tachycardia

IX.I30-I52.I49.0   Fibrillation and flutter of the ventricles

Contraindications:

Pheochromocytoma, acute disturbance of cerebral circulation, arterial hypotension, collapse, severe renal failure, aortic aortic stenosis, severe atherosclerosis, severe forms of pulmonary hypertension, pregnancy, lactation, cardiac glycosides intoxication, hypersensitivity to brethil tosylate.

Carefully:

It should be used with caution brethil tosylate in patients with impaired renal function (doses in such cases should be reduced), in elderly patients, in children and adolescents under the age of 18 years.

Pregnancy and lactation:

Bretilia tosylate is contraindicated in pregnancy and lactation (breastfeeding).

Dosing and Administration:

With intravenous jet injection, the initial dose is 5 mg / kg. It can also be administered intravenously drip at a rate of 1-2 mg / min or intramuscularly at a dose of 5-10 mg / kg. The frequency of administration and duration of use depend on the clinical situation and the therapy regimen.

Side effects:

From the cardiovascular system: arterial hypotension, an initial transient increase in blood pressure, an increase in the heart rate with a threat of cardiac arrhythmias (due to the release of norepinephrine).

From the digestive system: nausea, vomiting (most likely with rapid intravenous infusion).

Local reactions: rarely - tissue necrosis at the site of intramuscular injection.

Overdose:

Treatment is symptomatic.

Interaction:

With simultaneous use with cardiac glycosides, the risk of ventricular tachyarrhythmia increases due to the initial release of norepinephrine from the presynaptic nerve endings.

When used simultaneously with sympathomimetics of direct action (including norepinephrine), the pressor effects of norepinephrine are enhanced, since brethil tosylate violates its release, reverse capture and transformation processes under the influence of monoamine oxidase.

With the simultaneous use of indirect effects with sympathomimetics (including ephedrine), the effectiveness of brethil tosylate decreases, there is a risk of developing arterial hypertension.

With the simultaneous use of tricyclic antidepressants (including amitriptyline, imipramine, desipramine, nortriptyline), the effectiveness of brethil tosylate decreases as a result of its competition with tricyclic antidepressants for the mechanism of neural norepinephrine seizure.

With simultaneous application with cisapride, the QT interval significantly increases due to the additive effect on its duration, the risk of ventricular arrhythmia (including pirouette).

Special instructions:

It should be used with caution brethil tosylate in patients with impaired renal function (doses in such cases should be reduced), in elderly patients, in children and adolescents under the age of 18 years.

Instructions
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