Ethacizine

Pharmacological properties

Ethacizine is an antiarrhythmic drug of the IC class. It has a pronounced and prolonged antiarrhythmic effect. inhibits the rate of rise of the front of the action potential, does not change the resting potential. mainly affects the sodium channels (both on the outer and inner surfaces of the cell membrane), reduces the amplitude and slows down the inactivation and reactivation of the fast sodium stream. blocks the entry of calcium ions through the slow channels of the membrane. lengthens the duration of refractory periods of the atria and av node. slows down the rate of increase of the action potential in the atrial and ventricular fibers of Purkinje and additional ways of conducting excitation along the av node and the bundle of Kent. suppresses sinoatrial conduction, especially in case of sinus node weakness syndrome, expands the qrs complex to ECG (by about 25%), since it slows down the ventricular conduction (in the His – Purkinje system). has a negative inotropic effect, shows local anesthetic and antispasmodic activity. Ethacizine does not change heart rate with short-term use and reduces with prolonged use.

Pharmacokinetics When ingested, Ethacizine is rapidly absorbed in the digestive tract and is determined in the blood after 30-60 minutes. C_max Etazizine in blood plasma is recorded after 2.5-3 hours. Bioavailability - 40%. 90% binds to plasma proteins. T_½ is an average of 2.5 hours. All of the listed pharmacokinetic parameters are subject to significant individual fluctuations. Ethacizine is extensively metabolized during the initial passage through the liver. Some of the resulting metabolites have antiarrhythmic activity. Excreted in the urine in the form of metabolites.

Indications

Ventricular and supraventricular extrasystoles, paroxysms of atrial fibrillation and flutter, ventricular and supraventricular tachycardia, including in the case of the syndrome of premature ventricular arousal.

Application

Inside, regardless of food intake, starting with 50 mg 2-3 times a day. in case of insufficient clinical effect, the dose is increased (under the mandatory control of ecg) to 50 mg 4 times a day (200 mg) or 100 mg 3 times a day (300 mg).

When a stable antiarrhythmic effect is achieved, maintenance therapy is carried out in individually selected minimum effective doses. To achieve a stable antiarrhythmic effect, some patients require combined treatment with Ethacizine and β-adrenergic blockers.

Contraindications

• Hypersensitivity to the drug or excipients; severe conduction disturbances (including sinoatrial blockade, degree II – III av blockade in the absence of an artificial pacemaker), intraventricular conduction disturbance; severe left ventricular myocardial hypertrophy; the presence of post-infarction cardiosclerosis; cardiogenic shock; acute coronary syndrome; acute myocardial infarction and the period of 3 months after acute myocardial infarction; pronounced expansion of the heart cavity; a decrease in the ejection fraction of the left ventricle (echocardiography), a stop of the sinus node; severe arterial hypotension; chronic heart failure ііі and іv class; severe impaired liver and / or kidney function; electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia); concomitant use of MAO inhibitors; simultaneous use of antiarrhythmic drugs ic (morazizin (ethmosin), propafenone, allapinin) and ia class (quinidine, procainamide, disopyramide, aymalin); cardiac arrhythmias in combination with blockade conduction of a bundle of His - purkinje fibers through the system.

Side effects

They depend on the size of the dose, and in order to avoid the occurrence of side effects, maximum doses of the drug should not be prescribed.

In individuals with individual intolerance, allergic reactions are possible.

On the part of the cardiovascular system: stoppage of the sinus node, AV blockade, impaired intraventricular conduction, decreased myocardial contractility, decreased coronary blood flow, arrhythmia. Arrhythmogenic effect, the likelihood of which is highest after myocardial infarction and with other types of cardiac pathology, which leads to a decrease in myocardial contractile function and the development of heart failure, proarrhythmogenic effect with a risk of sudden death.

ECG changes: prolongation of the P – Q interval, expansion of the P wave and the QRS complex.

From the side of the central nervous system: dizziness, headache, staggering when walking or turning the head, slight drowsiness; in some cases diplopia, paresis of accommodation were noted.

From the digestive tract: nausea, pain in the epigastric region.

Perhaps a decrease in side effects or their disappearance after application of the drug for 3-4 days. With prolonged treatment with Ethacizine, adverse reactions do not increase, and with the cessation of taking the drug, they quickly disappear.

special instructions

With myocardial infarction, the drug can be prescribed subject to strict medical supervision

It is advisable to begin treatment 3 months after the development of myocardial infarction.

With special caution, they are prescribed for sinus node weakness syndrome, bradycardia, degree I AV block, IHD, severe peripheral circulation disorders, chronic functional heart failure of the first functional class, angle-closure form of glaucoma, benign prostatic hypertrophy, cardiomegaly (the risk of arrhythmogenic effect increases), patients with pacemakers (increased risk of arrhythmias), liver / renal failure.

Like other antiarrhythmic drugs, Ethacizine can act arrhythmogenously. Therefore, when prescribing Ethacizine, it is necessary:

1. Strictly consider contraindications to the use of the drug.

2. Pre-identify and eliminate hypokalemia.

3. To prevent the use of Ethacizine simultaneously with antiarrhythmic drugs of IA and IC class.

4. It is advisable to start a course of treatment in a hospital (especially during the first 3-5 days of using the drug and taking into account the dynamics of the ECG after a trial and repeated doses of Ethacizine or ECG monitoring data).

5. Immediately discontinue course treatment in case of increased ectopic ventricular complexes, manifestations of blockade or bradycardia. Treatment with Ethacizine should also be stopped immediately when the ventricular complexes expand by more than 25%, their amplitude decreases, when the P wave expands on an ECG of 0.12 s or Q – T intervals of 500 ms. The drug should be used with caution if the Q – T interval is 400 ms.

Risk factors for the arrhythmogenic effect of Ethacizine are considered: organic heart lesions (especially myocardial infarction), a decrease in the ejection fraction of the left ventricle.

The arrhythmogenic effect of the drug is not directly dependent on the dose. To reduce it, the simultaneous use of Ethacizine and β-adrenergic blockers in low doses is recommended.

During treatment, it is necessary to regularly monitor the patients condition and the function of the cardiovascular system (ECG, blood pressure, echocardiography).

The drug should not be used in patients with rare congenital fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase deficiency.

The composition of the shell of the tablets includes the dye yellow sunset (E110), which can cause allergic reactions.

Patients with sinus syndrome, especially when using the drug for the first time, need ECG monitoring 2–3 days after starting the drug.

Patients with impaired liver function during long-term treatment should be careful, since a hepatotoxic effect is possible (with severe impairment of liver function, use is contraindicated).

When treating with the drug Ethacizine, you can not drink alcohol.

Use during pregnancy or lactation. During pregnancy or lactation, the use of the drug is contraindicated.

Children. The use of the drug in children is contraindicated.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. During treatment with the drug should refrain from driving vehicles and working with potentially dangerous mechanisms.

Interactions

The simultaneous use of antiarrhythmic drugs of class ic - morazizin, enkainide, flecainide, propafenone - is contraindicated. The combination of β-adrenergic blockers with antiarrhythmic drugs of the IC class (ethacisin) enhances the antiarrhythmic effect, especially with respect to arrhythmias that are provoked by physical exertion or stress. this combination allows the use of an antiarrhythmic drug in low doses, which reduces the incidence of its side effects. this combination is indicated for the treatment and prevention of paroxysmal tachycardia, including ventricular.

Ethacizine can be combined with amiodarone (class III). In such cases, the dose of both drugs should be reduced. For the prevention of ventricular fibrillation or ventricular paroxysmal tachycardia, the combination of mexiletine + ethacisin + propranolol can be used.

With the simultaneous use of Ethacizine and digoxin, the antiarrhythmic effect of the drugs increases and the contractility of the myocardium improves. With their combined use, nausea and anorexia are possible, which is associated with an increase in the concentration of digoxin in blood plasma. In this case, it is required to reduce the dose of digoxin.

The use of glutamic acid in combination with Ethacizine eliminates the cardiodepressive effect of the latter in patients with initial signs of circulatory disorders.

Ethacizine should not be prescribed concurrently with MAO inhibitors.

When treating Ethacizineom should take into account its interaction with ethanol-containing drugs.

Overdose

Ethacizine has a small therapeutic breadth, so severe intoxication can easily occur (especially with the simultaneous use of other antiarrhythmic drugs).

Symptoms: prolongation of the P – R interval and expansion of the QRS complex, increase in the amplitude of T waves, bradycardia, sinoatrial and AV block, asystole, paroxysms of polymorphic and monomorphic ventricular tachycardia, decreased myocardial contractility, persistent decrease in blood pressure, dizziness, blurred vision, headache, digestive tract disorders.

Treatment: symptomatic; for the treatment of ventricular tachycardia, do not use antiarrhythmic drugs of IA and IC classes; sodium bicarbonate is able to eliminate QRS complex expansion, bradycardia and arterial hypotension.

Storage conditions

At a temperature not exceeding 25 ° c. Keep out of the reach of children.