Heart rhythm and conduction disorder: medications

Treatment is not always required; the approach depends on the manifestations and severity of the arrhythmia. Asymptomatic arrhythmias that are not associated with high risk do not require treatment, even if they occur with worsening examination data. In case of clinical manifestations, therapy may be needed to improve the patient's quality of life. Potentially life-threatening arrhythmias are an indication for treatment.

Therapy depends on the situation. If necessary, antiarrhythmic treatment is prescribed, including antiarrhythmic drugs, cardioversion-defibrillation, pacemaker implantation, or a combination of these.

Medicines used to treat arrhythmias. Most antiarrhythmic drugs are divided into four main classes (Williams classification) depending on their effect on electrophysiological processes in the cell. Digoxin and adenosine phosphate are not included in the Williams classification. Digoxin shortens the refractory period of the atria and ventricles and is a vagotonic, as a result of which it prolongs conduction through the AV node and its refractory period. Adenosine phosphate slows or blocks conduction through the AV node and can terminate tachyarrhythmias that pass through this node during impulse circulation.

1st class

Sodium channel blockers (membrane-stabilizing drugs) block fast sodium channels, slowing conduction through tissues with fast ion channels (functioning atrial and ventricular myocytes, the His-Purkinje system). On the electrocardiogram, their effect can be expressed by widening of the P wave, the PR complex, prolongation of the interval, or a combination of these signs.

Class I is subdivided depending on the rate of development of the effects of sodium channels, class lb is characterized by fast kinetics, lc - slow, la - medium speed. The kinetics of sodium channel blockade determines the heart rate at which the electrophysiological effects of the subgroup of drugs appear. Since class lb is characterized by fast kinetics, their electrophysiological effects appear only at a high heart rate. For this reason, an electrocardiogram recorded at a normal rhythm with a normal heart rate does not reflect a slowdown in conduction through the "fast-channel" tissue of the heart. Class lb drugs are not potent antiarrhythmic agents and have a minimal effect on atrial tissue. Since class 1c is characterized by slow kinetics, its electrophysiological effects appear at any heart rate. Thus, an electrocardiogram recorded at a normal rhythm and normal heart rate usually demonstrates a slowdown in conduction through the "fast-channel" tissue. Class 1c drugs are more potent antiarrhythmic agents. Since class 1a has intermediate kinetics, their effect on impulse conduction through "fast-channel" tissue may be visible, but may also be absent on an electrocardiogram obtained at a normal rhythm with a normal heart rate. Class 1a drugs also block repolarizing potassium channels, increasing the refractory period of "fast-channel" tissue. According to ECG data, this effect is expressed by prolongation of the QT interval even at a normal heart rate. Class 1b and 1c drugs do not directly block potassium channels.

Antiarrhythmic drugs (Williams classification)

Preparation

Doses

Target concentration

Side effects

Comments

1a class. Application: PES and PVCS, suppression of SVT and VT, suppression of AF, atrial flutter and VF

Disopyranide	Intravenous administration: initially 1.5 mg/kg over 5 minutes, then continue infusion at 0.4 mg/kg per hour. Oral administration (immediate-release preparation): 100 or 150 mg every 6 hours. Oral administration (slow-release form): 200-300 mg every 12 hours.	2-7.5 mcg/ml	Anticholinergic effects (urinary retention, glaucoma, dry mouth, double vision, gastrointestinal disorders), hypoglycemia, torsades de pointes, VT	The drug should be used with caution in patients with impaired LV function. The dose is reduced in renal failure. Side effects may lead to drug discontinuation. If the QRS complex widens (>50% with a baseline of <120 ms or >25% with a baseline of >120 ms), the number of infusions or the dose should be reduced (or the drug discontinued). Intravenous form is not available in the US
Procainamide	Intravenous administration: 10-15 mg/kg bolus at a rate of 25-50 mg/min, then continuous infusion of 1-4 mg/min. Oral administration: 250-625 mg (sometimes up to 1 g) every 3-4 hours	4-8 g/ml	Arterial hypotension (with intravenous administration), serological changes (mainly AHA) in almost 100% of those taking for 12 months, drug-induced lupus (arthralgia, fever, pleurisy) in 15-20% of patients; agranulocytosis in less than 1%, pirouette-type tachycardia, ventricular tachycardia	Slow-release dosage forms allow you to avoid frequent dosing. If the complex widens (more than 50% with a baseline <120 ms or >25% with a baseline >120 ms), the number of infusions or the dose should be reduced (or the drug should be discontinued)
Quinidine	Oral administration: 200-400 mg every 4-6 hours	2-6 mcg/ml	Diarrhea, colic and flatulence, fever, thrombocytopenia, liver dysfunction, pirouette-type tachycardia, VT, the total proportion of side effects is 30%.	If the complex widens (more than 50% with a baseline <120 ms or >25% with a baseline >120 ms), the number of infusions or the dose should be reduced (or the drug should be discontinued)

L b class. Application: suppression of ventricular rhythm disturbances (VES, VT, VF)

Lidocaine	Intravenous administration: 100 mg over 2 minutes followed by infusion of 4 mg/min (2 mg/min for patients over 65 years of age)	2-5 mcg/l	Tremor, convulsions; with very rapid administration drowsiness, delirium, paresthesia	To reduce the risk of toxicity, the dose or number of administrations should be reduced to 2 mg/min every 24 hours. Extensive first-pass metabolism through the liver
Mexiletine	Oral administration (immediate-release formulation): 100-250 mg every 8 hours. Oral administration (extended-release formulation): 360 mg every 12 hours. Intravenous administration: 2 mg/kg at a rate of 25 mg/min, then continue administration of 250 mg in 1 hour, 250 mg in the next 2 hours and continuously at a rate of 0.5 mg/min	0.5-2 mcg/ml	Nausea, vomiting, tremors, convulsions	Extended-release oral and intravenous formulations are not available in the United States.

1c class. Application: suppression of PES and PVCs, SVT and VT, AF or atrial flutter, and VF

Flecainide

Oral administration: 100 mg every 8-12 hours. Intravenous administration: 1-2 mg/kg over 10 min.

0.2-1 m kg/ml

Sometimes double vision and paresthesia; increases mortality in patients who have had an MI with asymptomatic or minimally symptomatic VES

The intravenous form is not available in the US. If the QRS complex widens (>50% at baseline <120 ms or >25% at baseline >120 ms) or the QTk interval increases >550 ms, the infusion rate or dose should be reduced (or the drug discontinued)

Class II (β-blockers). Use: SVT (PES, ST, SVT, AF, atrial flutter) and ventricular arrhythmias (often as adjuvant drugs)

Propranolol

Oral administration 10-30 mg 3-4 times a day. Intravenous administration 1-3 mg (can be repeated after 5 minutes if necessary)

Class III (membrane-stabilizing drugs). Application: any tachyarrhythmia, except for VT of the "pirouette" type

Amiodarone	Oral 600-1200 mg/day for 7-10 days, then 400 mg/day for 3 weeks, then maintenance dose (ideally 200 mg/day). Intravenous 150-450 mg over 1-6 hours (depending on urgency), then maintenance dose 0.5-2.0 mg/min.	1-2.5 mcg/ml	Pulmonary fibrosis (in approximately 5% of patients treated for more than 5 years), which can be fatal; prolongation of QTk; sometimes torsades de pointes, bradycardia	The drug has a non-competitive b-adrenoblocking effect, blocks calcium and sodium channels for a long time. Due to the prolongation of refractoriness, amiodarone can lead to adequate repolarization of the entire heart. The intravenous form can be used to restore rhythm
Azimilide	Oral administration 100-200 mg once a day	200-1000 ng/ml	VT of the “pirouette” type
Dofetilide	Intravenous administration 2.5-4 mcg/ml. Oral administration 500 mcg 2 times a day if CC> 60 ml/min; 250 mcg 2 times a day if CC 40-60 ml/min; 125 mcg 2 times a day if CC 20-40 ml/min	Not defined	VT of the “pirouette” type	The drug is contraindicated if the OTc is prolonged more than 440 ms or if the CC is < 20 ml/min.
Ibutilide	Intravenous administration to patients weighing 60 kg or more mg by intravenous infusion, to patients weighing less than 60 kg 0.01 mg/kg over 10 minutes, then repeat after 10 minutes if the first administration is ineffective	Not defined	VT of the “pirouette” type (in 2% of cases)	The drug is used to reduce the frequency of AF (the effect is manifested with a decrease in heart rate by 40%) and atrial flutter (65%, respectively)
Sotalol	Oral administration 80-160 mg every 12 hours. Intravenous administration 10 mg over 1-2 minutes.	0.5-4 mcg/ml	Similar to class II; may depress LV function and cause torsades de pointes	The drug is a b-adrenoblocker; the racemic (DL) form has class II properties, with predominant class III activity in the D-isomer. Only the racemic form of sotalol is used in clinical practice. The drug should not be prescribed in renal failure.
Bretyllium tosylate	Intravenous administration: Initial dose 5 mg/kg, then 1-2 mg/min as a continuous infusion. For MI: Initially 5-10 mg/kg, may be repeated up to a total dose of 30 mg/kg. Maintenance dose for MI 5 mg/kg every 6-8 hours	0.8-2.4 mcg/ml	Arterial hypotension	The drug has class II properties. The effect can develop in 10-20 minutes. Bretilium tosylate is used to treat potentially lethal refractory ventricular tachyarrhythmias (resistant VT, recurrent VF), in which it is usually effective within 30 minutes after administration.

Class IV (calcium channel blockers). Use: termination of SVT, slowing the frequency of AF and atrial flutter

Verapamil	Oral administration 40-120 mg 3 times or, when using the prolonged form, 180 mg 1 time per day up to 240 mg 2 times per day. Intravenous administration 5-15 mg over 10 minutes. Oral administration for prophylactic purposes 40-120 mg 3 times per day	Not defined	May provoke the development of VF in patients with VT; has a negative inotropic effect	The intravenous form is used to stop tachycardia with a narrow ventricular complex, including tachycardia from the AV node (the frequency of effectiveness is almost 100% when using 5-10 mg intravenously for 10 minutes)
Diltiazem	Oral administration (slow-release preparation) 120-360 mg 1 time per day. Intravenous administration of 5-5 mg/hour for up to 24 hours	0.1-0.4 mcg/ml	May provoke VF in patients with VT; has a negative inotropic effect	The intra-articular form is most often used to reduce the ventricular rate in AF or atrial flutter.

Other antiarrhythmic drugs

Adenosine phosphate	6 mg rapid intravenous bolus, repeat 2 times up to 12 mg if needed. Dissolve bolus in 20 ml isotonic sodium chloride solution	Not defined	Transient dyspnea, chest discomfort, facial flushing (in 30-60% of cases), bronchospasm	The drug slows or blocks conduction at the level of the AV node. The duration of action is extremely short. Contraindications include bronchial asthma and high-grade AV block. Dipyridamole enhances the effect of the drug.
Digoxin	Intravenous administration: loading dose 0.5 mg. Oral administration (maintenance dose) 0.125-0.25 mg/day	0.8-1.6 mcg/ml	Anorexia, nausea, vomiting and often serious arrhythmias (ventricular extrasystole, ventricular tachycardia; atrial extrasystole, sinus tachycardia; 2nd and 3rd degree AV block and combinations of these types of arrhythmias)	Contraindications include antegrade conduction or the presence of functioning accessory pathways (manifestation of WPW syndrome); excessive effect on the ventricular myocardium may develop (digoxin reduces the refractory period in the cells of accessory conduction pathways)

The main indication for the use of classes 1a and 1c is SVT, and for all class I - VT. The most dangerous side effect is proarrhythmic, i.e., arrhythmia caused by taking the drug, which is more severe than the previous one. Class 1a can provoke the development of VT of the "pirouette" type, drugs of classes 1a and 1c - cause atrial tachyarrhythmias to a sufficient extent to achieve atrioventricular conduction in a ratio of 1:1 with a marked increase in the frequency of conduction to the ventricles. All drugs of class I can aggravate VT. They also tend to suppress ventricular contractility. Since these side effects of class I antiarrhythmic drugs more often develop in patients with organic heart disease, in general these drugs are not recommended for such patients. These drugs are usually prescribed only to patients without structural heart disease or to patients with structural pathology who have no alternative in treatment.

II class

Class II drugs are represented by b-adrenergic blockers, which act primarily on tissues with slow channels (the SA and AV nodes), where they reduce automaticity, slow conduction velocity, and prolong the refractory period. As a result, the heart rate slows, the PR interval lengthens, and the AV node conducts frequent atrial depolarizations at a lower frequency. Class II antiarrhythmic drugs are used primarily to treat SVT, including sinus tachycardia, re-entry at the AV node level, AF, and atrial flutter. These drugs are also used to treat VT in order to increase the threshold for ventricular fibrillation (VF) and reduce ventricular proarrhythmogenic effects of b-adrenergic receptor stimulation. b-Adrenergic blockers are generally well tolerated; side effects include rapid fatigue, sleep disturbances, and gastrointestinal disorders. These drugs are contraindicated in patients with bronchial asthma.

III class

These are mainly calcium channel blockers that prolong the action potential duration and refractoriness in both fast-channel and slow-channel tissue. As a result, the ability of all cardiac tissues to conduct impulses at a high frequency is inhibited, but the conduction itself does not suffer significantly. Since the action potential is lengthened, the frequency of automaticity decreases. The leading change in the electrocardiogram is the prolongation of the QT interval. Drugs of this class are used to treat SVT and VT. Class III drugs have a risk of proarrhythmia, mainly VT of the "pirouette" type.

IV class

Includes non-dihydropyridine calcium channel blockers that inhibit calcium-dependent action potential in tissues containing slow calcium channels, thereby reducing automaticity, slowing conduction ability, and prolonging refractoriness. The heart rate slows, the PR interval lengthens, and the AV node conducts atrial impulses at a lower frequency. Drugs in this class are used primarily to treat SVT.