Antiarrhythmics

Most drugs used to antiarrhythmic therapy can be assigned to one of four main groups (Vaughan-Williams classification). The classification is based on the principal electrophysiological activity in the cell (see table: antiarrhythmics (Vaughan-Williams classification)).

The need to treat an arrhythmia depends on the symptoms and severity, which holds this arrhythmia in itself. The therapy is based on the reasons behind any particular arrhythmia. If necessary, a direct antiarrhythmic therapy with anti-arrhythmic drugs, cardioversion, defibrillation, implantable cardioverter-defibrillators (ICDs), pacemaker (and a special form of “pacing”, ? cardiac resynchronization therapy ?) or a combination of said forms of treatment may be necessary. Most drugs used to antiarrhythmic therapy can be assigned to one of four main groups (Vaughan-Williams classification). The classification is based on the principal electrophysiological activity in the cell (see table: antiarrhythmics (Vaughan-Williams classification)). Class I drugs of class I are divided into sub-classes, a, b and c. Drugs of class I are sodium channel blocker (membrane stabilizing drug) that block the fast sodium channels, the transition in tissues with rapid ion channels slow (atrial and ventricular cells of Arbeitsmyokards, His-Purkinje system). Class II: drugs of the class II are beta-blockers, which act primarily on fabric with slow-conducting channels (sinoatrial [SA], atrioventricular [AV] nodes). There they reduce the automaticity, slow conduction velocity and prolong the refractory period. Class III: drugs of class III are mainly potassium channel blockers which prolong the action potential duration and the refractory period in the tissues with fast and slow conducting channels. Class IV antiarrhythmics of class IV are calcium channel blockers from Nichtdihydropyridintyp that suppress the calcium-dependent action potentials in tissues with slow conducting channels and thereby reduce the discharge frequency automatic cookers, slow the line speed and extend the Refräktärzeit. Digoxin and adenosine are not included in the Vaughan-Williams classification. Digoxin shortens the atrial and ventricular refractory periods, acts vagoton, thereby prolonging the AV nodal conduction and AV node refractory. Adenosine slows or blocks the AV nodal conduction and may terminate tachyarrhythmias, their survival is dependent on the AV node conduction. Antiarrhythmics (Vaughan-Williams classification) active agent dosage target values ??Selected side effects Remarks Class Ia Applications: suppressing APB and VPB, SVT and VT, AF or atrial flutter and VF disopyramide iv: First 1.5 mg / kg for> 5 min, followed by an infusion of 0.4 mg / kg / h Oral immediate release: 100 or 150 mg every 6 h Oral controlled release: 200 or 300 mg every 12 h 2-7.5 ug / ml Anticholinergic effects (urinary retention, glaucoma, dry mouth, blurred vision, intestinal discomfort), hypoglycemia, torsades de pointes; (To heart failure or hypotension worsen) negative inotropic effects, the drugs should be used cautiously in patients with impaired left ventricular function. In patients with renal insufficiency, the dose should be reduced. Side effects may contribute to noncompliance. When the QRS interval is widened (> 50% when initial <120 ms, or> 25% when innitial> 120 ms) or the QTc interval increased to> 550 ms, the rate of infusion or the dosage should be reduced or the drug should be discontinued. In the US, it is not available in intravenous form. Procainamide * iv: 10-15 mg / kg bolus at 25-50 mg / min, followed by a constant infusion of 1-4 mg / min Oral: 250-625 mg (often up to 1 g) every 3 or 4 hours Oral controlled release: In patients <55 kg 500 mg; in patients 55-91 kg, 750 mg; or in patients> 91 kg, 1000 mg every 6 h 4-8 ug / ml hypotension (for infusion), serological abnormalities (particularly ANA) in almost 100% of patients taking the drug for> 12 months, Drug-induced Lupus (joint pain, fever, pleural effusions) at 15-20%, agranulocytosis in <1%, torsades de pointes sustained-release preparations make frequent dosing superfluous. When the QRS interval is widened (> 50% when initial <120 ms or> 25% when initial> 120 ms) or when the QTc interval increased to> 550 ms, the rate of infusion or the dosage should be reduced or the drug should be discontinued. Quinidine Oral: 200-400 mg every 4-6 h 2-6 ug / ml diarrhea, colic, flatulence, fever, thrombocytopenia, hepatic dysfunction, torsades de pointes; overall adverse event rate of 30%, when the QRS interval is widened (> 50% when initial <120 ms or> 25% when initial> 120 ms) or when the QTc interval increased to> 550 ms, the dosage should be reduced or the drug should be discontinued. Class Ib use: Suppression of ventricular arrhythmias (VPB, VT, VF) lidocaine iv: min 100 mg about 2, followed by continuous infusion of 4 mg / min (2 mg / min in patients> 65) and 5 minutes after the first dose a second 50-mg bolus 2-5 g / l tremor, seizures; when the drug is administered too quickly drowsiness, delirium, paresthesias; to reduce potentially increased risk of bradyarrhythmias after acute myocardial infarction To the toxicity risk, the physician should the dose or infusion rate after 24 h at 2 mg / min reduced. There is an extensive first-pass metabolism in the liver. Mexiletine Oral immediate release: 100-250 mg every 8 h oral slow release: 360 mg every 12 h i.v .: 2 mg / kg at 25 mg / min, followed by 250 mg i.v. over 1 h; then a 250 mg-infusion for the next 2 hours followed by a continuous infusion of 0.5 mg / min 0.5-2 ug / ml nausea, vomiting, shaking, spasms Oral and intravenous slow-release forms are not in the USA available. Class Ic Applications: suppressing APB and VPB, SVT and VT, AF or atrial flutter and VF flecainide Oral: 100 mg every 8 or 12 h iv: 1-2 mg / kg over 10 min 0.2-1 ug / ml Occasionally visual disturbances and paresthesia when the QRS interval is widened (> 50% when initial <120 ms and> 25% when initial> 120 ms), it must reduce the dose or the drug will be discontinued. The intravenous form is not available in the US. Propafenone Oral: First, 150 mg three times a day, then increase up to 150-300 mg 3 times a day i.v .: 2-mg / kg bolus followed by 2 mg / min iv 0.1-1.0 ug / ml betabblockierende effect, possible deterioration of reactive airway disease, occasionally gastrointestinal complaints pharmacokinetics is not linear; Increases in the dose should not vary by more than 50% of the previous dose amount bioavailability, and protein binding; the drug has a saturable first-pass metabolism. In the US, it is not available in intravenous form. Class II (beta blockers) using: supraventricular tachyarrhythmias (APB, ST, SVT, AF, atrial flutter) and ventricular arrhythmias (often in a supporting role) acebutolol Oral: 200 mg 2 times daily Beta blockers levels are not measured; The dose is adjusted to reduce the heart rate by> 25% typical for beta blockers arise gastrointestinal complaints, insomnia, nightmares, lethargy, erectile dysfunction, possibly heart block in patients with AV node dysfunction Beta blockers in patients with bronchospastic respiratory diseases contraindicated. Atenolol Oral: 50-100 mg of 1-times daily betaxolol Oral: 20 mg 1-times daily Bisoprolol Oral: 5-10 mg of 1-times daily oral carvedilol: First, 6.25 mg 2 times a day, followed by dose escalation to 25 mg 2 times daily esmolol iv: 50-200 mcg / kg / min metoprolol Oral: 50-100 mg 2 times daily iv: 5 mg every 5 minutes up to 15 mg nadolol Oral 60-80 mg of 1-times daily oral Propranolol: 10-30 mg 3 times or 2 times daily iv: 1-3 mg (if necessary once after 5 min repeat) timolol Oral: 10-20 mg 2 times a day class III (membrane-stabilizing medications) use: Each tachyarrhythmia except torsades de pointes amiodarone Oral: 600-1200 mg / day for 7-10 days, then 400 mg / d ag for 3 weeks followed by a maintenance dose (ideally ? 200 mg / day) iv: 150-450 mg over 1-6 h (depending on the urgency), followed by a maintenance dose of 0.5-2.0 mg / min 1 -2.5 ug / ml pulmonary fibrosis (up to 5% of the patients treated> 5 years), which can be fatal; QTc prolongation, torsades de pointes (rare); bradycardia; gray or blue discoloration of the sun-exposed skin; Sun sensitivity; Abnormal liver function; peripheral neuropathy; Micro deposits in the cornea (in nearly all treated patients), usually without serious visual effects completed by discontinuation of the drug; Changes in thyroid function; Increase in the serum creatinine by up to 10% without changing the glomerular filtration rate; slow clearance may require additional side effects, the drug blocks noncompetitive beta receptors and calcium and sodium channels; The effect occurs with a long delay. By extending the refractory period of the drug can lead to homogeneous conditions during the repolarization of the heart. The intravenous form may be used for the conversion. Azimilide Oral: 100-200 mg of 1-times daily 200-1000 ng / mL torsades de pointes – bretylium * iv: First, 5 mg / kg, followed by 1-2 mg / min as a constant infusion: First 5-10 mg / kg, can be up to a total dose of 30 mg / kg in repeated Maintenance dose of 5 mg / kg every 6-8 h 0.8-2.4 ug / ml hypotension The medicament has the characteristics of class II. The effects can occur only after 10-20 minutes. The drug is used to (stubborn VT recurrent VF) to treat potentially fatal refractory ventricular tachyarrhythmias, which are usually works within 30 minutes after injection. Dofetilide Oral: 500 mcg two times a day if the creatinine clearance is> 60 ml / min; 250 mcg 2 times a day, if the creatinine clearance is 40-60 ml / min; 125 mcg two times a day if the creatinine clearance 20-40 ml / min N / A torsades de pointes The drug is contraindicated in QTc> 440 ms or if the creatinine clearance is <20 ml / min. Dronedarone Oral: 400 mg two times a day N / A QTc prolongation, torsades de pointes (rare), bradycardia, gastrointestinal complaints, possible hepatotoxicity (rare) serum creatinine up to 20% increase with no change in glomerular filtration rate The drug amiodarone is a modified molecule (including deiodination) with a shorter half-life, smaller volume of distribution, fewer side effects and reduced efficacy. The drug should not be used in patients with a previous heart failure or with permanent atrial fibrillation. Ibutilide iv: In patients ? 60 kg, 1 mg per infusion or in patients <60 kg, 0.01 mg / kg over 10 min, min with repetition of the dose after 10 when the first infusion was not successful N / A torsades de pointes (2%) The medicine is used to terminate atrial fibrillation (success rate approximately 40%) and atrial flutter (success rate approximately 65%). Sotalol Oral: 80-160 mg every 12 h i.v .: 10 mg over 1-2 min 0.5-4 ug / ml Similar to class II; possibly decreased left ventricular function and torsades de pointes The racemic [d-l] form possesses the properties of class II (beta-receptor-blocking), the [d] -form not. Both forms have the activity of class III. Only racemic sotalol is available for clinical use. The drug should not be used in patients with renal insufficiency. Class IV (calcium channel blockers) Application: terminating the SVT and deceleration of the rapid atrial fibrillation or atrial flutter diltiazem oral slow release (Diltiazem CD): 120-360 mg of 1-times daily iv: 5-15 mg / h up to 24 h 0, 1-0.4 ug / ml Possible transition to VF in patients with VT, negative inotropy the intravenous form is most commonly used to slow the ventricular response to atrial fibrillation or atrial flutter. 180 mg once daily to 240 mg 2 times daily iv 40-120 mg 3 times a day or in retard form: Oral 5-15 mg verapamil about 10 min oral prophylaxis: 40-120 mg 3 times a day N / A Possible transition to VF in patients with VT, negative inotropy the intravenous form is used to terminate tachycardia with narrow QRS interval in which also the AV node affected (nearly 100% success rate with 5-10 mg IV over 10 minutes) is. Other antiarrhythmic drugs adenosine 6 mg i.v. faster Bolus, repeated if necessary twice with 12 mg; Bolus for rinsing with an additional 20 ml of saline N / A transient Dsypnoe, tightness in the chest, Flush (at 30-60%) and transient bronchospasm slows The drug or blocks the AV nodal conduction. The duration of the action is extremely short. Contraindications include asthma and severe atrioventricular block. Dipyridamole potentiates the effects. Digoxin iv Initial dose: 0.5 mg oral maintenance dose: 0.125 to 0.25 mg / day from 0.8 to 1.6 ug / ml of appetite, nausea, vomiting and often severe arrhythmia (VES, VT, APBs, atrial tachycardia, atrioventricular block second or 3rd degree, combinations of these arrhythmias) contraindications are the antegrade conduction via an accessory AV conduction path (manifest Wolff-Parkinson-White syndrome), because the ventricular response may be excessive when an atrial fibrillation occurs (digoxin shortens the refractory periods of the accessory pathway). * Availability unclear. AF = atrial fibrillation; ANA = anti-nuclear antibodies; APB = atrial premature beat; AV = atrioventricular; CrCl = creatinine clearance; LV = left ventricular; QTc = QT interval corrected for heart rate; SVT = supraventricular tachycardia; VF = ventricular fibrillation; VPB = ventricular premature beat, VT = ventricular tachycardia. Class I antiarrhythmic agents, sodium channel blocker (membrane stabilizing drug) block the fast sodium channels and slow the transition in tissues with rapid ion channels (atrial and ventricular cells of Arbeitsmyokards, His-Purkinje system). The ECG this effect in wider P-waves, QRS complexes wider, can be expressed in the prolongation of the PR interval or in a combination of both. Class I antiarrhythmic agents of the sodium channel effects are divided into sub-groups based on the kinetics. Class Ib drugs have fast kinetics. Drugs of the class Ic have a slow kinetics. Drugs of class Ia have an intermediate kinetics. The kinetics of sodium channel blockade determines the heart rate. Her the electrophysiological effects show. The antiarrhythmic agents of Class Ib show due to their rapid kinetics their electrophysiological effects only at very high heart rates. Therefore, shows an ECG recorded during a normal heart rhythm to normal frequencies no slowing of conduction in tissues with rapid ion channels. Antiarrhythmic agents of Class Ib are not very potent and have only a minimal effect on the atrial tissue. Because of their slow kinetics antiarrhythmic agents of Class Ic show their electrophysiological effects on all heart rates. Therefore, shows an ECG that has been recorded at normal frequency during a normal rhythm, the slowing of conduction to tissue with fast ion channels. Antiarrhythmic agents of Class Ic are potent. Since antiarrhythmic agents of Class Ia having an intermediate kinetics, may be its decelerating effect on the transition to tissue with fast ion channels in an ECG that has been recorded at normal frequency during a normal rhythm, point or not. Antiarrhythmics of class Ia also block repolarizing potassium channels and prolong the refractory period of the tissue with fast ion channels. The ECG shows this effect in a prolongation of the QT interval even at normal frequencies. Antiarrhythmic agents of Class Ib and Ic do not block potassium channels directly. The kinetics of sodium channel blockade determines the heart rate. Her the electrophysiological effects show. The primary indications are supraventricular tachycardia (SVT) for antiarrhythmic agents of Class Ia and Ic and ventricular tachycardia (VT) I. for all the antiarrhythmic agents of Class Among the side effects of the drugs of the class 1 include the occurrence of proarrhythmia, a drug-induced arrhythmia, the more serious than the originally treated arrhythmia, which is the most worrying side effect. All Class I antiarrhythmic drugs can worsen ventricular tachycardia. In addition, drugs of class I have to impair the force of contraction of the ventricle the property. Since these side effects more likely to occur in patients with structural heart disease, Class I antiarrhythmic agents are not generally suitable for this patient population and are therefore generally used only in patients without structural heart disease. Only if there is no therapeutic alternative, they are administered to patients with structural heart disease. There are other side effects of drugs of class I, which are specific to the subclass or individual drugs. Antiarrhythmics of class Ia drugs of class Ia have a kinetics which lies between the fast kinetics of class Ib and the slow kinetics of Class Ic. Its slowing effect on conduction to tissue with fast ion channels in an ECG that was recorded at normal frequency during a normal rhythm may be shown or not. Antiarrhythmic agents of Class Ia block repolarizing potassium channels, and prolong the refractory period of the tissue with fast ion channels. The ECG shows this effect in a prolongation of the QT interval even at normal frequencies. Drugs of class Ia are used for suppression of atrial extrasystoles (APB), ventricular extrasystoles (VES), supraventricular and ventricular tachycardia, atrial fibrillation (AF), atrial flutter and ventricular fibrillation employed. The primary indications are supraventricular and ventricular tachycardias. Antiarrhythmics of class Ia torsade de pointes tachycardia can cause. Antiarrhythmic agents of Class Ia atrial tachycardia can coordinate extent and slow that a 1: 1 AV conduction with a marked acceleration of the ventricular rate possible ist.Antiarrhythmika Class Ib The antiarrhythmic agents of Class Ib have fast kinetics; they show their electrophysiological effects only at very high heart rates. Therefore, shows an ECG recorded during a normal heart rhythm to normal frequencies no slowing of conduction in tissues with rapid ion channels. Antiarrhythmic agents of Class Ib are not very potent and have only a minimal effect on the atrial tissue. Drugs of the class Ib block the potassium channels directly. Drugs of the class Ib are for the suppression of ventricular arrhythmias (ventricular extrasystole, ventricular tachycardia, ventricular fibrillation) verwendet.Antiarrhythmika the class Ic antiarrhythmics of class Ic have a slow kinetics; they show their electrophysiological effects on all heart rates. Therefore, shows an ECG that has been recorded at normal frequency during a normal rhythm, the slowing of conduction to tissue with fast ion channels. Drugs of the class Ib are more potent antiarrhythmic agents than the class 1a or 1b. Drugs of the class Ib block the potassium channels directly. Drugs of the class Ic can coordinate so far atrial tachycardia and slow that a 1: 1 AV conduction with a noticeable acceleration of the ventricular rate is possible. Drugs of the class Ic, supraventricular to suppress atrial and ventricular premature beats and ventricular tachycardia, atrial fibrillation, atrial flutter and ventricular fibrillation employed. Antiarrhythmic agents of Class II antiarrhythmic agents of Class II are beta blockers, which mainly to tissues with slow-conducting channels act (sine, AV node). There they reduce the automaticity, slow conduction velocity and prolong the refractory period. It is to slow down the heart rate and an increase in the PR interval. The AV node transmits rapid atrial depolarizations at a slower frequency. These include sinus tachycardia, AV nodal reentrant tachycardia, VHF and atrial flutter. Antiarrhythmic agents of Class II are mainly used for the treatment of SVT. These drugs are also used to treat VT to raise the threshold for ventricular fibrillation (VF) and to reduce the pro-arrhythmic effects of beta-adrenergic receptors stimulation. Beta blockers are well-tolerated by patients in general. Side effects are disturbances in the form of fatigue, sleep disorders and gastrointestinal. This group of drugs is contraindicated in patients with asthma. Class III antiarrhythmic agents of Class III antiarrhythmic agents are membrane stabilizing drugs, mainly potassium channel blockers which prolong the action potential duration and the refractory period in the tissues with fast and slow conducting channels. The ability of the entire cardiac tissue, to transmit pulses of high frequencies is thereby reduced, but the line speed is not significantly affected. By extending the action potential discharge frequency automatic herd is reduced. The predominant effect on the ECG is reflected in the QT prolongation. This antiarrhythmic drugs used in the treatment of SVT and VT. Class III antiarrhythmic agents carry the risk of ventricular proarrhythmia, here v. a. the risk of torsades de pointes tachycardia and not be used in patients with torsades de pointes VT. Antiarrhythmic agents of Class IV antiarrhythmic agents of Class IV are the calcium antagonist of the Nichtdihydropyridintyp that suppress the calcium-dependent action potentials in tissues with slow conducting channels and thereby reduce the discharge frequency automatic cookers, slow the line speed and extend the Refräktärzeit. The heart rate is reduced, the PR interval and prolongs the AV-node transmits fast atrial depolarizations with a lower frequency. These drugs are used primarily to treat SVTs. They can also be used to slow rapid atrial fibrillation or atrial flutter. One form of VT (left septal or Belhassen VT) can be treated with verapamil.

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