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Antiarrhythmic Drugs (Vaughan Williams Classification)

Antiarrhythmic Drugs (Vaughan Williams Classification)

Drug

Dosage

Target Levels

Selected Adverse Effects

Comments

Class Ia

Uses: APB and VPB suppression, SVT and VT suppression, AF or atrial flutter, and VF suppression

Disopyramide

IV: Initially, 1.5 mg/kg over > 5 minutes followed by an infusion of 0.4 mg/kg/hour

Oral immediate-release: 100 or 150 mg every 6 hours

Oral controlled-release: 200 or 300 mg every 12 hours

2–7.5 mcg/mL

Anticholinergic effects (urinary retention, glaucoma, dry mouth, blurred vision, intestinal upset), hypoglycemia, torsades de pointes VT; negative inotropic effects (which may worsen heart failure or hypotension)

Drug should be used cautiously in patients with impaired LV function.

Dosage should be decreased in patients with renal insufficiency.

Adverse effects may contribute to nonadherence.

If QRS interval widens (> 50% if initially < 120 millisecond or > 25% if initially > 120 millisecond) or if QTc interval is prolonged > 550 millisecond, infusion rate or dosage should be decreased or drug stopped.

IV form is not available in the US.

Procainamide*

IV: 10–15 mg/kg bolus at 25–50 mg/minute, followed by a constant IV infusion of 1–4 mg/minute

Oral: 250–625 mg (rarely, up to 1 g) every 3 or 4 hours

Oral controlled-release: For patients < 55 kg, 500 mg; for patients 55–91 kg, 750 mg; or for patients > 91 kg, 1000 mg every 6 hours

4–8 mcg/mL

Hypotension (with IV infusion), serologic abnormalities (especially ANA) in almost 100% taking drug for > 12 months, drug-induced lupus (arthralgia, fever, pleural effusions) in 15–20%, agranulocytosis in < 1%, torsades de pointes VT

Sustained-release preparations obviate the need for frequent dosing.

If QRS interval widens (> 50% if initially < 120 millisecond or > 25% if initially >120 millisecond) or if QTc interval is prolonged > 550 millisecond, infusion rate or dosage should be decreased or drug stopped.

Quinidine*

Oral: 200–400 mg every 4–6 hours

2–6 mcg/mL

Diarrhea, colic, flatulence, fever, thrombocytopenia, liver function abnormalities, torsades de pointes VT; overall adverse effect rate of 30%

If QRS interval widens (> 50% if initially < 120 millisecond or > 25% if initially > 120 millisecond) or if QTc interval is prolonged > 550 millisecond, dosage should be decreased or drug stopped.

Class Ib

Uses: Suppression of ventricular arrhythmias (VPB, VT, VF)

Lidocaine

IV: 100 mg over 2 minutes, followed by continuous infusion of 4 mg/minute (2 mg/minute in patients > 65) and 5 minutes after the first dose, a 2nd 50-mg bolus

2–5 mcg/L

Tremor, seizures; if administration is too rapid, drowsiness, delirium, paresthesias; possibly increased risk of bradyarrhythmias after acute myocardial infarction

To reduce toxicity risk, clinicians should reduce dosage or infusion rate to 2 mg/minute after 24 hours.

Extensive first-pass hepatic metabolism occurs.

Mexiletine

Oral immediate-release: 100–250 mg every 8 hours

Oral slow-release: 360 mg every 12 hours

IV: 2 mg/kg at 25 mg/minute, followed by 250-mg infusion over 1 hour, 250-mg infusion over next 2 hours, and maintenance infusion of 0.5 mg/minute

0.5–2 mcg/mL

Nausea, vomiting, tremor, seizures

Oral slow-release and IV forms are not available in the US.

Class Ic

Uses: APB and VPB suppression, SVT and VT suppression, AF or atrial flutter, and VF suppression

Flecainide

Oral: 100 mg every 8 or 12 hours

IV: 1–2 mg/kg over 10 minutes

0.2–1 mcg/mL

Occasionally, blurred vision and paresthesias

If QRS complex widens (> 50% if initially < 120 millisecond and > 25% if initially > 120 millisecond), dose must be decreased or drug stopped.

IV form is not available in US.

Propafenone

Oral: Initially, 150 mg 3 times a day, titrated up to 225–300 mg 3 times a day if needed

IV: 2-mg/kg bolus, followed by 2 mg/minute infusion

0.1–1.0 mcg/mL

Beta-blocking activity, possible worsening of reactive airway disorders; occasionally GI upset

Pharmacokinetics are nonlinear; increases in dose should not exceed 50% of previous dose.

Bioavailability and protein binding vary; drug has saturable first-pass metabolism.

IV form is not available in the US.

Class II (beta-blockers)

Uses: Supraventricular tachyarrhythmias (APB, ST, SVT, AF, atrial flutter) and ventricular arrhythmias (often in a supportive role)

Acebutolol

Oral: 200 mg twice a day

Beta-blocker levels not measured; dose adjusted to reduce heart rate by > 25%

Typically for beta-blockers, GI disturbances, insomnia, nightmares, lethargy, erectile dysfunction, possible AV block in patients with AV node dysfunction

Beta-blockers are contraindicated in patients with bronchospastic airway disorders.

Atenolol

Oral: 50–100 mg once a day

Betaxolol

Oral: 20 mg once a day

Bisoprolol

Oral: 5–10 mg once a day

Carvedilol

Oral: Initially, 6.25 mg twice a day, followed by titration to 25 mg twice a day

Esmolol

IV: 50–200 mcg/kg/minute

Metoprolol

Oral: 50–100 mg twice a day

IV: 5 mg every 5 minutes up to 15 mg

Nadolol

Oral: 60–80 mg once a day

Propranolol

Oral: 10–30 mg 3 or 4 times a day

IV: 1–3 mg (may repeat once after 5 minutes if needed)

Timolol

Oral:10–20 mg twice a day

Class III (membrane-stabilizing drugs)

Uses: Any tachyarrhythmia except torsades de pointes VT

Amiodarone

Amiodarone is given as a loading dose followed by a maintenance dose. Doses and intervals vary significantly according to the arrhythmia†.

1–2.5 mcg/mL

Pulmonary fibrosis (in up to 5% of patients treated for > 5 years), which may be fatal; QTc prolongation; torsades de pointes VT (rare); bradycardia; gray or blue discoloration of sun-exposed skin; sun sensitivity; hepatic abnormalities; peripheral neuropathy; corneal microdeposits (in almost all treated patients), usually without serious visual effects and reversed by stopping the drug; changes in thyroid function; serum creatinine increased up to 10% without change in GFR; slow clearance possibly prolonging adverse effects

Drug has noncompetitive beta-blocking, calcium channel blocking, and sodium channel blocking effects, with a long delay in onset of action.

Although drug prolongs refractoriness, it does so more homogeneously than other QT prolonging drugs, so torsades de pointe VT is less common

IV form can be used for conversion.

Azimilide*

Oral: 100–200 mg once a day

200–1000 ng/mL

Torsades de pointes VT

Bretylium*

IV: Initially, 5 mg/kg, followed by 1–2 mg/minute as a constant infusion

IM: Initially, 5–10 mg/kg, which may be repeated to a total dose of 30 mg/kg

IM maintenance dose of 5 mg/kg every 6–8 hours

0.8–2.4 mcg/mL

Hypotension

Drug has class II properties.

Effects may be delayed 10–20 minutes.

Drug is used to treat potentially lethal refractory ventricular tachyarrhythmias (intractable VT, recurrent VF), for which it is usually effective within 30 minutes of injection.

Dofetilide

Oral: 500 mcg twice a day if creatinine clearance (CrCl) is > 60 mL/minute; 250 mcg twice a day if CrCl is 40–60 mL/minute; 125 mcg twice a day if CrCl is 20–40 mL/minute

N/A

Torsades de pointes VT

Drug is contraindicated if QTc is > 440 millisecond or if CrCl is < 20 mL/minute.

Dronedarone

Oral: 400 mg twice a day

N/A

QTc prolongation, torsades de pointes VT (rare), bradycardia, GI upset, possible hepatotoxicity (rare), serum creatinine increased up to 20% without change in GFR

Drug is a modified amiodarone molecule (including deiodination) with shorter half-life, smaller volume of distribution, fewer adverse effects, and less efficacy.

Drug should not be used in patients with history of heart failure or with permanent AF.

Ibutilide

IV: For patients 60 kg, 1 mg infusion or, for patients < 60 kg, 0.01 mg/kg over 10 minutes, with dose repeated after 10 minutes if the first infusion is unsuccessful

N/A

Torsades de pointes VT (in 2%)

Drug is used to terminate AF (success rate, about 40%) and atrial flutter (success rate, about 65%).

Sotalol

Oral: 80–160 mg every 12 hours

IV: 10 mg over 1–2 minutes

0.5–4 mcg/mL

Similar to class II; possible depressed left ventricular function and torsades de pointes VT

Racemic [d-l] form has class II (beta-blocking) properties, [d] form does not. Both forms have class III activity. Only racemic sotalol is available for clinical use.

Drug should not be used in patients with renal insufficiency.

Vernakalant

3 mg/kg IV over 10 minutes (maximum 339 mg)

If conversion to sinus rhythm does not occur, follow up with 2nd infusion of 2 mg/kg over 10 minutes (maximum 226 mg)

N/A

Hypotension (especially in patients with heart failure)

Bradyarrhythmias (especially with concomitant beta-blockade)

Drug is not available in the United States.

Class IV (Calcium channel blockers)

Uses: Termination of SVT and slowing of rapid AF or atrial flutter

Diltiazem

Oral slow-release (diltiazem CD): 120–360 mg once a day

IV: 5–15 mg/hour for up to 24 hours

0.1–0.4 mcg/mL

Possible precipitation of VF in patients with VT, negative inotropy

IV form is most commonly used to slow ventricular response rate to AF or atrial flutter.

Verapamil

Oral: 40–120 mg 3 times a day or, for sustained-release form, 180 mg once a day to 240 mg twice a day

IV: 5–15 mg over 10 minutes

Oral prophylaxis: 40–120 mg 3 times a day

N/A

Possible precipitation of VF in patients with VT, negative inotropy

IV form is used to terminate narrow-complex tachycardias involving the AV node (success rate, almost 100% with 5–10 mg IV over 10 minutes).

Other antiarrhythmics

Adenosine

6 mg rapid IV bolus, repeated twice at 12 mg if needed; flush bolus with additional 20 mL saline

N/A

Transient dyspnea, chest discomfort, and flushing (in 30–60%), transient bronchospasm

Drug slows or blocks AV nodal conduction.

Duration of action is extremely short.

Contraindications include asthma and high-grade heart block.

Dipyridamole potentiates effects.

Digoxin

IV loading dose: 0.5 mg

Oral maintenance dose: 0.125–0.25 mg once a day

0.8–1.6 mcg/mL

Anorexia, nausea, vomiting, and often serious arrhythmias (VPBs, VT, APBs, atrial tachycardia, 2nd-degree or 3rd-degree AV block, combinations of these arrhythmias)

Contraindications include antegrade conduction over an accessory AV connection pathway (manifest Wolff-Parkinson-White syndrome) because if AF occurs, ventricular responses may be excessive (digoxin shortens refractory periods of the accessory connection).

*Availability uncertain.

Amiodarone dosing varies significantly; manufacturer's prescribing information should be checked. In general, oral loading dose for stable supraventricular arrhythmias is about 5 g given over 1 to 2 weeks at a dose between 200 mg twice a day to 400 mg 3 times a day. Oral loading dose for ventricular arrhythmias is 10 g given at a similar dose over 1 to 4 weeks. In general, the oral maintenance dose is 200 mg once a day, although 100 mg once a day can be used for older or frail patients and 300 or 400 mg once a day can be used for prevention of serious ventricular arrhythmias.

Amiodarone IV loading dose is typically 150 mg over 10 minutes followed by a 1 mg/minute infusion for 6 hours then 0.5 mg/minute for 18 hours. For VF or pulseless VT, a 300-mg IV bolus is given followed if needed by a 150-mg IV bolus.

AF = atrial fibrillation; ANA = antinuclear antibody; APB = atrial premature beat; AV = atrioventricular; CrCl = creatinine clearance; GFR = glomerular filtration rate; GI = gastrointestinal; LV = left ventricular; QTc = QT interval corrected for heart rate; SVT = supraventricular tachycardia; VF = ventricular fibrillation; VPB = ventricular premature beat; VT = ventricular tachycardia.