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Table 213–2. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION)   TARGET SELECTED DRUG DOSAGE

Table 213–2. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION)

 

TARGET

SELECTED

DRUG

DOSAGE

LEVELS

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

> 5 min fol- lowed by an infusion of

mg/kg/h

0.4

mg/kg over

Oral immediate- release: 100 or

150

mg q 6 h

Oral controlled- release: 200 or

mg q 12 h

300

2–7.5 µ g/mL Anticholinergic effects (urinary re- tention, glaucoma, dry mouth, blurred vision, intestinal upset), hypoglyce- mia, torsades de pointes VT; nega- tiveinotropiceffects (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 insuffi- ciency. Adverse effects may contribute to non- adherence. If QRS interval widens ( > 50% if initially < 120 msec or

> 25% if initially > 120 msec) or if QTc inter- val is prolonged > 550 msec, infusion rate or dosage should be decreased or drug stopped.

IV form is not available

Procainamide

IV: 10–15 mg/

48 g/mL Hypotension (with IV

in the US. Sustained-release

kg

bolus at

infusion), serologic

preparations obviate

25–50 mg/

abnormalities (espe-

the need for frequent

min, followed

cially ANA) in al-

dosing.

by

a constant

most 100% taking

If QRS interval widens

IV

infusion of

drug for > 12 mo,

(

> 50% if initially

1–4 mg/min

 

drug-induced lupus

< 120 msec or > 25% if

Oral: 250–625

(arthralgia, fever,

initially > 120 msec) or

mg

(rarely, up

pleural effusions)

if QTc interval is pro-

to

1 g) q 3 or

 

in 15–20%, agranu-

longed > 550 msec, in-

4

h

locytosis in < 1%, torsades de pointes VT

fusion rate or dosage should be decreased or drug stopped.

Quinidine

Oral: 200–400

2–6 µg/mL

Diarrhea, colic,

If QRS interval widens

mg q 4–6 h

flatulence, fever,

(

> 50% if initially

 

thrombocytopenia, liver function abnor- malities, torsades de pointes VT; overall adverse effect rate of 30%

< 120 msec or > 25% if initially > 120 msec) or if QTc interval is pro- longed > 550 msec, in- fusion rate or dosage should be decreased or drug stopped.

Class Ib

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

Lidocaine

IV: 100 mg over

2–5 µg/L

Tremor, seizures;

To

reduce toxicity risk,

2

min, followed

if administration is

clinicians should re-

by

continuous

too rapid, drowsi-

duce dosage or infusion

infusion of

ness, delirium,

rate to 2 mg/min after

4

mg/min

paresthesias;

24 h.

Table 213–2. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION) (Continued )

 

TARGET

SELECTED

DRUG

DOSAGE

LEVELS

ADVERSE EFFECTS

COMMENTS

Lidocaine

(2 mg/min in

possibly increased

Extensive first-pass

(cont’d)

patients > 65);

risk of bradyar-

hepatic metabolism

min after first dose, a 2nd 50-mg bolus

5

rhythmias after acute MI

occurs.

is

given

 

Mexiletine

Oral immediate-

0.5–2 µ g/mL Nausea, vomiting,

Oral slow-release and

release: 100–

tremor, seizures

IV forms are not

250

mg q 8 h

available in the US.

Oral slow-

release: 360

mg q 12 h

IV: 2 mg/kg at

25 mg/min, fol-

lowed by 250-

mg infusion over

1 h, 250-mg in-

fusion over next

2 h, and mainte-

nance infusion

of 0.5 mg/min

Class Ic

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

Flecainide

Oral: 100 mg

0.2–1 µ g/mL Occasionally,

IV

form is not available

8 or 12 h

IV: 1–2 mg/kg

q

 

blurred vision and paresthesias

in US. If QRS complex widens

over 10 min

 

(

> 50% if initially < 120

 

msec and > 25% if ini- tially > 120 msec), dose must be decreased or drug stopped.

Propafenone

Oral: Initially,

0.1–1.0 µ g/

β-blocking activity,

Pharmacokinetics are

150

mg tid,

mL

possible worsening

nonlinear; increases

protein binding

titrated up to 150–300 mg tid IV: 2-mg/kg bolus, followed by 2 mg/min infusion

of reactive airway disorders; occa- sionally GI upset

in dose should not exceed 50% of previous dose. Bioavailability and

vary; drug has saturable first-pass metabolism.

IV form is not available

in the US.

Class II

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

(β-blockers)

Atenolol

Oral: 50–100

β -Blocker

Typically for β -blockers, GI dis- turbances, insomnia, nightmares, lethargy, erectile dysfunction, possible AV block in

patients with AV node dysfunction

β -blockers are contrain- dicated in patients with bronchospastic airway disorders.

mg

once/day

levels not

Carvedilol

 

measured;

Oral: Initially, 6.25 mg bid, followed by titration to

dose ad-

 

justed

 

to reduce

heart rate by > 25%

25

mg bid

Table 213–2. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION) (Continued )

 

TARGET

SELECTED

DRUG

DOSAGE

LEVELS

ADVERSE EFFECTS

COMMENTS

Class II

(β-blockers) (cont’d)

Acebutolol Oral: 200 mg bid

Betaxolol

Oral: 20 mg

Bisoprolol

once/day Oral: 5–10 mg

Esmolol

once/day IV: 50–200 µ g/ kg/min

Metoprolol Oral: 50–100 mg bid IV: 5 mg q 5 min up to 15 mg

Nadolol

Oral: 60–80 mg

Propranolol

once/day Oral: 10–30 mg

Timolol

tid or qid IV: 1–3 mg (may repeat once after 5 min if needed) Oral: 10–20 mg bid

Class III

(membrane-

stabilizing

drugs)

Uses: Any tachyarrhythmia except torsades de pointes VT

Amiodarone

Oral: 600–1200 mg/day for 7–10 days, then 400 mg/day for 3 wk, fol- lowed by a maintenance dose (ideally, 200 mg/day) IV: 150–450 mg over 1–6 h (de- pending on ur- gency), fol- lowed by a maintenance dose of 0.5–2.0 mg/min

1–2.5 µ g/mL Pulmonary fibrosis (in up to 5% of patients treated for > 5 yr), which may be fatal; QTc prolongation; torsades de pointes

Drug has noncompetitive β-blocking, Ca channel blocking, and Na chan- nel blocking effects, with a long delay in onset of action.

VT (rare); bradycar-

By

prolonging refractori-

dia; gray or blue discoloration of sun- exposed skin; sun

ness, drug may cause homogeneous condi- tions of repolarization

sensitivity; hepatic

throughout the heart.

abnormalities; peri-

IV

form can be used for

pheral neuropathy; corneal microdepos- its (in almost all treated patients), usu- ally without serious visual effects and reversed by stopping the drug; changes in thyroid function; slow clearance possi- bly prolonging adverse effects

conversion.

Table 213–2. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION) (Continued )

 

TARGET

SELECTED

DRUG

DOSAGE

LEVELS

ADVERSE EFFECTS

COMMENTS

Azimilide

Oral: 100–200

40–60mL/min;

Bretylium *

mg once/day IV: Initially, 5

Dofetilide

mg/kg, followed by 1–2 mg/min 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 q 6–8 h IV: 2.5–4 µ g/mL

Oral: 500 µg bid if CrCl > 60 mL/min; 250 µ g bid if CrCl is

Ibutilide

125 µ g bid if CrCl is 20–40 mL/min IV: For patients

Sotalol

60 kg, 1 mg infusion or, for patients < 60 kg, 0.01 mg/kg over 10 min, with dose re- peated after 10 min if the first infusion is unsuccessful Oral: 80–160 mg q 12 h IV: 10 mg over 1–2 min

200–1000

Torsades de pointes

ng/mL

VT

0.8–2.4 µ g/

Hypotension

Drug has class II

mL

properties. Effects may be delayed 10–20 min.

N/A

Torsades de pointes VT

Drug is contraindicated if QTc > 440 msec or if CrCl < 20 mL/min.

N/A

Torsades de pointes VT (in 2%)

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

0.5–4 µ g/mL Similar to class II; possible depressed left ventricular function and torsades de pointes VT

Racemic [D-L] form has class II (β -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.

Table 213–2. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION) (Continued )

 

TARGET

SELECTED

DRUG

DOSAGE

LEVELS

ADVERSE EFFECTS

COMMENTS

Class IV

(Ca channel

blockers)

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

Diltiazem

Oral slow-

0.1–0.4 µ g/

Possible precipita-

IV

form is most

release (dil-

mL

tion of VF in pa- tients with VT,

commonly used to slow ventricular response rate to

tiazem CD):

120

mg to

negative inotropy

360

mg once/day IV: 5–15 mg/h for up to 24 h

 

AF

or atrial flutter.

Verapamil

Oral: 40–120 mg tid or, for sus- tained-release form, 180 mg once/day to

N/A

Possible precipita- tion of VF in pa- tients 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

240

mg bid

IV: 5–15 mg over 10 min Oral prophy- laxis: 40–120 mg tid

 

IV

over 10 min).

Other antiarrhythmics

 

Adenosine

6 mg rapid IV bolus, re- peated 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 mainte- nance dose:

0.125–0.25

0.8–1.6 µ g/

Anorexia, nausea,

Contraindications

mL

vomiting, and often serious arrhyth- mias (VPBs, VT, APBs, atrial tachy- cardia, 2nd-degree or 3rd-degree AV block, combina- tions of these ar- rhythmias)

include antegrade con-

duction over an acces- sory AV connection pathway (manifest

mg/day

Wolff-Parkinson-

 

White syndrome) because if AF occurs, ventricular responses may be excessive (digoxin shortens re- fractory periods of the accessory connection).