Page 253 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 14 Agents Used in Cardiac Arrhythmias 239

TABLE 14–2 Membrane actions of antiarrhythmic drugs.

Block of Sodium Channels Refractory Period
Calcium Effect on
Normal Depolarized Normal Depolarized Channel Pacemaker Sympatholytic
Drug Cells Cells Cells Cells Blockade Activity Action
Adenosine 0 0 0 0 + 0 +
Amiodarone + +++ ↑↑ ↑↑ + ↓↓ +
Diltiazem 0 0 0 0 +++ ↓↓ 0
Disopyramide + +++ ↑ ↑↑ + ↓ 0
Dofetilide 0 0 ↑ ? 0 0 0
Dronedarone + + na na + na +
Esmolol 0 + 0 na 0 ↓↓ +++
Flecainide + +++ 0 ↑ 0 ↓↓ 0
Ibutilide 0 0 ↑ ? 0 0 0
Lidocaine 0 +++ ↓ ↑↑ 0 ↓↓ 0
Mexiletine 0 +++ 0 ↑↑ 0 ↓↓ 0
Procainamide + +++ ↑ ↑↑↑ 0 ↓ +
Propafenone + ++ ↑ ↑↑ + ↓↓ +
Propranolol 0 + ↓ ↑↑ 0 ↓↓ +++
Quinidine + ++ ↑ ↑↑ 0 ↓↓ +
Sotalol 0 0 ↑↑ ↑↑↑ 0 ↓↓ ++
Verapamil 0 + 0 ↑ +++ ↓↓ +
Vernakalant 1 + + + + na 0 na
1 Not available in the USA.
na, data not available.

therapy, serologic abnormalities (eg, increased antinuclear anti- The half-life of NAPA is considerably longer than that of pro-
body titer) occur in nearly all patients, and in the absence of cainamide, and it therefore accumulates more slowly. Thus, it is
symptoms, these are not an indication to stop drug therapy. important to measure plasma levels of both procainamide and
Approximately one third of patients receiving long-term procain- NAPA, especially in patients with circulatory or renal impairment.
amide therapy develop these reversible lupus-related symptoms. If a rapid procainamide effect is needed, an intravenous load-
Other adverse effects include nausea and diarrhea (in about ing dose of up to 12 mg/kg can be given at a rate of 0.3 mg/kg/
10% of cases), rash, fever, hepatitis (<5%), and agranulocytosis min or less rapidly. This dose is followed by a maintenance dosage
(approximately 0.2%). of 2–5 mg/min, with careful monitoring of plasma levels. The risk
of gastrointestinal (GI) or cardiac toxicity rises at plasma concen-
Pharmacokinetics & Dosage trations greater than 8 mcg/mL or NAPA concentrations greater
than 20 mcg/mL.
Procainamide can be administered safely by intravenous and To control ventricular arrhythmias, a total procainamide dos-
intramuscular routes and is well absorbed orally. A metabolite age of 2–5 g/d is usually required. In an occasional patient who
(N-acetylprocainamide, NAPA) has class 3 activity. Excessive accumulates high levels of NAPA, less frequent dosing may be
accumulation of NAPA has been implicated in torsades de pointes possible. This is also possible in renal disease, where procainamide
during procainamide therapy, especially in patients with renal fail- elimination is slowed.
ure. Some individuals rapidly acetylate procainamide and develop
high levels of NAPA. However, the lupus syndrome appears to be Therapeutic Use
less common in these patients.
Procainamide is eliminated by hepatic metabolism to NAPA Procainamide is effective against most atrial and ventricular
and by renal elimination. Its half-life is only 3–4 hours, which arrhythmias. However, many clinicians attempt to avoid long-term
necessitates frequent dosing or use of a slow-release formulation therapy because of the requirement for frequent dosing and the
(the usual practice). NAPA is eliminated by the kidneys. Thus, common occurrence of lupus-related effects. Procainamide is the
procainamide dosage must be reduced in patients with renal drug of second or third choice (after lidocaine or amiodarone) in
failure. The reduced volume of distribution and renal clearance most coronary care units for the treatment of sustained ventricular
associated with heart failure also require reduction in dosage. arrhythmias associated with acute myocardial infarction.