Page 254 - Basic _ Clinical Pharmacology ( PDFDrive )

240 SECTION III Cardiovascular-Renal Drugs

TABLE 14–3 Clinical pharmacologic properties of antiarrhythmic drugs.

Effect on Usefulness in Arrhythmias
AV Nodal
Effect on SA Refractory QRS Supra-
Drug Nodal Rate Period PR Interval Duration QT Interval ventricular Ventricular Half-Life
Adenosine ↓↑ ↑↑↑ ↑↑↑ 0 0 ++++ ? <10 s
Amiodarone ↓↓ 1 ↑↑ Variable ↑ ↑↑↑↑ +++ +++ (weeks)
Diltiazem ↑↓ ↑↑ ↑ 0 0 +++ - 4–8 h
Disopyramide ↑↓ 1,2 ↑↓ 2 ↑↓ 2 ↑↑ ↑↑ + +++ 7–8 h
Dofetilide ↓(?) 0 0 0 ↑↑ ++ None 7 h
Dronedarone ↑ +++ - 24 h
Esmolol ↓↓ ↑↑ ↑↑ 0 0 + + 10 min
Flecainide None,↓ ↑ ↑ ↑↑↑ 0 + 3 ++++ 20 h
Ibutilide ↓(?) 0 0 0 ↑↑ ++ ? 6 h
Lidocaine None 1 None 0 0 0 None 4 +++ 1–2 h
Mexiletine None 1 None 0 0 0 None +++ 8–20 h
Procainamide ↓ 1 ↑↓ 2 ↑↓ 2 ↑↑ ↑↑ + +++ 3–4 h
Propafenone 0, ↓ ↑ ↑ ↑↑↑ 0 + +++ 5–7 h
Propranolol ↓↓ ↑↑ ↑↑ 0 0 + + 5 h
Quinidine ↑↓ 1,2 ↑↓ 2 ↑↓ 2 ↑↑ ↑↑ + +++ 6 h
Sotalol ↓↓ ↑↑ ↑↑ 0 ↑↑↑ +++ +++ 7–12 h
Verapamil ↓↓ ↑↑ ↑↑ 0 0 +++ - 7 h
Vernakalant ↑ ↑ +++ - 2 h
1 May suppress diseased sinus nodes.
2
Anticholinergic effect and direct depressant action.
3 Especially in Wolff-Parkinson-White syndrome.
4
May be effective in atrial arrhythmias caused by digitalis.

QUINIDINE (SUBGROUP 1A) Extracardiac Effects

Adverse GI effects of diarrhea, nausea, and vomiting are observed
Cardiac Effects in one third to one half of patients. A syndrome of headache,
Quinidine has actions similar to those of procainamide: it slows dizziness, and tinnitus (cinchonism) is observed at toxic drug
the upstroke of the action potential, slows conduction, and concentrations. Idiosyncratic or immunologic reactions, including
prolongs the QRS duration of the ECG, by blockade of sodium thrombocytopenia, hepatitis, angioneurotic edema, and fever, are
channels. The drug also prolongs the action potential duration by observed rarely.
blockade of several potassium channels. Its toxic cardiac effects
include excessive QT-interval prolongation and induction of Pharmacokinetics & Therapeutic Use
torsades de pointes arrhythmia. Toxic concentrations of quinidine Quinidine is readily absorbed from the GI tract and eliminated
also produce excessive sodium channel blockade with slowed con- by hepatic metabolism. It is rarely used because of cardiac and
duction throughout the heart. It also has modest antimuscarinic extracardiac adverse effects and the availability of better-tolerated
actions in the heart.
antiarrhythmic drugs.
O CH 3
DISOPYRAMIDE (SUBGROUP 1A)

H N Cardiac Effects
N C CH CH 2 The effects of disopyramide are very similar to those of procain-
OH amide and quinidine. Its cardiac antimuscarinic effects are even
Quinidine more marked than those of quinidine. Therefore, a drug that slows