DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 29–3
Major Electrophysiologic Actions of Anti-Arrhythmic Drugs
NA + CHANNEL BLOCK
τ RECOVERY1
, STATE Ca 2+ CHANNEL
DRUG SECONDS DEPENDENCE 1 ↑APD BLOCK AUTONOMIC EFFECTS OTHER EFFECTS
Lidocaine
Phenytoin
Mexiletine a
Procainamide
Quinidine
Disopyramide b
Propafenone b
Flecainide a
β Blockers:
Propanolol b
Sotalol b
Amiodarone,
dronedarone
0.1
0.2
0.3
1.8
3
9
11
11
1.6
I > O
I
O
O
O
O ≈ I
O
I
✓
✓
✓
✓
(x)
✓
✓
(x)
(x)
(x)
Ganglionic blockade
(especially
intravenous)
α Blockade, vagolytic
Anticholinergic
Anticholinergic
β Blockade (variable
clinical effect)
β Blockade
β Blockade
Noncompetitive
β blockade
✓: Metabolite
prolongs APD
Na + channel block
in vitro
Antithyroid action
Dofetilide
Ibutilide
Verapamil a
Diltiazem a
Digoxin
Adenosine
Magnesium
✓
✓
✓
✓
✓
? ✓
✓: Vagal stimulation
✓:Adenosine receptor
activation
✓: Inhibition of
Na + , K + -ATPase
✓: Activation of
outward K +
current
Mechanism not
well understood
✓Indicates an effect that is important in mediating the clinical action of a drug. (x)Indicates a demonstrable effect whose relationship to drug action
in patients is less well established. a Indicates drugs prescribed as racemates, and the enantiomers are thought to exert similar electrophysiologic
effects. b Indicates racemates for which clinically relevant differences in the electrophysiologic properties of individual enantiomers have been
reported (see text). One approach to classifying drugs is: Class Major action
I Na + channel block
II β blockade
III action potential prolongation (usually by K + channel block)
IV Ca 2+ channel block
Drugs are listed here according to this scheme. It is important to bear in mind, however, that many drugs exert multiple effects that contribute to their
clinical actions. It is occasionally clinically useful to subclassify Na + channel blockers by their rates of recovery from drug-induced block (τ recovery
)
under physiologic conditions. Because this is a continuous variable and can be modulated by factors such as depolarization of the resting potential,
these distinctions can become blurred: class Ib, τ recovery
<1 s; class Ia, τ recovery
1–10 s; class Ic, τ recovery
>10 s. These class and subclass effects are associated
with distinctive ECG changes, characteristic “class” toxicities, and efficacy in specific arrhythmia syndromes (see text). 1 These data are
dependent on experimental conditions, including species and temperature. The τ recovery
values cited here are from Courtney (1987). O, open-state
blocker; I, inactivated-state blocker; APD, action potential duration.