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

A
Normal rhythm
1 sec
F
Atrial flutter with 1:1 AV conduction
QRS
T
P
G
Monomorphic ventricular tachycardia
B
Premature ventricular beat
H
Torsades de Pointes
C
Paroxysmal supraventricular tachycardia
(PSVT)
D
Atrial fibrillation
I
Ventricular fibrillation
E
Atrial flutter with variable AV conduction
Figure 29–9. ECGs showing normal and abnormal cardiac rhythms. The P, QRS, and T waves in normal sinus rhythm are shown in
panel A. Panel B shows a premature beat arising in the ventricle (arrow). Paroxysmal supraventricular tachycardia (PSVT) is shown
in panel C; this most likely is re-entry using an accessory pathway (see Figure 29–7) or re-entry within or near the atrioventricular
(AV) node. In atrial fibrillation (panel D), there are no P waves, and the QRS complexes occur irregularly (and at a slow rate in this
example); electrical activity between QRS complexes shows small undulations (arrow) corresponding to fibrillatory activity in the atria.
In atrial flutter (panel E), the atria beat rapidly, ~250 beats/minute (arrows) in this example, and the ventricular rate is variable. If a
drug that slows the rate of atrial flutter is administered, 1:1 AV conduction (panel F) can occur. In monomorphic ventricular tachycardia
(VT, panel G), identical wide QRS complexes occur at a regular rate, 180 beats/min. The electrocardiographic features of the
torsades de pointes syndrome (panel H) include a very long QT interval (600 ms in this example, arrow) and ventricular tachycardia
in which each successive beat has a different morphology (polymorphic VT). Panel I shows the disorganized electrical activity
characteristic of ventricular fibrillation.
Drugs may slow automatic rhythms by altering
any of the four determinants of spontaneous pacemaker
discharge (Figure 29–10):
• decrease phase 4 slope
• increase threshold potential
• increase maximum diastolic potential
• increase APD
Adenosine and acetylcholine may increase maximum
diastolic potential, and β receptor antagonists
(see Chapter 12) may decrease phase 4 slope. Blockade
of Na + or Ca 2+ channels usually results in altered threshold,
and blockade of cardiac K + channels prolongs the
action potential.
Anti-arrhythmic drugs may block arrhythmias
owing to DADs or EADs by two major mechanisms:
• inhibition of the development of afterdepolarizations
• interference with the inward current (usually through
Na + or Ca 2+ channels), which is responsible for the
upstroke
Thus, arrhythmias owing to digitalis-induced DADs
may be inhibited by verapamil (which blocks the
development of DAD by reducing Ca 2+ influx into the
cell, thereby decreasing sarcoplasmic reticulum Ca 2+
load and the likelihood of spontaneous Ca 2+ release
from the sarcoplasmic reticulum) or by quinidine
(which blocks Na + channels, thereby elevating the
threshold required to produce the abnormal upstroke).
Similarly, two approaches are used in arrhythmias
related to EAD-triggered beats (Tables 29–1 and
29–2). EADs can be inhibited by shortening APD; in
practice, heart rate is accelerated by isoproterenol infusion
or by pacing. Triggered beats arising from EADs
can be inhibited by Mg 2+ , without normalizing repolarization
in vitro or QT interval, through mechanisms
that are not well understood. In patients with a congenitally
prolonged QT interval, torsades de pointes
often occurs with adrenergic stress; therapy includes
β adrenergic blockade (which does not shorten the QT
interval) as well as pacing.