Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

DRUGS USED TO TREAT TACHYARRHYTHMIAS
A
B
Fast sodium
channels
K + Na +
Na 2+ Ca 2+
Cardiac cell
Outward potassium
current
Cardiac cell
Slow calcium
channels
Slow calcium
channels
Slow sodium
channels
formation of impulses that arise from ectopic foci and
have spontaneous activity or the abnormal propagation
of impulses, where an extra anatomical or functional
circuit exists so that the electrical impulse may take two
possible pathways with different conduction velocities
and refractory periods. The latter mechanism is termed
re-entry.
Abnormal automaticity is a common form of abnormal
impulse formation in small animals. In this abnormality,
partly damaged cells become partially depolarized,
attaining a resting membrane potential similar to automatic
cells in the heart, such as the sinus node. When
this occurs these cells attain the property of automaticity.
When they depolarize at a rate faster than the
normal pacemaker (i.e. automatic) cells, they take over
control of the heart rate, sometimes for only one beat
and at other times for long periods. All forms of abnormal
impulse arrhythmia tend to be exacerbated by ischemia,
high catecholamine concentrations and electrolyte
imbalances, particularly decreased potassium and magnesium
concentrations. Other forms of abnormal
impulse formation are early and delayed or late afterdepolarizations
and triggered activity.
Outward potassium
current
Fig. 17.1 Generation of action potentials in (A) normal
myocardial cells and (B) normal pacemaker cells.
● During electrical diastole ionic balances are restored
by membrane pumps that exchange sodium for
potassium and calcium for sodium.
Pacemaker cells (SA and AV nodes), ischemic
myocardial cells (Fig. 17.1B)
● The initial part of the action potential in these cells
is due to a slow inward calcium current. This results
in the initial part of the action potential being very
slow, thus slowing conduction through the SA and
AV nodes. This results in a delay between atrial and
ventricular contraction, allowing time for adequate
ventricular filling.
● Diastolic depolarization occurs because of a steadily
declining outward potassium current and an increasing
slow diastolic inward, predominantly sodium,
current. The inward sodium current eventually reaches
a threshold so that calcium ions start to flow in, hence
initiating another action potential – automaticity.
Arrhythmias
Arrhythmias originate in either the atria (supraventricular
arrhythmias) or the ventricles (ventricular arrhythmias).
They can arise as a result of either the abnormal
DRUGS USED TO TREAT
TACHYARRHYTHMIAS
The effective treatment of tachyarrhythmias is predicated
on an accurate rhythm diagnosis and a working
knowledge of the available antiarrhythmic drugs. The
reader is referred elsewhere to learn rhythm diagnosis.
Classes of antiarrhythmic agents
The drugs used to treat supraventricular and ventricular
tachyarrhythmias can be divided into separate classes
based on their generalized mechanisms of action.
Antiarrhythmic drugs exert their effects primarily by
blocking sodium, potassium or calcium channels, or β-
receptors. This classification scheme is somewhat helpful
clinically when deciding to use particular drugs for specific
arrhythmias. However, clinical experience with
these drugs is the more important means of determining
efficacy of various drugs to suppress different tachyarrhythmias.
The common arrhythmias, the mechanisms
responsible for their generation and the drugs most
commonly effective clinically are listed in Table 17.6.
The doses of the common antiarrhythmic agents are
listed in Table 17.7.
Class I
Class I drugs are most frequently used to treat ventricular
tachyarrhythmias, although they may also be used
to treat supraventricular tachyarrhythmias. They are the
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