Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
Table 17.6 Common arrhythmias and drugs used in their treatment
Ventricular arrhythmias: hemodynamically
important VPCs or Vtach
Supraventricular arrhythmias:
hemodynamically importanty SVPBs or
atrial fibrillation
Both ventricular and supraventricular
arrhythmias
Acute (intravenous)
1. Lidocaine (Class I) [5+]
2. Procainamide (Class I )[1+]
3. β-blockers (Class II) [1+]
1. Procainamide (Class I) [1+]
2. CCB: Diltiazem (Class IV) [2+]
3. β-blockers (Class II) [1+]
4. Quinidine (Class I, only horses) [1+]
1. Procainamide (Class I) [1+]
2. β-blockers (Class II) [1+]
Chronic (oral)
1. Sotalol (Class III and II) [3+]
2. Amiodarone (Class III, II and IV) [2+]
3. Procainamide (Class I) [1+]
4. Mexiletine (Class I) [1+]
5. β-blockers (Class II) [1+]
– not generally used as monotherapy but rather
combined with a Class I
1. Amiodarone (Class III, II and IV) [2+]
2. CCB: Diltiazem (Class IV) [2+]
3. β-blockers (Class II) [2+]
4. Digoxin (Class V) [2+]
5. Quinidine (Class I, only horses) [1+]
1. Amiodarone (Class III, II and IV) [2+]
2. β-blockers (Class II) [1+]
Note: Class I antiarrhythmics work on Na + channels, Class II are beta-blockers, Class III work on K + channels (prolong action potential), Class
IV are calcium channel blockers, Class V is digoxin and some agents have properties from more than one class. All agents are scored relative
to how often they are used clinically to manage heart disease 1+ to 5+ where 5+ is the most common.
so-called ‘membrane stabilizers’. Their common mechanism
of action is the blockade of a certain percentage
of the fast sodium channels in the myocardial cell membrane.
Sodium channel blockade results in a decrease in
the upstroke (phase 0) velocity of the action potential
in atrial and/or ventricular myocardium and Purkinje
cells. The upstroke velocity is a major determinant of
conduction velocity. Consequently, class I drugs slow
conduction velocity in normal cardiac tissue, abnormal
cardiac tissue, or both.
Class I agents have variable effects on repolarization.
Some of them prolong repolarization while others
shorten it or have no effect. Primarily on the basis of
differences in repolarization characteristics, class I
agents are subdivided into classes Ia, Ib and Ic.
● Class Ia agents include quinidine, procainamide and
disopyramide. These agents depress conduction in
normal and abnormal cardiac tissue and prolong
repolarization.
● Class Ib agents include lidocaine (lignocaine) and its
derivatives, tocainide and mexiletine, along with
phenytoin. Class Ib agents do not prolong conduction
velocity in normal cardiac tissue nearly as much
as class Ia drugs. They do, however, have profound
effects on conduction velocity in abnormal cardiac
tissue. They also shorten the action potential duration
by accelerating repolarization. A greater degree
of shortening occurs in fibers that have a longer
action potential duration. Consequently, this effect
is most profound in Purkinje fibers and does not
significantly alter the effective refractory period of
normal atrial and ventricular muscle. In contrast,
class Ib agents may prolong the effective refractory
period of damaged myocardium.
● Class Ic antiarrhythmic drugs include encainide and
flecainide. These drugs slow conduction and have
little effect on action potential duration.
Class II
Class II drugs are the β-adrenergic blocking drugs and
are useful for treating both supraventricular and ventricular
tachyarrhythmias. Although few tachyarrhythmias
are the direct result of catecholamine stimulation,
β-adrenergic receptor stimulation by catecholamines
commonly exacerbates abnormal cellular electrophysiology.
This can result in initiation or enhancement of a
tachyarrhythmia. β-Blockers have additional properties
including positive lusiotropy and neuroendocrine modulation
in heart failure and further discussion of these
uses can be found in the positive lusiotropy (p. 422) and
neuroendocrine modulation (p. 412) sections of this
chapter respectively.
Drugs that block β-adrenergic receptors do not have
direct membrane effects at clinically relevant concentrations.
Consequently, their action is indirect and related
to blocking catecholamine enhancement of abnormal
electrophysiology or related to other effects of the drug.
An example of the latter is β-adrenergic receptor blockade
resulting in a decrease in myocardial contractility
and so in myocardial oxygen consumption. The resultant
improvement in myocardial oxygenation might
improve cellular electrophysiology and reduce arrhythmia
formation.
Class II drugs are most commonly used to alter the
electrophysiological properties of the AV junction in
patients with supraventricular tachyarrhythmias. β-
Receptor blockade at the AV junction results in an
increase in conduction time through the AV junction
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