Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
L-type calcium channels on cardiac cell membranes.
Slow calcium channels are responsible for depolarization
of sinus node and AV junctional tissues and for
initiation of excitation–contraction coupling in myocardial
cells. Calcium channel blockers have additional
properties including positive lusiotropy and vasodilation
and discussions of their utility in these settings can
be found in the positive lusiotropy (p. 422) and vasodilator
(p. 404) sections of this chapter respectively.
Calcium channel-blocking drugs slow the upstroke
velocity of sinus node and AV junctional cell action
potentials, resulting in slowing of sinoatrial and AV
junctional conduction times. They may also slow the
depolarization rate of the sinus node. Calcium channelblocking
drugs prolong the time for recovery from inactivation
of the slow calcium channel and, as a result,
markedly prolong the refractory period of the AV junctional
tissue. Calcium channel-blocking drugs are also
negative inotropic agents because of their effects on L-
type slow calcium channels during phase 2 of the action
potential in myocardial cells.
Because the primary effects of the calcium
channel-blocking drugs are on the sinus node and the
AV junction, these drugs are most effective for treating
supraventricular tachyarrhythmias. Although they
have been shown to suppress delayed afterdepolarizations
(DADs) that occur secondary to digitalis
intoxication and to depress automaticity in abnormally
automatic cells, clinically they are generally considered
not to be efficacious for treating ventricular
tachyarrhythmias.
CLASS I ANTIARRHYTHMIC DRUGS
Lidocaine (lignocaine)
Clinical applications
Lidocaine (lignocaine) is used clinically to treat acute
life-threatening ventricular arrhythmias in many different
clinical settings. Its rapid onset of action, effectiveness,
safety and short half-life make it ideal for acute
interventions. Its short half-life also allows rapid changes
in serum concentration so that lidocaine’s effects can
be titrated quickly. It is usually the most effective
antiarrhythmic drug one can use to treat a ventricular
arrhythmia. It does not affect supraventricular
tachyarrhythmias.
Mechanism of action
Lidocaine is a class Ib antiarrhythmic agent that is also
used for local anesthesia. It has little effect on atrial
conduction or refractoriness and is not used for atrial
tachyarrhythmias. Lidocaine can abolish both automatic
and re-entrant ventricular arrhythmias. Lidocaine
can abolish ventricular re-entrant arrhythmias either by
increasing or decreasing conduction velocity within the
circuit or by prolonging the refractory period.
The cellular actions of lidocaine are dependent on the
extracellular potassium concentration. When the resting
membrane potential is decreased, as when potassium
concentration is high, lidocaine acts by suppressing
the activity of fast sodium channels in a similar way
to quinidine and procainamide. Lidocaine has more
marked effects on automaticity, conduction velocity and
refractoriness in damaged cells (where resting membrane
potential is also often decreased) than in normal
cells.
Lidocaine can also hyperpolarize partially depolarized
cells and so can improve conduction in a region
of damaged myocardium. Lidocaine’s many potential
effects on variables that cause re-entrant arrhythmias
make it an especially effective drug for abolishing reentrant
arrhythmias. Lidocaine’s ability to hyperpolarize
partially depolarized cells gives it the ability to
suppress arrhythmias due to abnormal automaticity in
ventricular myocardium (e.g. accelerated idioventricular
rhythm).
Although lidocaine has no direct effect on early
afterdepolarizations (EADs), it may hyperpolarize or
accelerate repolarization in cells with EADs, indirectly
terminating the arrhythmia. However, in German shepherds
with inherited ventricular arrhythmias due to
EADs, lidocaine is not very effective. Lidocaine is effective
at suppressing DADs due to digitalis intoxication.
Because of this and because it is easy to use, lidocaine
is the preferred drug for the acute termination of digitalis-induced
ventricular tachyarrhythmias.
Formulations and dose rates
Lidocaine is supplied for intravenous administration in concentrations
ranging from 10 mg/mL to 200 mg/mL. Concentrations above
20 mg/mL are used for infusion rather than bolus administration.
Lidocaine is administered parenterally because it has a short halflife
and is extensively metabolized by the liver to toxic metabolites
after oral administration. Although intramuscular lidocaine administration
is feasible in the dog, clinical experience is limited at this
time.
Lidocaine is generally administered as an initial intravenous loading
dose followed by a constant intravenous infusion. If a loading dose is
not administered, maximum infusion rates will take 1–2 h to achieve
a therapeutic concentration. The initial loading dose in dogs is 2–
4 mg/kg IV administered over 1–3 min, followed by an infusion of
25–100 µg/kg/min. The dose is titrated while observing the electrocardiogram.
When the arrhythmia is suppressed, drug administration
is discontinued. Half the initial loading dose may need to be repeated
in 20–40 min if the arrhythmia recurs.
In cats the initial dose is 0.25–0.75 mg/kg IV, followed by an infusion
administered at 10–40 µg/kg/min. Cats more commonly develop
seizures with lidocaine. It must be used cautiously in this species.
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