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Chapter 23 - Antiarrhythmic agents

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What is an arrhythmia?
an abnormality in the rate, regularity, or site of origin of the cardiac impulse or a disruption in impulse conduction such that the normal sequence of atrial and ventricular activation is changed
What are arrhythmias associated with?
the imbalance of the parasympathetic and sympathetic branches of the ANS; changes in serum electrolyte concentrations (K+ and Ca++); hypoxemia; acidosis; changes in concentration of carbon dioxide; excessive stretch of cardiac tissue; mechanical trauma; myocardial disease states (CHF and viral myocarditis); numerous drugs; ischemia and infarction of the heart muscle
What are Class I drugs?
local anesthetic agents and membrane stabilizers
How can Class I drugs control arrhythmias?
by enhanced automaticity
What is the original and prototypical Class I drug?
quinidine
What are Class II drugs?
B-blockers
What do Class III drugs produce?
a prominent prolongation of the action potential, thereby extending the refractory period
What are Class IV drugs?
calcium channel blockers
Class I drugs are most frequently used to treat what?
ventricular tachyarrhythmias
What is the common mechanism of action of Class I drugs?
blockade of fast sodium channels in the myocardial cell membrane
What are the Class IA agents?
quinidine, procainamide, and disopyramide
What do Class IA agents do?
depress conductino in normal and abnormal cardiac tissue and prolongs repolarization
What are the Class IB agents?
lidocaine and its derivatives (tocainide and mexiletine) along with phenytoin
What are Class II drugs useful for treating?
supraventricular and ventricular tachyarrhythmias
What are Class III drugs commonly used to prevent?
sudden death due to ventricular tachyarrhythmias
Class III drugs can be effective in suppressing what?
ventricular arrhythmias
How do Class IV drugs act?
by inhibiting the function of the slow L-type calcium channels on cardiac cell membranes
What type of inotropic agents are calcium channel blocking drugs?
negative
What is the obvious drug of choice when severe sinus bradycardia or sinus arrest is presented secondary to vagal discharge and accumulation of acetylcholine?
atropine
What is epinephrine indicated for?
in attempts to restart the heart after cardiac arrest
Does quinidine have direct or indirect effects on cardiac rhythmicity?
both
What is quinidine?
a Class I antiarrhythmic agent
The capability of quinidine to directly prolong the refractory period of atrial fibers is thought to account for what?
its ability to convert atrial fibrillation to sinus rhythm
What has limited the use of quinidine?
formulations are difficult to obtain
Quinidine has generally been less successful in treatment of what in small dogs?
atrial fibrillation
Quinidine has been used in the treatment of atrial fibrillation in what animal?
horses
Procainamide is more effective in controlling what?
ventricular arrhythmias rather than atrial arrhythmias
What is procainamide?
a Class I antiarrhythmic agent
What is phenytoin?
a Class I antiarrhythmic agent
What characteristic does phenytoin exert in the heart?
antiarrhythmic activity
Why is phenytoin classified as a Class IB drug?
because it minimally shortens the refractory period
In general, phenytoin is considered to be effective in controlling what?
digitalis-induced arrhythmias of all types and is useful in treating ventricular arrhythmias
What is the IV dose for phenytoin?
5-10 mg/kg at an infusion rate of about 25-50 mg/min
What is lidocaine?
a Class I antiarrhythmic agent
Lidocaine is a local anesthetic drug that has been found to exert what effect?
antidysrhythmic action
Lidocaine can be used in treating what?
ventricular tachyarrhythmias
Lidocaine is not recommended for controlling what?
supraventricular arrhythmias
Which species is particularly susceptible to adverse effects of lidocaine and therefore need to be dosed carefully?
cats
IV infusions of lidocaine are used in horses to treat what?
postoperative ileus
What is mexiletine?
a Class I antiarrhythmic agent
What is mexiletine indicated for treatment of?
chronic treatment of ventricular tachyarrhythmias in dogs
What are the toxic effects of mexiletine?
vomiting and disorientation/ataxia
What is propranolol?
a Class II antiarrhythmic agent
What is the mechanism of action for propranolol?
it slows the rate of spontaneous discharge of the SA and ectopic pacemakers and slows both antegrade and retrograde conduction through anomalous pathways of the heart
Propranolol is well absorbed from what and is eliminated largely by what?
the gut; the liver
What is atenolol?
a Class II antiarrhythmic agent
What is atenolol used for in dogs and in combination with what?
slow the heart rate in patients with atrial fibrillation combined with digoxin
What is atenolol used for?
slow heart rate with atrial fibrillation, treat supraventricular tachycardia and ventricular tachyarrhythmias and is used in attempts to prevent sudden death in dogs with severe subaortic stenosis
What is the dose for atenolol in dogs?
6.25-50 mg every 12 hours orally
What is esmolol?
a Class II antiarrhythmic agent
What is esmolol used for?
acute termination of supraventricular tachycardia
Which Class II antiarrhythmic agent is ultrashort-acting and used commonly for intravenous administration?
esmolol
What is metoprolol?
a Class II antiarrhythmic agent
What is metoprolol more effective in blocking?
B1 receptors of the heart
Metoprolol may be the B-blocking agent in patients with a history of what?
COPD
Beta-blocking agents should be administered with caution in patients with what?
reduced cardiac reserve
What is carvedilol?
a Class II antiarrhythmic agent (a 3rd generation beta blocker)
What is the generic of carvedilol?
coreg
What is the generic of metoprolol?
lopressor
What is the generic of propranolol?
inderal
What is amiodarone?
a Class III antiarrhythmic agent
What is the generic of amiodarone?
cordarone
What should be monitored during treatment with amiodarone and why?
thyroid function because amiodarone inhibits T3 and T4 secretion from canine thyroid glands
What is sotalol?
a Class III antiarrhythmic agent
What is sotalol as effective as quinidine in doing?
treating various arrhythmias
What is a major indication of sotalol?
treating severe ventricular tachyarrhythmias and syncope
How much of sotalol is metabolized?
less than 1%
Elimination of sotalol is via what?
renal clearance and is linearly related to the GFR
The drug dose of sotalol must be decreased in which animals?
animals that have compromised renal function
Sudden cessation of sotalol can produce what?
fatal ventricular arrhythmias
What is verapamil?
a Class IV antiarrhythmic agent
What is diltiazem?
a Class IV antiarrhythmic agent
Verapamil has application in several types of what?
atrial arrhythmias