antiarrhythmic therapy

Question 1

what are the goals of antiarrhythmic therapy

Answer 1

• restore normal sinus rhythm and conduction
• prevent more serious/lethal arrhythmias (AADs are no guarantee to prevent arrhythmic sudden death)
• decrease clinical signs

Question 2

what are the clinical signs of arrhythmias

Answer 2

• syncope
• weakness
• poor performance
• congestive heart failure

Question 3

what causes arrhythmias

Answer 3

• scars in myocardium from ischemia, cardiomyopathy
• drugs, stress (adrenaline)
• genetic defects in ion channels or myocardial ultrastructure -> disturbance of ionic homeostasis in myocytes can trigger arrhythmias

Question 4

what type of channels control the ionic balance and are good targets for antiarrhythmic drugs

Answer 4

ion channels

Question 5

what makes up the supraventricular conduction system

Answer 5

• sino-atrial node
• atrial myocardium
• atrio-ventricular node

Question 6

what makes up the ventricular conduction system

Answer 6

• purkinje fibers
• ventricular myocardium

Question 7

what type of channel are nodal cells

Answer 7

Ca channel

Question 8

what type of channel are atrial myocardium, purkinje fibers, and ventricular myocardium

Answer 8

Na channel

Question 9

what is the drug target with atrial/ventricular myocardial cells and purkinje fibers

Answer 9

• block sodium channel
• block potassium channel

Question 10

what is the drug target in the SA and AV nodal cells

Answer 10

• block calcium channel
• block k channel

Question 11

what is the basic classification of antiarrthythmic agents based on predominant electrophysiologic properties

Answer 11

• class I: Na channel blockers
• class II: beta blockers
• class III: K channel blockers
• class IV: Ca channel blockers

Question 12

how are these drugs antiarrhythmic

Answer 12

alter the conduction velocity of the cardiac conduction system

• decrease rate of spontaneous depolarization (blocking entry of Ca, Na ions)
• increase length of repolarization (increase AP duration, make refractory period of all cells uniform)

change balance of autonomic tone
* sympathetic - parasympathetic

Question 13

what do Na channel blockers do

Answer 13

slow conduction velocity in myocytes and purkinje

• decrease slope of phase 0
• prolong repolarization (slope of phase 4 (Ia)

Question 14

what are the subtypes of Na channel blockers

Answer 14

• IA, IB, IC
• degree of blockage and effect on refractory period

Question 15

what are the IA Na channel blockers

Answer 15

quinidine, procainamide

Question 16

what are the IB Na channel blockers

Answer 16

lidocaine, mexiletine

Question 17

what are the IC Na channel blockers

Answer 17

flecainide, propafenone

Question 18

what is the clinical use of Na channel blocker: IA - quinidine

Answer 18

• IV and per os (nasogastric tube)
• HORSE: conversion of AF to sinus rhythm
• does NOT work for AF in dogs/cats

Question 19

what are the side effects of of Na channel blocker: IA - quinidine

Answer 19

• GI disturbances
• hypotension
• seizures
• pro-arrhythmia: bc it also blocks K channels
• vagolytic
• negative inotrope

Question 20

what is the clinical use of Na channel blocker - Class IA: procainamide

Answer 20

• relatively poor efficacy - works occasionally
• IV
• life threatening ventricular tachycardia (second line agent if lidocaine - class IB, doesnt work)
• supraventricular tachycardia
• per os: short half-life (3-5hr), makes oral dosing impractical

Question 21

what are the side effects of Na channel blocker - Class IA: procainamide

Answer 21

• reduced contractility (neg ionotrope)
• hypotension

Question 22

what is lidocaine

Answer 22

Na channel blocker - class IB

• IV only: ER situation
• 1st choice for life-threatening ventricular tachycardia
• not effective for supraventricular arrhythmias
• lower efficacy if hypokalemia
• works well

Question 23

what are the side effects of lidocaine

Answer 23

• minimal myocardial depressant effects
• vomiting, depression, seizures

Question 24

what is mexiletine

Answer 24

Na channel blocker - IB

• oral (less effective) analogue of liodcaine
• long-term tx of VT associated with myocardial dysfunction (not effective for supraventricular arrhythmias)
• weak monotherapy

Question 25

what are the side effects of mexiletine

Answer 25

**common** GI: anorexia, vomiting

Question 26

how do beta blockers work (class II)

Answer 26

block sympathetic tone to heart * decrease SA node discharge rate: HR goes down - neg chronotrop * slow AV node conduction: neg dromotrop * but also decrease contractility: **neg inotrop = side effect**

Question 27

what are the indications to use beta blockers

Answer 27

* arrhythmias caused by increased catecholamines (exercise, thyroid, stress) * sinus tachycardia, ventricular arrhythmias * second line agent, combined with class I or class III drugs

Question 28

what are 1st generation beta blockers

Answer 28

non-selective B1 and B2 receptor * propanolol: IV and PO (B2 effect: bronchocontriction)

Question 29

what are 2nd generation beta blockers

Answer 29

cardiac - selective for B1 * PO: atenolol, metroprolol * IV: esmolol

Question 30

what do class III K channel blockers do

Answer 30

* prolong repolarization (phase 3) * lengthens AP duration: QT interval increased (pro-arrhythmia)

Question 31

what are the indications to use sotalol

Answer 31

* PO * **class III: K channel blocker** * **first line oral** drug for tx of life-threatening VT * also effective for suppression of some atrial arrhythmias * **works well**

Question 32

what are the side effects of sotalol

Answer 32

* rare * neg inotrope bc of mild class II effects

Question 33

what is amiodarone (route & side effects)

Answer 33

PO and IV - **class III: K channel blocker ** * class I, class II, and class IV effects (less neg inotrope compared to sotalol) * side effects: reversible elevation of liver enzymes and neutropenia, hypothyroidism

Question 34

what is benzothiazepines (diltiazem)

Answer 34

* class IV: Ca channel blocker

Question 35

what is the primary effect of diltiazem

Answer 35

* to slow the conduction through the AV node * depress slope of depolarization

Question 36

what are the indications to use diltiazem PO and IV

Answer 36

* **slow the ventricular response rate in atrial fibrillation** * terminate supraventricular reentrant arrhythmias which rely on the AV node * no benefits for ventricular arrhythmias

Question 37

what are the side effects of diltiaxem

Answer 37

* anorexia * if overdosed: bradycardia, hypotension

Question 38

what is amlodipine

Answer 38

* different class of Ca-channel blocker * anti-hypertensive: relax vascular smooth muscle (no effect on cardiac conduction)

Question 39

what are class IV drugs: Ca channel blockers great for | heart problems

Answer 39

* atrial tachycardias * **atrial fibrillation**

Question 40

what are the side effects of using diltiazem PO

Answer 40

* mild neg inotrope * 2nd or 3rd degree AV block/bradycardia: dose-depenent * cats: anorexia * can be added to sotalol or digoxin to slow AVN conduction even more (monitor HR)

Question 41

what are the side effects of using diltiazem IV

Answer 41

* horse and dog: hypotension - but dose -dependent * sinus arrest, 2nd or 3rd degree AV block/bradycardia: dose-depenent (monitor BP and ECG during infusion)

Question 42

what are cardiac glycosides

Answer 42

* digoxin: PO * indirect antiarrhythmic effect: vagomimetic * slows AV node conduction by prolonging AV nodal refractoriness * **works for AFib only**

Question 43

cardiac glycosides - use

Answer 43

* **weak as monotherapy** * **only antiarrhythmic infication: AFib** * goal: slowing of ventricular response * best rate control if combined with a Ca channel blocker

Question 44

what are the adverse effects of digoxin

Answer 44

narrow therapeutic window and eady to cause toxicity * GI: anorexia, vomiting, diarrhea * cardiac arrhythmias (intracellular Ca overload -> ventricular arrhythmias) * neurological (depression) bc of high individual variablility, serum digoxin concentrations must be checked 5-7 days after starting digoxin