antiarrhythmic therapy Flashcards
what are the goals of antiarrhythmic therapy
- restore normal sinus rhythm and conduction
- prevent more serious/lethal arrhythmias (AADs are no guarantee to prevent arrhythmic sudden death)
- decrease clinical signs
what are the clinical signs of arrhythmias
- syncope
- weakness
- poor performance
- congestive heart failure
what causes arrhythmias
- 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
what type of channels control the ionic balance and are good targets for antiarrhythmic drugs
ion channels
what makes up the supraventricular conduction system
- sino-atrial node
- atrial myocardium
- atrio-ventricular node
what makes up the ventricular conduction system
- purkinje fibers
- ventricular myocardium
what type of channel are nodal cells
Ca channel
what type of channel are atrial myocardium, purkinje fibers, and ventricular myocardium
Na channel
what is the drug target with atrial/ventricular myocardial cells and purkinje fibers
- block sodium channel
- block potassium channel
what is the drug target in the SA and AV nodal cells
- block calcium channel
- block k channel
what is the basic classification of antiarrthythmic agents based on predominant electrophysiologic properties
- class I: Na channel blockers
- class II: beta blockers
- class III: K channel blockers
- class IV: Ca channel blockers
how are these drugs antiarrhythmic
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
what do Na channel blockers do
slow conduction velocity in myocytes and purkinje
- decrease slope of phase 0
- prolong repolarization (slope of phase 4 (Ia)
what are the subtypes of Na channel blockers
- IA, IB, IC
- degree of blockage and effect on refractory period
what are the IA Na channel blockers
quinidine, procainamide
what are the IB Na channel blockers
lidocaine, mexiletine
what are the IC Na channel blockers
flecainide, propafenone
what is the clinical use of Na channel blocker: IA - quinidine
- IV and per os (nasogastric tube)
- HORSE: conversion of AF to sinus rhythm
- does NOT work for AF in dogs/cats
what are the side effects of of Na channel blocker: IA - quinidine
- GI disturbances
- hypotension
- seizures
- pro-arrhythmia: bc it also blocks K channels
- vagolytic
- negative inotrope
what is the clinical use of Na channel blocker - Class IA: procainamide
- 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
what are the side effects of Na channel blocker - Class IA: procainamide
- reduced contractility (neg ionotrope)
- hypotension
what is lidocaine
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
what are the side effects of lidocaine
- minimal myocardial depressant effects
- vomiting, depression, seizures
what is mexiletine
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
what are the side effects of mexiletine
common
GI: anorexia, vomiting
how do beta blockers work (class II)
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
what are the indications to use beta blockers
- arrhythmias caused by increased catecholamines (exercise, thyroid, stress)
- sinus tachycardia, ventricular arrhythmias
- second line agent, combined with class I or class III drugs
what are 1st generation beta blockers
non-selective B1 and B2 receptor
- propanolol: IV and PO (B2 effect: bronchocontriction)
what are 2nd generation beta blockers
cardiac - selective for B1
- PO: atenolol, metroprolol
- IV: esmolol
what do class III K channel blockers do
- prolong repolarization (phase 3)
- lengthens AP duration: QT interval increased (pro-arrhythmia)
what are the indications to use sotalol
- 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
what are the side effects of sotalol
- rare
- neg inotrope bc of mild class II effects
what is amiodarone (route & side effects)
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
what is benzothiazepines (diltiazem)
- class IV: Ca channel blocker
what is the primary effect of diltiazem
- to slow the conduction through the AV node
- depress slope of depolarization
what are the indications to use diltiazem PO and IV
- slow the ventricular response rate in atrial fibrillation
- terminate supraventricular reentrant arrhythmias which rely on the AV node
- no benefits for ventricular arrhythmias
what are the side effects of diltiaxem
- anorexia
- if overdosed: bradycardia, hypotension
what is amlodipine
- different class of Ca-channel blocker
- anti-hypertensive: relax vascular smooth muscle (no effect on cardiac conduction)
what are class IV drugs: Ca channel blockers great for
heart problems
- atrial tachycardias
- atrial fibrillation
what are the side effects of using diltiazem PO
- 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)
what are the side effects of using diltiazem IV
- horse and dog: hypotension - but dose -dependent
- sinus arrest, 2nd or 3rd degree AV block/bradycardia: dose-depenent (monitor BP and ECG during infusion)
what are cardiac glycosides
- digoxin: PO
- indirect antiarrhythmic effect: vagomimetic
- slows AV node conduction by prolonging AV nodal refractoriness
- works for AFib only
cardiac glycosides - use
- weak as monotherapy
- only antiarrhythmic infication: AFib
- goal: slowing of ventricular response
- best rate control if combined with a Ca channel blocker
what are the adverse effects of digoxin
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
