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