Arrhythmias Flashcards
class I
sodium channel blockers
class II
beta blockers
class III
potassium channel blockers
class IV
calcium channel blockers
class IA agents
quinidine, procainamide, disopyramide
class IB agents
lidocaine, mexiletine, phenytoin
class IC agents
flecainide, propafenone
class II agents
metoprolol, esmolol
class III agents
amiodarone, dronedarone, sotalol, dofetilide, ibutilide
class IV agents
verapamil, diltiazem
class I agents affect phase _ of the action potential
0
class IA cause Na channels to have a _______ recovery time
intermediate (intermediate potency)
class IA agents also inhibit _ channels
K+ (increasing action potential duration by prolonging repolarization)
class IB cause Na channels to have _____ recovery time
fast (low potency)
class IB ______ the action potential duration
decrease; shorten repolarization (opposite to IA agents)
class IC agents cause Na channels to have a ____ recovery time
slow (high potency)
effect of class IC agents on length of action potential duration
no effect
effects of quinidine on action potential
shifts phase 0 and phase 3 to the right, QT prolonged (torsades)
quinidine side effects that are mediated by blockade of autonomic nervous system receptors
anticholinergic effect (muscarinic receptors), increased HR, fast ventricular rate, hypotension (alpha receptor blockade)
therapeutic use of quinidine
limited, may be used for ventricular arrhythmias refractory to other therapies
other adverse effects of quinidine that lead to discontinuation
GI: diarrhea/n/v, cardiotoxicity, torsades, hypotension, cinchonism, increases plasma digitalis concentration and may precipitate digitalis toxicity
procainamide pearls
similar to quinidine but less anticholinergic effects, unique toxic effect: lupus erythematosus-like syndrome
disopyramide pearls
very anticholinergic, mostly used for a type of heart failure called hypertrophic cardiomyopathy
how is lidocaine administered
IV only (rapid first pass liver metabolism–> unsuitable for oral administration)
therapeutic use of lidocaine
ventricular arrhythmias only
adverse effects of lidocaine
it is lipophilic so crosses BBB so CNS effects– drowsiness, slurred speech, tremors, seizures
lidocaine effects on fast fibers
blocks Na channels–> channels unresponsive to stimulation for longer time–> channels in damaged tissue are in inactivated state longer–> decreases responsiveness/slows conduction in damaged tissue
what is mexiletine essentially
PO version of lidocaine
mexiletine therapeutic use
ventricular arrhythmias
mexiletine side effects
significant GI effects
flecainide mech
blocks sodium and some potassium channels
flecainide therapeutic use
atrial arrhythmias like AF/AFl
propafenone mech
blocks sodium and some potassium channels, some beta-blocking properties (structurally similar to propranolol)
propafenone therapeutic use
atrial arrhythmias like AF/AFl
what did the cardiac arrhythmia suppression trial demonstrate about flecainide and propafenone
they may actually exacerbate arrhythmia and worsen outcome in patients with structurally abnormal hearts (post-MI)
how do beta blockers have antiarrhythmic action
they block effects of endogenous norepinephrine on beta-one receptors
what are the actions of norepinephrine that lead to arrhythmia
increase the automaticity of normal and abnormal pacemaker cells, increase conduction velocity in the AV node
what do you see on the ECG after beta-blocker administration
prolongation of PR interval
beta blockers ____ the effective refractory period of AV node
increase
how are beta blockers able to prevent fatal arrhythmias after MI
the presence of norepinephrine may lead to augmented automaticity of cardiac muscle cells, allowing them to generate abnormal rhythms, but beta blockers block the effects of norepi
therapeutic use of beta blockers for arrhythmias
supraventricular arrhythmias: AF, AFl, paroxysmal atrial tachycardia
what causes “sudden death” after MI
ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation
esmolol pearls
short acting beta blocker given IV, can be used in a clinical situation to suppress arrhythmias related to excess norepi
class III mech
block K+ channels, prolong refractory period (repolarization)
amiodarone has mechanistic properties of which classes
ALL: blocks inactivated Na channels, blocks Ca channels, blocks K channels, blocks beta receptors
amiodarone therapeutic uses
oral therapy for severe ventricular arrhythmias (recurrent V tach or fib), also used for a fib and a flutter
PK profile of amiodarone
variable absorption and hepatic metabolism (CYPA3A4) to active metabolite, very long half-life of approx. 50 days, highly lipophilic with extensive volume of distribution
toxicity with amiodarone
PK profile explains multi-organ adverse effects: pulmonary fibrosis or pneumonitis, microdeposits in the cornea, thyroid toxicity (iodine-related, hypo or hyperthyroidism), skin blue-grey discoloration (smurf syndrome), photosensitivity, many others
dronedarone therapeutic uses
paroxysmal or persistent AFib or AFL
dronedarone is a derivative of _____
amiodarone; but it is free of iodine and less lipophilic than amio (less ADE but less effective)
sotalol mech
prolongs action potential by blocking K channels, non-selective beta blocker with class III effect
sotalol therapeutic uses
AFib/AFL, sometimes for ventricular arrhythmias
dofetilide therapeutic uses
AFib/AFL
what does dofetilide require
inpatient initiation with monitoring of QTc interval, creatinine clearance (renal dose adjustment), and screening for drug-drug interactions
dofetilide pearls
PO only, pure class III K channel blocker
Ibutilide pearls
pure class III K channel blocker, only available IV, higher risk of causing torsades
ibutilide therapeutic uses
cardioversion of AFib/AFL
calcium channel blockers mech for arrhythmias
decrease Ca current by blocking a fraction of the Ca channels participating in upstroke of AP–> slows conduction of AV node (slow response fibers). block activated and inactivated channels
electrophysiologic effects of calcium channel blockers
decrease AV node conduction velocity, increase AV node refractory period
effect of CCBs on ECG
prolongation of PR interval
therapeutic uses of CCBs
slows ventricular RATE to supraventricular arrhythmias: treatment of reentrant supraventricular tachycardia when reentry circuit involves AV node, reduces ventricular response in AFib and AFL
do not use CCBs in patients with ____
AV conduction problems, or severe ventricular dysfunction
other antiarrhythmic agents
adenosine, digoxin, magnesium
adenosine is a naturally occurring ____
nucleoside
adenosine acts on ____
specific adenosine receptors (A1)
why is adenosine’s use limited to the clinical setting
ultrashort half-life: given by rapid IV bolus administration, rapidly metabolized with a half-life of seconds
the adenosine A1 receptor is a ______ receptor
G-protein coupled receptor
adenosine therapeutic uses
acute termination of supraventricular tachycardia (SVT)
what is digoxin used for
controlling ventricular response to AFib (common in heart failure)
what is the mechanism of digoxin
increases vagal tone, slows conduction through AV node, decreases ventricular rate
what is magnesium used for
Torsades first line, used to manage a variety of arrhythmias that occur in the setting of hypomagnesemia
mech of magnesium
slows the rate of SA node impulse formation, prolongs conduction time. magnesium is necessary for movement of Ca, Na, and K and membrane stabilization
