ANTIARRHYTHMIC DRUGS

DRUG MECHANISM EFFECTS THERAPEUTIC USE SIDE EFFECTS

CLASS 1- SODIUM CHANNEL BLOCKERS: depress phase 0 depolarization (conduction velocity) in fast response cells & can decrease automaticity
1A: prolong AP & increase refractory period; moderate effects on conduction in normal cells
QUINIDINE -Na channel blocker -increases threshold for excitability -primary use = treat reentry arrhythmias -prolongs QT interval- risk for torsades
(Quinaglute) -binds preferentially to open state of -decreases automaticity (esp in Purkinje) involving myocytes or Purkinje cells (that -hypotension due to α-adrenergic blockade
channel (tau = 3sec) -blocks potassium channels (prolong use fast sodium channel for AP) -high incidence diarrhea (30-50%)
-selectivity for: cells at higher HR, cells at refractory period) -variety supraventricular & ventricular -cinchonism (headache, dizziness, tinnitus)
less negative RMP -prolonged APs tachyarrhythmias at high dose
-QRS interval -well-tolerated in pts w/ congestive heart -avoid taking w/ phenobarbital or
-elicits EADs at slow HR (when [K] is low) failure phenytoin d/t induced quinidine metabolism
-α-adrenergic blockade -interacts w/ digoxin (digoxin serum
-atropine like effect (anticholinergic) level)
PROCAINAMIDE -Na channel blocker -lacks vagolytic & α-adrenergic blockade -3rd line for sustained VT after acute MI -fatal bone marrow aplasia
(Procan) -analog of procaine (local anesthetic) -slows conduction -short-term tx of supraventricular + -lupus-like syndrome
-prolongs AP duration & refractory period -QRS interval ventricular arrhythmias -hypotension
-torsades de pointes
DISOPYRAMIDE -Na channel blocker -does not prolong AP -maintain sinus rhythm in Afib or atrial flutter -torsades de points
(Norpace) pts -heart failure
-prevent VT or ventricular fib recurrence -metabolism accelerated by phenytoin
1B: no effect on AP; minimal effects in normal cells
LIDOCAINE -Na channel blocker -increased threshold excitability -acute suppression ventricular arrhythmias -CNS effects: seizures (very rapid
(Xylocaine) -binds preferentially to inactivated state of -decreases automaticity -must be given parentally b/c extensive first administration) & drowsiness, dysarthria &
channel (tau = 0.1sec, falls off b/w beats) -secondary effect: shorten AP by activating pass effect (IV bolus or infusion- modified w/ dysesthesia (more gradual increase in serum
-selectivity for: ventric cells (over atrial), K channels liver dx & HF) levels)
cells w/ fast rate, cells w/ less neg RMP - no significant effect on QT, PR or QRS -local anesthetic -depression cardiac function
interval duration
-reduces phase 4 slope
MEXILETINE -Na channel blocker -corrects congenital long QT syndrome -tx of ventricular arrhythmias -fatal bone marrow aplasia (tocainide only)
(Mexitil) -analog of lidocaine (modified to reduce caused by abnormal Na channel inactivation -combination w/ sotalol or quinidine -pulmonary fibrosis (tocainide only)
TOCAINIDE first-pass hepatic metabolism + permit oral INCREASES efficacy while DECREASING
(Tonocard) use) s/e
1C: minimal effect on AP; marked effects on conduction in normal cells
FLECAINIDE -Na channel blocker -increased threshold excitability -maintenance of sinus rhythm in pts w/ -proarrhythmic: esp in presence of severe
(Tambocor) -K channel blocker -decreases automaticity supraventricular tachycardias heart dz
-binds pref to open state (tau = 11sec) -can block potassium channels (prolong -life-threatening ventricular arrhythmias -blurred vision
-selectivity for cells at high HR but greater refractory period) -heart block (pts w/ conduction system dx)
depression at normal rates than 1A or 1B -does not cause EADs or torsades de -depression of LV function
-shorter AP  Purkinke cells pointes
-longer AP  ventricular cells -PR, QRS & QT intervals
PROPAFENONE -Na channel blocker -lacks vagolytic & α-adrenergic blockade -3rd line for sustained VT after acute MI -acceleration of ventricular response (pts w/
(Rythmol) -K channel blocker -prolongs PR and QRS duration -maintains sinus rhythm in SVT pts atrial flutter)
-slows conduction in fast-response tissues -bronchospasm
-sinus bradycardia
-exacerbation of HF
-increased frequency or severity of re-entrant
VT

MORICIZINE -Na channel blocker -effect persists for many hours after single -tx of ventricular arrhythmias
(Ethmozine) -analog of phenothiazine dose (active metabolites)
CLASS 2- β-ADRENERGIC BLOCKERS: block β-adrenergic influences on conducting system
PROPRANOLOL -blockade of β-adrenergic receptors (β1 in -AV conduction velocity -chronic ventricular arrhythmias -impotence, exacerbation of asthma, CV
(Inderal) myocardium) -reduce mortality in early period & -control ventricular rate in Afib or Aflutter effects (bradycardia, AV block, CHF)
SOTALOL (Betapace) -increase Ca/K/Cl currents (decrease Ca subsequently after acute MI -PSVT, symptomatic sinus tachycardia -CNS effects: sedation, sleep alterations
ESMOLOL (Brevibloc) overload) -DAD and EAD-mediated arrhythmias -catecholamine-related ventric arrhythmias -use w/ caution in diabetics (can mask
-propranolol = non-selective -PR interval -blocks epinephrine-induced hypokalemia hypoglycemia)
-esmolol = β1 selective -useful in treating congenital long QT
syndrome triggered by physical or emotional
stress
CLASS 3- POTASSIUM CHANNEL BLOCKERS: prolong duration of AP  increase refractory period
AMIODARONE -prolongs AP duration & refractory -noncompetitive blockade of α- & β- -FDA: only for life-threatening ventricular -potentially lethal pulmonary fibrosis
(Cordarone)Anti period adrenergic & muscarinic receptors arrhythmias refractory to all other forms -hyperthyroidism or hypothyroidism
 -blocks sodium channel (phase 0) -SA node automaticity therapy -hypotension
-blocks calcium channels (phase 2) -AV node conduction velocity -powerful inhibitor of pacemaker -pneumonia (early toxicity)
-mech for antiarrhythmic effect unclear -prolongs AV node & ventricular refractory automaticity -hepatic dysfxn
periods -long term oral use: Afib & atrial flutter; -neuromuscular sxs
-PR, QRS, & QT intervals SVT; life-threatening (sustained) VT -hypo- or hyperthyroidism
-causes sinus bradycardia -IV use: Vfib, sustained VT -corneal microdeposits  blurred vision
-long half life (SS can require 1 year), slow -photosensitivity, GI disturbances
onset (need large dose in ER situations) -C: pulmonary dz or hyperthyroidism,
-additive effect w/ other drugs increasing QT
interval,  effect of warfarin & digoxin
DRONEDARONE -noniodinated form of amiodarone -same, but lower efficacy -Afib & Aflutter -fewer side effects but lower efficacy
(Multaq) -stronger anti-adrenergic effects than -causes dose-dependent QT prolongation -GI disturbances (diarrhea, N/V)
amiodarone -torsades de pointes is rare -fatal hepatotoxicity (monitor hepatic
-decreases inward rapid Na and L-type Ca enzyme)
currents -increased mortality in severe heart failure
pts
-avoid taking w/ CYP3A4 inhibitors
(Ketoconazole) or metabolized by CYP2D6
(Digoxin)
SOTALOL -K channel blocker, non-selective β-blocker -ventricular & atrial arrhythmias -dose-dependent Torsades de pointes
(Betapace) (doesn’t circumvent like Amiodarone does)
IBUTILIDE -K channel blocker, Na channel activator -Afib (acute IV conversion)
(Corvert) -prolongs AP duration
DOFETILIDE -K channel blocker -Afib -torsades de pointes
(Tikosyn) -no extracardiac pharmacological actions
CLASS 4- CALCIUM CHANNEL BLOCKERS (CCB): depresses slow response AP in AV & SA nodes
VERAPAMIL -blocks voltage gated L-type calcium -depresses slow response AP in AV & SA -control of ventricular rate in Aflutter & -hypotension (bolus)
(Isoptin, Calan) channels (non-dyhydropyridines, have nodes (where depolarization mediated Afib -severe sinus bradycardia or AV block (B-
DILTIAZEM effects at AV & SA node) primarily by calcium influx- phase 2) -PSVT due to reentry involving AV node blockers)
(Cardizem) -work in slow-response tissues (sinus + AV -slows HR -prophylaxis to convert supraventricular -cardiac arrest (ventricular tachycardia)
nodes) -PR interval tachycardia to sinus rhythm
-AV node conduction velocity
CLASS 5- OTHER
ADENOSINE -acts through A1 adenosine receptors to -hyperpolarization & slowing SA node firing -acute conversion of PSVT due to reentry -atrial fibrillation
(Adenocard) activate potassium channels -shortening AP of atrial cells involving AV node (highly effective) -short-lived d/t rapid deamination by
-inhibits effects of increased cAMP -depression conduction vel through AV node -IV bolus (effects transient- max 10-20sec) adenosine deaminase
-works in atrium, sinus and AV nodes -effect blocked by theophylline and -acute termination of re-entrant -transient asystole
caffeine (use larger dose) supraventricular arrhythmia
-DAD-mediated ventricular tachycardia
ATROPINE -muscarinic blockade - acetylcholine induced activation of K -sinus bradycardia (e.g., acute MI) -hot as a hare, dry as a bone, red as a beet,
channels thru M2 receptors blind as a bat, mad as a hatter
- spont phase 4 depolarization SA node
DIGOXIN -stimulates cardiac contractility via block of -increases vagal tone -control of ventricular rate in Afib & -one of most prevalent adverse drug
(Lanoxin) Na/K-ATPase   amount of intracellular -suppresses AV node activity via Aflutter reactions encountered (digitalis
Ca2+ baroreceptor reflex & depresses SA node intoxication): arrhyth-mias any type, GI &
-works in atrium and AV nodes -conditions heart to be more responsive to neuro disturbances
acetylcholine -metabolism accelerated by phenytoin and
-increases phase 4 slope rifampin
-interaction w/ diuretics, amphotericin B,
corticosteroids (potentiate digitalis-induced
arrhythmias)
MAGNESIUM -unclear mech of action -can work even if serum Mg normal -prevention recurrent episodes of torsades -does not effect QT interval
-possibly compete w/ Ca at transport site of -1-2 g given IV (no evidence oral Mg works -may successfully treat digoxin-related
Ca channel even if it restores serum Mg) arrhythmias
-prevention of hypomagnesemia

MECHANISMS OF ARRHYTHMIAS: abnormality in rate, regularity, site of origin, and/or sequelae of activation (range in severity)
Abnormalities of impulse generation
ALTERED NORMAL AUTOMATICITY -change in spontaneous phase 4 depolarization (normally limited to SA node & His-Purkinje fibers
-examples: sinus tachy/brady
-cardiac cells grouped into unstable RMPs (SA node, part of AV node, His-Purkinje cells) & those with stable RMPs
 strategies to reduce rate spontaneous discharge: decrease slope phase 4 (β-blockers), increase threshold potential (Na channel blockers, Ca channel
blockers), increase MDP (adenosine, acetylcholine), increase/prolong AP duration (K channel blockers)
-favoring rapid phase 4 depolarization:
1. SNS (catecholamines)
2. hypokalemia
3. cell damage (ischemia, myocardial stretch, trauma)
4. drugs (atropine, cardiac glycosides- His-Purkinje
-favoring slow phase 4 depolarization:
1. PSNS- acetylcholine
2. hyperkalemia
3- drugs (class 1 antiarrhythmics- quinidine, verapamil, propranolol)
-any type of cell in heart can manifest spontaneous phase 4 depolarization when damaged or subjected to conditions such as hypoxia
TRIGGERED IMPULSES -normal action potential is interrupted or followed by abnormal depolarization
1. DAD- secondary depolarizations that occur after full depolarization has developed
-phase 0 carried by Na w/ fast conduction
-factors:  intracellular Ca load (ischemia, cardia glycosides) &  SNS activity
2. EAD- secondary depolarizations that occur before repolarization is complete
-phase 0 may be carried by Ca, Na or mixture
-factors: prolonged QT interval (delayed repolarization) or cell damage (hypoxia, myocardial stress)
Abnormalities of conduction
REENTRY -requires abnormal conduction pathway to form self-perpetuating circuit (arrhythmia re-excites/re-enters region already depolarized)
-common properties: divided conduction pathway, unidirectional block to conduction, slow conduction
-suites & conditions promoting reentry arrhythmia: regions of anatomically split pathways, regions affected by ischemia or other injury, reentry in AV node
(PSVT)
-AV node has two parallel tracks cells (α & β): one has fast conduction by long refractory period & other has slow conduction but short refractory period
-normally, they extinguish each other at bundle His and only conduct forward into ventricle
-but in ischemia, 2 tracks generate reentry entirely within AV node w/ fast conduction times
-examples: WPW syndrome, functional reentry w/ EAD
-treatment: decrease conduction velocity, increase refractory period (if reentry process broken even once, will terminate arrhythmia)
-therapy:
1. for fast (sodium) conducting cells- class 1A or 1C (decrease conduction rate) or class 3 drugs (prolong refractory period)
2. for slow (calcium) conducting cells- CCBs (decrease conduction rate), class 3 drugs (prolong refractory period)
TREATMENT BY DIAGNOSIS
CONDITION MECHANISM/EFFECTS TREATMENT NOTES
Premature Atrial or Ventricular Contractions:
PACs altered P-wave morphology, compensatory pause,
PVCs narrow QRS -remove source of increased spontaneous activity -reasons serious concerns: frequent PVCs, runs of
-β-blockers consecutive PVCs, multiform PVCs, PVCs after acute MI,
PVCs falling on T wave previous beat
Atrial Arrhythmias:
SVT -enhanced automaticity acute: -DC cardioversion generally only if symptomatic & >48hrs
-DAD-related automaticity -restore sinus rhythm (DC cardioversion) duration (perfusion in periphery can lead to concern for
-reentry w/in the atria -control ventricular response (AV node block) stroke)
A-FLUTTER -stable re-entry circuit w/in the RA chronic:
-continual AV stimulation w/ rapid, irregular ventricular -maintain normal (sinus) rhythm
rate -class 1 antiarrhythmic drug (Tau > 1sec) or class 3
AFIB -disorganized, functional re-entry -control ventricular response (AV node block)
-most commonly in elderly, assoc w/ CHF
UNRESPONSIVE potential problems: rhythm control: -patient would also be put on anticoagulant
AFIB -insufficient ventricular filling – reduced exercise -try to terminate arrhythmia & return control of HR to SA -focal ablation if drugs not therapeutic
capacity node (relies on class IA/C & class 3 drugs)
-stroke from thrombus formation- treat w/ anticoagulants rate control:
-risk of vfib -if atrial arrhythmia cannot be eliminated, concern fast
atrial rate will cause ventricular arrhythmia (can be
fatal)- use CCBs, BBs or digoxin to slow conduction
through AV node & keep ventricular rate <80bpm
Arrhythmias involving AV node (primarily):
PSVT -rerentry within AV node, episodic acute: -focal ablation is persistent & common (decreased ability
-occurs above bundle of His -vagal maneuvers to function)
 -properties & treatment determined by calcium AP -adenosine, CCBs (verapamil)
chronic:
-CCBs, β-blockers, digoxin
Arrhythmias involving accessory pathway & AV node:
WPW SYNDROME -reentry arrhythmia involving AV node & access pathway acute: -chronic tx = focal ablation
-two variants: w/ or w/out pre-excitation (wide QRS) -amiodarone or DC conversion (w/ high persistent
rates)
AV Block:
AV BLOCK -inability of impulses to enter ventricle from atria -identify & remove cause -can be partial or complete block
-increased vagal tone, MI, drug induced (digoxin, -pacemaker
verapamil, β-blockers, clonidine)
Ventricular Arrhythmias
TOSADE DE -EAD: triggered activity  functional reentry acute: torsade de pointes  Vtach  Vfib
POINTES -genetic (long QT syndrome): increases SNS activity  -eliminate cause of EAD
high catecholamines -magnesium (acquired), isoproterenol (acquired)
-acquired (drug or pathology related): cell damage chronic:
(hypoxia, myocardial stretch), slow HR, hypokalemia, -β-blocker (genetic)
prolonged QT interval (delayed repolarization), drug- -pacing (acquired)
induced (antiarrhythmics, antidepressants)
VFIB -disorganized reentry arrhythmias acute: -life threatening medical emergency
-DC conversion
-amiodarone, lidocaine, procainamide
-pacing
chronic:
-ICD (treatment of choice)
-amiodarone, Na channel blocker (class 1), K
channel blocker (class 3)
Others:
SINUS -rate below 60bpm acute: first choice to correct precipitating event
BRADYCARDIA -increased PSNS activity -atropine
chronic:
pacemaker

SINUS -rate about 100bpm -β-blockers

TACHYCARDIA -increases SNS activity
-ischemia (MI)

TACHYARRHYTHMIA -similar to tachycardia

-rapid heart rhythm d/t abnormal or premature impulse
-can lead to presyncope, syncope or cardiac arrest

BRADYARRHYTHMIA -similar to bradycardia

-slow heart rate d/t failure of impulse initiation
-can lead to presyncope, syncope or cardiac arrest
FAST RESPONSE CELL SLOW RESPONSE CELL

K BLOCKER NA BLOCKER

CA BLOCKER BETA BLOCKER