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Flashcards in antiarrhythmics 63/64 Deck (68):


Class 1A
inhibits Na+ channels but also K+ channels
used for variety of arrhythmias, but limited by SEs
increased used for vfib, *Brugada syndrome (inherited ion channelopathy-->vfib)*: can also be stopped with cardioversion, and afib in short-QT syndrome

past: used to keep cardioverted a fib pts in the cardioverted state



Class 1A
quite similar to quinidine except K+ channels are inhibited by an *acetylated hepatic metabolite (NAPA)
*only IV use*



Class 1B
rapidly interact with phase 0 Na channels, shortens phase 3 depolarization, dec. AP duration and ERP
*inhibition of small population of late opening sodium channels still open during the AP plateau (opened more by ischemic conditions)*
emergent ventricular arrhythmias, during MI
decrease slope phase 4
abolishes ventricular reentry
stops TdP because decreases AP duration
*IV only* (1st past effect: dec. action and increases toxic metabolites)

MOA: not always logical, can stop reentry via decreasing AP duration?
stop torsades by reducing EAD



Class 1C
reserved for severe cases resistant to other drugs for (FA: SVTs, including afib; only last resort in refractory VT)
block phase 0 Na+ the most, markedly suppresses phase 0 slope, slows conduction
inhibits some K+ channels, but no net effect as it blocks late Na+ channels as well
increases threshold for phase 0 and decrease slope of phase 4 (both reduce abnormal automaticity)



Class II
non-selective (B1, B2-block)
reduces adrenergic-driven arrhythmic death after MI
membrane stabilization at unacceptably high doses-not used this way



Class II
B1-selectivity, less bronchospasm
partial agonist activity (ISA) may decrease risk of too much suppression of normal cardiac function



Class II
short duration of action (only IV)
acute arrhythmias during emergent situations, surgery



Class III: block K+ channels
actions similar to I, II and IV, decrease cell-to-cell coupling, slows functional movement of AP, slows velocity of AP

severe and refractory (resistant) SVT and Vtach, combined with auto ICD (reduces how often shock must deliver shocks: "reduced tachyarrhythmic burden")
severely limited by SEs
FA: afib, aflutter, vtach

*fast IV, slow oral*
may be used emergently when lidocaine not recommended



Class III
inhibits only K+ channels (mimics NAPA) prolongs phase 3, no multiple mechanisms like amiodarone
mostly for SVTs, i.e. afib
corrects reentry phenomenon



Class IV



Class IV



miscellaneous (not a class)
synthetic form, *IV*
used to tx emergent arrhythmias, short duration
*stops acute PSVTs (paroxysmal)* (due to WPW or AV nodal origin)
*very short duration of action* (less than 15s)

decreases conduction and abnormal AP formation in AV node by dec. Ca2+ influx and increasing *ACh-sensitive phase 4 K+ current (hyper polarizing resting potential)*
also prolongs AV node refractory period


Class I antiarrhythmics block

Na+ channels


Class II antiarrhythmics block..

Ca2+ channels


Class III antiarrhythmics block

K+ channels


APs occur in phases

Phase 0: upstroke: fast depolarization -85mV to 0mV
Phase 1: early-fast repolarization (we ignored this)
Phase 2: important plateau phase (drugs affect here)
Phase 3: repolarization phase back to resting
Phase 4: in between phase (resting, diastole)


AP phases travel from place to place in heart

start in SA node

also change shape based on location


threshold for phase 0

need something to get it to threshold, will get up the rest on on

some tissues can do this on own, i.e. SA node, AV node, purkinje: have *automaticity*
steepest slope, reaches AP *1st*-->atria-->AV node-->Purkinje fibers-->rest of heart
*before these tissues reach threshold on their own*

when these other tissues reach threshold on own: pathological


channels for phase 0

1st reach threshold
then Na+ enters cell (also Ca2+) neutralize the internal negative charge: upstroke: goes from -85 mV to 0mV
very steep, much Na+ coming in

*some Na+ channels may remain open, esp. during ischemia: late Na+ channels*


Phase 1 channels

some K+ outflux, we mostly ignore


Phase 2 channes

Ca2+ comes in, keeps above 0 mV
then close! and K+ channels open, K+ flows out, some downward movement


Phase 3

more K+ flowing out, back down to resting potential


Phase 4

refractory to AP from phase 0-beginning phase 4

only digoxin acts here
leakage of Na+ and Ca2+ in, K+ out, can influence slope of phase 4 (if flat: no net change)
if more + charge in, may reach threshold, shows automaticity (pacemaker cells)

Na+/K+ ATPase (sodium pump) (Na+ out, K+ in)

Na+/Ca2++ exchanger (Ca2+ out, Na+ in)


Na+ channel blockers may ??

suppress slope of Phase 0, may depress rate of depolarization


abnormal AP can spontaneously arise from cardiac sites other than the SA node (sometimes called ectopic sites) if ??

K+ too high or too low (e-lyte imbalance)
scar tissue
abnormal cardiac anatomy (WPW)
abnormal automatic nerve activity

*abnormal AP formation*: steep slope in phase 4
(also abnormal conduction)


abnormal AP formation

EADs and DADs
triggered by a previous AP


early after depolarizations (EADs) that "pop out" of phase 3

should be refractory!
esp. in Purkinje and Ventricles
can be due to ischemic conditions or if duration of AP is lengthened, slow HR, low EC K+ and certain AP-prolonging drugs

if happen earlier, involve Ca2+ current, if later, involve both Na+ and Ca2+ current


delayed after depolarizations (DAD)

happen after phase 3, beginning of phase 4 (NOT abnormal automaticity)

intracellular Ca2+ overload from:
too much SNS (adrenergic stress)
digoxin toxicity
ischemic conditions

more likely if HR is rapid, upstroke may involve nonspecific mix of cations


both EADs and DADs are due to

ion fluctuations
inhibiting these channels may prevent abnormalities

suppress EADs by decreasing AP duration
suppress DADs by correcting Ca2+ overload (or cause)
drugs can suppress both upstrokes by blocking influx of Na+/Ca2+


how to stop abnormal automaticity

suppress slope of phase 4 diastolic depolarization by inhibiting Na+, Ca2+ channels that are allowing influx

some drugs increase threshold to reach AP in phase 0

delay recovery phase by decrease AP, delays phase 4, delays abnormal pacemaker activity

can hyperpolarize cell (lower negative voltage) will take more time to reach threshold: makes diastolic resting membrane potential more negative (impacts diastolic K+ channel)


abnormal AP conduction

purkinje fibers bifucate, AP goes in both directions, spreads throughout ventricles
ischemia, scar tissue may slow down one pathway (impulse block), AP may *REENTER* normal pathway and produce another AP producing an abnormal rhythm ("circus phenomenon")


mechanisms to tx abnormal AP conduction

1. drugs that slow conduction
decrease slope of phase 0
will not slow down already slowed pathway, will slow pathologic pathway
-both traveling slow now may cancel each other out (bidirectional block) may stop reentry phenomenon

2. extend refractory period (phase 4) can't get another reentry


many arrhythmias can start

in atria and travel through AV node
drugs: *may slow through AV node* stop them from reaching ventricle
B-blockers, CCBs


supraventricular arrhythmias

a flutter


atrial flutter

single ectopic site in atria, abnormal automaticity
HR: 250-350 bpm but regular
about 50% impulses reach ventricle


atrial fibrillation

multiple ectopic sites, abnormal automaticity or reentry phenomenon
HR: 400 bpm and irregular! ventricles beat from 100-200/min
"multifocal atrial tachycardia"



anatomical situation
familial (autosomal dominant)
bypass of AV conduction pathway: abnormal pathway that connects atria and ventricles ("Bundle of Kent")--> reentry phenomenon: normal impulses may be transferred back to atria by
retrograde conduction through the bypass tract (Bundle of Kent)

also, abnormal atrial impulses may travel directly from atria to ventricles down the bypass tract (WPW + afib)
names: ventricular arrhythmia, PSVT, or atriventricular reciprocating tachycardia (AVRT)


paroxysmal supra-ventricular tachycardia

abrupt start/stop
most likely site is AV node
reentry phenomenon (may have automaticity)


ventricular arrhythmias

Torsades De Pointes (TdP)
ventricular circus phenomenon


Torsades De Pointes

collation of EADs
atypical ventricular tachycardia APs abnormally prolonged by drugs/ischemia
*long QT intervals*
one form: "pause-dependent TdP"


premature ventricular contraction (PVC)

single ectopic abnormal ventricular discharge, abnormal automaticity, DADs, reentry phenomena
1 extra beat
may be seen with drug toxicity (digitalis)
unifocal, multifocal, or paired


ventricular tachycardia

more PVCs, i.e. 3-4, fire quite regularly
extra beats
HR may be 150-250 bpm +
dangerous if sustained, may progress to vfib


ventricular fibrillation

several ectopic sites, non-synchronous irregular ventricular impulses
any/all arrhythmic mechs may be involved
"whole bunch" of PVCs/extra beats
fatal if not corrected by defib/cardioversion


Class I drugs

selectivity: mainly Na+ channels, also some K+ (quinidine)

use-dependence: many are capable of only inhibiting channels that are in USE, not when resting, largely attack abnormal APs (good!) don't interfere much with normal channels

subdivisions: A, B, C:
*various currents that are affected* and speed of interation with channels (not as important) , secondary action on recovery phase

*ALL INCREASE THRESHOLD FOR PHASE 0* can stop arrhythmias from abnormal automaticity


All 3 Class I drugs inhibit ??

*ALL 3 INHIBIT Na+ CHANNELS* (upstroke and diastolic: stops both by direct suppression of slope


Class 1A

delay recovery, slope comes out, increase AP duration and duration of refractory period via inhibiting phase 3 K+ channels, inhibit ions responsible for recovery phase (+ charge flowing out) (some drugs only do this-later)

can stop reentry arrhythmias

FA: increase AP duration, inc. ERP in ventricular AP, increase QT interval
FA: used in both atrial and ventricular arrythmias, esp. reentry and ectopic SVT and VT


Class 1B

DECREASE duration of refractory period (counterintuitive?)

inhibit the late Na+ channels that contribute to plateau, decrease AP duration
MORE late Na+ channels open during ischemia (lidocaine, see later)

less inhibition of phase 0 Na+ currents, have less slowing effect on rate of rise of phase 0 than Class 1A drugs

FA: preferentially affect ischemic or depolarized Prukinje and ventricular tissue
FA: uses: acute ventricular arrhythmias (esp. postMI), dig-induced arrhythmias


Class 1C

curve travels close to control curve, does not effect recovery phase as much
still influence channels: inhibit late open Na+ channels or K+ channels (balance out, don't see shift)
little to no net effect on AP duration or ERP
inhibits phase 3 K+ channels, prolong recovery phase (NOT diastolic K+ channels), delay AP duration, stop reentry arrhythmias
inhibit phase 0 Na+ currents, depress rate of phase 0 rise: slows conduction velocity much more than Classes 1A and 1B
*may increase likelihood of AEDs (tosades), but don't see too much; other mechs stop this (increase threshold for phase 0)


most of these drug preps

IV and oral


Quinidine SEs

can cause other arrhythmias (i.e. TdP) due to prolonging ventricular AP duration (long QT)
GI probs (N/V/D)
cinchonism (ear ringing)-more serious
dec. BP and inc. regular sinus rate via a-block and "atropine-like" actions
*can increase blood digoxin*


Procainamide SEs

lupus syndrome (common but less for *rapid acetylators)
CNS (confusion)
GI problems
a-block/atropine actions and risk of TdP
*less than quinidine*


Lidocaine SEs

good things: (wide toxic to therapeutic ratio, little negative inotropic effect)

CNS effects (convulsions, slurred sleep, drowsiness, confusion)
*may be pro-arrhythmic by mainly in presence of hyperkalemia*


Flecainide SEs

negative inotropic effects (aggravate CHF)
significant pro-arrhythimc effects, aggravate pre-existing arrhythmias, exacerbate vtach (amplified by hyperkalemia)
FA: contraindicated in structural and ischemic heart disease
CNS (dizziness, ha, nausea, blurred vision)
increase mortality


Amiodarone SEs

may continue after drug stopped
*pulmonary fibrosis (fatal)*
iodine problems (amIODarone): blue skin, iodine sensitivity
TdP can occur due to inc. APDs in ventricular tissues but rare compared to other APD-proloning drugs
FA: also has hepatotoxicity, CNS effects, constipation, CV effects *check PFTs, LFTs, TFTs*
FYI: cataracts (acts as a hapten), optic nerve damage, slow down HepC drugs


FYI new Class III drugs

Dronedarone: no iodine probs, high mort in CHF pts (black box)

Vernakalant: not out yet, some saying too dangerous in afib


Dofetilide SEs

TdP, especially due to high IV does, due to EADs
*more than amiodarone*

FYI: black box warning: hospitalize pt with defib. ready


FYI: Sotalol

blocks B-receptors as well as K+ channels, prevent arrhythmia recurrence (like amiodarone for pts ICD)

SEs: like B-blockers, TdP


Class IV drugs (CCBs: Verapamil, Diltiazem)

block CARDIAC voltage-sensitive L-type Ca2+ channels
*mostly AV node* (Ca2+-rich)

*phase 4: inhibits automaticity from influx of Ca2+ in AV node
*phase 0: Ca2+ influx for depolarization in heart (vs. Na+), suppress phase 0 slope, suppress conduction velocity, slow AP in *AV node* where most currents go thru, stop abnormal APs coming thru atria-->ventricle (SA node impulse will still get through-stronger)
phase 2 Ca2+ channels

extension of refractory period in phase 3: how? : secondary/indirect inhibition of *late Ca2+-activated K+channels* (less + charge flowing out)


more Class IV

error in BOARD books: will list Na+ in place of Ca2+ for AV node: wrong!
AV node (also SA node) is Ca2+ dependent

FYI: why is voltage-sensitive important? (esp. phase 2): channels open up due to charges

FA: decrease conduction velocity, increase ERP, increase PR interval


Class IV uses
(non-dihydr. CCBs)

work well on AV nodal Ca2+currents
can stop atrial and AV nodal arrhythmias from reaching ventricles (SVTs>Varrhythmias)
also stop DAD formation even in ventricles
*avoid if WPW accompanied by afib* IV use
WPW may have reentry circuits that go from ventricle-->atria-->AV node-->back to ventricle
works for pure WPW to stop accessory pathway
works for pure afib
both: afib will go through ectopic node from atria-->ventricle if WPW and add class IV

FA: uses: prevention of nodal arrhythmias (SVT) rate control in afib


Class IV SEs
(non-dihydr. CCBs)

can decrease normal cardiac functions too much
negative inotropic action
don't combo with B-blockers

FA: constipation, flushing, edema, CV effects (FA, AV block, sinus node depression)


Class II: B-blockers

similar to CCB actions (slow conduction thru AV node)
stop arrhythmias caused by high SNA and or high circulating catecholamines (pheochromocytoma)

FA: decrease SA and AV nodal activity by dec. cAMP-->dec. Ca2+ currents, suppress abnormal pacemakers by dec. slope of phase 4
diminish phase 4 depolarization, depress automaticity (nodal tissue), decrease phase 0 slope (slow conduction)
increase AP duration and ERP
aflutter, afib, AV nodal reentry tachycardia, prevent SVTs, suppress adrenergic-induced DADs


Class II SEs

B-blocker SEs
avoid combo w/ CCBs (too much suppression)

FA: Impotence, exacerbation of COPD and asthma, CV effects (bradycardia, AV block, HF), CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia.
Metoprolol can cause dyslipidemia.
Propranolol can exacerbate vasospasm in Prinzmetal angina.
β-blockers cause unopposed α1-agonism if given alone for pheochromocytoma or cocaine toxicity.
Treat β-blocker overdose with saline, atropine, glucagon.


MISCELLANEOUS antiarrhythmics




may also cause arrhythmias (including TdP) as well as tx them
lidocaine IV used to stop digoxin ventricular arrhythmias

increases K+ current through Ca2+‐activated potassium channels due to the increased intracellular Ca++ caused by decreased Na/K‐ATPase activity: shortens AP duration and ERP but LENGTHENS ERP and DECREASES conduction velocity in AV node and purkinje fibers
protects ventricular rates in afib/flutter


Adenosine SEs

flushing, hypotension (FA)
SOB, related chest pain (bronchospasm, not cardiac)
*get sense of impending doom!* (remember Marshall)
FA: effects blunted by theophylline and caffeine (adenosine rec. antagonists)


Magnesium for...

Torsades de Point
FA: TdP and digoxin toxicity


future agents

stop ventricles from going thru anatomical changes that may cause arrhythmias: