antiarrhythmics 63/64

Question 1

Quinidine

Answer 1

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

Question 2

Procainamide

Answer 2

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

Question 3

Lidocaine

Answer 3

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

Question 4

Flecainide

Answer 4

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)

Question 5

Propranolol

Answer 5

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

Question 6

Acebutolol

Answer 6

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

Question 7

Esmolol

Answer 7

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

Question 8

Amiodarone

Answer 8

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

Question 9

Dofetilide

Answer 9

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

Question 10

Verapamil

Answer 10

Class IV

Question 11

Diltiazem

Answer 11

Class IV

Question 12

Adenosine

Answer 12

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

Question 13

Class I antiarrhythmics block

Answer 13

Na+ channels

Question 14

Class II antiarrhythmics block..

Answer 14

Ca2+ channels

Question 15

Class III antiarrhythmics block

Answer 15

K+ channels

Question 16

APs occur in phases

Answer 16

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)

Question 17

AP phases travel from place to place in heart

Answer 17

start in SA node

also change shape based on location

Question 18

threshold for phase 0

Answer 18

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

Question 19

channels for phase 0

Answer 19

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

Question 20

Phase 1 channels

Answer 20

some K+ outflux, we mostly ignore

Question 21

Phase 2 channes

Answer 21

Ca2+ comes in, keeps above 0 mV

then close! and K+ channels open, K+ flows out, some downward movement

Question 22

Phase 3

Answer 22

more K+ flowing out, back down to resting potential

Question 23

Phase 4

Answer 23

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)

Question 24

Na+ channel blockers may ??

Answer 24

suppress slope of Phase 0, may depress rate of depolarization

Question 25

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

Answer 25

``` K+ too high or too low (e-lyte imbalance) ischemia acidosis scar tissue drugs abnormal cardiac anatomy (WPW) abnormal automatic nerve activity ``` *abnormal AP formation*: steep slope in phase 4 (also abnormal conduction)

Question 26

abnormal AP formation

Answer 26

EADs and DADs | triggered by a previous AP

Question 27

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

Answer 27

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

Question 28

delayed after depolarizations (DAD)

Answer 28

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

Question 29

both EADs and DADs are due to

Answer 29

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+

Question 30

how to stop abnormal automaticity

Answer 30

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)

Question 31

abnormal AP conduction

Answer 31

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")

Question 32

mechanisms to tx abnormal AP conduction

Answer 32

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

Question 33

many arrhythmias can start

Answer 33

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

Question 34

supraventricular arrhythmias

Answer 34

a flutter afib WPW PSVT

Question 35

atrial flutter

Answer 35

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

Question 36

atrial fibrillation

Answer 36

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

Question 37

WPW

Answer 37

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)

Question 38

paroxysmal supra-ventricular tachycardia

Answer 38

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

Question 39

ventricular arrhythmias

Answer 39

``` Torsades De Pointes (TdP) PVC Vtach Vfib ventricular circus phenomenon ```

Question 40

Torsades De Pointes

Answer 40

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

Question 41

premature ventricular contraction (PVC)

Answer 41

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

Question 42

ventricular tachycardia

Answer 42

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

Question 43

ventricular fibrillation

Answer 43

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

Question 44

Class I drugs

Answer 44

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

Question 45

All 3 Class I drugs inhibit ??

Answer 45

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

Question 46

Class 1A

Answer 46

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

Question 47

Class 1B

Answer 47

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

Question 48

Class 1C

Answer 48

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)

Question 49

most of these drug preps

Answer 49

IV and oral

Question 50

Quinidine SEs

Answer 50

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*

Question 51

Procainamide SEs

Answer 51

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

Question 52

Lidocaine SEs

Answer 52

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* ```

Question 53

Flecainide SEs

Answer 53

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

Question 54

Amiodarone SEs

Answer 54

may continue after drug stopped *pulmonary fibrosis (fatal)* hyper/hypothyroid 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 dizziness 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

Question 55

FYI new Class III drugs

Answer 55

Dronedarone: no iodine probs, high mort in CHF pts (black box) Vernakalant: not out yet, some saying too dangerous in afib

Question 56

Dofetilide SEs

Answer 56

TdP, especially due to high IV does, due to EADs *more than amiodarone* FYI: black box warning: hospitalize pt with defib. ready

Question 57

FYI: Sotalol

Answer 57

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

Question 58

Class IV drugs (CCBs: Verapamil, Diltiazem)

Answer 58

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)

Question 59

more Class IV

Answer 59

``` 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

Question 60

Class IV uses | non-dihydr. CCBs

Answer 60

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

Question 61

Class IV SEs | non-dihydr. CCBs

Answer 61

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)

Question 62

Class II: B-blockers

Answer 62

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

Question 63

Class II SEs

Answer 63

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.

Question 64

MISCELLANEOUS antiarrhythmics

Answer 64

Digoxin Adenosine Magnesium

Question 65

digoxin

Answer 65

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

Question 66

Adenosine SEs

Answer 66

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)

Question 67

Magnesium for...

Answer 67

Torsades de Point | FA: TdP and digoxin toxicity

Question 68

future agents

Answer 68

stop ventricles from going thru anatomical changes that may cause arrhythmias: ACE-inhibitors ARBS