Antiarrhythmic Drugs Chpt 14 Katzung

Front 1

arrythmias often associated with the following disorders

Back 1

hyperthyroidism (Afib), electrolyte disorders, anesthesia and digitalis toxicity

Front 2

what are the four classes of antiarrythmics (also called Singh-vaughan williams classification)

Back 2

class I: na channel blockers, Class II: beta-blockers, Class III: Potassium channel blockers, Class IV: Calcium channel blockers

Front 3

what arrythmia is often induced by antiarrythmic drugs that prolong QT interval

Back 3

Torsade de pointes

Front 4

Torsade is also assoc with long QT syndrome which is

Back 4

a heritable abnormal prolongation of QT interval caused by mutations in Ik or Ina channel molecules

Front 5

what current dominates phase 0

Back 5

sodium current, Ina dominates the upstroke and conduction velocity

Front 6

In the AV node, what dominates the upstroke and AP conduction velocity

Back 6

calcium current, Ic

Front 7

plateau of AP is what phase

Back 7

2; dominated by calcium current and potassium repolarization current, Ik

Front 8

at the end of plateau, what current is imp in phase 3

Back 8

Ik for rapid repolarization

Front 9

what is the refractory period a fxn of

Back 9

how rapidlysodium channels recover from inactivation

Front 10

recovery form inactivation depends on both

Back 10

the membrane potential, which varies with repol time and EC potassium conc, and the actions of drugs that bind the sodium channel

Front 11

what carrier processes contribute little to the shape of the AP

Back 11

sodium pump and sodium-calcium exchanger

Front 12

what is abnormal conduction

Back 12

impulse that does not follow the path defined or reenters tissue previously excited

Front 13

what is supraventricular tachycardia

Back 13

a reentrant arrythmia that travels thru the AV node, may alos be conducted thru atria/vent tissue as reentrant ckt

Front 14

what is Vtach

Back 14

common, assoc with MI; may invlv abnormal automaticicy or conduction; usuallly impairs CO, and may deteriorate into Vfib; react fast

Front 15

the miscellaneous group of antiarrythmics includes

Back 15

adenosine, postassium and magnesium ion

Front 16

class I drugs subdivided based on effect on AP duration, class IA does what

Back 16

prolong AP, procainamide is prototype

Front 17

what do class IB drugs do

Back 17

shorten AP, lidocaine is prototype

Front 18

what does class IC do

Back 18

no effect on AP duration, prototype is flecainide

Front 19

what does PR interval measure

Back 19

conduction from atrium to ventricles thru the AV node

Front 20

what does QRS duration indicate

Back 20

the time reqd for all of the ventricular cells to be activated (IV conduction time)

Front 21

what does QT interval reflect

Back 21

duration of ventricular AP

Front 22

what is mechanism of all class I drugs

Back 22

to slow or block conduction in ischemic and depolarized cells and slow or abolish abnormal pacemakers wherever these processes depend on sodium channels

Front 23

what class I agent is most selective

Back 23

class IB have significant effects on sodium channels in ischemic tissue but minimal effects on channels in normal cells; other class Is do all cells

Front 24

sodium channel blocking drugs bind to their receptors more readily when the channel is

Back 24

open or inactivated than when it is fully replarized and recovered from previous activity.

Front 25

Ion channels in arrythmic tissue spend more time in inactivated state than do channels in normal tissue. Therefore antiarrythmic drugs block channels in ______ tissue more effectevily

Back 25

abnormal

Front 26

what does it mean when blockers are "use dependent" or "state dependent"

Back 26

selectively depress tissue that is frequently depolarizing, ie during a fast tachy or tissue that is relatively depolarized during rest by hypoxia

Front 27

other drugs with class IA actions (prolong AP) include

Back 27

quinidine and disopyramide

Front 28

amiodarone, often classified as class III also has typical class ? Action

Back 28

class IA

Front 29

class I A affect both Atrial and ventricular arrythmias, block Ina therefore slow conduction velocity in

Back 29

atria, PJ fibers and vent cells; at high doses also slow AV conduction, slow vent conduction inc QRS duration

Front 30

in addition to Ina, class IA also blocks Ik therefore they inc

Back 30

AP duration and effective refractory period (ERP) in addition to slowing conduction velocity and ectopic pacemakers; inc in AP inc QT interval

Front 31

which drug has the greatest AP prolonging effect

Back 31

amiodarone

Front 32

lidocaine reduces AP duration but does not shorten (may even prolong) ERP because

Back 32

it slows recovery of sodium channels from inactivation

Front 33

because lido and mexi have little effect on normal cardiac cells they have little effect on

Back 33

ECG

Front 34

class IC drugs have no effect on

Back 34

ventricular AP duration or QT interval, however they are powerful depressants of sodium current and can slow conduction in atria and vent cells - inc QRS duration

Front 35

characterize phase 4 in pacemaker cells

Back 35

potassium current is smaller and depolarizing currents (na, ca or both) are large enuf to gradually deploarize the cell during diastole

Front 36

amiodarone, class III, IA has half life of

Back 36

1-10 wks; slightly inc PR int, mod inc in QRS duration nd big inc in QT int

Front 37

Disopyramide (IA) may precipitate heart failure due to marked

Back 37

anti-muscarnic effects

Front 38

what class I drugs may precipitate new arrythmias

Back 38

class IA drugs

Front 39

what exacerbates toxicity of class I drugs

Back 39

hyperkalemia

Front 40

how do you treat overdose of class I drugs

Back 40

sodium lactate (reverse drug induced arrythmas) and pressor sympathomimetics (reverse drug induced hypotension)

Front 41

flecainide (class IC) only approved for

Back 41

refractory Vtach and for certain intractable supraventricular arrhthmias; altho effectiv in both atrial and vent arrhythmias

Front 42

what class of drugs are more likely to precipiate arrythmias

Back 42

class IC - flecainide, propafenone, moricizine (that is why used only in persistant arr. - cause local anesthetic like CNS toxicity)

Front 43

what are the class II antiarrythmics

Back 43

beta-blockers (Propranolol and esmolol are prototypic)

Front 44

what is mechanism of action of of class II

Back 44

beta-adrenoceptor blockade and reducation in CAMP which results in reduction of both sodium and calcium currents and suppression of abnorm pacemakers

Front 45

AV node is particularly sensitive to which class

Back 45

class II beta blockers and PR is prolonged

Front 46

what class III drugs have class II beta blocking effects

Back 46

sotalol and amiodarone

Front 47

which class II is short acting and used only in acute arrythmias

Back 47

esmolol

Front 48

which class II's are used prophylactically for pts who had MI

Back 48

propranolol, metoprolol and timolol (beta blockers reduc progression of chronic heart failure and reduces incidence of fatal arrythmias)

Front 49

what are the typial class III (Ik blockers)

Back 49

sotalol and ibutilide

Front 50

what is the hallmark of class III drus

Back 50

prolongation of the AP duration, via blockade of Ik potassium channels resp for repolarization

Front 51

prolonged AP results in

Back 51

inc ERP and reduces ability of the heart to respond to rapid tachycardias

Front 52

sotalol, ibultilide, dofetilide and amiodarone prolong AP and therefore

Back 52

inc QT interval

Front 53

sotalol is commonly used may precipitate

Back 53

torsades as well as signs of excessive beta blockade like sinus brady or asthma

Front 54

what is recommended for atrial flutter and fibrillation

Back 54

ibutilide and dofetilide (can also induce torsades)

Front 55

what is considered most efficacious of antiarrythmics

Back 55

amiodarone due to its broad spectrum of use (blocks na, ca, K and beta-adrenos) but since toxic only approved for use in persistant arryths

Front 56

amiodarone causes microcrystalline deposits in

Back 56

cornea, skin, thyroid dysfxn, parasthesias, tremor and pulm fibrosis; rarely causes arrythmias

Front 57

dronedarone is an amiodarone analog under investigation that may be less

Back 57

toxic

Front 58

class IV - calcium channel blocker prototype

Back 58

verapamil; effective in arrythmias that must traverse the calcium dep tissue (the AV node)

Front 59

class IV cause state and use dependent selective depression of _______ current in tissues

Back 59

calcium

Front 60

what effect does class IV have on AV conduction velocity, ERP and PR interval

Back 60

AV conduction velocity is dec, ERP inc, PR interval inc

Front 61

what are CCB effective for

Back 61

converting AV nodal reentry (nodal tach) to NSR

Front 62

what is most imp toxicity of class IV CCBs

Back 62

excessive pharmacologic effect, because cardiac contractility, AV conduction and BP can be signif depressed

Front 63

Normally in tissues but when given in high doses markedly slows or block conduction in AV node

Back 63

Adenosine; by hyperpolarizing the tissue (thru inc Ik1) and by reducing calcium current

Front 64

Adenosine is extremely effective in

Back 64

abolishing AV nodal arrythmias - drug of choice due to low toxicity; extremely short duration of action 15s

Front 65

how does potassium act as an antiarrythmic

Back 65

depresses ectopic pacemakers even if caused by digitalis tox

Front 66

what electrolyte imbalance is associated with an increased incidence of arrythmias

Back 66

hypokalemia

Front 67

what electrolyte imbalance is associated with reentry arrythmias

Back 67

hyperkalemia - excessive potassium depress conduction and cause reentry arrythmia

Front 68

how does magnesim act as an antiarrythmic

Back 68

similar depressant effects as potassium on digitalis-induced arrhythmias; appears to be effective in some cases of torsade de pointes

Front 69

nonpharm treatment of arrhythmias include

Back 69

external defib, implanted defibs, implanted pacemakers, RF ablation of arrhythmogenic foci via catheter

Front 70

what is the prototype drug and other signif agents in subclass IA

Back 70

procainamide: amiodarone, quinidine

Front 71

what is the prototype drug and other signif agents in subclass IB

Back 71

lidocaine: mexiletine

Front 72

what is the prototype drug and other signif agents in subclass IC

Back 72

flecainide: propafenone

Front 73

what is the prototype drug and other signif agents in subclass II

Back 73

propranolol: esmolo, sotalol

Front 74

what is the prototype drug and other signif agents in subclass III

Back 74

sotalol, amiodarone: ibutilide, dofetilide

Front 75

what is the prototype drug and other signif agents in subclass IV

Back 75

verapamil: diltiazem

Front 76

what is the prototype drug and other signif agents in misc antiarrhythmics

Back 76

adenosine: potassium, magnesium

Front 77

Class of anti-arrhythmics that has a pro-arrhythmic effect (CAST trial), therefore are used as last line agents

Back 77

Class IC (flecainide, propafenone, moricizine)

Front 78

Antiarrhythmic that exhibits Class II and III properties

Back 78

sotalol

Front 79

Side effect of sotalol

Back 79

prolongs QT inerval and PR interval

Front 80

Used intravenously for acute arrhythmias during surgery

Back 80

esmolol

Front 81

Anti-arrhythmics that decrease mortality

Back 81

beta blockers

Front 82

Class III antiarrhythmic that exhibits properties of all 4 classes

Back 82

amiodarone

Front 83

Specific pharmacokinetic characteristic of amiodarone

Back 83

prolonged half life up to 6 wks

Front 84

SE of Amiodarone

Back 84

Dysfunction, photosensitivity, skin (blue smurf syndrome), Pulmonary fibrosis, thyroid and corneal deposits

Front 85

Life threatening cardiac event that prolong QT leads to

Back 85

torsades

Front 86

Agent to treat torsades de pointes

Back 86

magnesium sulfate

Front 87

Drug used supraventricular arrhythmias

Back 87

digoxin

Front 88

DOC for paroxysmal supraventricular tachycardia (PSVT)

Back 88

adenosine

Front 89

Adenosine's MOA

Back 89

Activates acetylcholine sensitive K+ channels in SA and AV node

Front 90

Anti-arrhythmic with 15 second duration of action

Back 90

adenosine

Front 91

limiting side effect of Quinidine

Back 91

prolongs QT interval

Front 92

MOA of class I A (eg. Procainamide), class IB (eg. Lidocaine), and class IC (eg. Flecainide) antiarrhythmics

Back 92

sodium channel blockers

Front 93

SE of procainamide

Back 93

lupus like syndrome (also hypotension)

Front 94

Other side effects of Quinidine

Back 94

thrombocytopenic purpura and CINCHONISM (headache, vertigo, tinnitus)

Front 95

major drug interaction with quinidine

Back 95

inc conc of digoxin (ie reduces clearance fo digoxin)

Front 96

DOC for management of acute vent arrythmias

Back 96

lidocaine

Front 97

DOC for digoxin induced arrythmias

Back 97

phenytoin (lacks significant effects on ECG like lidocaine)

Front 98

SE of phenytoin

Back 98

gingival hyperplasia

Front 99

Class of anti-arrhythmics that has a pro-arrhythmic effect (CAST trial), therefore are used as last line agents

Back 99

class IC - flecainide, propafenone, moricizine

Front 100

class IB oral agent

Back 100

Mexiletine

Front 101

class IB IV agent prototypical selectively effects ischemic or depol PJ and vent tissue little effect on atrial tissue

Back 101

lidocaine