Cp2, Anti-Arrhythmics I And Ii, Pharmacology Dr. Mcrae

Front 1

describe mechanisms of arrhythmias

Back 1

impulse initiation, conduction or both
1) supreventricular or ventricular problems

Front 2

what can worsen or initiate arrythmias

Back 2

drug toxicity, ischemia, acidosis, alkalosis, electrolyte problems, scarred or diseased tissues.

Front 3

what ion is the major determinant of velocity of impulse conduction through the ventricles

Back 3

Sodium. (phase 0 depolarization is primarly because of Na+ in non-pacemaker cells. and primarily Calcium in pacemaker cells) (Class 1 drugs)

Front 4

Which phase of the cardiac cycle do potassium channel blockers work?

Back 4

the plateau and repolarization phase

Front 5

Phase 4 depolarization occurs because of...

Back 5

pacemaker current, which is comprised mostly of Na+ channels because the driving force for Na}+ is stronger than K+ (This is the spontaneous depolarization phase...pacemakers)

Front 6

Phase 0 upstroke is dependent on ____ in the pacemaker cell

Back 6

Calcium (sodium in non-pacemaker cell)

Front 7

Vaughn williams classifications of antiarrhytmics

Back 7

Class I through Class 5 depending on what channels they inhibit

Front 8

Class I antiarrhythmic drugs

Back 8

inhibit Na+ channels mostly (except Class Ia inhibits K+ channels, too)

Front 9

Class II antiarrhythmic

Back 9

B-Blockers

Front 10

Class III antiarrhythmic drugs

Back 10

inhibit K+ channels (K+ channel blockers)

Front 11

Class IV antiarrhthmics

Back 11

Ca+ channel blockers

Front 12

Class V

Back 12

miscelaneous (adenosine and Digoxin)

Front 13

What are the class I antiarrhthmics

Back 13

Qunidine, Procainamide, Disopyramide, lidocain, mexiletin, phenytoid, flecainide,propafenone

Front 14

What are the class II anti-arrhthmics

Back 14

Propranolol, acebutolol, esmolol, sotalol

Front 15

What are the class III antiarrhytmics

Back 15

Amiodarone, Dofetilide, Ibutilide, Sotalol

Front 16

What are the class IV antiarrhytmics

Back 16

Verapamil and diltiazem

Front 17

Sotalol

Back 17

is a beta blocker and also a K+ blocker (listed as class II and class III)

Front 18

3 classes of Class I antiarrhytmics

Back 18

IA, IB, IC

Front 19

MOA of class I anti-arrhythmics

Back 19

inhibit Na+ channels, has pacemaker cell effect. Primarily effects phase IV depolarization. SA node effects. Decreases slope of depolarization therefore slowing the action potential and increasing the threshold for membrane potential.

Front 20

Class one drugs work 2 ways

Back 20

Decrease automaticity of SA node by slowing depolarization and increasing the threshold for membrane potential.

Front 21

How do Class I anti-arrhytmics effect nonpacemaker cells

Back 21

general effect is to decrease phase 0 upstroke. Difference in IA, IB, IC is with respect to prolongation of repolarization. (makes it take longer for non-pacemaker cells to decrease.

Front 22

in summary Class I drugs MOA

Back 22

effect both pacemaker and nonpacemaker cells
1) decrease automaticity (pacemaker cells)
2) increase threshold for excitability
3) decreases conduction velocity through AV node in ventricular tissue (non-pacemaker cells)

Front 23

Class IA drugs. List the 3 and MOA

Back 23

1) Procaianamide
2) quinidine
3) Disophyramide
Inhibit Na and K channels
because it also inhibits K channels it also prolongs repolarization phase and further slows conduction time.

Front 24

Which class has longer Action potential duration...Ia or Ib

Back 24

IA

Front 25

compare effects of class IA, IB and IC antiarrhthmics on Phase 0 (repolarization)

Back 25

IA has moderate effect
IB has weak effect
IC has strong effect

Front 26

compare effects of class Ia, IB and IC antiarrhtmics on repolarization

Back 26

IA prolongs repolarization
IB shortens repolarization
IC has no effect of repolarization

Front 27

Compare effects of Class IA, IB and IC antiarrhthmics on Action potential duration

Back 27

IA increased AP duration
IB decreases AP duration
IC has no effect on AP duration

Front 28

Binding of channels and Class IA, IB and IC antiarrhytmics

Back 28

Class IA binds to open channels
Class IB and IC bind to open and also inactivated channels

Front 29

indications for Class IA drugs

Back 29

useful for treating supraventricular and ventricular arrhytmias. (because effect pacemaker and non-pacemaker cells)

Front 30

Quinidine

Back 30

Class IA
made from tree bark (cinchona)
blocks fast Na channels and delayed K channels. Alpha adrenergic receptor blocker

Front 31

adverse effects of quinidine

Back 31

anticholinergic effects
Diarrhea (30-50%)
* cinchonism=HA, dizziness, tinnitus,diarrhea, nausea
QT prolongation-torsades in 2-8%

Front 32

What are anti-cholinergic effects?

Back 32

confusion, delirium, falls, urinary retention and constipation, blurred vision

Front 33

Drug interactions and quinidine

Back 33

lots of reactions. P450
**decreases the clearance of digoxin** decrease dose of dig when pt is on both dig and quinidine

Front 34

clinical uses for Quinidine

Back 34

Supraventricular and ventricular arrhthmias. (V tach, A fib) but rarely used today because too many adverse effects

Front 35

Procainamide

Back 35

similar to quinidine except less anticholinergic effects, does not black a-adrenergic receptors. Class IA drug

Front 36

Adverse effects of procainamide

Back 36

**Lupus-like synrome=develop antinuclear Abs, with or w/o joint pain and rash, some get pleruitis, pericarditis, pulmonary disease. occurs in 1/3 of patients and symptoms go away when DC drug. Not used much today because of side effects

Front 37

NAPA

Back 37

is a metabolite of procainamide that can accumulate in body with pts with renal dysfunctin, NAPA accumulation increases adverse effects of procainamide.

Front 38

Clinical uses of procainamide

Back 38

Atrial and ventricular arrhytmias.limited use b/c of short 1/2 life. currently 2nd line for sustained Ventricular arrhthmias associated with acute MI

Front 39

Disopyramide

Back 39

Class IA drug. similar to Procainamide and quinidine (all are class IA drugs) Disopyramide has greatest amt of anticholinergic effects.

Front 40

What are anticholinergic effects

Back 40

dry mouth, constipation, urinary retention, blurred vision, can precipitate glaucoma. (effects elderly more)
Depresses heart contractility so can precipitate heart failure. torsades

Front 41

What specific effect do class IA antiarrhtymics have that causes torsaddes

Back 41

prolongs the QT duration

Front 42

Rank the 3 Class IA ant-arrhythmics in terms of antimuscarinic effects. (anticolinergic)

Back 42

From least to most is Procainamide, quinidine then disopyramide

Front 43

Which antiarrhytmic drug can cause lupus-like syndrom

Back 43

procainamide

Front 44

MOA for Class IB drugs

Back 44

mild blockade of Na channels. (no K effect like class IA)
most useful in depolarized tissues/rapidly driven tissues (frequency dependent) preferentially has effect on the damaged tissues. in general slows conduction

Front 45

Lidocaine

Back 45

Class IB, frequency dependent. Decreases automaticity and increases threshold for excitability. DOES not prolong QT interval. no risk for Torsades

Front 46

Adverse effects of lidocaine

Back 46

It is best tolerated of class I drugs. Can get drowsiness/slurred speech. IV only and short term use only. short 1/2 life.

Front 47

clinical uses of lidocaine

Back 47

local anesthetic. Prevents V fib after cardioversion. Drug of choice for V tach*** not used for atrial arrhytmias. Used more for treatment than prevention.

Front 48

Mexiletine

Back 48

class IB, oral version of lidocaine. similar effects. Used for Ventricular arrhytmias (not atrial)

Front 49

Phenytoin

Back 49

class IB, primary use is as an antiseizure drug. (Dilantin)
limited efficacy as antiarrhytmic (second line antiarrhythmic)

Front 50

how does phenytoin work?

Back 50

Suppresses ectopic deviation by blocking Na and Ca channels. Especially effective against Digitalis induced arrhytmias.

Front 51

Unique side effect for Phenytoin

Back 51

gingival hyperplasia (40%)

Front 52

Class IC drugs (flecainide and propafenone) MOA

Back 52

Strong inhibition of Na+ channels. Markedly depresses phase 0 depolarization. AP duration stays same because no effect on repolarization.

Front 53

Flecainide uses;

Back 53

local anesthetic and antiarrhytmic. Used in pts with supraventricular arrhythmias who DO NOT have structural heart disease. Can prolong PR interval and QRS interval

Front 54

CAST trial

Back 54

in post MI pts this trial showed that Flecainide increased mortality. class IC drugs cannot be used to prevent arrhytmias in post MI patients

Front 55

Propafenone

Back 55

Class IC. used for life threatening ventricular arrhythmias. Can be used to terminate A fib, but not typically. Differs from Lecainide because has minor B-blocking activity)

Front 56

Adverse effects of propafenone

Back 56

**agranulocytosis** (rare and reversible, but unique to propafenone)taste disturbances, dizziness, blurred vision, N/V, exacerbation of heart failure. Can introduce re-entry arrythmias. Drug interactions=Digoxin, fluoxetine and quinidine.

Front 57

Which class I antiarrythmic increases AP duration

Back 57

Class IA

Front 58

which class I antiarrhytmic decrases AP potential

Back 58

Class IB

Front 59

Which Class I antiarrhtymic prolonges repolarization? shortens repolarization?

Back 59

Prolongs=IA
Shortens=IB
(IC has no effect on repolarization)

Front 60

MOA for Class IA

Back 60

moderate Na+ blocker, lengthen AP duration by prolonged repolarization

Front 61

Class IB MOA

Back 61

mild Na+ channel blocker, no effect or possibly shortens AP, shortens repolarization

Front 62

Class IC

Back 62

Most Na+ channel blocking effect. No effect on AP duration, no change in repolarization

Front 63

Of the class I antiarrhytmics which side effect is unique to procainamide

Back 63

lupus-like syndrome

Front 64

Class II antiarrythmics MOA

Back 64

B-blockers. decreases SA node automaticity, decreases AV node conduction and decreases bundle of His purkinje conduction

Front 65

B-adrenergic stimulation will

Back 65

increase contractility, increases conduction velocity, decrease refractory period of the node. increases HR

Front 66

B blocker effects on the action potential

Back 66

Decreases automaticity, prevents re-entry, Decrease HR and slows conduction. AV node is more sensitive to B-blockers than the SA node. Increases refractory period

Front 67

Only antiarrhytmic found to decrease sudden cardiac death in pts with prior MI...

Back 67

Class II antiarrhytmics (b-blockers) most often used drugs for Supraventricular arrhytmias due to sympatheic stimulation.

Front 68

List some B-blockers

Back 68

non-selective=Propranolol
Beta 1 selective=Bisoprolol, atenolol, acebutolol, metoprolol, esmolol
Nonselective with alpha blockade also=:Labetalol and carvedilol

Front 69

Which class II drug is effective for short term emergency treatmetn of sinus tach or SVT. especially those during/after cardiac surgery

Back 69

Esmolol (short 1/2 life about 9 minutes)

Front 70

therapuetic uses for Class II antiarrythmics

Back 70

prevent re-entry arrhtymias involveing AV node, controlling ventricular response in A fib/flutter

Front 71

Adverse effects of Beta blockers (Class II antiarrhythmic drugs)

Back 71

Hypotension, fatique, depression, impotence, aggravation of heart failure, AV blocks. Non-selective B-blockers can cause bronchospasms

Front 72

Class III antiarrhytmics MOA

Back 72

K+ channel blockers= prolongs plateau phase and prolongs repolarization, increases refractoriness (amiodarone, sotalol, dofetilide, ibutilide)

Front 73

amiodarone

Back 73

Class III antiarrhtymic. blocks K, Na and Ca, alpha and beta adrenergic receptors. Prolongs repolarization, increases effective refractory period in ALL cardiac tissues, decreases rate of firing in pacemaker cells (Na blockade). Can cause serious AV node block and bradycardia (due to Ca+ channel blockade)
blocks all recepors but classified as K+ blocker)

Front 74

clinical uses for amiodarone

Back 74

used IV and orally. used for sustained V tach, V fib, maintenance of normal sinus rhythm in a fib and long term suppression of SVT (Vtach, Vfin, SVT, A fib)

Front 75

Adverse effects of amiodarone

Back 75

*****Asymptomatic AV block, pulmonary fibrosis=rapidly progressive and fatal, risk factors are underlying lung disease, large doses of amiodaron, recent pulmonary insult) Also corneal microdeposits=often asymptomatic
hepatic dysfunction, neuromuscular symptoms, photosenstitivity, thyroid dysfunction (hypo- or hyper-)

Front 76

Adverse effects unique to amiodaronephilic

Back 76

corneal microdeposits and pulmonary fibrosis

Front 77

Drug interactions with amiodarone

Back 77

metabolized via P450. LOTS of drug interactions we need to look up. Follows nonlinear pharmacokinetics, highly lipophilic, Long half life-53 days

Front 78

Sotalol

Back 78

Class III (beta blocker/K+ blocker)
decreases HR, increases refractoriness, prolongs AP duration, prolongs QT interval.

Front 79

Adverse effects of sotalol

Back 79

fatigue, bradycardia, dyspnea (b-block effects)
torsades (dose related, do to K+ blockade)
not metabolized, it's renally eliminated so decrease dose with renal dysfunction

Front 80

Uses for Sotalol

Back 80

life threatening Ventricular arrhytmias, maintanence of sinus rhythm in afib (acute maintenence only0

Front 81

Ibutilide

Back 81

class III, K+ channel blocker. enhances Na+ channels. IV drug administered rapid infusion to convert A fib /flutter to normal sinus rhythm. More effective in flutter.

Front 82

main adverse effect of ibutilide

Back 82

prolongation of QT interval can lead to torsades. Generally not given to people with pre-existing long QT syndrome

Front 83

what is the only pure K+ channel blocker

Back 83

Dofetilide

Front 84

Dofetilide

Back 84

class III, K+ channel blocker
Slows action potential, increases AP duration, increases refractory period in atria and ventricle

Front 85

Adverse effects of Dofetilide

Back 85

Prolonged QT interval and torsades (dose dependent)

Front 86

uses for dofetilide

Back 86

conversion of A fib or a flutter . also used for maintenance of normal sinus rhythm

Front 87

Class IV drugs MOA

Back 87

Ca+ channel blockers (verapamil and diltiazem)

Front 88

Major cardiac effects of Ca++ channel blockers

Back 88

decrease AP upstroke (phase 0) in AV node/pacemaker cells
decrease contractility, resuced SA node impulse (decreases HR) slows conduction through AV node

Front 89

adverse effects of Ca++ blockers

Back 89

large doses may cause AV block

Front 90

nondihydropyridines and dihydropyridines

Back 90

1) non=verapamil and diltiazem
2) dihydro=nifedipine, amlodipide, nimodipine
nondihydropyridines are used as antiarrhythmics because the dihydropyridines have vascular effects that may cause reflex tachycardia.

Front 91

clinical uses of Ca++ blockers

Back 91

used to reduce ventricular rate in atrial fib/flutter.
terminate and prevent recurrences of many SVTs

Front 92

adverse effects of verapamil and diltiazem

Back 92

hypotension, bradycardia, AV block
Verapamil=constipation
both drugs can increase serum digoxin concentrations

Front 93

Miscellaneous agents

Back 93

adenosine and digoxin (lanoxin)

Front 94

Adenosine

Back 94

naturally occuring nucleoside, ACTIVATES K+ channels in AV and SA node. Hyperpolarizes atrial tissue.
decreases slope of phase 4 sponaneous depolarization. can cause transient AV block that lasts about 5 seconds.

Front 95

Uses for adenosine

Back 95

acute termination of re-entry arrhytmias. Drug of choice for SVT arrhytmias which are AV node dependent. IV only,

Front 96

adverse effects of adenosine

Back 96

short lived because drug effect is so short lived (10 seconds)
flushing, SO?b, broncospasm, caustion in pts with asthma.
can have proarrhythmic effects but only lasts a few seconds

Front 97

digoxin (digitalis glycoside) 3 modes of action

Back 97

Lanoxin is brand name.
1) indirectly increases vagal tone
2) reduction in sympathetic tone
3) inhibits Na/K ATPase pump in cardiac myocites

Front 98

Effects of digoxin

Back 98

decreases HR, decreases AV node conduction, decreases HIs purkinje conduction. Increases contractility (because Na/K ATPase pump inhibition) positive inotropic effect

Front 99

digoxin effect on Na/K ATP ase pump

Back 99

Digoxin inhibits Na/K ATPase pump which decreases extrusion of Na and causes increase of Na intracellularly. Na in the cell causes decrease of Ca+ extrusion from cell. More Ca is available to increase contraction

Front 100

digoxin effects

Back 100

positive inotrope, decreased chronotrope

Front 101

2 clinical uses of digoxin

Back 101

1) Heart failure=increases contractility and modulates sympathetic activity by enhancing parasympathetic activity
2) A fib or other SVT=slows HR, slows electical conduction through AV node

Front 102

Nitche for Digoxin

Back 102

pts with Heart failure and Atrial fibrillation. (decreases symptoms of heart failure, increases quality of life and decreases hospitalization. )
If withdraw Dig you will increase mortality. Stay on Digoxin for life...

Front 103

therapuetic index for Digoxin

Back 103

Narrow, so monitoring closely is needed to avoid toxicity. Lots of drug interactions with Digoxin also.

Front 104

Adverse effects of digoxin

Back 104

arrhytmias=can be fatal. most common cause of digoxin death is V fib
GI effects=earliest sign of toxicity (N/V and anorexia)
CNS=visual disturbances (color perception is green/yellowish usually), HA, weakness, seizures, confusion

Front 105

risk factors for digoxin toxicities

Back 105

electrolyte abnormalities (might have to give potassium), increase age, decreased renal function.

Front 106

A 56 year old woman being treated for A fib is C/O being tired, cold, and muscle weakness. Her skin is bluish. what toxicity explains her symptoms?

Back 106

amiodarone--has iodine in it and can cause bluish tint. Also amiodarone is used to treat A fib, amiodarone has thyroid side effects so can cause her to be tired and cold sensitive. Muscle weakness and peripheral neuropathies are side effects of amiodarone

Front 107

a 54 y/o woman CO rash,myalgias, fever and oral ulcers for 4 weeks. she began treatment for Vent arrythmia 8 wks ago. ANA testing reveals + antihistone Abs. what drug is most likely responsible?

Back 107

Procainamide (lupus-like syndrome)

Front 108

properties of Class IA antiarrhytmics include:

Back 108

Reduces automaticity, prolongs PR and QT intervals
decreases the rate of rise and amplitude of phase 0 depolarization

Front 109

cinchonism is an adverse RXN associated with which drug

Back 109

quinidine only

Front 110

class IC antiarrhtymics posses what electrophysiologic properties

Back 110

markedly depresses phase 0 depolarization and inhibits sodium entry during phase 0 depolarization

Front 111

adverse effects associated with disopyramide therapy include

Back 111

urinary retention, constipation and blurred vision (anticholinergic symptoms)

Front 112

a 25 y/o female CO palpitations, weakness, dizziness and light headedness. pulse is rapid and regular rat of 150. BP 100/58, RR 16. TX?

Back 112

adenosine (drug of choice for SVT) she is unstable

Front 113

50 y/o male with new onset a fib with rapid ventricular response. bp 140/80 what drug would you use to control his a fib?

Back 113

diltiazem=Ca++ channel bklocker, decreases HR, delay conduction through AV node.

Front 114

major adverse effects of amiodarone

Back 114

pulmonary adverse effects, hypo or hyper thyroid, blud skin liver test, corneal microdeposits. class of amiodarone is K++ channel blocker although it blocks almost everything.

Front 115

A 46 y/o female SOB,palpitations intermittent for weak. Hx asthma, EKG shows A fib. Pt was given diltiazem but HR still 140-150's what would you give

Back 115

metoprolol would help but she has asthma and risk of broncospasm. So you would use Digoxin

Front 116

what drug is used to maintain a pt in sinus rhythm after cardioversion from V tach or V fib?

Back 116

amiodarone