Antiarrhythmic Drugs

Question 1

what part of the cardiac action potential do class 1 antiarrhythmic drugs affect

Answer 1

phase 0

Question 2

what part of the cardiac action potential do class 3 antiarrhythmic drugs affect

Answer 2

phases 2 and 3

Question 3

what part of the nodal action potential do class 2 antiarrhythmic drugs affect

Answer 3

prolongs phase 4 (delays progression to phase 0)

Question 4

what part of the nodal action potential do class 4 
 antiarrhythmic drugs affect

Answer 4

prolongs phase 4 (delays progression to phase 0)

Question 5

describe phase 0 of the cardiac action potential

Answer 5

voltage-dependent fast Na+ channels open as a result of depolarization and Na+ enters the cells down its gradient

Question 6

describe phase 1 of the cardiac action potential

Answer 6

K+ exits the cell down its gradient while fast Na+ channels close, causing some depolarization

Question 7

describe phase 2 of the cardiac action potential

Answer 7

the plateau phase which results from K+ exiting the cells offset by Ca2+ entering the cells through slow voltage- dependent Ca2+ channels

Question 8

describe phase 3 of the cardiac action potential

Answer 8

Ca2+ channels close and K+ begins to exit more rapidly, resulting in repolarization

Question 9

describe phase 4 of the cardiac action potential

Answer 9

resting membrane potential is gradually restored by Na+/K+ ATPase and Na+/Ca2+ exchanger

Question 10

describe phase 4 of the pacemaker action potential

Answer 10

slow spontaneous depolarization; pacemaker current (funny current) opens and lets Na+ into the cell

Question 11

describe phase 0 of the pacemaker action potential

Answer 11

upstroke of action potential; Ca2+ influx through L-type Ca2+ channels

Question 12

describe phase 3 of the pacemaker action potential

Answer 12

Repolarization; inactivation of Ca2+ channels with increased K+ efflux

Question 13

describe resting state of sodium channels

Answer 13

channel closed but ready to generate an action potential

Question 14

describe activated state of sodium channels

Answer 14

depolarization to the threshold opens m-gates which greatly increases sodium permeability

Question 15

describe inactivated state of sodium channels

Answer 15

h-gates are closed, inward sodium flux is inhibited, channel not available for reactivation
–> responsible for the refractory period

Question 16

describe the state-dependent block of class 1 antiarrhythmics

Answer 16

they block activated or inactivated Na+ channels with very little affinity toward channels in a resting state

Question 17

class 1A antiarrhythmics:

• state dependent block
• binding strength
• effect on ECG

Answer 17

• preferentially bind to open (activated) channels
• dissociate with intermediate kinetics (medium strength)
• prolong QRS and QT

Question 18

what does procainamide do in addition to Na+ channel block

Answer 18

• directly depresses SA and AV node
• antimuscarinic activity
• reduces PVR and can cause hypotension

Question 19

non-cardiac adverse effects procainamide

Answer 19

• lupus-like syndrome (arthritis, pleuritis, hepatitis)

- nausea, diarrhea

Question 20

non-cardiac adverse effects quinidine

Answer 20

• GI stuff
• tinnitus, dizziness, HA
• thrombocytopenia

Question 21

non-cardiac adverse effects disopyramide

Answer 21

• urinary retention
• dry mouth
• blurred vision

Question 22

cardiac adverse effects of all class 1A drugs

Answer 22

• QT prolongation
• torsades de pointes
• excessive inhibition of conduction

Question 23

class 1B antiarrhythmics:

• state dependent block
• binding strength
• effect on ECG

Answer 23

• bind preferentially to inactivated Na+ channels
• dissociate with fast kinetics (weak binding)
• doesn’t block K+ so does not prolong QT or action potential on ECG

Question 24

how does lidocaine make damaged tissue “electrically silent”

Answer 24

it selectively blocks conduction in depolarized tissue

Question 25

why do class 1B drugs have no effect on cardiac conductivity in normal tissue

Answer 25

fast kinetics of dissociation from Na+ channels results in recovery from block between action potentials

Question 26

adverse effects lidocaine

Answer 26

- hypotension in pts with heart failure | - paresthesias, tremor, slurred speech, convulsions

Question 27

adverse effects mexiletine

Answer 27

- tremor - blurred vision - nausea - lethargy

Question 28

class 1C antiarrhythmics: - state dependent block - binding strength - effect on ECG

Answer 28

- preferentially bind to activated sodium channels - dissociate from channel with slow kinetics (strong binding) - prolongs QRS, does not prolong action potential or QT on ECG

Question 29

which class 1 drugs also block K+ channels

Answer 29

``` class 1A class 1C ```

Question 30

adverse effects Flecainide

Answer 30

severe exacerbation of ventricular arrhythmias in pts with preexisting ventricular tacchyarrhyhtmias, previous MIs, or ventricular ectopic rhythms

Question 31

adverse effects Propafenone

Answer 31

- exacerbation of ventricular arrhythmias - metallic taste (purple phone tastes like metal) - constipation

Question 32

sympathetic effect of beta blockers on funny channel and T-type Ca2+ channels in nodal AP

Answer 32

increased slope

Question 33

sympathetic effect of beta blockers on L type Ca2+ channels in nodal AP

Answer 33

reduced threshold

Question 34

effect of esmolol on SA and AV node and ECG

Answer 34

SA node: decreases HR (increase RR interval) | AV node: decreases AV conductance (increase PR interval)

Question 35

based on its half life, how must esmolol be administered

Answer 35

continuous IV infusion with rapid onset and termination of its action (half life is 10 min b/c hydrolysis by blood esterases)

Question 36

contraindications beta blockers

Answer 36

- asthma - PVD - Raynaud's - type 1 DM on insulin - bradyarrhythmias and AV conductance abnormalities

Question 37

adverse effects beta blockers

Answer 37

- reduced CO - bronchoconstriction - impaired liver glucose mobilization - increase VLDL and decreases HDL - sedation, depression

Question 38

effect of class 3 drugs on ECG

Answer 38

prolong QT

Question 39

effect of class 3 drugs on refractory period

Answer 39

prolong refractory period

Question 40

effects of amiodarone on Na+ and Ca2+ channels

Answer 40

blocks Ca2+ and inactivated sodium channels as well as K+ channels

Question 41

what is amiodarone metabolized by

Answer 41

CYP3A4

Question 42

effect of cimetidine or rifampin on amiodarone

Answer 42

they inhibit CYP3A4, which affects metabolism of amiodarone

Question 43

how does amiodarone affect metabolism of other drugs

Answer 43

it inhibits many CYP enzymes

Question 44

cardiac adverse effects amiodarone

Answer 44

- AV block and bradycardia | - torsade de pointes

Question 45

extracardiac adverse effects amiodarone

Answer 45

- fatal pulmonary fibrosis - hepatitis - photodermatitis (blue-gray skin) - deposits of drug in cornea - hypo or hyperthyroidism

Question 46

adverse effects sotalol

Answer 46

- depression of cardiac function | - torsades de pointes

Question 47

adverse effects dofetilide and ibutilide

Answer 47

QT interval prolongation and increased risk of ventricular arrhythmias

Question 48

why are the effects of dofetilide and ibutilide more pronounced at lower heart rates

Answer 48

they specifically block the rapid component of the delayed rectifier potassium current

Question 49

effect of class 4 drugs on nodal action potential

Answer 49

- decrease slope of phase 0 - increase L-type Ca2+ channel threshold potential - prolong refractory period in AV node

Question 50

adverse effects of class 4 drugs

Answer 50

- negative inotropy - AV block - SA node arrest - bradyarrhythmias - hypotension

Question 51

non-cardiac adverse effect verapamil

Answer 51

constipation

Question 52

effect of adenosine on nodal action potential

Answer 52

- inhibits Ca2+ and funny currents - causes hyperpolarization and suppression of AP in slow cells - inhibits AV conduction - increases refractory period

Question 53

adverse effects adenosine

Answer 53

- SOB - bronchoconstriction - chest burning - AV block - hypotension