Arrhythmias

Question 1

Almost all arrhythmias are ____

Answer 1

acquired= myocardial infarction (MI), ischemia, acidosis, alkalosis, electrolyte abnormalities.

Drug toxicity is a common cause of arrhythmia

Question 2

when are antiarrhythmic drugs used

Answer 2

1) treating some arrhythmias (e.g., supraventricular

2) used with ICDs- decr arrhythmic episodes, decr discharges

Question 3

Familial Long QT

Answer 3

cardiac AP is extended

prolonged phase 2 –> too much Ca2+ entry –> afterdepolarizations –> torsades –> v-fib and sudden death

Question 4

which phase is prolonged in familial long QT

Answer 4

phase 2 –> too much Ca2+ entry

Question 5

how do mutations in K+ channels lead to long QT

Answer 5

mutations = decr expression of K+ channels so less K+ current to end Phase 2

Question 6

how do mutations in Na+ channels lead to long QT

Answer 6

prevent Na+ channels from inactivating completely –> continued flow of Na+ –> prolong phase 2

Question 7

Triggered afterpolarizations are a cause of _____

Answer 7

inappropriate impulse initiation –> abnormally depolarized diastolic membrane potential triggered by an AP

Question 8

when do Early afterdepolarizations arise

Answer 8

late phase 2 or phase 3

Question 9

what causes Early afterdepolarizations

Answer 9

1) prolonged phase 2
2) reactivation of Ca2+ channels so more Ca2+ enter into cytoplasm
3) allows 2nd AP to fire releasing more Ca2+ from SR

Question 10

when do delayed afterpolarizations arise

Answer 10

phase 4

Question 11

what causes delayed afterpolarizations

Answer 11

NCX exchanger working fast enough to trigger depol

1) elevated cytoplasmic Ca2+
2) causes NCX to pump out Ca2+
3) but NCX leads to net positive charge inward
4) depolarization

Question 12

Criteria for re-entry arrhythmia

Answer 12

1) unidirectional conduction block in a functional circuit

2) conduction time around circuit is longer than refractory period

Question 13

what triggers re-entry arrhythmia

Answer 13

triggered by afterpolarizations

Question 14

what happens in re-entry arrhythmia

Answer 14

block in normal conduction –> prevents current from flowing in norma pathway

current cirumvents block and excites damaged area on other side of block not in refractory (due to incr conduction time)

Question 15

what does use-dependent block mean for class 1

Answer 15

channel must be open before it is blocked by drug
drug enters pore –> binds, and blocks ions from crossing

more a channel open, more chance drug has to bind

Question 16

what do class 1 drugs preferentially target with use dependent block

Answer 16

abnormally high firing rates or abnormally depolarized membranes

Question 17

2 effects of class 1 antiarrhythmics

Answer 17

increase Na+ channel refractory period by (2)

1) use dependent mechanism
2) prolonged phase 2

Question 18

class 1 use dependent mechanisms

Answer 18

class 1 have high affinity for inactive state of channel –> stabilizes in inactive state and prolong refractory period

Question 19

class 1 prolonged phase 2 duration

Answer 19

during phase 2, more Na+ channels inactivated –> prolongs refractory period

ONLY CLASS 1A AND 1C (CLASS 3 EFFECT BY BLOCKING K+ CHANNELS)

Question 20

which class 1 prolong phase 2

Answer 20

CLASS 1A AND 1C

Question 21

how do beta blockers help suppress arrhythmias?

Answer 21

reducing If, ICa-L and IKs

decreasing

1) diastolic depolarization
2) upstroke rate
3) refractory rate

–> decr HR and prolong refractory period in SA and AV cells

Question 22

which cells are beta blockers effective against

Answer 22

AV node

used to treat arrhythmias with AV nodal re-entry
control ventricular rate during a-fib

Question 23

how do class 3 drugs increase refractory period

Answer 23

increasing fast response phase 2

inactivation of more Na+ channels and extended refractory period

Question 24

how do class 4 reduce re-entry ?

Answer 24

decreasing conduction velocity

prolonging refractory period (especially AV node)

Question 25

how do class 4 decrease conduction velocity

Answer 25

blocking of L-type Ca2+ channels in upstroke (phase 0) of slow AP

therefore, slower and less likely to cross cardiac tissue in re-entry

Question 26

how do class 4 increase refractory period

Answer 26

use-dependent block of calcium channels (stabilize inactive state) –> refractive cells can’t conduct AP

Question 27

how does increasing refractory period help decrease re-entry arrhythmias

Answer 27

refractory tissue can’t generate AP

AP that reaches refractory tissue is extinguished.

Question 28

why is decreasing cardiac automaticity good for treating arrhythmia?

Answer 28

rogue cardiomyocytes generating AP independent of AP node (ectopic foci)

Question 29

which antiarrhythmic drugs treat arrhythmias by decr cardiac automaticity?

Answer 29

class 2, 3, 4, and adenosine