7, 8. Molecular Mechanisms of Arrhythmias and Drugs Flashcards Preview

CVPR Exam I > 7, 8. Molecular Mechanisms of Arrhythmias and Drugs > Flashcards

Flashcards in 7, 8. Molecular Mechanisms of Arrhythmias and Drugs Deck (54):
1

Cardiac arrhythmias are acquired subsequent to what 7 things?

MI, ischemia, acidosis, alkalosis, electrolyte abnormalities, drug toxicitiy, or excessive catecholamine exposure

2

Name a cardiac glycoside that can cause arrhythmias.

digoxin

3

Name some antihistamines that can cause arrhythmias.

astemizole, terfenadine

4

Name an antibiotic that can cause arrhythmias.

sulfamethoxazole

5

What are the 1a targets of antiarrhythmic drugs?

1. cardiac Na+ channels (INa)
2, Ca2+ channels (ICa-L)
3. K+ channels (IKs and IKr)
4. β-adrenergic receptors

6

What drugs can reduce the incidence of sudden cardiac death?

β-blockers

7

What is familial long QT syndrome?

a genetic prolongation of the duration of the cardiac AP (phase 2 plateau phase in the QT interval) that can lead to ventricular arrhythmia and death

8

What is torsades de pointes?

a polymorphic ventricular tachycardia that can degenerate into v-fib

9

What triggers torsades de pointes?

an abrupt increase in sympathetic tone

10

How are long QT patients treated?

β-adrenergic receptor blockers (β-blockers)

11

What is Brugada syndrome?

an inherited v-fib with only 40% survival to age 5- caused by mutations in Na+ channels

12

What is yotiao?

a protein that normally targets PKA, the effector of β receptors in cardiac Ca and K channels

13

What are the 2 general mechanisms of arrhythmia generation?

1. inappropriate impulse initiation at the SA node or ectopically
2. disturbed impulse conduction in nodes, Purkinje cells, or myocytes

14

Why do ectopic foci occur?

SA nodal pacemaker is abnormally slow or ectopic focus is abnormally fast; infarct

15

What does EAD stand for?

early afterdepolarizations

16

When do EADs occur?

in late phase 2 or early phase 3

17

What causes EADs?

re-activation of Ca2+ channels in response to elevated Ca2+

18

What does DAD stand for?

delayed afterdepolarizations

19

When do DADs occur?

during early phase 4

20

What causes DADs?

initiated by elevated [Ca2+]in and elevated Na+/Ca2+ exchange

21

What is NCX?

the sodium-calcium exchanger

22

What is the current the NCX generates?

I NCX

23

Re-entrant arrhythmias require what two conditions?

1. uni-directional conduction block in a functional circuit
2. conduction time around the circuit is longer than the refractory period

24

In many cases, arrhythmia is triggered by _____ but is maintained by _____.

afterdepolarizations; re-entry

25

Why does increased sympathetic tone increase the likelihood of triggered afterdepolarizations?

Ca2+ influx is enhanced by β-adrenergic receptor activity

26

What is the mechanism of action of Class I Anti-arrhythmic Drugs?

voltage-gated Na+ channel blockers

27

All Na+ channel blockers decrease _____ and
nearly all increase _____.

conduction rate; refractory period

28

All _____ decrease conduction rate and nearly all increase refractory period.

Na+ channel blockers

29

Class I action results in _____.

slowed upstroke

30

_____ action results in slowed upstroke.

Class I

31

_____ drugs slow upstroke and also decrease action potential duration.

Class Ib

32

Class Ib drugs slow _____ and also decrease _____.

upstroke; action potential duration

33

_____ and _____ drugs delay phase 3 onset by blocking K+ channels.

Class Ia; class Ic

34

Class Ia and class Ic drugs delay ____ onset by blocking K+ channels.

phase 3

35

Class Ia and class Ic drugs delay phase 3 onset by blocking _____.

K+ channels

36

Name 3 specific class 1a Na+ channel blockers.

quinidine, procainamide, disopyramide

37

All ____ drugs slow the upstroke of the fast response, and they also delay the onset of repolarization.

class Ia

38

All class Ia drugs slow the _____, and they also delay the ____.

upstroke of the fast response; onset of repolarization

39

Class Ia drugs prolong the refractory period via two processes: _______ and _____.

1. classic, use-dependent mechanism, similar to local anesthetics in action
2. depolarization (phase 2 duration) is prolonged

40

Quinidine has important effects not related to Na+ channel block, including ____, ____, and ____.

1. blocks K+ channels particularly well, thereby prolonging action potential duration
2. it is a vagal inhibitor (anti-cholinergic)
2. it is an α-adrenergic receptor antagonist

41

Name 3 specific Class Ib Na+ channel blockers.

lidocaine, mexiletine, phenytoin

42

Lidocaine, mexiletine, and phenytoin are all what kind of drug?

Class Ib Na+ channel blockers

43

How are class 1b drugs similar to class 1a drugs?

they are use-dependent blockers of voltage-gated Na+ channels

44

In contrast to class Ia drugs, ____ drugs do not prolong phase 2 of the action potential.

class Ib

45

In contrast to class Ia drugs, class Ib drugs do not ____.

prolong phase 2 of the action potential

46

What is the most important class 1b drug for the treatment of arrhythmias?

lidocaine

47

Name 3 specific Class Ic Na+ channel blockers.

propafenone, flecainide, encainide

48

Propafenone, flecainide, and encainide are all what kind of drug?

Class Ic Na+ channel blockers

49

_____ produce the most pronounced slowing of upstroke rate; the net effect is powerful prolongation of tissue refractory period.

Class Ic drugs

50

Class Ic drugs produce the most pronounced slowing of upstroke rate; the net effect is powerful ____.

prolongation of tissue refractory period

51

What does it mean that class 1c drugs preferentially target cells?

Na+ channels in myocytes with abnormally high firing rates or abnormally depolarized membranes will be blocked to a greater degree than are Na+ channels in normal, healthy myocyte

52

What is the mechanism of action for class 1c drugs that allows their preferential targeting?

the channel must be open

53

_____ is the fundamental mechanism of prolongation of cellular refractory period.

Prolongation of channel inactivation

54

How do use-dependent channel blockers prolong the refractory period?

they stabilize the inactive state after entering the open channel