antiarrhythmia drugs

Question 1

Re-entry can be defeated by

Answer 1

1. slowed conduction velocity or

2. longer refractory period

Question 2

Re-entry could be terminated by:

Answer 2

(1) converting uni- to bi-directional block

(2) or by prolonging refractory time

Question 3

Unidirectional block can be converted to bi-directional block by:

Answer 3

(1) slowing action potential conduction velocity or
(2) by prolonging refractory period

Class I drugs generate both of these effects, and therefore these drugs may terminate re-entrant arrhythmias by either mechanism.

Question 4

Steeper upstroke =

• Partial block of INa causes retrograde conduction to fail in a depressed region, which is the intent with the use of these drugs

Answer 4

1. faster propagation of action potential
2. steeper voltage gradient along the conduction pathway
3. This causes a larger flow of action current

Question 5

Larger action current pushes

Answer 5

pushes adjacent regions to firing threshold sooner

Question 6

Drug-induced ↓ in upstroke rate results in

Answer 6

↓ conduction velocity

Question 7

Conduction velocity reports____

Answer 7

action current density

it is easier to measure conduction velocity than action current

Question 8

Slower action potentials may not propagate through a _____ because ____

Answer 8

depressed region

Smaller action current fails to excite tissue beyond depressed region

Unidirectional block is converted to bi-directional block this way

Question 9

↓ conduction velocity reports

Answer 9

drug-mediated block of Na+ channels

Question 10

Prolonged refractoriness can suppress re-entrant arrhythmias because:

Answer 10

1. refractory tissue will not generate an action potential

2. and so the re-entrant wave of excitation is extinguished

Question 11

One way to convert uni- to bi-directional block is by

Answer 11

slowing conduction velocity.

Question 12

Yet slowing conduction velocity makes it less likely that

Answer 12

conduction time around the circuit will be shorter than the refractory period.

Question 13

Paradoxically, the two fundamental means of terminating re-entry—

Answer 13

slowing conduction velocity and prolonging refraction—work via conflicting processes.

Question 14

Class III antiarrhythmic drugs: function to

Answer 14

prolongers of phase 2

Question 15

ibutilide and dofetilide specifically block

Answer 15

IKr channels

Question 16

Class III: Prolongation of refractory period is due to ______, this leads to_______.

Answer 16

prolongation of phase 2

↑ inactivation of Na+ channels

↑ refractoriness is different from use-dependent class I action class IIIs are thus especially effective against re-entrant arrhythmias

Question 17

Amiodarone mechanism

Answer 17

1. reduces conduction velocity (but not other class III drugs)
2. ↑ refractory period
3. ↓ rate of diastolic depolarization in automatic cells
   thus reducing firing rate

Question 18

how does amiodarone ↑ refractory period?

Answer 18

by blocking Na+ channels

Question 19

Class 4 drugs are

Answer 19

are use-dependent blockers of L-type Ca2+ channels

Question 20

Class 4 principle effects are on

Answer 20

Ca2+ channels in nodal cells also block Ca2+ channels in fast response myocytes

Question 21

Ca2+ channel blockers function to

Answer 21

↓ upstroke rate in slow response tissue this in turn ↓ conduction velocity, particularly in the AV node

Question 22

Just like class I blockers of Na+ channels, class IV Ca2+ channel blockers can:

Answer 22

prolong refractory period and thereby suppress re-entrant arrhythmias