arrhythmia mech 4

Question 1

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

Answer 1

1. the drugs block initially by entering the open channel
2. they have a higher affinity for the inactivated state of the channel (whether Na channel blocker like lidocaine or Ca2+ channel blocker like verapamil).
3. They prolong the time the channel spends in its inactivated state.
4. This prolongation of channel inactivation is the fundamental mechanism of prolongation of cellular refractory period.

Question 2

High affinity for the inactivated state of the channel means that

Answer 2

these use-dependent blockers stabilize the inactivated state.

Question 3

What is a vital part of the mechanism by which re-entrant arrhythmias are suppressed by these drugs?

Answer 3

prolongation of channel inactivation is the fundamental mechanism of prolongation of cellular refractory period, whether with Na+ channels in non-pacemaker cells or with Ca2+ channels in SA nodal or AV nodal cells.

Question 4

Use-dependence: mechanism of drug action.

Answer 4

1. there are fewer channels available to open.
2. exact percentage available to open depends upon the membrane potential, with depolarization reducing the percentage.
3. Depolarization also reduces the percentage of channels available to open in control because of depolarization causes inactivation of these channels.
4. drug-treated channels recover from inactivation more slowly than do control channels
5. they have a longer time constant for recovery from inactivation.
6. This means that the use-dependent channel blocking drug will prolong the refractory period.

Question 5

Re-entry could be terminated by

Answer 5

1. converting unidirectional block into bi-directional block

2. by prolonging the refractory time.

Question 6

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

Answer 6

(1) by slowing action potential conduction velocity or

(2) by prolonging refractory period.

Question 7

Terminating re-entry by slowing conduction velocity will cause?

Answer 7

reducing upstroke rate.

Unidirectional block can be converted to bi- directional block via this mechanism.

Question 8

The steeper the upstroke of the action potential, the ___ the action potential will propagate.

Answer 8

faster

because the steeper upstroke corresponds to a steeper voltage gradient along the conduction pathway, which in turn makes a larger flow of action current.

Question 9

larger action current pushes the adjacent, previously resting section of the conduction pathway, up to firing threshold more ____ than would a smaller action current.

Answer 9

quickly

Question 10

A drug-induced reduction in upstroke rate therefore results in ?

Answer 10

slower conduction velocity.

Question 11

Slower conducting action potentials are more likely to fail to propagate through a ?

Answer 11

depressed region, for the simple reason that the underlying action current density is smaller and therefore may fail to actively re-excite tissue beyond the depressed region.

Question 12

Thus slowed conduction velocity is an ____

Answer 12

easy-to-measure reporter of drug-mediated block of some of the Na+ channels in the re-entrant circuit.

Question 13

partial block of INa by drugs such as lidocaine means that?

Answer 13

in a depressed region, retrograde or circus conduction is more likely to fail, which is the intent with the use of these kinds of drugs

Question 14

Prolonged refractoriness can help suppress re-entrant arrhythmias because?

Answer 14

the refractory tissue will not generate an action potential, and so the re-entrant wave of excitation is extinguished.

Question 15

slowing conduction velocity makes it?

Answer 15

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

Question 16

Class II Antiarrhythmic Drugs: β-blockers Drugs:

Answer 16

1. propranolol
2. metoprolol
3. esmolol

Question 17

The action of class II drugs — β-adrenergic receptor blockers:

Answer 17

reduce If current, L-type Ca2+ current, and K+ current.

Question 18

Reduction of If, ICa-L and IKs will cause ?

Answer 18

1. a reduction in the rate of diastolic depolarization in pacing cells,
2. reduction in the upstroke rate
3. slows repolarization particularly in AV nodal myocytes.
4. If pacing rate is reduced and refractory period is prolonged in SA and AV nodal cells.

Question 19

β-blockers are thus used to ?

Answer 19

terminate arrhythmias that involve AV nodal re-entry, and in controlling ventricular rate during atrial fibrillation.

Question 20

I-Ca-L effect on symp (NE)

Answer 20

increase current

Question 21

I-f effect on NE (symp)

Answer 21

increase current

Question 22

I-ks effect on symp (NE)

Answer 22

increase current

Question 23

I-ca-L effect on parasymp (Ach)

Answer 23

decrease current

Question 24

I-f effect on parasymp (Ach)

Answer 24

decrease current

Question 25

I-ks effect on parasymp (Ach)

Answer 25

decrease current

Question 26

I-k-Ach effect on parasymp (Ach)

Answer 26

opens channel

Question 27

Class II action

Answer 27

blocking cardiac K+ channels, with ibutilide and dofetilide specifically blocking IKr channels.

Question 28

The consequences of K+ channel block are

Answer 28

prolongation of fast response phase 2, and a prominent prolongation of refractory period.