Lecture 11: Anti-Arrythmic Drugs (Part I)

Question 1

____: Any change from normal sequence of cardiac impulse (may be fast, slow, or erratic beat) that result in ineffective pumping of blood to vital organs

Answer 1

Cardiac Arrythmia

Question 2

True or False: A change in beat velocity or rhythm is considered arrhythmic

Answer 2

True

Question 3

_____ is made up of continuous cycles of depolarization and re-polarization of cardiac muscle tissue. During this period, cardiac muscle cells are refractory to any further stimuli, which is known as ____

Answer 3

Cardiac action potential; effective refractory period (ERP) /absolute refractory period (ARP)

Question 4

Which AP corresponds to pacemaker cells (SA/AV Node) and which correspond to non-pacemaker cells?

Answer 4

Left = non-pacemaker
Right = pacemaker cells

Question 5

How many phases are present in pacemaker cell action potential?

How many phases are present in non-pacemaker cell action potential?

Answer 5

Pacemaker cell action potential = three phase s(Phase 4, 0, and 3)

Non-pacemaker cell action potential = five phases (Phase 0, 1, 2, 3, and 4)

Question 6

What initiates Phase 4 in pacemaker cell action potential?

Answer 6

Slow and spontaneous depolarization by:

1) inward pacemaker current (inward funny current) - maintains automaticity
2) HCN channels

Question 7

By the end phase 4 of pacemaker cell action potential, there is an increase in ___ (influx), which stimulates ___ entry

Answer 7

Na; Ca2+

Question 8

Phase 0 of pacemaker cell action potential is characterized by rapid ____. What causes this?

Answer 8

rapid depolarization
- cause: opening of VG Ca2+ channel

Question 9

What causes phase 3 of pacemaker cell action potential (repolarization phase)?

Answer 9

1) Opening of K+ selective channels via: delayed rectifier outward current

Question 10

During phase 3 of pacemaker cell AP, are Ca2+ channels open or closed?

Answer 10

Closed

Question 11

Following repolarization (phase 3 of pacemaker cell AP) - once the membrane potential reaches ___, it triggers the opening of __, for the next slow and spontaneous depolarization

Answer 11

-60 mV; If

Question 12

True or False: In pacemaker cell action potential, phase 4 is associated with Na influx, phase 0 is associated with Ca influx, and phase 3 is associated with K efflux

Answer 12

True

Question 13

What is the order in which the pacemaker cell AP phases occur in?

What is the order in which the non-pacemaker cell AP phases occur in?

Answer 13

Pacemaker: Phase 4→Phase 0 →Phase 3

Non Pacemaker: Phase 4→ 0 → 1→ 2 → 3 →4

Question 14

What happens in phase 4 (first stage of non-pacemaker cell AP)?

Answer 14

K+ ions efflux via: delayed rectifier outward K+ currents - IKs - maintains negative potential

Question 15

Which stage of the non-pacemaker cell action potential is associated with rapid depolarization (and, ultimately, a shift from negative (-90 mv) to positive potential) ?
A. Phase 1
B. Phase 4
C. Phase 0

Answer 15

C. Phase 0

Question 16

During phase 0 of non-pacemaker cell AP, there is fast influx of __ ions. Which channels are closed at this time?

Answer 16

Na; Outward K

Question 17

Which stage of the non-pacemaker cell action potential is associated with a rapid, transient repolarization stage? Cause?

Answer 17

Phase 1 is the initial rapid transient repolarization stage in Non-Pacemaker Cell Action Potential
- Due to opening of transient outward K+ channels

Question 18

What factors lead to Phase 2 (plateau phase) of non-pacemaker cell action potential?

Answer 18

• Inward flow of calcium
• Outward K+ current

Question 19

IKr and Iks are rapid and slow acting delayed rectifiers that allows for K+ efflux at what phase of non-pacemaker cell action potential?

Answer 19

Phase 2 (plateau) and Phase 3

Question 20

By the end of phase 2 in the non-pacemaker cell action potential, the ___ channel closes and is following by steady and fast efflux of K+ via ___ and ___

Answer 20

Ca2+; IKr/IKs

Question 21

What happens in phase 4 of the non-pacemaker cell action potential? How it it achieved?

Answer 21

Re-establishment of resting membrane potential
- Achieved by opening of outward K+ currents (IKr/IKs*) - time independent, but depends on potential of -90 mV

Question 22

Which of the following corresponds to the following description?
“Atrial depolarization”

A. P wave
B. PR interval
C. QRS complex
D. ST segment

Answer 22

A. P wave

Question 23

Which of the following corresponds to the following description?

“Time between atrial depolarization and ventricular depolarization”
A. P wave
B. PR interval
C. QRS complex
D. ST segment

Answer 23

B. PR interval

Question 24

Which of the following corresponds to the following description?
“Ventricular depolarization”
A. P wave
B. PR interval
C. QRS complex
D. ST segment

Answer 24

C. QRS complex

Question 25

Which of the following corresponds to the following description? "Time taken for both ventricles to get completely depolarization - corresponds to plateu phase)" A. P wave B. PR interval C. QRS complex D. ST segment

Answer 25

D. ST segment

Question 26

Which of the following corresponds to the following description? "Ventricular repolarization" A. P wave B. PR interval C. QRS complex D. ST segment E. T waves

Answer 26

E. T waves

Question 27

Two types of defects that can lead to arrythmia?

Answer 27

1) Defects in impulse formation 2) Defects in impulse conduction

Question 28

What are two factors that can cause defects in impulse formation?

Answer 28

1) Altered automaticity 2) Triggered activity

Question 29

What is the normal path taken by electrical activity?

Answer 29

SA Node→AV Node→Bundle of His→Purkinje

Question 30

____: a condition in which there is a defect in either pacemaker cells OR non-pacemaker cell activity, leads SA Nodal firing rate to become altered/impairs downstream conduction

Answer 30

Altered Automaticity

Question 31

____: Process by which the initial AP triggers an immediate and addition depolarization PRIOR to completion of one cycle, leads to arrythmia

Answer 31

Triggered activity

Question 32

What are the two types of triggered activity?

Answer 32

1) Early After Depolarization (EAD) 2) Delated After Depolarization (DAD)

Question 33

When does Delayed After Depolarization commonly occur? When does Early After Depolarization occur?

Answer 33

DAD = Phase 3 or end of Phase 3 EAD = End of Phase 2 or early part of Phase 3

Question 34

True or False: Early After Polarization is most likely to happen towards the enter of plateau or beginning of rapid repolarization

Answer 34

True

Question 35

If Early After Depolarization persists, what condition could it lead to? How is this condition characterized?

Answer 35

Torsade de Pointes - characterized by: 1) ventricular tachyarrythmia 2) prolonged QT intervals 3) heart rate (200-250 beats/min)

Question 36

What three drugs are known to induce Torsade de Pointes? What three gene mutations are known to induce the condition?

Answer 36

Drugs: anti-arrythmic drugs; tricyclic antidepressants; anti-virals Mutations: KCNQ1, HERG, SCN5A

Question 37

True or False: Digitalis can induce torsade de pointes (TdP)

Answer 37

True - can be treated by MgSO4 IV infusion

Question 38

Delayed After Depolarization typically occurs after repolarization (phase _) due to a rise in ___, leading another depolarization to occur before completion of one cycle

Answer 38

phase 3; Ca2+

Question 39

Three factors that can lead to defects in impulse conduction?

Answer 39

1) Re-entry 2 ) Conduction block 3) Accessory Tract Pathways

Question 40

What are two factors that lead to re-entry?

Answer 40

1) Uni-directional block 2) Slow retrograde conduction velocity

Question 41

_____ is due to failure to propagate impulses due to damage induced reduced excitability of cardiac tissue. Often results in decrease contractility of ___

Answer 41

Conduction Block; myocyte

Question 42

True or False: Accessory fibers, such as Bundle of Kent, can bypass SA-AV Path

Answer 42

True

Question 43

Supraventricular Tachyarrythmia (WPW Syndrome) could lead to ______ if it is AV Nodal in origin

Answer 43

Paroxysmal Supraventricular Tachycardia

Question 44

True or False: Impulses from accessory path and normal path can trigger impulses

Answer 44

True

Question 45

What four drug classes are associated with QT Prolongation and TdP?

Answer 45

1) Anti-arrhythmics 2) Anti-microbials 3) Anti-depressants 4) Anti-psychotics