Antiarrhythmic Drug Pharmacology

Question 1

Ionic conductances in heart cells

• where two gradients are important
• what ions are important
• what is the electrical charge of a cell like

Answer 1

Gradients

• electrical
• concentration

Na+ and K+

• Na outside
• K inside

Cells are more negative inside

**understand how all of these points tie together

Question 2

What interval on ECG is used as the time it takes the myocardium to repolarize?

Answer 2

QT interval

Question 3

Important features of pacemaker cells

Answer 3

They are specialized non-contractile cells

They are physiological depolarized - meaning they normally sit at a depolarized resting membrane potential compared to myocytes

They have high automaticity - the ability to generate AP regardless of input from outside the cell (although influences can change this automaticity)

They have Ca2+ dependent spikes

Question 4

Important features of ventricular myocytes

Answer 4

They are contractile cells

They are hyper polarized

They exhibit less automaticity than pacemaker cells

They have Na+ dependent spikes

Question 5

What currents are important for pacemaker cell APs?

Answer 5

Ica - carries AP upstroke (0)
Ik - repolarizing K+ current (3)
If - diastolic pacemaker current (4)
Ik(ACh) - K+ current activated by vagus (4)

Question 6

Where are most automaticity mechanisms found for pacemaker cells?

Answer 6

In phase 4 - diastolic pacemaker current - If

This is mediated by HCN channels

Question 7

What currents are important for mycocyte APs?

Answer 7

INa - carries AP upstroke (0)
Ikto - “transient outward” repolarizing K+ current (1)
IcaL - plateau Ca2+ current critical for mm contraction (2)
Ik - repolarizing K+ current (3)
If - pacemaker curent (4, very minimal)

Question 8

The later and later you move in the relative refractory period, a stimulus of the same strength results in

Answer 8

stronger and stronger depolarizing

Question 9

What causes the refractory period in electrically excitable cells?

Answer 9

The behavior of voltage gated sodium channels
-“h” gate closure inactivates the channel and during this period, it cannot open to depolarization — this is the absolute refractory period

Question 10

What has a strong influences upon the recovery of cells from inactivation?

Answer 10

the membrane potential of the cell

–a hyperpolarized membrane potential promotes recovery from inactivation

Question 11

What is an arrhythmia?

Answer 11

A depolarization of the heart deviating from normal with respect to one or more of the following:

1. rate or regularity (altered automaticity)
2. site of origin (ectopic pacemaker)
3. conduction pathway (direction of conduction)

Question 12

What are the mechanisms of arrhythmia?

Answer 12

1. Enhanced automaticity - abnormal pacemaker rate or location
2. Triggered activity - abnormal secondary depolarization triggered by a sinus AP
3. Re-entry - abnormal conduction pathway

Question 13

When is there enhanced automaticity?

Answer 13

Where there is strong sympathetic drive to SA node

When AV node depolarized faster than SA and assumes control of its pacing

When myocytes have increased expression of HCN channels - these channels are important for controlling automaticity

Question 14

What are the two main examples of triggered activity?

Answer 14

EAD - early after depolarization

DAD - delayed after depolarization

Question 15

What are the key features of EAD?

Answer 15

Caused by prolonged AP

Arises from a depolarized Vm
–before cell has a chance to return to its normal resting membrane potential

Caused by

• slowed HR
• hypokalemia
• long QT syndrome

Question 16

What are the key features of DAD?

Answer 16

Caused by Ca2+ overload

• -Increased Na/Ca exchanger current
• -leading to increased depolarizing sodium current

Arises from normal Vm

Often seen with rapid HR or conditions that lead to rapid HR like:

• myocardial ischemia
• adrenergic stress
• digoxin intoxication

Question 17

How does a re-entry circuit cause an arrhythmia?

Answer 17

by creating an ectopic pacemaker

Question 18

There are three key features that must be met for a reentrant circuit to be established. What are they?

Answer 18

1. There must be multiple (2+) parallel pathways
2. There must be some kind of obstacle to conduction that creates a unidirectional block
3. The timing of the circus waveform is such that the conduction time around the circuit must be slower (take longer time) than the effective refractory period of tissue

Question 19

Class I anti-arrhythmics

Answer 19

Na+ channel blockers

Question 20

Class II anti-arrhythmics

Answer 20

Beta adrenergic antagonists

Question 21

Class III anti-arrhythmics

Answer 21

Agents that prolong refractory period (K+ channel blockers)

Question 22

Class IV anti-arrhythmics

Answer 22

Ca2+ channel blockers

Question 23

Which classes of anti-arrhythmics are mainly concerned with the action of the pacemaker cells?

Answer 23

Classes II and IV

Question 24

Which classes of anti-arrhythmics are mainly concerned with the action of myocytes?

Answer 24

Classes I and III

Question 25

What currents are modulated by B-adrenergic activity?

Answer 25

the two key currents of pacemaker APs

1. L-type Ca+ for upstroke (0)
2. “funny” currents (4) that spontaneously depolarize

these are important for setting HR