CPRS 20: Antiarrhythmic Drugs

Question 1

For slope of Phase 4 (Spontaneous depolarization)
The slope is increased by activation of ___________ nervous system, decreased by activation of ___________ nervous system.

Answer 1

For slope of Phase 4 (Spontaneous depolarization)
The slope is increased by activation of sympathetic nervous system, decreased by activation of parasympathetic nervous system.

Question 2

Afterdepolarization

Torsades de Pointes are caused by which 2 types of ion changes?

Answer 2

Afterdepolarization
Torsades de Pointes are caused by which 2 types of ion changes?
- Hypokalemia
- Hypercalcemia

Question 3

Name Class I II III IV antiarrhythmic Drugs

Answer 3

I: Sodium Channel Blockers
II: Beta-adrenergic Receptor Blockers
III: Potassium Channel Blockers
IV: Calcium Channel Blockers

Question 4

Sodium Channels
From resting state to activated state
_____ gates need to be open for Na+ to rush into the cells

From activated state to inactivated state
_____ gates need to be closed to disallow further Na+ to rush into the cells. During this process, ____ gates are still open.

Answer 4

Sodium Channels
From resting state to activated state
m gates need to be open for Na+ to rush into the cells

From activated state to inactivated state
h gates need to be closed to disallow further Na+ to rush into the cells. During this process, m gates are still open.

Question 5

Class I drugs can only bind to Sodium Channels in _______ and ______ state but not _______ state.

Answer 5

Class I drugs can only bind to Sodium Channels in activated and inactivated state but not resting state.

Question 6

Class 1B drugs have (rapid/slow) kinetics.
It dissociates _____ (rapidly/slowly) from Na+ channels within the time frame of normal heartbeat.

For normal heartbeat, will there be effect?

For tachycardia, will there be effect?

Answer 6

Class 1B drugs have rapid kinetics.
It dissociates RAPIDLY from Na+ channels within the time frame of normal heartbeat.

For normal heartbeat, will there be effect? NO

For tachycardia, will there be effect?
YES, gradually increases blockage of Na+ channels, slows down the heartbeat and reduces the maximum membrane potential

Question 7

Name 2 examples of Class 1B drugs

Answer 7

Lidocaine

Mexiletine

Question 8

Name 2 examples for Class 1C drugs

Answer 8

Flecainide

Propafenone

Question 9

Class 1C drugs have (rapid/slow) kinetics.
It dissociates _____ (rapidly/slowly) from Na+ channels within the time frame of normal heartbeat.

For normal heartbeat rate, will there be effect?

Answer 9

Class 1C drugs have slow kinetics.
It dissociates slowly from Na+ channels within the time frame of normal heartbeat.

For normal heartbeat rate, will there be effect? YES

Question 10

Name 1 specific adverse effect for Class 1C drugs

Try and name 1 specific adverse effect for using Propafenone

Answer 10

Pro-arrhythmia, increase sudden death

Propafenone: Structure similar to propranolol, which is non-selective beta antagonist, reducing heart rate and stroke volume

Question 11

Name 3 Examples of Class 1A drugs

Answer 11

Procainamide
Quinidine
Disopyramide

Question 12

For Class 1A drugs
What is the relative speed of dissociation?
What channels will this drug block as well?

Answer 12

Intermediate rate of dissociation

Block potassium channels

Question 13

Name 2 Adverse effects of Class 1A drugs

Answer 13

Pro-arrhythmia (Inhibit K+ channels, lower the K+ efflux, increase the chance of early depolarization)

GI disturbances

Question 14

Class II drugs
Name 2 examples: Selective B1 Blockers
Name 1 example: Non-selective Beta Blockers

Answer 14

Class II drugs
Name 2 examples: Selective B1 Blockers- Metoprolol, Esmolol
Name 1 example: Non-selective Beta Blockers- Propranolol

Question 15

Name 2 adverse effects of Class II drugs

Answer 15

1. Reduce force and rate of heart contraction, may lead to heart failure
2. Bronchospasm

Question 16

Class III Drugs

Name 4 examples

Answer 16

Amiodarone
Dofetilide
Ibutilide
Sotalol

Question 17

Consider Amiodarone

• It has a broad spectrum of activities by blocking potassium, sodium and calcium channels
• Name an advantage
• Which functional group is present?
• What might be resulted due to the functional group? (try and name 2 effects)
• What is the drug called for the same mechanism of action but without the functional group?
• What enzyme is used to metabolize Amiodarone

Answer 17

Consider Amiodarone

• It has a broad spectrum of activities by blocking potassium, sodium and calcium channels
• Name an advantage: Low incidence of Torsades De Pointes
• Which functional group is present? Iodine
• What might be resulted due to the functional group? Pulmonary fibrosis, Photosensitivity
• What is the drug called for the same mechanism of action but without the functional group? Dronedarone
• Enzyme metabolizing amiodarone: CYP3A4

Question 18

Amiodarone is metabolized by CYP3A4 enzyme

• Cimetidine, drug inhibiting CYP3A4, will lead to _______ level of amiodarone
• Rifampin, drug inducing the action of CYP3A4, will lead to ________ level of amiodarone

Answer 18

Amiodarone is metabolized by CYP3A4 enzyme

• Cimetidine, drug inhibiting CYP3A4, will lead to increased level of amiodarone
• Rifampin, drug inducing the action of CYP3A4, will lead to decreased level of amiodarone

Question 19

Consider Dofetilide

• Which type of potassium channels does it block
• Name 1 adverse effect
• Where is it metabolized

Answer 19

Consider Dofetilide

• Which type of potassium channels does it block: Delayed-rectifier Potassium channels
• Name 1 adverse effect: Torsades de Pointes
• Where is it metabolized: Kidneys

Question 20

Consider Sotalol

• it has d-sotalol and I-sotalol mixture, which isomer contains the class II action (beta receptor blocking activity?)
• Name 1 adverse effect
• It can treat arrhythmias in which age group?

Answer 20

Consider Sotalol

• it has d-sotalol and I-sotalol mixture, which isomer contains the class II action (beta receptor blocking activity?) I-sotalol
• Name 1 adverse effect: Increase risk of Torsades de Pointes
• It can treat arrhythmias in which age group? Pediatric age group

Question 21

Class IV drugs

Name 2 examples

Answer 21

Verapamil

Diltiazem

Question 22

Consider Class IV drugs,

• With reduced calcium entry, it can treat __________ which is caused by calcium-induced-calcium release
• Name 2 adverse effects
• It is avoided in people with _____ dysfunction

Answer 22

Consider Class IV drugs,
- With reduced calcium entry, it can treat after depolarization which is caused by calcium-induced-calcium release
- Name 2 adverse effects:
Reduce force and rate of heart contraction
Hypotension
- It is avoided in people with hepatic dysfunction

Question 23

Adenosine inhibits the ______ nervous system
It reduces the release of _______.

The half-life is ______. (long or short), so even for adverse effects, they would ______ resolve.

Name another adverse effect.

Answer 23

Adenosine inhibits the sympathetic nervous system. It reduces the release of NE.

The half-life is short, so even for adverse effects, they would quickly resolve.

Name another adverse effect: Chest pain and shortness of breath

Question 24

Digoxin stimulates the ________ nervous system
Reduces heart rate and reduces conduction velocity

Name 2 adverse effects in addition to pro-arrhythmia

How would Digoxin lead to pro-arrhythmia (Important)
With reference to the channels

Answer 24

Digoxin stimulates the parasympathetic nervous system
Reduces heart rate and reduces conduction velocity

Name 2 adverse effects

• GI disturbances
• CNS disturbances

Proarrhythmia

• Digoxin inhibits Na/K ATPase
• Less K+ pumped into the cell and less Na+ pumped out of cell
• Less Na+ influx and less Ca2+ outflux by the Na/Ca exchanger
• Increase Ca2+ inside the cell causing more afterdepolarizations

Question 25

Atropine blocks the ________ nervous system

What will it cause

Name 1 adverse effect

Answer 25

Atropine blocks the parasympathetic nervous system

Increase heart rate and increased conduction velocity

Tachycardia