CPRS 20: Antiarrhythmic Drugs Flashcards
For slope of Phase 4 (Spontaneous depolarization)
The slope is increased by activation of ___________ nervous system, decreased by activation of ___________ nervous system.
For slope of Phase 4 (Spontaneous depolarization)
The slope is increased by activation of sympathetic nervous system, decreased by activation of parasympathetic nervous system.
Afterdepolarization
Torsades de Pointes are caused by which 2 types of ion changes?
Afterdepolarization
Torsades de Pointes are caused by which 2 types of ion changes?
- Hypokalemia
- Hypercalcemia
Name Class I II III IV antiarrhythmic Drugs
I: Sodium Channel Blockers
II: Beta-adrenergic Receptor Blockers
III: Potassium Channel Blockers
IV: Calcium Channel Blockers
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.
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.
Class I drugs can only bind to Sodium Channels in _______ and ______ state but not _______ state.
Class I drugs can only bind to Sodium Channels in activated and inactivated state but not resting state.
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?
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
Name 2 examples of Class 1B drugs
Lidocaine
Mexiletine
Name 2 examples for Class 1C drugs
Flecainide
Propafenone
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?
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
Name 1 specific adverse effect for Class 1C drugs
Try and name 1 specific adverse effect for using Propafenone
Pro-arrhythmia, increase sudden death
Propafenone: Structure similar to propranolol, which is non-selective beta antagonist, reducing heart rate and stroke volume
Name 3 Examples of Class 1A drugs
Procainamide
Quinidine
Disopyramide
For Class 1A drugs
What is the relative speed of dissociation?
What channels will this drug block as well?
Intermediate rate of dissociation
Block potassium channels
Name 2 Adverse effects of Class 1A drugs
Pro-arrhythmia (Inhibit K+ channels, lower the K+ efflux, increase the chance of early depolarization)
GI disturbances
Class II drugs
Name 2 examples: Selective B1 Blockers
Name 1 example: Non-selective Beta Blockers
Class II drugs
Name 2 examples: Selective B1 Blockers- Metoprolol, Esmolol
Name 1 example: Non-selective Beta Blockers- Propranolol
Name 2 adverse effects of Class II drugs
- Reduce force and rate of heart contraction, may lead to heart failure
- Bronchospasm
Class III Drugs
Name 4 examples
Amiodarone
Dofetilide
Ibutilide
Sotalol
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
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
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
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
Consider Dofetilide
- Which type of potassium channels does it block
- Name 1 adverse effect
- Where is it metabolized
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
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?
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
Class IV drugs
Name 2 examples
Verapamil
Diltiazem
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
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
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.
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
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
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
Atropine blocks the ________ nervous system
What will it cause
Name 1 adverse effect
Atropine blocks the parasympathetic nervous system
Increase heart rate and increased conduction velocity
Tachycardia
