Anti-Arrhythmic Drugs Flashcards
What is normally the primary determinant of the refractory period in cardiac myocytes?
AP duration
In pacemaker cells (SA node/AV node), what causes the initial upstroke (depolarization)?
Ca2+ influx through T and L-type Ca2+ channels
In pacemaker cells (SA node/AV node), what causes diastolic depolarization?
If (funny) current
Inward Na+ current activated at repolarization
What is normally the primary determinant of the refractory period in pacemaker cells?
Time
In general, what are the two problems that can lead to arrhythmias?
Disturbed impulse formation (EADs, DADs)
Disturbed impulse conduction (blocks, reentry)
When do drugs that inhibit Na+ channels bind best to the receptor?
When the M gate is open (during activation of inactivation)
Binds poorly during resting state (M gate closed)
What drug should you give as prophylaxis for the formation of arrhythmias?
No drug!
Anti-arrhythmic drugs do not act specifically and can depress conduction in normal cells, leading to drug-induced arrhythmias. You only use anti-arrhythmics when there is an arrhythmia already present.
List the 4 Vaughan Williams classes of anti-arrhythmic drugs
Class I: Na+ channel blockers
Class II: Beta-adrenoceptor blockers
Class III: Prolongation of AP duration
Class IV: Ca2+ channel blockers
What is the general mechanism of Class I anti arrhythmics?
Na+ channel blockers, slowing the phase 0 upstroke of the AP
Local anesthetic action
What drugs are in the Class IA anti arrhythmics?
Procainamide
Quinidine
Disopyramide
What drugs are in the Class IB anti arrhythmics?
Lidocaine
Mexiletine
What drugs are in the Class IC anti arrhythmics?
Flecainide
Propafenone
What is the effect of Class IA, IB, and IC on the AP duration?
Class IA: Prolongs AP duration
Class IB: Shortens AP duration
Class IC: variable
Procainamide
MOA
Class IA Na+ channel blocker
Blocks the Na+ channel and slows upstroke of the AP
Lengthens APD
Procainamide
Indications
Atrial and Ventricular arrhythmias
Drug of 3rd choice for ventricular arrhythmias after acute MI
Procainamide
Adverse Effects
Ganglion blocking properties
Hypotension
Torsades de Pointes induction through its metabolite (NAPA)
Long term - Lupus syndrome (arthritis, pleuritis…)
Quinidine
MOA
Class IA Na+ channel blocker
Lengthens APD
Quinidine
Indications
Atrial and ventricular arrhythmias
Quinidine
Adverse Effects
Hypotension
Anticholinergic effects - increase sinus rate and AV conduction
Ventricular fibrillation
Torsades de Pointes
Long term - Cinchonism: headache, dizziness, tinnitus
Lidocaine
MOA
Class IB Na+ channel blocker
Shortens APD
Lidocaine
Indications
DOC for ventricular tachycardia or fibrillation
Arrhythmias after MI
Lidocaine
Adverse Effects
Least cardiotoxic among Class I
Hypotension
Neurologic effects due to anesthesia
Mexiletine
MOA
Class IB Na+ channel blocker
Shortens the APD
Mexiletine
Adverse Effects
Similar to lidocaine
Hypotension
Neurologic effects
Flecainide
MOA
Class IC Na+ channel blocker
Also blocks K+ channels
No anti-cholinergic effects
Flecainide
Indications
Supraventricular arrhythmias in patients with otherwise normal hearts
Propafenone
MOA
Class IC Na+ channel blocker that also blocks K+ channels
Some weak Beta-blocking activity
Propafenone
Indications
Supraventricular arrhythmias in patients with otherwise normal hearts
Flecainide
Adverse Effects
Increase mortality in ventricular tachyarrhtyhmias, MI, and ventricular ectopy
Propafenone
Adverse Effects
Do NOT use in ventricular tachyarrhythmias
Sinus bradycardia (B-blockage)
Bronchospasm (B-blockage)
What are the class II anti arrhythmics known as?
Beta blockers
List some nonselective Beta Blockers
Propranalol
Nadolol
Timolol
Sotalol
List some cardioselective Beta Blockers
Metoprolol
Atenolol
Esmolol
Which beta blocker also has some Class III action?
Sotalol
Class II Anti Arrhythmics
MOA
Inhibit sympathetic influences on cardiac conduction Reduce HR Lower contractility Decrease pacemaker currents Reduce conduction velocity
Class II Anti Arrhythmics
Indications
Prevention of recurrent infarction and sudden death Exercise-induced arrhythmias Atrial fibrillation Atrial flutter AV nodal reentry
Class II Anti Arrhythmics
Adverse Effects
Bradycardia
Bronchospasm
May mask tachycardia associated with hypoglycemia in diabetics
Class II Anti Arrhythmics
Contraindications
AV block
Sinus bradycardia
Asthma
What is the general mechanism of Class III anti arrhythmics?
Prolong the action potential duration by blocking K+ channels responsible for repolarization
Amiodarone
MOA
Class III
Prolongs the APD
Blocks K+ and Na+ channels
May inhibit Beta receptors
Weakly blocks Ca2+ channels
Suppresses abnormal automaticity
Amiodarone
Indications
Oral
Recurrent V tachycardia
V fibrillation
Atrial fibrillation
IV
1st DOC for cardiac arrest outside of hospital
Termination of ventricular tachycardia or fibrillation
Amiodarone
Adverse Effects
- Bradycardia and heart block in patients with AV/SA node disease
- Pulmonary toxicity (fibrosis)
- Hypothyroid symptoms (block T4 -> T3 conversion)
- Photodermatitis
- Corneal microdeposits
Dronedarone
MOA
Class III
Prolongs the AP duration by blocking K+ channels
Why would dronedarone be used instead of amiodarone?
Dronedarone does not have iodine atoms, so it does not block T4 -> T3 conversion
What is the general mechanism of action for Class IV anti arrhythmics?
Block Ca2+ channels on vascular smooth muscle, cardiac myocytes, SA/AV nodes
What is the only dihydropyridine Class IV drug we discussed? What was its only indication?
Nifedipine
Only used for HTN due to high vascular smooth muscle selectivity
Verapamil
MOA
Class IV
Blocks activated and inactivated Ca2+ channels in the heart
Slows AV node conduction
Slows SA node automaticity
Lowers HR and prolongs PR interval
Verapamil
Indications
- Supraventricular arrhythmias
- Reentry arrythmias/tachycardias involving the AV node
- Slows ventricular rate in atrial flutter/fibrillation
Verapamil
Adverse Effects
Vasodilation
Negative inotropic effects
Verapamil
Contraindications
Could cause heart block in patients on beta blockers
Should NOT be used in patients with a diseased heart and ventricular tachycardia
Diltiazem
MOA
Class IV
Blocks Ca2+ channels to lower HR and prolong PR interval
Increase AV refractoriness and slow SA automaticity
Adenosine
MOA
Produces transient cardia arrest
Slows AV node conduction and increases AV refractoriness
Adenosine
Indications
Used to convert paraoxysal supraventricular tachycardia to sinus rhythm
Adenosine
Half life
Short (5-6 seconds)
Adenosine
Administration
Always administered as a rapid IV bolus
Adenosine
Adverse Effects
Flushing SOB Sinus Bradycardia Sinus pauses AV Block
What are some non-pharmacological anti-arrhythmic therapies?
Vagal maneuvers
- Carotid sinus massage
- Diving reflex
- Valsalva
Radiofrequency ablation of the aberrant cells
Electrical cardioversion
Implantable Cardioverter Defibrillator (ICD)
