SM 140 Pharmacology of Antiarrhythmic Drugs Flashcards
What types of arrhythmias are treated with antiarrhythmic drugs?
Tachyarrhythmias
What are the modalities of antiarrhythmic therapy?
Behavior, device-based, and procedural
What is an example of a behavioral antiarrhythmic therapy?
The Valsalva maneuver
How does the Valsalva maneuver exert antiarrhytmic effects?
The Valsalva maneuver results in increased Vagal tone at the AV Node, and can treat AVNRT and AVRT, both of which are subtypes of PVNRT
How do device-based approaches to antiarrhythmic therapy work?
Use an ICD to administer shocks to reset the heart rhythm when an abnormal rhythm is detected
How do procedural approaches to antiarrhythmic therapy work?
Ablate the cells responsible for an abnormal rhythm, such as those that conduct along a slow pathway
What ion is responsible for Phase 0 of the Myocyte AP, and in what direction does it flow?
Sodium is responsible for the Myocyte AP during phase 0, which represents the upshoot due to Sodium influx
What ion is responsible for Phase 2 of the Myocyte AP, and in what direction does it flow?
Calcium is responsible for the Myocyte AP during phase 2, and is responsible for the plateau due to Calcium influx
What ion is responsible for Phase 3 of the Myocyte AP, and in what direction does it flow?
Potassium is responsible for the Myocyte AP during phase 3, which causes repolarization due to Potassium efflux as well as inactivation of the L type Cav
What is significant about Phase 2 during the Myocyte AP?
Ca influx through DihydropyridineR during Phase 2 is responsible for Calcium induced Calcium release from RyanodineR during the Myocyte AP and contraction
What ion is responsible for Phase 4 of the Pacemaker AP, and in what direction does it flow?
Sodium is responsible for the unstable resting membrane potential during Phase 4, and enters via the funny current
What ion is responsible for Phase 0 of the Pacemaker AP, and in what direction does it flow?
Calcium is responsible for Phase 0 of the Myocyte AP, and causes the upshoot
What are the order of phases in Myocyte APs, starting from rest?
Phase 4 -> Phase 0 -> Phase 1 -> Phase 2 -> Phase 3
What are the order of phases in Pacemaker AP’s, starting from rest?
Phase 4 -> Phase 0 -> Phase 3; No Phase 1 or 2
What phases are missing in comparing the Pacemaker AP to the Myocyte AP?
Phase 1 and 2 are missing in the Pacemaker AP, so no brief hyperpolarization and no plateau
What is special about Phase 4 of the Pacemaker AP?
Unstable = automaticity
How do B agonists affect the Pacemaker cells?
Increase the slope of Phase 4 to reach Vt faster = increase Heart Rate
How does the Vagus nerve affect the Pacemaker cells?
Decreases the slope of Phase 4 to reach Vt slower = decrease Heart Rate
Where on the ECG trace does SA Node firing occur, and is it visible?
SA Node fires before the P wave, and is not visible
Where on the ECG trace does Atrial Contraction occur, and is it visible?
Atria contract during the P wave, and is visible
Where on the ECG trace does AV Node firing occur, and is it visible?
AV Node fires during the PR segment, and is not visible
How can SA and AV Node firing be seen on EKG?
Normally not visible because they are so small, but inserting a catheter can visualize them
Where on the ECG trace does the Ventricle depolarize, and is it visible?
Ventricles depolarize during the QRS complex, and is visible
Where on the ECG trace do the Atria repolarize, and is it visible?
Atria repolarize during the QRS complex, and not visible due to being masked by Ventricular depolarization
Where on the ECG trace does the Ventricle repolarize, and is it visible?
Ventricles repolarize during the T wave, and is visible
What phase or interval on the EKG corresponds to SA node firing?
P wave
What phase of the myocyte AP corresponds to the PR Interval?
Phase 4 of the Myocyte AP = PR Interval, waiting for atrial signal
What phase of the Myocyte AP corresponds to the the initiation of the QRS complex?
Phase 0 = initial influx of Sodium = Beginning of QRS on EKG
What phase of the Myocyte AP corresponds to the QT interval?
QT Interval = Calcium influx for contraction = Phase 2
What can cause a narrow QRS complex?
Normal use of the His-P system for Ventricular Contraction
What can cause a wide QRS complex?
Abnormal Ventricular contraction that does not use the His-P system
What are the 2 basic mechanisms of bradyarrhythmias?
Diminished Automaticity and Block
What are the types of SA Node bradyarrhythmias?
Sinus Bradycardia (decreased Automaticity), Sinus Node Exit Block, Tachy-Brady Syndrome
What are the types of AV Node bradyarrhythmias?
First, Second, and Third Degree AV Blocks
What are the mechanisms of tachyarrhythmias?
Enhanced automaticity, reentry, and triggered activity
What can cause enhanced automaticity and what arrhythmia results?
Sharper slope of Phase 4 of the AP + More negative Vt = Tachyarrhythmia
What are the requirements for a reentry arrhythmia to form?
An anatomical barrier, a fast pathway and a slow pathway, and a block
What causes triggered activity and what arrhythmia results?
Defects in calcium balance lead to after depolarizations; Early afterdepolarizations (Phase 3) and Delayed afterdepolarizations (Phase 4) cause triggered activity, which results in tachyarrythmia
What type of depolarization can occur during a prolonged action potential duration?
Prolonged APD = Long QT = Early Afterdepolarization risk
What type of depolarization can occur from Digoxin toxicity?
Delayed Afterdepolarization risk
What are the types of Supraventricular tachyarrhythmias?
Sinus Tachycardia + Paroxysmal Supraventricular Tachycardia (AVNRT + AVRT + AT) + Atrial Flutter + Atrial Fibrillation
What are the types of Ventricular tachyarrhythmias?
Monomorphic Ventricular Tachychardia + Polymorphic Ventricular Tachycardia + Ventricular Flutter + Ventricular Fibrillation
What pathophysiology causes AVNRT?
Reentry within the AV Node using Fast + Slow pathways
What pathophysiology causes AVRT?
Reentry between Atria and Ventricules using the AV Node as a Slow Pathway and an Accessory Pathway as the Fast Pathway
How does Atrial Flutter present on EKG?
Atrial Rate > Ventricular Rate, Sawtooth Pattern of P waves
How does Atrial Fibrillation present on EKG?
Undulating P waves and Irregular Irregular QRS complexes
Does Atrial Flutter use the AV Node?
No, entirely in the R. Atrium
Does Atrial Fibrillation use the AV Node?
No, entirely in the R. Atrium
How does Monomorphic Ventricular Tachycardia present on EKG?
Regular Ventricular rhythm + Monomorphic QRS + Wide QRS
What causes Monomorphic Ventricular Tachycardia?
Reentrant Ventricular rhythm
What causes Polymorphic Ventricular Tachycardia?
Early Afterdepolarization
How does Polymorphic Ventricular Tachycardia present on EKG?
QRS complexes of varying shape
How can enhanced automaticity be treated?
Hyperpolarize resting membrane potential + make the threshold more positive + slow the slope of Phase 4 depolarization = slow heart rate
How can reentry be treated?
Block the slow pathway or suppress premature beats to prevent reentry loops for forming
How can triggered activity be treated?
Modify the milieu/electrolyte balance
Should rational evidence or empirical evidence be trusted more?
Empirical evidence such as Clinical Trials are the gold standard and should be trusted
What are the two ways to treat Atrial Fibrillation?
Rhythm control and Rate control
How does Rhythm control work and what does it treat?
Rhythm control modifies the electrical properties of the Atria to restore sinus rhythm = treat Atrial Fibrillation
How does Rate control work and what does it treat?
Rate control slows the AV node to control the Ventricular rate and does not treat the Atrial dysregulation = treat Atrial Fibrillation
Which form of Atrial Fibrillation treatment does not affect the atrial rhythm?
Rate control does not affect the atrial rhtym and allows for the Atria to continue to fibrillate
How can Ventricular Fibrillation and Ventricular Tachycardia be treated without drugs?
Shock
What effect do Class I antiarrhythmics have?
Block Na channels
What effect do Class II antiarrhythmics have?
Beta blockers
What effect do Class III arrhythmics have?
Block K channels
What effect do Class IV arrhythmics have?
Block Ca channels
What are the activation gates of Nav channels?
M gates = activation
What are the inactivation gates of Nav channels?
H gates = inactivation
How do Na Channel blockers work?
Na Channel blockers bind the active + inactive states of Nav channels to inhibit Na influx
What state can Na Channel blockers not bind?
Na channel blockers cannot bind the resting state of Nav channels
What class are Na channel blockers?
Class I
Why are Na channel blockers described as “use dependent”?
Since Na channel blockers can only bind the active and inactive states of Nav channels, and rapid firing causes these states to be present more often, the Na channel blockers are use dependent
When do Na channel blockers have the strongest effect?
Strongest effect in Tachycardia due to “use dependence”
What effects do Class Ia Nav blockers have on the Na channel and Phase 0 slope?
Class Ia Nav blockers have a Medium effect on the Nav channel and a Medium effect on the Phase 0 slope
What effects do Class Ib Nav blockers have on the Na channel and Phase 0 slope?
Class Ib Nav blockers have a Low effect on the Nav channel and a Low effect on Phase 0 slope
What effects do Class Ic Nav blockers have on the Na channel and Phase 0 slope?
Class Ic Nav blockers have a Strong effect on the Nav channel and a Strong effect on the Phase 0 slope
What effect do Class Ia Nav blockers have on the AP duration?
Class Ia Nav blockers lengthen the AP Duration leading to Long QT intervals
What effect do Class Ib Nav blockers have on the AP duration?
Class Ib Nav blockers shorten the AP duration leading to short QT intervals
What effect do Class Ic Nav blockers have on the AP duration?
Class Ib Nav blockers have no effect on AP duration
Rank the Nav blockers by magnitude of effect on the Na channel?
Ib < Ia < Ic
Rank the Nav blockers by magnitude of effect on the Phase 0 slope?
Ib (minor decrease) < Ia (moderate decrease) < Ic (large decrease)
Rank the Nav blockers by magnitude of effect on the AP duration?
Ib (shorten) < Ic (neutral) < Ia (lengthen)
List the Class Ia drugs?
Procainamide, Quinidine, Disopyramide
What are the side effects of Procainamide, and what class is it?
Ia Nav blocker: Drug-induced lupus and Torsades de Pointes
Why do Class Ia drugs have a risk of Torsades de Pointes?
Ia drugs prolong the AP duration, increasing the QT interval and the risk for Torsades de Pointes
What is N-aceylprocainamide?
A first pass metabolite of Procainamide with strong K channel activity
What are the side effects of Quinidine, and what class is it?
Ia Nav blocker: vagolytic effects such as dry mouth and urinary retention, cinchonism = tinnitus and psychosis, Torsades de Pointes
What are the side effects of Disopyramide, and what class is it?
Ia Nav blocker: strong vagolytic effects, negative inotropic effects, antimuscarinic effects, and Torsades de Pointes
What are antimuscarinic effects?
Urinary retention, constipation, blurred vision and dry mouth
What drug has utility in Ischemia?
Lidocaine, because ischemic tissue is more depolarized and preferentially bound by Lidocaine
What are the side effects of Lidocaine and Mexelitine, and what class of drugs are they?
Class Ib: CNS toxicity = seizures, delerium, confusion
What are the Class Ic Nav blockers?
Flecainide and Propafenone
What are the side effects of Flecainide and Propafenone, and what class are they?
Class Ic: negative inotropy, slow conduction
How does Propafenone compare to Flecainide?
Both Flecainide and Propafenone are Ic Nav blockers, but Propafenone has additional beta blocking effects
When are Ic drugs contraindicated?
LV systolic dysfunction
What are the Class II Antiarrhythmics?
Beta blockers such as Metroprolol and Esmolol
How do Beta Blockers work?
Beta blockers prolong Phase 4 in the SA and AV Nodes
What are the side effects of Beta Blockers?
Hypotension, Bradycardia, Depression
What are the Class III Antiarrhythmics?
Kv blockers
List the Class III drugs?
Amiodarone, Sotalolol, Dofetilide, Ibuitilide
How do Kv blockers work?
Block outward Potassium current in Phase 3 of the AP to prolong APD
What Class of Antiarrhythmic is Amiodarone?
Class III, but also has Class I, II, and IV effects
Which antiarrhythmic is the most powerful?
Amiodarone, due to it’s Class I - IV effects
What are the side effects of Amiodarone?
Thryoid dysfunction, pulmonary fibrosis, blue skin
What Class II effect does Amiodarone have?
Bradycardia
What Class IV effect does Amiodarone have?
Heart Block
What Class I effect does Amiodarone have?
Prolonged QT interval, but Torsades de Pointes is rare
What drug must be dose adjusted with Amiodarone?
Coumadin
What risks do Sotalolol, Dofetilide, and Ibutilide carry?
Prolonged QT interval, hard to use with renal issues
What are Class IV antiarrhythmics?
Cav Blockers
List the Class IV antiarrhythmics?
Verapamil and Diltiazem
How do Cav Blockers work?
Prolong Phase 4 in the AV and SA Node as well as increases the AP duration = slow heart rate
What are side effects of Class IV antiarrhythmics?
Constipation + Peripheral Edema, Bradycardia + Heart Block
When should Class IV antiarrhythmics not be used?
Heart Failure
How does Adenosine work?
Binds to AdenosineR to activate K channel and hyperpolarize myocytes, leading to a transient heart block
What is the benefit of Adenosine and what is it’s effect?
Adenosine is very fast acting and causes a transient elective heart block
What are the two mechanisms of Digoxin?
Direct Membrane Inotropic effects as well as Vagomimetic effects, that act independently
How does Digoxin work?
Digoxin inhibits the Na/K ATPase to potentiate Na/Ca exchange, increasing intracellular calcium and contractility
What is the Inotropic effect of Digoxin?
Increased contractility
What is the Electrophysiologic effect of Digoxin?
Vagomimetic slowing of the sinus rate and prolonging AV Node refractory period
What is the therapeutic window for Digoxin?
Narrow Therapeutic Window
What is the toxicity of Digoxin?
Nausea, diarrhea, yellow vision
How is Digoxin treated?
Anti-digoxin Fab fragments
What should be used to disrupt AVNRT/AVRT actuely and chronically?
Acute effect = Adenosine; Chronic = Beta Blocker + CCB
What can be used to treat AFib and AFlutter via Rate Control?
Beta Blockers + Calcuim Blockers + Digoxin
What can be used to treat AFib and AFlutter via Rhythm Control?
Class Ic agents and Class III Agents
What can be used to suppress VT and PVCs?
Beta Blockers, Sotalol + Amiodarone, Ib agents
What should be used to suppress VT and PVCs in the context of MI?
Beta Blockers, Amiodarone, Ib agents
What should be used to treat Torsades de Pointes?
Magnesium Isoproterenol, Phenytoin, Overdrive Pacing, Shock
What are the Class Ib drugs?
Lidocaine and Mexiletine
What are the Class Ic drugs?
Flecainide and Propafenone
What type of CCB’s are Class IV drugs?
Non-dihydropine (Verapamil + Diltiazem)
Which antiarrythmic drugs decrease Heart Rate and what are they used for?
Rate Control = Class II + Class IV + Digoxin, used for SVTs
Which antiarhythmic durgs are used for cardioverision?
Rhythme control = restoring normal sinus rhythm = Class Ia, Ib, Ic, III
What must be blocked to terminate an SVT?
The AV Node must be blocked to terminate SVTs, such as AVNRT/AVRT; Adenosine is most commonly used
List the drugs for treating Atrial Fibrillation and Atrial Flutter via Rate Control?
Beta Blockers, centrally acting CCB’s, and Digoxin
List the drugs for treating Atrial Fibrillation and Atrial Flutter via Rhythm Control?
Class Ic + III = Flecainide, Propafenone + Amiodarone, Sotalol, Ibutilide, Dofetilide
What is the drawback of Flecainide and Propafenone, and when should they be used?
Flecainide and Propafenoen are proarrhytmic in patients with structural heart disease and ischemic heart disease, and should be used in young, healthy patients
When should Sotalol not be used?
Do not use Sotalol in patients with prolonged QT or renal failure
When should Ibutilide be used?
Acute IV cardioversion
Can Amiodarone, Dofetilide, Sotalol, and Ibutilide be used in patients with structural heart disease?
Amiodarone, Dofetilide, and Sotalol can be used in patients with structural heart disease but Ibuitilide cannot
Which Class III antiarrhythmics require monitoring and why?
Dofetilide and Sotalol require inpatient monitoring to monitor the QT interval - Amiodarone does not predispose Torsades despite lengthening the QT and Ibutilide is used for acute cardioversion
Which is easier to cardiovert, Atrial Fibrillation or Atrial Flutter?
Atrial Flutter
Which is easier to rate control, Atrial Fibrillation or Atrial Flutter?
Atrial Fibrillation
What should be done, from a physiological point of view, to terminate an SVT?
Use an AV Nodal blocking agent to terminate the reentrant pathway and restore normal sinus rhythm
What can be used to terminate AVNRT?
Beta Blocker, Centrally Acting CCB’s, and Digoxin
What is the difference between the Dihydropyridine and Nondihydropyridine subclasses of CCBs?
Dihydropyridine CCB’s tend to act peripherally to vasodilate arteries while Nondihydropyridine CCB’s act centrally on the heart to lower HR and Contractility
How do Dihdyropyridines, Benzothiazipines, and Phenylalkamines differ?
Dihydropyridines (amlodipine) primary lower SVR in the peripheral arteries; Non-dihydropyridines are Benzo’s and Phenyl. Benzothiazipine (Diltiazem) has moderate effects on both Cardiac Output and SVR while Phenylalkamines (Verapamil) primarily lower Cardiac Output
Which type of CCB’s tend to be useful for arrhythmias?
Centrally acting Non-dihydropyridine agents such as Verapamil and Diltiazem
What can be used to terminate SVT?
IV Adenosine
What is the preferred method for treating AVRT?
Ablation
When should Adenosine not be used?
Patients with antegrade conduction and WPW who go into Atrial Fibrillation, because Adenosine would block the AV Node and force Ventricular Fibrillation to occur
What class of drugs are contraindicated in Ventricular Tachycardia?
Class Ic agents are contraindicated due to increased mortality
What should be used to treat monomorphic or idiopathic VT?
Amiodarone and Sotalol (Class III), Class II, and Class Ib (in the setting of MI)
What should be used to treat Polymorphic VT if due to long QT?
IV Magnesium + Isopterenol + Overdrive Pacing
What should be used to treat Polymorphic VT due to ischemia?
Lidocaine and Amiodarone
What are the side effects of Quinidine?
Anticholinergic, ,Cinchonism, Prolonged QT
What are the side effects of Procainamide?
Lupus-like syndrome, fever
When is Disopyramide used?
Disopyramide is used to treat hypertrophic cardiomyopathy by decreasing contractility
What are the side effects of Disopyramide?
Anti-cholinergic effects and prolonged QT
What is a side effect of Lidocaine?
Seizure at high doses
What are the side effects and contraindications for Flecainiade?
Increased mortality in ischemic VT and can cause CHF with LV Systolic Dysfunction
What are the side effects of Beta Blockers?
Decreased contractility and hypotension
What is the common side effect of Class III agents?
All prolong QT, and Ibutilide, Dofetilide, and Sotalol predispose Torsades while Amiodarone does not
Where does Amiodarone exert side effects?
The Liver, Lung, and Thyroid
What are the side effects of Amiodarone on major organ systems?
Liver damage measured by LFTs, Pulmonary Fibrosis, and Hypo/Hyperthyroidism
What are the side effects of Amiodarone on the rain?
Neurologic effects such as Ataxia as well as hypotension
What drug does Amiodarone interact with?
Warfarin, so reduce Warfarin dose when taking Amiodarone
What are the side effects of Sotalol?
Prolonged QT predisposing Torsades, especially in patients with CHF and in women
How is Sotalol excreted and why is this significant?
Sotalol is primarily excreted by renal excretion, and is therefore contraindicated in renal insufficiency
What are the side effects of Dofetilide?
Prolonged QT predisposing Torsades, also not recommended in patients with renal insufficiency
Which Class III drugs are contraindicated in renal insufficiency?
Sotalol and Dofetilide
What are the side effects of centrally acting CCB’s?
Verapamil and Diltiazem can cause decreased contractility, hypotension, and heart block
Which phase of the AP and in what cell type do centrally acting CCB’s act on?
Centrally acting CCBs act on Phase 0, the L-type Cav upshoot, in AV Nodal pacemaker cells
What are the side effects of Digoxin?
Hypokalemia, yellow-green vision, and essentially every arrhythmia
