Module 2: Antidysrhythmic Drugs Flashcards
Origin of dysrhythmias
Arises from impulse formation disturbances
* Tachydysrhythmias: Supraventricular (SVT) and ventricular
* Bradydysrhythmias
Virtually all drugs that treat dysrhythmias can
also cause dysrhythmias
Cardiac Action Potentials: Fast Potentials
Cardiac action potentials, particularly the fast potentials, are crucial for the normal electrical activity that controls the heart’s rhythm. These fast action potentials occur in specialized heart cells, including those in the His-Purkinje system and in atrial and ventricular muscle. Understanding these phases helps in comprehending how the heart functions electrically and how certain heart medications work.
Phase 0 - Depolarization:
This is the initial phase where the heart cell suddenly becomes more positively charged inside.
It’s triggered by the rapid influx of sodium ions into the heart cell, which changes the cell’s electrical state and initiates the contraction of the heart muscle.
Phase 1 - (Partial) Repolarization:
After depolarization, the cell begins a brief process of repolarization, where it starts to return to its resting state.
This involves a small outward movement of potassium ions and inactivation of sodium channels.
Phase 2 - Plateau:
The plateau phase is a unique feature of cardiac muscle action potentials.
During this phase, calcium ions enter the cell while some potassium ions continue to leave. This balance of ion flow maintains a prolonged depolarized state, which is important for the heart’s muscle cells to contract effectively.
Phase 3 - Repolarization:
In this phase, repolarization is completed, which means the cell returns to its resting electrical state.
This occurs as more potassium ions flow out of the cell, restoring the negative charge inside the cell.
Phase 4 - Stable Potential:
This is the resting phase where the heart cell is ready to start the next action potential.
The cell maintains a stable, negative resting potential due to the steady flow of ions across its membrane, mainly the efflux of potassium
Slow Potentials
Slow potentials, also known as slow response action potentials, occur primarily in the cells of the sinoatrial (SA) node and the atrioventricular (AV) node in the heart. These regions are crucial for initiating and regulating the heart’s rhythm. Slow potentials differ from the fast potentials observed in other cardiac muscle fibers in several key aspects.
Phase 0 - Slow Depolarization:
Unlike the fast depolarization in atrial and ventricular muscle cells (which is primarily due to sodium influx), the depolarization in SA and AV nodal cells is slower and is mediated by a gradual influx of calcium ions.
This slower depolarization is responsible for the inherent pace-making activity of these cells, setting the rhythm of the heart.
Phases 1, 2, and 3:
In slow potentials, Phase 1 is absent. This is a major distinction from fast potentials, where Phase 1 involves initial repolarization.
Phases 2 (the plateau phase) and 3 (final repolarization) are not significant in slow potentials. These phases are prominent in fast potentials and are important for the contraction of the ventricular muscle, but they play a less significant role in the pacemaker cells of the heart.
Phase 4 - Spontaneous Depolarization:
In SA and AV nodal cells, Phase 4 is characterized by spontaneous depolarization. This means that after a cell returns to its resting state, it gradually starts to depolarize again on its own, without needing an external stimulus.
This spontaneous depolarization is critical for the pacemaking function of these cells. The SA node, being the primary pacemaker of the heart, automatically generates impulses at a regular rhythm due to this property.
The ECG
Provides a graphic representation of cardiac electrical activity
Major components of an ECG
P wave
* Depolarization in the atria
QRS complex
* Depolarization of the ventricles
T wave
* Repolarization of the ventricles
Three other components
PR interval
QT interval
ST segment
Causes of dysrhythmias
-Two fundamental causes
- Disturbances of automaticity can occur in any
part of the heart
-Disturbances of conduction
Atrioventricular block
Reentry (recirculating activation)
Classifications of Antidysrhythmic Drugs
The Vaughan Williams classification is a widely used system to categorize antidysrhythmic drugs (medications used to treat abnormal heart rhythms) based on their mechanism of action.
Class I: Sodium Channel Blockers
These drugs work by blocking sodium channels in the cardiac cells, which slows the rate of rise of the action potential and reduces the excitability of the heart muscle.
Subdivided into IA, IB, and IC, each with slightly different effects.
Examples:
IA: Quinidine, Procainamide
IB: Lidocaine, Mexiletine
IC: Flecainide, Propafenone
Class II: Beta Blockers
Beta blockers reduce the effects of adrenaline and other stress hormones on the heart, slowing the heart rate and reducing the force of contraction.
They are effective in treating a variety of arrhythmias, especially those caused by increased sympathetic activity.
Examples: Metoprolol, Propranolol, Atenolol
Class III: Potassium Channel Blockers
These drugs prolong the repolarization phase (phase 3) of the cardiac action potential, which helps to stabilize the cardiac rhythm.
They are often used in the treatment of atrial fibrillation and ventricular tachycardia.
Examples: Amiodarone, Sotalol, Dofetilide
Class IV: Calcium Channel Blockers
These drugs block calcium channels in the heart and blood vessels, leading to a slower heart rate and reduced force of cardiac muscle contraction.
They are particularly useful in treating supraventricular tachycardias.
Examples: Verapamil, Diltiazem
Other: Miscellaneous Agents
This category includes drugs that don’t fit neatly into the other four classes but are still used to treat arrhythmias.
Adenosine: Used for rapid termination of certain types of supraventricular tachycardia.
Digoxin: Slows the heart rate and increases contractility; used in atrial fibrillation and heart failure.
Ibutilide: Used for chemical cardioversion of atrial fibrillation and flutter.
Cons of these drugs
Prodysrhythmic effects refer to the potential of antidysrhythmic drugs to cause new dysrhythmias or worsen existing ones. This paradoxical risk is a significant concern in the use of these medications.
Prolongation of the QT Interval:
The QT interval is a measurement on an electrocardiogram (ECG) that represents the time it takes for the heart’s ventricles to depolarize and repolarize (contract and then relax).
Many antidysrhythmic drugs, particularly those in Class I and Class III, can prolong the QT interval. This means they can slow down the electrical recovery time of the heart after each beat.
A prolonged QT interval increases the risk of a type of dangerous arrhythmia known as Torsades de Pointes.
Torsades de Pointes:
Torsades de Pointes is a specific type of ventricular tachycardia (a fast heart rhythm originating in the ventricles) characterized by a distinctive pattern on an ECG.
It can lead to symptoms like dizziness, palpitations, fainting, or even sudden cardiac death.
Drugs that prolong the QT interval can trigger Torsades de Pointes, especially in patients with other risk factors such as electrolyte imbalances or underlying heart disease.
Given these risks, the use of antidysrhythmic drugs follows a careful risk-benefit assessment:
Use Only When Necessary: These drugs should be used only when the dysrhythmias cause significant symptoms or pose a risk to the patient, and when the benefits of controlling the dysrhythmia clearly outweigh the risks of potential side effects.
Monitoring: Patients on these medications often require regular monitoring, including ECGs to check the QT interval and blood tests to monitor for electrolyte imbalances.
Individualized Treatment: The choice of an antidysrhythmic drug should be tailored to the individual, taking into account their specific type of dysrhythmia, overall heart function, and any other health issues.
Supraventricular Dysrhytmias + Treatment
Supraventricular dysrhythmias are a group of heart rhythm disorders that originate above the ventricles, specifically in the atria or the atrioventricular (AV) node. These types of arrhythmias are generally characterized by rapid heartbeats.
Atrial Fibrillation (AFib):
In AFib, the atria (upper chambers of the heart) beat irregularly and chaotically, leading to an irregular and often rapid heartbeat.
This can cause symptoms like palpitations, shortness of breath, fatigue, or chest discomfort, although some people may have no symptoms.
AFib increases the risk of stroke, as the chaotic rhythm can lead to the formation of blood clots in the atria.
Atrial Flutter:
Atrial flutter is similar to AFib but is typically more organized and less chaotic. The atria beat rapidly but with a regular rhythm.
It can cause symptoms similar to AFib and also carries a risk of stroke.
The heart rate in atrial flutter is often fast but regular.
Sustained Supraventricular Tachycardia (SVT):
SVT is a broad term that includes several types of rapid heart rhythms originating above the ventricles.
It’s characterized by a sudden onset and a sudden end of rapid heartbeats, often with rates exceeding 100 beats per minute.
Symptoms can include palpitations, dizziness, chest pain, or shortness of breath.
Management and Treatment:
Rate Control: Medications like beta-blockers and calcium channel blockers are used to control heart rate.
Rhythm Control: In some cases, medications or procedures like electrical cardioversion are used to restore normal heart rhythm.
Stroke Prevention: For AFib and atrial flutter, anticoagulant medications might be prescribed to reduce the risk of stroke.
Catheter Ablation: This procedure can be used to treat some forms of SVT and atrial flutter by destroying the tissue causing the abnormal rhythm.
Ventricular Dysrhythmias + Treatment
Ventricular dysrhythmias are heart rhythm disorders that originate in the ventricles, the lower chambers of the heart. These types of arrhythmias can be serious and potentially life-threatening.
Sustained Ventricular Tachycardia (VT):
A rapid heartbeat that starts in the ventricles and persists for a significant duration.
Symptoms can include palpitations, dizziness, fainting (syncope), or even cardiac arrest in severe cases.
Treatment often involves antiarrhythmic drugs, electrical cardioversion (if unstable), or catheter ablation. In some cases, implantable cardioverter-defibrillators (ICDs) are used for prevention.
Ventricular Fibrillation (VFib):
An erratic, disorganized firing of impulses from the ventricles. The heart cannot effectively pump blood, leading to a collapse of blood circulation.
VFib is a medical emergency that leads to sudden cardiac arrest. Immediate treatment with cardiopulmonary resuscitation (CPR) and defibrillation (electric shock) is essential.
Post-resuscitation, treatment includes antiarrhythmic drugs and often an ICD.
Premature Ventricular Complexes (PVCs):
Extra, abnormal heartbeats that originate in the ventricles. PVCs are common and often benign but can be more serious in people with heart disease.
Treatment is not always necessary unless they are frequent or symptomatic. Beta-blockers or other antiarrhythmics may be used.
Digoxin-Induced Ventricular Dysrhythmias:
Ventricular arrhythmias can occur as a side effect of the medication digoxin, especially at high blood levels.
Treatment involves stopping digoxin and managing the dysrhythmias with medications or other interventions. In severe cases, digoxin-specific antibody fragments may be used.
Torsades de Pointes:
A specific type of VT that can occur with prolonged QT interval. It appears as a twisting pattern on an ECG.
It can be triggered by certain medications or electrolyte imbalances.
Treatment involves immediate electrical cardioversion if unstable, magnesium sulfate, and withdrawal of any QT-prolonging drugs. Beta-blockers or temporary pacing might be used in some cases.
Treating Dysrhythmias, Risks vs Benefits
Consider Properties of Dysrhythmias:
Sustained vs. Nonsustained: Sustained dysrhythmias (lasting longer, typically more than 30 seconds) are often more serious and may require more aggressive treatment compared to nonsustained (brief, self-terminating) dysrhythmias.
Asymptomatic vs. Symptomatic: Treatment urgency and approach can depend on whether the dysrhythmia causes symptoms. Symptomatic dysrhythmias, especially those that impair heart function or cause discomfort, often necessitate treatment. Asymptomatic cases might be managed more conservatively.
Supraventricular vs. Ventricular: Ventricular dysrhythmias (originating in the heart’s lower chambers) are generally more dangerous than supraventricular dysrhythmias (originating in the upper chambers) and may require more immediate intervention.
Acute and Long-Term Treatment Phases:
Acute Treatment: Focuses on immediately stabilizing the heart rhythm and preventing short-term complications. This might involve medication, electrical cardioversion, or other emergency interventions.
Long-Term Treatment: Aims to prevent recurrence and manage underlying conditions. This can include lifestyle changes, ongoing medication, or procedures like catheter ablation or implantation of a pacemaker or defibrillator.
Minimizing Risk:
Patient-Specific Factors: Consideration of the patient’s age, overall health, comorbidities, and preferences is vital. For instance, a medication that is effective in treating dysrhythmias might be less suitable for a patient with certain other medical conditions.
Monitoring and Adjustment: Regular follow-up and monitoring are important to assess the effectiveness of treatment and to adjust it as necessary. This includes monitoring for side effects of medications and potential changes in the dysrhythmia.
Risk of Treatment vs. Risk of Dysrhythmia: In some cases, the risks associated with treatment (such as side effects of medication or complications from a procedure) may outweigh the risks posed by the dysrhythmia itself, especially if it’s mild or asymptomatic
Class IA: Sodium Channel Blockers
Quinidine
Effects on the heart
* Blocks sodium channels
* Slows impulse conduction
* Delays repolarization
* Blocks vagal input to the heart
Effects on the ECG
* Widens the QRS complex
* Prolongs the QT interval
Therapeutic uses
* Used for supraventricular and ventricular dysrhythmias
Adverse effects
* Diarrhea
* Cinchonism
* Cardiotoxicity
* Arterial embolism
* Alpha-adrenergic blockade, resulting in hypotension
* Hypersensitivity reactions
Drug interactions
* Digoxin
Procainamide [Procanbid]
Similar to quinidine
Only weakly anticholinergic
Adverse effects: Symptoms of systemic lupus
erythematosus
Disopyramide [Norpace]
Similar to quinidine
Prominent side effects have limited its use
Class IB Agents: Na Channel Blockers
Lidocaine [Xylocaine]
Effects on the heart and ECG
* Blocks cardiac sodium channels
Slows conduction in the atria, ventricles, and His-Purkinje system
* Reduces automaticity in the ventricles and His-Purkinje system
* Accelerates repolarization
Adverse effects
* CNS effects
* Drowsiness
* Confusion
* Paresthesias
Phenytoin
* Antiseizure medication also used to treat digoxin-induced dysrhythmias
Mexiletine
* Oral analog of lidocaine
* Used for symptomatic ventricular dysrhythmias
Class IC Agents: Na Channel Blockers
Block cardiac sodium channels
Delay ventricular repolarization
All class IC agents can exacerbate existing
dysrhythmias and create new ones
Two class IC agents
Flecainide
Propafenone
Class II - Beta Blockers
Only four approved for treating dysrhythmias
1. Propranolol
2. Acebutolol
3. Esmolol
4. Sotalol
Propanolol
Propranolol [Inderal]: Nonselective beta-
adrenergic antagonist
Effects on the heart and ECG
* Decreased automaticity of the SA node
* Decreased velocity of conduction through the AV node
* Decreased myocardial contractility
Therapeutic use
* Dysrhythmias caused by excessive sympathetic stimulation
* Supraventricular tachydysrhythmias
Suppression of excessive discharge
Slowing of ventricular rate
Adverse effects
* Heart block
* Heart failure
* AV block
* Sinus arrest
* Hypotension
* Bronchospasm (in asthma patients)
