Pharmacology - ANTIARRHYTHMIC DRUGS (MADE EASY)

Summary

This lecture delves into the world of antiarrhythmic drugs, explaining the heart's electrical system and how it controls the heartbeat. It covers the role of specialized cells, the conduction system, and the action potential differences between pacemaker and cardiac muscle cells. The script also explores arrhythmias, their mechanisms, and the Vaughan Williams classification of antiarrhythmic drugs, detailing the function and effects of each class. Additionally, it touches on other agents like Digoxin, Adenosine, and Magnesium Sulfate, concluding with their applications in treating various cardiac conditions.

Takeaways

• 💓 The heart's pumping action is controlled by its electrical system, involving specialized cells that generate and transmit electrical impulses to the cardiac muscle.
• 🔌 The cardiac conduction system consists of five elements: the sinoatrial (SA) node, atrioventricular (AV) node, bundle of His, bundle branches, and Purkinje fibers, which coordinate the heart's rhythm.
• 📈 The normal heart rhythm is initiated by the SA node and is represented on an electrocardiogram (ECG) by the P wave for atrial contraction, the PR interval for AV node delay, the QRS complex for ventricular contraction, and the T wave for ventricular recovery.
• 🔑 Cardiac cells are divided into contractile cells that generate force for heart contraction and conducting cells that initiate electrical impulses, with the latter exhibiting automaticity.
• 🌡️ The action potential of pacemaker cells differs from that of cardiac muscle cells, with pacemaker cells having a resting membrane potential of about -60 mV and undergoing a unique depolarization process.
• 🚫 Arrhythmias are deviations from the normal heart rhythm, classified as bradyarrhythmias (<60 bpm) or tachyarrhythmias (>100 bpm), with the latter involving mechanisms like abnormal automaticity, triggered activity, and reentry.
• 🛡️ Vaughan Williams classification categorizes antiarrhythmic drugs into four classes based on their primary mechanism of action, influencing sodium and calcium channels, and potassium channels, among others.
• 💊 Class 1 antiarrhythmics, such as Procainamide, Quinidine, and Disopyramide, work by blocking sodium channels to slow down depolarization and are used for various arrhythmias but can cause adverse effects.
• 🛡️ Class 2 drugs are beta blockers that reduce heart rate and contractility, useful for arrhythmias caused by increased sympathetic activity, with examples like Propranolol and Metoprolol.
• 🔋 Class 3 agents, including Amiodarone and Dronedarone, block potassium channels to prolong the action potential and are effective against atrial fibrillation and ventricular tachyarrhythmias but can have significant side effects.
• 🚰 Class 4 drugs, like Verapamil and Diltiazem, block calcium channels to slow conduction in the SA and AV nodes, treating supraventricular tachycardia and atrial fibrillation.
• 🌿 Other antiarrhythmic agents not fitting into the Vaughan Williams classes include Digoxin, which enhances contractility and slows AV node conduction, Adenosine for acute supraventricular tachycardia, and Magnesium Sulfate for specific arrhythmias like torsades de pointes.

Q & A

What are antiarrhythmic drugs and why are they important?

Antiarrhythmic drugs are medications used to treat abnormal heart rhythms, or arrhythmias. They are important because they help regulate the heart's electrical system, ensuring the heart beats at a normal rhythm and preventing potentially life-threatening conditions.

What is the role of the sinoatrial (SA) node in the heart's electrical system?

The SA node serves as the heart's natural pacemaker, initiating the electrical signals that cause the atria to contract and push blood into the ventricles. It is the starting point of the cardiac conduction system.

How does the cardiac conduction system consist of five elements?

The cardiac conduction system is made up of the sinoatrial node (SA node), atrioventricular node (AV node), bundle of His, bundle branches, and Purkinje fibers. These elements work together to generate and transmit electrical signals for the heart's contractions.

What is the significance of the P wave, Q wave, R wave, S wave, and T wave on an electrocardiogram (ECG)?

The P wave on an ECG represents atrial depolarization and the beginning of atrial contraction. The Q wave indicates the start of ventricular depolarization. The R wave is the peak of ventricular depolarization, the S wave follows and represents the end of depolarization. Lastly, the T wave represents the recovery phase of the ventricles as they repolarize.

What are the two types of cardiac cells and their functions?

There are contractile cells, which generate force for heart contractions and make up most of the atrial and ventricular walls, and conducting cells, which initiate the electrical impulses controlling heart contractions.

What is automaticity and why is it important in the heart?

Automaticity is the ability of certain cardiac cells, particularly in the SA node, AV node, bundle of His, and Purkinje fibers, to spontaneously initiate an action potential. It is important because it allows the heart to maintain a regular rhythm without external stimulation.

What are the three basic mechanisms responsible for the initiation of tachyarrhythmias?

The three mechanisms are abnormal automaticity, triggered activity, and reentry. Abnormal automaticity occurs when cells become more permeable to sodium, leading to increased automaticity. Triggered activity involves abnormal leakage of positive ions causing afterdepolarizations. Reentry is a loop of electrical activation circulating through heart tissue, often due to an accessory pathway.

How does the Vaughan Williams classification categorize antiarrhythmic drugs?

The Vaughan Williams classification divides antiarrhythmic drugs into four classes based on their dominant mechanism of action: Class 1 (sodium channel blockers), Class 2 (beta blockers), Class 3 (potassium channel blockers), and Class 4 (calcium channel blockers).

What are the potential adverse effects of class 1 antiarrhythmic drugs?

Class 1 antiarrhythmic drugs can cause adverse effects such as blurred vision, headache, tinnitus, and in some cases, they may even cause arrhythmias themselves. The specific side effects can vary depending on the drug within this class.

How do class 2 antiarrhythmic drugs, such as beta blockers, affect the heart?

Class 2 antiarrhythmic drugs, which are beta blockers, work by acting on beta-1 receptors to prevent the action of catecholamines on the heart. This results in decreased heart rate, reduced contractility, and slowed conduction through the AV node.

What is unique about sotalol among class 3 antiarrhythmic drugs?

Sotalol is unique because it has both potassium channel blocking activity, like other class 3 drugs, and beta receptor blocking activity. This dual mechanism makes it effective for treating certain types of arrhythmias.

How does Digoxin work and what are its main uses?

Digoxin works by inhibiting the sodium-potassium pump, leading to increased intracellular calcium which enhances myocardial contractility. It also stimulates the parasympathetic system, slowing sinus node discharge rate and AV node conduction. It is used particularly for patients with heart failure and atrial fibrillation.

What is the primary indication for Adenosine and what are its common side effects?

Adenosine is primarily indicated for the acute treatment of supraventricular tachycardia. Its common side effects include chest pain, flushing, and hypotension due to its very short duration of action and need for IV administration.

What is the role of Magnesium Sulfate in treating arrhythmias?

Magnesium Sulfate is effective for treating certain types of arrhythmias, such as torsades de pointes and those induced by Digoxin. Its precise mechanism is not fully understood, but it is known to play a role in the transport of sodium, potassium, and calcium across cell membranes.

Outlines

00:00

💓 Introduction to Antiarrhythmic Drugs

This paragraph introduces the topic of antiarrhythmic drugs, explaining the heart's electrical system and how it controls the pumping action. It details the components of the cardiac conduction system, including the sinoatrial (SA) node, atrioventricular (AV) node, bundle of His, bundle branches, and Purkinje fibers. The normal heart rhythm is described, starting from the SA node and culminating in the contraction of the ventricles, represented by the P wave, PR interval, QRS complex, and T wave on an electrocardiogram. The paragraph also distinguishes between contractile and conducting cells in the heart, emphasizing the automaticity of the latter and the role of the SA node as the primary pacemaker. It concludes with a comparison of action potentials in pacemaker cells versus heart muscle cells, highlighting the unique depolarization and repolarization processes in pacemaker cells.

05:02

🔋 Understanding Cardiac Muscle Cells and Arrhythmias

The second paragraph delves into the action potential of cardiac muscle cells, contrasting it with that of pacemaker cells. It describes the resting membrane potential of cardiac muscle cells and the phases of an action potential, including the rapid depolarization (phase 0), the brief dip (phase 1), the plateau (phase 2), and repolarization (phase 3). The concept of arrhythmias is introduced as deviations from the normal heart rhythm, with classifications into bradyarrhythmias and tachyarrhythmias based on heart rate. The paragraph then focuses on the mechanisms of tachyarrhythmias, including abnormal automaticity, triggered activity, and reentry, providing examples such as Wolff-Parkinson-White syndrome and atrioventricular nodal reentry tachycardia (AVNRT).

10:08

🛡️ Vaughan Williams Classification of Antiarrhythmics

This paragraph discusses the Vaughan Williams classification of antiarrhythmic drugs, which categorizes them into four classes based on their primary mechanism of action. Class 1 drugs are explained as sodium channel blockers that slow down the rate of depolarization and conduction velocity. They are further subdivided into three subclasses: Class 1A, which prolongs the action potential and effective refractory period; Class 1B, which shortens the action potential and effective refractory period; and Class 1C, which markedly depresses phase 0 depolarization. Specific drugs and their uses, as well as potential adverse effects, are mentioned for each subclass. The paragraph also notes the risk of proarrhythmic effects with Class 1 agents.

15:11

💊 Exploring Class 2 to 4 Antiarrhythmic Drugs

The fourth paragraph continues the discussion on antiarrhythmic drugs, starting with Class 2, which includes beta blockers that act on beta-1 receptors to decrease heart rate and contractility. Examples of beta blockers and their uses are provided. Class 3 drugs are described as potassium channel blockers that increase the duration of the action potential and effective refractory period, with Amiodarone being highlighted for its broad effectiveness and potential adverse effects. Class 4 drugs are characterized by their action on calcium channels, slowing conduction in the SA and AV nodes. Verapamil and Diltiazem are mentioned as examples. The paragraph concludes with a brief mention of other antiarrhythmic agents like Digoxin, Adenosine, and Magnesium Sulfate, setting the stage for further discussion.

20:14

🌐 Additional Antiarrhythmic Agents and Their Mechanisms

The final paragraph provides insights into Digoxin, Adenosine, and Magnesium Sulfate, which do not fit neatly into the Vaughan Williams classification. Digoxin is explained as an inhibitor of the sodium-potassium pump, leading to increased intracellular calcium and enhanced contractility, and its use in heart failure and atrial fibrillation is noted. Adenosine is described as a nucleoside that stimulates A1 receptors, reducing automaticity and conduction velocity, and is used for acute supraventricular tachycardia with brief mention of its side effects. Magnesium Sulfate's role in arrhythmia treatment, particularly for torsades de pointes and Digoxin-induced arrhythmias, is highlighted, despite its mechanism being less understood. The paragraph ends with a thank you note to the viewers.

Keywords

💡Antiarrhythmic drugs

Antiarrhythmic drugs are medications used to treat abnormal heart rhythms, or arrhythmias. They work by affecting the electrical system of the heart to restore a normal rhythm. In the video, these drugs are the central theme, with the script discussing their classifications, mechanisms of action, and specific uses in treating various types of arrhythmias.

💡Cardiac conduction system

The cardiac conduction system is a network of cells responsible for generating and transmitting electrical impulses that regulate the heartbeat. It consists of the sinoatrial node, atrioventricular node, bundle of His, bundle branches, and Purkinje fibers. The script explains how this system is integral to the heart's pumping action and how antiarrhythmic drugs can affect its function.

💡Sinoatrial node (SA node)

The sinoatrial node, or SA node, is a group of cells that act as the heart's natural pacemaker. It initiates the electrical signals for each heartbeat. The script emphasizes the SA node's role in starting the normal heart rhythm and how arrhythmias can disrupt this process.

💡Electrocardiogram (ECG/EKG)

An electrocardiogram is a test that measures and records the electrical activity of the heart. The script describes how different waves in an ECG (P wave, QRS complex, T wave) correspond to different phases of the heartbeat and how they can indicate arrhythmias.

💡Action potential

An action potential is an electrical signal that travels along cells, particularly in the heart, causing them to contract. The script details the phases of the action potential in pacemaker cells and cardiac muscle cells, which is crucial for understanding how antiarrhythmic drugs affect these cells.

💡Automaticity

Automaticity refers to the ability of certain cells, like those in the SA and AV nodes, to generate their own electrical impulses without external stimulation. The script explains how automaticity is a normal feature of the heart's conduction system and how it can become abnormal in arrhythmias.

💡Arrhythmia

Arrhythmia is a term used to describe any deviation from the normal heart rhythm. The script provides an overview of arrhythmias, including their classification into bradyarrhythmias and tachyarrhythmias, and the mechanisms by which they occur.

💡Vaughan Williams classification

The Vaughan Williams classification is a system used to categorize antiarrhythmic drugs based on their predominant mechanism of action. The script uses this classification to organize the discussion of different types of antiarrhythmic drugs and their effects on the heart's electrical activity.

💡Beta blockers

Beta blockers are a class of drugs that work by blocking beta-1 receptors, reducing the heart's response to adrenaline-like substances. The script mentions beta blockers as a type of antiarrhythmic drug, particularly effective for arrhythmias related to increased sympathetic activity.

💡Potassium channels

Potassium channels are proteins that allow the passage of potassium ions across cell membranes, playing a critical role in the repolarization phase of the cardiac action potential. The script discusses how class 3 antiarrhythmic drugs work by blocking these channels to prolong the action potential and refractory period.

💡Calcium channels

Calcium channels are integral to the heart's electrical activity, allowing calcium ions to enter cells during depolarization, which is essential for contraction. The script explains that class 4 antiarrhythmic drugs block these channels, slowing conduction in the SA and AV nodes.

Highlights

Introduction to antiarrhythmic drugs and the heart's electrical system.

Description of the five elements of the cardiac conduction system.

Explanation of the normal heart rhythm and its representation on an electrocardiogram.

Differentiation between contractile and conducting cardiac cells.

Importance of the SA node as the heart's natural pacemaker.

Potential for other conduction tissues to become latent pacemakers.

Comparison of action potentials in pacemaker cells versus cardiac muscle cells.

Role of electrolyte ions in generating action potentials in the heart.

Mechanisms of arrhythmias including abnormal automaticity, triggered activity, and reentry.

Overview of the Vaughan Williams classification of antiarrhythmic drugs.

Function of class 1 antiarrhythmic drugs and their subclasses.

Use of class 2 antiarrhythmic drugs as beta blockers in arrhythmia treatment.

Class 3 antiarrhythmic drugs' impact on potassium channels and action potential duration.

Class 4 antiarrhythmic drugs' effect on calcium channels and heart conduction.

Discussion of other antiarrhythmic agents like Digoxin, Adenosine, and Magnesium Sulfate.

Digoxin's mechanism of action through the inhibition of the sodium-potassium pump.

Adenosine's unique role in treating acute supraventricular tachycardia.

Magnesium Sulfate's effectiveness in treating specific arrhythmias despite an unclear mechanism.

Transcripts

in this lecture I'm going to talk about antiarrhythmic drugs so let's get right

into it as you may already know the pumping action of the heart is

controlled by the heart's electrical system the heart contains specialized

cells that are able to create their own electrical impulses and send them to the

cardiac muscle causing it to contract now the cardiac conduction system is

made up of five elements number one the sinoatrial node SA node for short number

two the atrioventricular node AV node for short number three the bundle of His

number four the bundle branches and number five the Purkinje fibers so the

normal heart rhythm begins when electrical signals are sent from the SA

node the signal from the SA node causes the atria to contract pushing blood

through the open valves into the ventricles on the typical

electrocardiogram this is represented by the P wave next electric signal arrives

at the AV node and is briefly delayed so that the contracting atria have enough

time to pump all the blood into the ventricles this is represented by the

line between the P and the Q wave at this point the signal travels to the

bundle of His into the bundle branches this is represented by the Q wave and

finally this signal travels through the Purkinje fibers which causes the

ventricles to contract and thus pump blood from the right ventricle into the

lungs and from the left ventricle into the rest of the body this is represented

by the R and S wave the last T wave represents the recovery of the

ventricles now cardiac cells can be divided into

two types first contractile cells which make up most of the walls of the atria and

ventricles and when stimulated they generate force for contraction of the

heart and the second type conducting cells which initiate the electrical impulse

that controls those contractions now while contractile fibers can't generate an

action potential on their own the conducting fibers are capable of

spontaneously initiating an action potential by themselves they exhibit

so-called automaticity the conducting cells are primarily concentrated in the

tissues of the SA node AV node bundle of His and Purkinje fibers now normally SA

node reaches threshold potential the fastest which is why it serves as the

natural pacemaker of the heart when the SA node drives the heart rate the cells

of AV node bundle of His and Purkinje fibers do not express automaticity or in

other words their spontaneous depolarization is suppressed however

under certain conditions when activity of the SA node becomes suppressed or the

firing rate of these other conducting tissues becomes faster one of them can

become the new pacemaker of the heart this is why the AV node bundle of His

and Purkinje fibers are called latent pacemakers now before we move on let's

take a closer look at the action potential of the pacemaker cells versus

the heart muscle cells as there are some important differences between them so in

the heart each cardiac cell contains and is

surrounded by electrolyte fluids the main ions responsible for the electrical

activity within the heart are sodium calcium and potassium

when cardiac cells are stimulated by an electrical impulse their membrane's

permeability change and ions move across the membrane thus generating an action

potential so now the membrane potential in the pacemaker cells starts at about

negative 60 millivolt when spontaneous flow of sodium mainly

through slow sodium channels and opening of the voltage-gated T-type calcium

channels continue slow depolarization this is referred to as phase 4

once threshold potential of about negative 40 millivolt is reached the

voltage-gated L-type calcium channels open calcium rushes in and rapidly

depolarizes cell to about positive 10 millivolts this is referred to as phase 0

finally the L-type calcium channels

close and the voltage-gated potassium channels open which allows potassium

ions to escape thus repolarizing the cell back to negative 60 millivolts this

is referred to as phase 3 after this the cycle just repeats itself

also note that there is no phase 1 or phase 2 in the action potential of the

pacemaker cells okay so now let's take a look at the action potential of the

cardiac muscle cells unlike pacemaker cells the cardiac muscle cells have

resting membrane potential of about negative 90 millivolts

due to the constant outward leak of potassium through the inward-rectifier

channels this resting phase is referred to as phase 4 now when an action

potential is triggered in a neighboring cell the voltage-gated sodium channels

open and sodium rushes in causing a rapid depolarization to about positive

40 millivolts this is referred to as phase 0 at this point the sodium

channels become inactivated and other voltage-gated channels begin to open

mainly potassium channels which allow potassium to escape thus bringing about

a small dip in membrane potential this is referred to as phase 1 now

something that I didn't mention is that during depolarization at phase 0

voltage-gated L-type calcium channels began to open slowly allowing calcium

enter into the cell so now with the positive potassium ions leaving and the

positive calcium ions steadily coming in we have this electrically balanced

ion exchange which keeps the membrane potential on a plateau this is

referred to as phase 2 lastly the plateau phase is followed by

a rapid repolarization referred to as phase 3 which is caused by a gradual

inactivation of the calcium channels and continuous outflow of potassium

this brings the membrane potential back to the resting phase 4 so now let's

switch gears and let's talk about arrhythmias so what is arrhythmia well

arrhythmia is simply a deviation of heart from a normal rhythm so normal

heart rhythm will have a heart rate of between 60 to 100 beats per minute with

each beat generated from the SA node each cardiac impulse will also propagate

through normal conduction pathway with normal velocity now arrhythmias are

generally classified based on heart rate as bradyarrhythmias when the rate

is below 60 beats per minute or tachyarrhythmias when the rate is above

100 beats per minute however in order to understand pharmacology of antiarrhythmic

drugs we need to focus on mechanisms of tachyarrhythmias so there are three

basic mechanisms responsible for the initiation of tachyarrhythmias first

abnormal automaticity also referred to as enhanced automaticity this occurs when

the cell membrane becomes abnormally permeable to sodium

during phase 4 which results in increase in the slope of phase 4

depolarization this can cause other cells to accelerate their automaticity and

thus generate impulses faster than the SA node the second mechanism is called

triggered activity triggered activity involves the abnormal leakage of

positive ions into the cardiac cell leading to this bump on the action

potential called afterdepolarization these afterdepolarizations can occur

during phase 2 3 or 4 and if they have sufficient magnitude they can

trigger premature action potentials now the third mechanism of

tachyarrhythmias is called reentry example of this is wolff-parkinson-white

syndrome in which an extra or so-called accessory pathway exists between the

upper and lower chambers of the heart so normally the electrical signal travels

from the SA node to AV node to bundle branches and once it reaches the

Purkinje fibers it stops and waits for another signal from the SA node

now when the accessory pathway appears the signal travels through this pathway

from ventricles back to atria causing them to contract before SA node fires

again this creates this abnormal loop of electrical activation circulating

through a region of heart tissue causing tachyarrhythmia another example of

reentry is atrioventricular nodal reentry tachycardia AVNRT for short

so typically there are two anatomic pathways for carrying signal through the

AV node first pathway is called the fast pathway because it allows fast

conduction however it has a long refractory period meaning it recovers

slowly on the other side this second pathway is called the slow pathway

because it only allows slow conduction and because of that it has short

refractory period meaning it recovers fast so now the signal comes down from

the SA node and then it splits and travels fast through the fast pathway

and slow through the slow pathway so the fast pathway signal reaches the common

pathway on the other end well before the slow pathway signal gets there from

there the fast pathway signal spreads to the ventricles as well as up the slow

pathway where it hits the slow signal causing it to terminate

now if a premature beat occurs at the time when the fast pathway signal is

still in the refractory period the signal will travel down the slow pathway

as the slow signal approaches the common pathway fast pathway comes out of

refractory period so now the slow signal spreads to the ventricles and it also

travels up the fast pathway but let's not forget that the slow pathway has a

short refractory period so by the time the signal reaches the top the

slow pathway is ready to conduct another signal so what ultimately happens here

is that this signal continues to circle around sending fast impulses which

result in tachycardia now let's move on to discussing the actual antiarrhythmic

drugs so most commonly used classification of antiarrhythmics is the

Vaughan Williams classification which groups most antiarrhythmics into four

classes based on their dominant mechanism of action now let's discuss

each of these classes so first we have class 1 drugs which work mainly by

blocking sodium channels in the open or inactivated state inhibition of sodium

channels decreases the rate of rise of phase 0 depolarization and slows

conduction velocity class 1 drugs are subdivided into three subclasses

according to their effect on the cardiac action potential first we have class 1A

drugs which moderately depress the phase 0 depolarization by blocking fast

sodium channels they also prolong repolarization by blocking

some potassium channels so what we'll see with class 1A agents is prolonged

action potential and prolonged effective refractory period the agents in this

class include Procainamide Quinidine and Disopyramide these agents are used in

the treatment of a wide variety of arrhythmias

such as ventricular tachycardias and recurrent atrial fibrillation adverse

effects include blurred vision headache and tinnitus which may occur with large

doses of Quinidine and some anticholinergic effects which may occur

with the use of Disopyramide secondly we have class 1B drugs which have

relatively weak effect on the phase 0 depolarization due to minimal blockade

of fast sodium channels however these agents shorten repolarization by

blocking sodium channels that activate during late phase 2 of the action

potential so what we'll see with class 1B agents is shorten duration of

action potential and shorten effective refractory period the agents in this

class include Lidocaine and Mexiletine which are mainly used in the treatment

of ventricular arrhythmias when it comes to adverse effects Lidocaine can cause

CNS toxicity including seizures while Mexiletine can cause nausea and

vomiting now the third and the last subtype that we have is class 1C drugs

which are powerful fast sodium channel blockers which depress the phase 0

depolarization markedly they also inhibit the His-Purkinje conduction

system with a limited effect on repolarization and refractory period the

agents in this class include Flecainide and Propafenone which are mainly used in

the treatment of refractory ventricular arrhythmias when it comes to adverse effects

the most common ones include dizziness blurred vision and nausea also something

that I haven't mentioned yet is that one of the risk associated with the class 1

agents actually all of them is that they have potential to actually cause

arrhythmias themselves so weighing the risk versus benefit is very important before

initiating therapy with these agents now let's move on to class 2

antiarrhythmic drugs so agents in this class act on the beta-1 receptors

preventing the action of catecholamines on the heart so class 2 agents

are simply beta blockers beta blockers depress sinus node automaticity and slow

conduction through the AV node which results in decreased heart rate and

decreased contractility examples of beta blockers commonly used for arrhythmia

are Propranolol Metoprolol Atenolol and Esmolol now Esmolol unlike the other

beta blockers is somewhat special in that it's given intravenously in an

emergency acute arrhythmias and the reason for that is that it has fast

onset of action and very short half-life which allows it to be titrated rapidly

when necessary so the bottom line is that beta blockers are good choice for

treatment of arrhythmias provoked by increased sympathetic activity and if

you want to learn more about them check out my other videos about adrenergic

receptors and beta blockers now let's move on to class 3 antiarrhythmic

drugs so class 3 agents work mainly by blocking the potassium channels that

are responsible for the Phase 3 repolarization this leads to increase in

duration of action potential and increase in effective refractory period

the agents in this class include Amiodarone Dronedarone Sotalol

Dofetilide and Ibutilide there are mainly used in treatment of

supraventricular and ventricular tachyarrhythmias as well as atrial fibrillation

and flutter the most widely used drug in this class is Amiodarone which

is very effective for the treatment of these aforementioned arrhythmias

Amiodarone has multiple actions and besides blocking potassium channels

Amiodarone also blocks sodium channels calcium channels and even some alpha and

beta receptors unfortunately Amiodarone is also associated with many adverse

effects such as pulmonary fibrosis blue-grey skin discoloration neuropathy

hepatotoxicity corneal microdeposits and because it contains iodine

Amiodarone also can cause thyroid dysfunction

leading to hypo or hyperthyroidism lastly due to its long

half-life Amiodarone can linger in many tissues for months after discontinuation

of therapy now on the other hand we have Dronedarone which is derivative of Amiodarone

it's less lipophilic and has shorter half-life it also

doesn't contain iodine so in general it has better side effect profile unfortunately

in many cases Dronedarone doesn't seem to be as effective as Amiodarone

now Sotalol is a unique drug in this class because it not only has potassium

channel blocking activity but also beta receptor blocking activity

lastly Dofetilide and Ibutilide are the most selective potassium channel

blockers in this class however they're also most likely to cause arrhythmias

themselves and therefore are typically initiated in the inpatient setting only

now let's move on to class 4 antiarrhythmic drugs so class 4 agents work

by blocking voltage-sensitive calcium channels during depolarization

particularly in the SA and AV nodes which results in slower conduction in

these tissues and reduced contractility of the heart the agents in this class

include Verapamil and Diltiazem which are the nondihydropyridine calcium

channel blockers unlike dihydropyridines which act primarily in the

periphery causing vasodilation nondihydropyridines are much more selective

for the myocardium and therefore they show antiarrhythmic actions Verapamil and

Diltiazem are most commonly used in treatment of supraventricular

tachycardia and atrial fibrillation and now before we end this lecture I wanted

to briefly discuss some other antiarrhythmic agents that do not quite

fit into any of the classes that we covered thus far and these are

Digoxin Adenosine and Magnesium Sulfate so

let's talk about Digoxin first and in order to understand how it works let's

picture a cardiac cell under resting conditions sodium slowly leaks into the

cell and potassium leaks out however during an action potential additional

sodium enters in along with calcium and additional potassium leaves the cell so

at some point we have this imbalance that has to be restored and this

restoration is accomplished by pumps such as sodium-potassium ATPase which

transports sodium ions to the outside of the cell and potassium to the inside of

the cell and we also have sodium-calcium exchanger which removes calcium from the

cell in exchange for sodium and as a side note here keep in mind that

sodium-calcium exchanger can carry sodium and calcium in both directions so now what

happens when Digoxin comes around is that it inhibits sodium-potassium pump

by binding to the potassium binding site this results in the increase in

intracellular sodium which then in turn causes the sodium-calcium exchanger to

pump sodium out and bring more calcium in now this increase in intracellular

calcium leads to enhanced myocardial contractility Digoxin also

stimulates parasympathetic system which increases activity of the vagus nerve

this results in the slowing of sinus node discharge rate and decreased

conduction through the AV node these actions make Digoxin particularly useful

for patients with both heart failure and atrial fibrillation now let's talk about

the second agent which is Adenosine unlike all the other agents Adenosine is

a naturally occurring nucleoside it works by stimulating A1 type

adenosine receptors on the atrium as well as on the SA node and AV node which

results in decreased automaticity decreased conduction velocity and

prolonged refractory period due to its very short duration of action

adenosine has to be administrated by IV its main indication is an acute

supraventricular tachycardia one of the biggest benefits of Adenosine is that

it's relatively non-toxic with the most common side effects being chest pain

flushing and hypotension now finally let's talk about our third agent which

is Magnesium Sulfate Magnesium Sulfate plays an important role in transport of

sodium potassium and calcium across the cell membranes unfortunately its precise

mechanism of action for treating arrhythmias is largely unknown however

what we know is that Magnesium Sulfate administered intravenously is very

effective for treatment of torsades de pointes and Digoxin induced

arrhythmias and with that I wanted to thank you for watching I hope you

enjoyed this lecture and as always stay tuned for more