This document provides an overview of cardiac arrhythmias and anti-arrhythmic drugs. It discusses the electrophysiology of normal heart rhythm, heart automaticity and action potentials, causes of cardiac arrhythmias, types of cardiac arrhythmias including those originating from the atria, AV node, and ventricles. It also covers how the parasympathetic and sympathetic nervous systems control heart rhythm and the classification of anti-arrhythmic drugs.

1. CARDIAC
ARRHYTHMIA
AND ANTI-
ARRHYTHMIC
DRUGS
PRESENTED TO : SIR ZEGHAM
PRESENTED BY : GROUP 7

2. TABLE OF CONTENT
▪ What Is Arrhythmia
▪ Electro-physiology of Normal Heart Rhythm
▪ Heart automaticity and action potential
▪ Causes of Cardia Arrhythmias
▪ Types of Cardia Arrhythmias
▪ Anti-arrhythmic drugs and their classification

3. WHAT IS ARRHYTHMIA
Abnormality in
The site of
origin of the
impulse
Its rate or
regularity
Its
conduction

4. ELECTRO-PHYSIOLOGY
OF NORMAL HEART
RHYTHM

5. ELECTRO-PHYSIOLOGY OF
NORMAL HEART RHYTHM
▪Conduction
system of
heart
Sino-atrial
node (SA)
Atrio-
venticular
node (AV)
Bundle of
His
Bundle
Branches
Purkinje
Fibers
Sinoatrial
node (SA)
Atrioventicular
node (AV)
Bundle of
His
Bundle
Branches
Purkinje
Fibers

6. ELECTRO-PHYSIOLOGY OF
NORMAL HEART RHYTHM
 In first step, signal from SA-node
depolarizes atria due to which
atria contracts.
 On ECG it is shown by P wave.
 The blood is pumped into
ventricles
Atria
Contracted

7. ELECTRO-PHYSIOLOGY OF
NORMAL HEART RHYTHM
Delay in the
passage of
impulse
The signal reaches the AV node
There is a small delay so that all
the blood is ejected from atria to
ventricles
It is represented by the line
between P and Q wave.

8. ELECTRO-PHYSIOLOGY OF
NORMAL HEART RHYTHM
Signal reaches
bundle
branches
The signal moves from bundle of
His to bundle branches
It is represented with a Q wave

9. ELECTRO-PHYSIOLOGY OF
NORMAL HEART RHYTHM
Finally, the signal reaches
Purkinje fibers
This causes Ventricles to
contract
Blood from right Ventricles
moves toward lungs and from
left ventricles to the body

10. HEART AUTOMATICITY
AND ACTION POTENTIAL

11. HEART AUTOMATICITY AND
ACTION POTENTIAL
▪ Automaticity :
▪ Some cardiac fibers have the capability of self-excitation, a process that can
cause automatic rhythmical discharge and contraction
▪ Types of Cardiac cells :
▪ Contractile cells
▪ Conducting cells
▪ Contractile cells
▪ Makeup the walls of Atria and Ventricles
▪ Cannot generate action potential by themselves
▪ When stimulated, generate force of contraction for the heart

12. HEART AUTOMATICITY AND
ACTION POTENTIAL
▪ Conducting cells
▪ Present in SA node, Av node, Bundle of His and Purkinje fibers
▪ Can generate action potential and exhibit automaticity
▪ Initiate impulses that control contraction of contractile cells

13. SA-NODE AS THE PACEMAKER OF
THE HEART
▪ SA-node reaches the threshold potential the fastest so serve as
the Natural Pacemaker of the cell
▪ AV-node and Purkenji fibers can also undergo self excitation and
generate action potential
▪ When SA-node drives the heart rate, AV-node and Purkenji fibers
does not exhibit automaticity
▪ This is due to the reason that the action potential generated by SA-
node suppresses the self excitation of these fibers
▪ Under certain conditions, when SA-node is suppressed or other
conducting cells depolarizes fast, AV-node and Purkenji fiber can
act as new pacemaker and are called Latent Pacemakers

14. MECHANISM OF SA-NODE
RHYTHMICITY
▪ Cardiac fibers has three types of membrane ion channels
▪ Fast Sodium channels
▪ Slow Sodium-Calcium channels
▪ Potassium channels
▪ Resting membrane potential of SA-node fiber is -55 to -60
millivolts

15. MECHANISM OF SA-NODE
RHYTHMICITY
 Due to the high Sodium ion concentration in the extracellular fluid , as
well as a moderate number of already open Sodium channels, positive
Sodium ions from outside the fibers normally tend to leak to the inside
 This causes a slow rise in the resting membrane potential. This is
called phase 4
 When the potential reaches a threshold voltage of about -40 millivolts,
the Sodium-calcium channels become activated
 When Calcium channels open, calcium rushes in and rapidly
depolarizes it to +10 millivolts and generates action potential. This is
called phase 0
 After reaching action potential, Sodium-Calcium Channels become
inactivated thus blocking their influx
 At the same time Voltage Gated Potassium Channels opens which
causes the large quantity of Potassium ions to move outside the cell
thus, repolarizing the cell back to -60 millivolts. This is called phase 3
 After reaching the resting membrane potential the inward-leaking
Sodium and Calcium ions once again overbalance the outward flux of
potassium ions hence again depolarizing the cell and the process
repeats
Threshold voltage

16. MECHANISM OF CARDIAC MUSCLE
RHYTHMICITY
 Resting membrane potential of cardiac muscle cell is -90 millivolts due to
constant outward leak of Potassium ions. This resting phase is referred as
Phase 4
 When an action potential is generated in neighboring cell the Voltage gated
Sodium Channels open and Sodium rushes in causing rapid depolarization
to about +40 millivolts. This is called Phase 0
 At this point Sodium channels become inactivated and Voltage gated
Potassium channels open which allow Potassium to escape bringing a
small depth in membrane potential. This is called Phase 1
 During depolarization at Phase 0, Calcium channels also start opening
slowly, allowing Calcium to enter the cell
 Now with the +ve Potassium ions Leaving and +ve Calcium ions entering
the cell, there is a electrically balanced ion exchange which keeps the
membrane potential at plateau. This is called Phase 2
 This is followed by Phase 3 in which there is rapid repolarization due to
inactivation of Calcium channel.
 At the same time the continues out flux of Potassium channels brings the
membrane potential to -90 millivolts which is resting membrane potential
and the process repeats
Plateau

17. CONTROL OF HEART RHYTHMICITY BY
PARASYMPATHETIC NERVES
▪ Effects of Parasympathetic stimulation
▪ The parasympathetic nerves are distributed mainly to the S-A and A-V nodes, to a
lesser extent to atria, and very little directly to the ventricular muscle
▪ Weak to moderate parasympathetic stimulation slows the rate of heart pumping,
often to as little as one half of normal
▪ Strong stimulation can stop completely the rhythmical excitation by the sinus node or
block completely transmission of the cardiac impulse from the atria into the ventricles
through the A-V node
▪ Mechanism of Parasympathetic effect
▪ Stimulation of the parasympathetic nerves to causes the hormone acetylcholine to be
released
▪ The acetylcholine greatly increases the permeability of the fiber membranes to
potassium ions, which allows rapid leakage of potassium out of the conductive fibers.
▪ This causes increased negativity inside the fibers, an effect called hyperpolarization,

18. CONTROL OF HEART RHYTHMICITY BY
PARASYMPATHETIC NERVES
▪ The state of hyperpolarization decreases the resting
membrane potential of the sinus nodal fibers to a level
considerably more negative than usual, to -65 to -75
millivolts rather than the normal level of -55 to -60
millivolts.
▪ Therefore, the initial rise of the sinus nodal membrane
potential caused by inward sodium and calcium leakage
requires much longer to reach the threshold potential
for excitation.
▪ This greatly slows the rate of rhythmicity of these nodal
fibers.
▪ If the vagal stimulation is strong enough,it is possible to
stop entirely the rhythmical self-excitation of this node.

19. CONTROL OF HEART RHYTHMICITY BY
SYMPATHETIC NERVES
▪ Effect of Sympathetic Stimulation
▪ The sympathetic nerves, conversely, are distributed to all parts of the heart, with
strong representation to the ventricular muscle as well as to all the other areas.
▪ First, it increases the rate of sinus nodal discharge
▪ Second, it increases the rate of conduction as well as the level of excitability in all
portions of the heart
▪ Third, it increases greatly the force of contraction of all the cardiac musculature,
both atrial and ventricular
▪ Maximal stimulation can almost triple the frequency of heartbeat and can increase
the strength of heart contraction as much as twofold
▪ Mechanism of Sympathetic Effect
▪ Stimulation of the sympathetic nerves releases the hormone norepinephrine
▪ It increases the permeability of the fiber membrane to sodium and calcium ions

20. CONTROL OF HEART RHYTHMICITY BY
SYMPATHETIC NERVES
 In the sinus node, an increase of sodium-calcium
permeability causes a more positive resting potential
thus accelerating self-excitation and, therefore,
increasing the heart rate
 In the A-V node and A-V bundles, increased sodium-
calcium permeability makes it easier for the action
potential to excite thereby decreasing the conduction
time from the atria to the ventricles

21. CAUSES OF CARDIA
ARRHYTHMIAS

22. CAUSES OF CARDIA ARRHYTHMIAS
▪ Drug abuse
▪ Smoking
▪ Alcohol abuse
▪ Caffeine
▪ Some medications
▪ Some vitamin supplements and herbal
remedies
▪ Stress or anxiety
▪ Diabetes
▪ Damage to the heart muscle due to a
heart attack or coronary artery disease
▪ Heart failure
▪ High blood pressure (hypertension)
▪ Obesity
▪ Sleep apnea (temporary stoppage of
breathing during sleep)
▪ Thyroid disease
▪ Mineral imbalances, including calcium,
magnesium, potassium, and sodium.

23. TYPES OF
CARDIAC
ARRHYTHMI
AS

24. CLASSIFICATION OF CARDIAC ARRHYTHMIAS
▪ Arrhythmias can be classified into 3 categories on the basis of their site of origin
▪ Arrhythmias originating from atria
▪ Arrhythmias involving the AV-node
▪ Arrhythmias originating from Ventricles
▪ Arrhythmias occur because one or more regions of the heart are
▪ Beating too slowly (sinus bradycardia)
▪ Beating too fast (sinus or ventricular tachycardia)
▪ Beating automatically without regard for impulses originating from the SA node (atrial
fibrillation, ventricular fibrillation)
▪ Allowing impulses to travel along an accessory pathway to areas of the heart which
should not be depolarized at that particular moment (A-V reentry, Wolff-Parkinson
White syndrome).

25. ARRHYTHMIAS ORIGINATING FROM ATRIA
▪ Sinus Bradycardia
▪ It happens due to increased parasympathetic stimulation.
▪ It is characterized by regular heart beat but at lower rate i.e. <60 beats per
minute
▪ Sinus bradycardia may also be caused by the sick sinus syndrome, which
involves a dysfunction in the ability of the sinus node to generate or
transmit an action potential to the atria.
▪ Sinus Tachycardia
▪ It happens due to increased sympathetic stimulation.
▪ It is characterized by regular heart beat but at higher rate i.e. 100-
160 beats per minute
▪ Multifocal Atrial Tachycardia (MAT)
▪ Multifocal atrial tachycardia (MAT) is caused by multiple sites of competing
atrial activity.
▪ It is characterized by an irregular atrial rate i.e. 100-200 beats per minute

26. ARRHYTHMIAS ORIGINATING FROM ATRIA
▪ Premature Atrial Depolarization (PAT)
▪ In this type of arrhythmia there is a ectopic pacemaker (pacemaker other
then SA-node) in atria
▪ Heart beats prematurely because the ectopic pacemaker fires
spontaneously before the SA-node is ready to fire
▪ Atrial Flutter
▪ In atrial flutter the atrial impulses reenters and depolarizes atria again.
▪ It is characterized by regular rhythms but at higher rate i.e. 250-300 beats
per minute and some degree of AV-node conduction block
▪ Arial Fibrillation
▪ It is due to the presence and firing of multiple ectopic foci or pacemakers
present in atria
▪ It is characterized by irregular heart beat at higher rate i.e. 350-450 beats
per minute

27. Arrhythmias involving the AV-node
▪ AV-node Reentry Tachycardia (AVNRT)
▪ Av-node has two pathways, a fast pathway and a slow pathway. Normally
an impulse moves through fast pathway and enter bundle of His and also
terminates the slow pathway.
▪ In AVNRT, due to fast pathway block, impulse reaches the bundle of His
through slow pathway. The impulse also moves upward into the fast
pathway and reenters slow pathway. The impulse continues to circle
around sending fast impulses causing tachycardia
▪ Wolff-Parkinson-White Syndrome
▪ In this syndrome an extra or accessory pathway exist between upper and
lower chambers of the heart
▪ Normally, the impulse is terminated in Purkinje fibers. When accessory
pathway appears the signal travels through this pathway from ventricles
back to atria, causing it to contract before SA-node fires again and cause
tachyarrhythmia

28. ARRHYTHMIAS ORIGINATING FROM
VENTRICLES
▪ Ventricular Premature Depolarization
▪ It is caused due to the presence of ectopic pacemaker in ventricles
▪ The ectopic pacemaker generates an impulse causing ventricles to
contract before they are stimulated by impulse from SA-node
▪ Ventricular Tachycardia
▪ It is caused due to AV-node reentry tachycardia or Wolff-Parkinson-White
Syndrome
▪ It is characterized by increased ventricular contractions before SA-node
stimulation
▪ Ventricular Fibrillation
▪ It is caused due to presence of many ectopic pacemakers in ventricles
▪ It is characterized by irregular beats at a higher rate i.e. 350-450 beats per
minutes

29. ANTI-ARRHYTHMIC
DRUGS AND THEIR
CLASSIFICATION

30. ANTI-ARRHYTHMIC DRUGS
▪ Anti-Arrhythmic drugs are classified according to VAUGHAN-WILLIAM
classification system
▪ This system classifies anti-arrhythmic drugs into 4 main classes
▪ Class I drugs (Sodium Channel Blockers)
▪ Further divided into Class IA, Class IB and Class IC drugs
▪ Class II drugs (β-Receptor Blockers)
▪ Class III drugs (Potassium Channel Blockers)
▪ Class IV drugs (Calcium Channel Blockers)
▪ There are some other drugs used for arrhythmias but not classified in
this system. They include
▪ Digoxin
▪ Adenosine
▪ Magnesium Sulfate

31. CLASS I DRUGS (SODIUM
CHANNEL BLOCKERS)

32. CLASS IA DRUGS (SODIUM CHANNEL
BLOCKERS)
▪ All Class I drugs act by blocking voltage gated Sodium channels
▪ Drugs Included
▪ Quinidine (prototype)
▪ Procainamide
▪ Disoperamide
▪ Mechanism of Action
▪ Quinidine binds to open and inactivated sodium channels and
prevents sodium influx, thus slowing the rapid upstroke during phase
0
▪ It decreases the slope of phase 4 spontaneous depolarization, inhibits
potassium channels, and blocks calcium channels.
▪ Because of these actions, it slows conduction velocity and increases
refractoriness. Quinidine also has mild α-adrenergic blocking and
anticholinergic actions.
▪ Procainamide and Disopyramide have actions similar to those of
Quinidine

33. CLASS IA DRUGS (SODIUM CHANNEL
BLOCKERS)
▪ However, there is less anticholinergic activity associated with
Procainamide and more with Disopyramide.
▪ Neither Procainamide nor Disopyramide has α-blocking activity
▪ Disopyramide produces a negative inotropic effect that is
greater than the weak effect exerted by Quinidine and
Procainamide, and also causes peripheral vasoconstriction.
▪ The drug may produce a clinically important decrease in
myocardial contractility in patients with systolic heart failure.
▪ Therapeutic uses
▪ Quinidine is used in the treatment of a wide variety of
arrhythmias, including atrial, AV junctional, and ventricular
tachyarrhythmia's
▪ Procainamide is available in an intravenous formulation only
and may be used to treat acute atrial and ventricular
arrhythmias

34. CLASS IA DRUGS (SODIUM CHANNEL
BLOCKERS)
▪ Disopyramide is used in the treatment of ventricular arrhythmias as an alternative to
procainamide or quinidine and may also be used for maintenance of sinus rhythm in
atrial fibrillation or flutter
▪ Pharmacokinetics
▪ Quinidine sulfate or gluconate is rapidly and almost completely absorbed after oral
administration. It undergoes extensive metabolism primarily by the liver, forming
active metabolites
▪ Procainamide has a relatively short duration of action of 2 to 3 hours. A portion of
procainamide is acetylated in the liver to N-acetylprocainamide (NAPA), which
prolongs the duration of the action potential. Thus, NAPA has properties and side
effects of a class III drug. NAPA is eliminated via the kidney
▪ Disopyramide is well absorbed after oral administration. It is metabolized in the liver
to a less active metabolite and several inactive metabolites. About half of the drug is
excreted unchanged by the kidneys

35. CLASS IA DRUGS (SODIUM CHANNEL
BLOCKERS)
▪ Adverse effects:
▪ Quinidine
▪ Blurred vision
▪ Tinnitus
▪ Headache
▪ Disorientation
▪ Psychosis
▪ Intravenous administration of procainamide
▪ Hypotension.
▪ Disopyramide
▪ Dry mouth
▪ Urinary retention
▪ Blurred vision
▪ Constipation

36. ▪ Drugs Included
▪ Lidocaine
▪ Mexiletine
▪ Mechanism of Action
▪ In addition to sodium channel blockade, lidocaine and
Mexiletine shorten phase 3 repolarization and decrease the
duration of the action potential
▪ Therapeutic uses:
▪ Lidocaine is used as alternative for Amiodarone in ventricular
fibrillation or pulseless ventricular tachycardia (VT)
▪ Lidocaine may also be used in polymorphic VT or in combination
with Amiodarone for VT storm
▪ Mexiletine is used for chronic treatment of ventricular
arrhythmias, often in combination with amiodarone
CLASS IB DRUGS (SODIUM CHANNEL
BLOCKERS)

37. CLASS IB DRUGS (SODIUM CHANNEL
BLOCKERS)
▪ Pharmacokinetics
▪ Lidocaine is given intravenously because of extensive first-pass
transformation by the liver. The drug is de-alkylated to two less
active metabolites. As lidocaine is a high extraction drug, drugs
that lower hepatic blood flow (β-blockers) may require lidocaine
dose adjustment.
▪ Mexiletine is well absorbed after oral administration. It is
metabolized in the liver primarily to inactive metabolites and
excreted mainly via the biliary route.
▪ Adverse effects:
▪ Lidocaine has a wide therapeutic index. Central nervous system
(CNS) effects include nystagmus (early indicator of toxicity),
drowsiness, slurred speech, paresthesia, agitation, confusion, and
convulsions
▪ Mexiletine has a narrow therapeutic index. Nausea, vomiting, and
dyspepsia are the most common adverse effects.

38. ▪ Drugs Included
▪ Flecainide
▪ Propafenone
▪ Mechanism of Action
▪ Flecainide suppresses phase 0 upstroke in Purkinje and
myocardial fibers . This causes marked slowing of conduction in
all cardiac tissue. Automaticity is reduced by an increase in the
threshold potential, rather than a decrease in slope of phase 4
depolarization. Flecainide also blocks potassium channels
leading to increased action potential duration, even more so
than Propafenone.
▪ Propafenone , like Flecainide, slows conduction in all cardiac
tissues but does not block potassium channels.
CLASS IC DRUGS (SODIUM CHANNEL BLOCKERS)

39. ▪ Therapeutic uses:
▪ Flecainide is useful in the maintenance of sinus rhythm in atrial
flutter or fibrillation in patients without structural heart disease
refractory ventricular arrhythmias. Flecainide has a negative
inotropic effect and can aggravate chronic heart failure.
▪ Propafenone is restricted mostly to atrial fibrillation or flutter
and paroxysmal supraventricular tachycardia prophylaxis in
patients with AV reentrant tachycardia's.
▪ Pharmacokinetics:
▪ Flecainide is absorbed orally and is metabolized in liver to
multiple metabolites. The parent drug and metabolites are
mostly eliminated renally through urine
▪ Propafenone is also metabolized in liver to active metabolites.
The metabolites are excreted in the urine and the feces.
CLASS IC DRUGS (SODIUM CHANNEL BLOCKERS)

40. CLASS IC DRUGS (SODIUM CHANNEL BLOCKERS)
▪ Adverse effects:
▪ Flecainide
▪ Blurred vision
▪ Dizziness
▪ Nausea
▪ Propafenone
▪ Similar side effects
▪ Also cause bronchospasm due to its β-blocking effects.
▪ Should be avoided in patients with asthma.

41. CLASS II DRUGS (β-
RECEPTOR BLOCKERS)

42. CLASS II DRUGS (β-RECEPTOR BLOCKERS)
▪ Drugs Included
▪ Propranolol
▪ Metoprolol
▪ Atenolol
▪ Esmolol
▪ Mechanism of Action
▪ Class II agents are β-adrenergic antagonists, or β-blockers.
▪ These drugs diminish phase 4 depolarization and, thus, depress automaticity, prolong
AV conduction, and decrease heart rate and contractility
▪ Therapeutic uses
▪ Class II agents are useful in treating tachyarrhythmia's caused by increased
sympathetic activity

43. CLASS II DRUGS (β-RECEPTOR BLOCKERS)
▪ They are also used for atrial flutter and fibrillation and for AV nodal reentrant
tachycardia
▪ In addition, β-blockers prevent life-threatening ventricular arrhythmias following a
myocardial infarction
▪ Metoprolol as compared to nonselective β-blockers, such as Propranolol it reduces
the risk of bronchospasm
▪ Esmolol is a very-short-acting β-blocker used for intravenous administration in acute
arrhythmias that occur during surgery or emergency situations. It has a fast onset of
action and a short half-life, making it ideal for acute situations and also limiting its
adverse effect profile
▪ Pharmacokinetics
▪ Metoprolol is extensively metabolized in the liver and has CNS penetration
▪ Esmolol is rapidly metabolized by esterases in red blood cells

44. CLASS II DRUGS (β-RECEPTOR BLOCKERS)
▪ Adverse effects
▪ Fatigue
▪ Bronchospasm
▪ Hypotension
▪ Impotence
▪ Depression
▪ Aggravation of heart failure
▪ Abrupt discontinuation of
chronic β-blocker therapy can
lead to “rebound” symptoms,
including hypertension,
increased angina, and
arrhythmias

45. CLASS III DRUGS
(POTASSIUM CHANNEL
BLOCKERS)

46. CLASS III DRUGS (POTASSIUM
CHANNEL BLOCKERS)
▪ Drugs Included
▪ Amiodarone
▪ Dronedarone
▪ Sotalol
▪ Dofetilide
▪ Ibutilide
▪ Mechanism of Action
▪ Amiodarone contains iodine and is related structurally to
thyroxine. It has class I, II, III, and IV actions, as well as α-
blocking activity. Its dominant effect is prolongation of the
action potential duration and the refractory period by blocking
K+ channels
▪ Dronedarone is a benzofuran Amiodarone derivative. It does not
have the iodine moieties. Like Amiodarone, it has class I, II, III,
and IV actions

47. CLASS III DRUGS (POTASSIUM
CHANNEL BLOCKERS)
▪ Sotalol although a class III antiarrhythmic agent, also has potent
nonselective β-blocker activity. l-Sotalol has β-blocking activity,
and D-Sotalol has class III antiarrhythmic action. Sotalol blocks a
rapid outward potassium current. This blockade prolongs both
repolarization and duration of the action potential
▪ Dofetilide is a pure potassium channel blocker hence prolongs
both repolarization and duration of the action potential
▪ Ibutilide is a potassium channel blocker that also activates the
inward sodium current (mixed class III and IA action)
▪ Therapeutic uses
▪ Amiodarone is effective in the treatment of severe refractory
supraventricular and ventricular tachyarrhythmias. Amiodarone
has been a mainstay of therapy for the rhythm management of
atrial fibrillation or flutter. Despite its adverse effect profile
Amiodarone is most commonly employed antiarrhythmic drug

48. CLASS III DRUGS (POTASSIUM
CHANNEL BLOCKERS)
▪ Dronedarone is used to maintain sinus rhythm in atrial fibrillation or flutter, but it is
less effective than amiodarone.
▪ Sotalol is used for maintenance of normal sinus rhythm in patients with atrial
fibrillation, atrial flutter, or refractory paroxysmal supraventricular tachycardia and in
the treatment of ventricular arrhythmias. Since Sotalol has β-blocking properties, it is
commonly used for in patients with left ventricular hypertrophy or atherosclerotic
heart disease
▪ Dofetilide can be used as a first-line antiarrhythmic agent in patients with persistent
atrial fibrillation and heart failure or in those with coronary artery disease
▪ Ibutilide is the drug of choice for chemical conversion of atrial flutter
▪ Pharmacokinetics
▪ Amiodarone is incompletely absorbed after oral administration. The drug is unusual
in having a prolonged half-life of several weeks, and it distributes extensively in
adipose tissue

49. CLASS III DRUGS (POTASSIUM
CHANNEL BLOCKERS)
▪ Dronedarone is less lipophilic, has lower tissue accumulation, and has a
shorter serum half-life than Amiodarone
▪ Sotalol is well absorbed orally. Excretion is predominantly by the kidneys
in the unchanged form with a half-life of approximately 12 hours
▪ Dofetilide has half-life of 10 hours. The drug is mainly excreted
unchanged in the urine
▪ Ibutilide undergoes extensive first-pass metabolism and is not used orally.
Ibutilide is rapidly cleared by hepatic metabolism and the elimination
half-life averages 6 hours. The metabolites are excreted by the kidney
▪ Adverse effects
▪ Amiodarone shows a variety of toxic effects, including pulmonary fibrosis,
neuropathy, hepatotoxicity, corneal deposits, optic neuritis, blue-gray skin
discoloration, and hypo- or hyperthyroidism
▪ Dronedarone has a better adverse effect profile than amiodarone but
may still cause liver failure. The drug is contraindicated in those with
symptomatic heart failure or permanent atrial fibrillation due to an
increased risk of death

50. CLASS III DRUGS (POTASSIUM
CHANNEL BLOCKERS)
▪ Sotalol can cause the typical adverse effects associated with β-blockers but has a low
rate of adverse effects when compared to other antiarrhythmic agents. It has the risk
proarrhythmia
▪ Dofetilide causes Torsades de pointes; i.e. QT interval elongation. Also cause
proarrhythmia
▪ Ibutilide has the risk of QT prolongation and proarrhythmia

51. CLASS IV DRUGS
(CALCIUM CHANNEL
BLOCKERS)

52. CLASS IV DRUGS (CALCIUM
CHANNEL BLOCKERS)
▪ Drugs Included
▪ Verapamil
▪ Diltiazem
▪ Mechanism of Action
▪ Although voltage-sensitive calcium channels occur in many
different tissues, the major effect of calcium channel blockers is
on vascular smooth muscle and the heart.
▪ Verapamil shows greater action on the heart than on vascular
smooth muscle, and Diltiazem is intermediate in its actions.
▪ In the heart, Verapamil and Diltiazem bind only to open
depolarized voltage-sensitive channels, thus decreasing the
inward current carried by calcium
▪ They prevent repolarization until the drug dissociates from the
channel, resulting in a decreased rate of phase 4 depolarization

53. CLASS IV DRUGS (CALCIUM
CHANNEL BLOCKERS)
▪ They also slow conduction in tissues that are dependent on
calcium currents, such as the AV and SA nodes
▪ Therapeutic uses
▪ These agents are more effective against atrial than against
ventricular arrhythmias.
▪ They are useful in treating reentrant supraventricular tachycardia
and in reducing the ventricular rate in atrial flutter and
fibrillation
▪ Pharmacokinetics
▪ The half-life of Verapamil is approximately 4–7 hours
▪ These agents are extensively metabolized by the liver
▪ After oral administration, bioavailability of Verapamil is only
about 20%. Therefore, Verapamil must be administered with
caution in patients with hepatic dysfunction

54. ▪ Adverse effects
▪ Verapamil is contraindicated in patients with Wolff–Parkinson– White
syndrome and is ineffective and dangerous in ventricular dysrhythmias
▪ Other ADRs include
▪ dizziness
▪ slow heartbeat
▪ constipation
▪ nausea
▪ headache
▪ tiredness
CLASS IV DRUGS (CALCIUM
CHANNEL BLOCKERS)

55. UNCATEGORIZED DRUGS
(NOT PRESENT IN VAUGHAN-
WILLIAM CLASSIFICATION
SYSTEM)

56. DIGOXIN

57. DIGOXIN
▪ Mechanism of action
▪ In resting condition Sodium slowly leaks in and Potassium slowly leaks
out of the cell
▪ During an action potential, additional Sodium enters the cell along with
Calcium and additional Potassium leaves the cell. This causes an
imbalance which has to be restored
▪ This restoration is done by pumps such as Sodium-Potassium-ATPase
(Na-K-ATPase) and Sodium-Calcium Exchanger
▪ Na-K-ATPase moves Sodium out of the cell and Potassium inside of the
cell by using ATP
▪ Sodium-Calcium Exchanger removes Calcium from the cell in exchange
for Sodium. This pump can move Sodium and Calcium both ways
▪ When Digoxin is administered it inhibits the Na-K-ATPase by binding to
the Potassium Binding site. This inhibition cause an increase in
intracellular sodium
Digitalis Purpurea

58. DIGOXIN
▪ This increase in intracellular sodium causes Sodium-Calcium Exchanger to
pump more Sodium out and Pump more Calcium Inside the cell
▪ This increased intracellular Calcium leads to enhanced myocardial
contractility
▪ Digoxin also stimulate parasympathetic system which results in slowing of
SA-node discharge rate and decrease conduction through the AV-node
▪ Therapeutic uses
▪ Digoxin is used for the treatment of Atrial Arrhythmias mainly atrial flutter
and atrial fibrillation
▪ It slows AV-nodal conduction so is used for the treatment of AV-nodal re-entry
tachycardia
▪ It is also used for the Treatment of Heart Failure
▪ Pharmacokinetics
▪ Its half-life in normal renal function is around 1.7 days and in renal
insufficiency it is between 3 to 5 days

59. DIGOXIN
▪ About 30% of Digoxin is bound to protein and only 16% of Digoxin
is metabolized by liver, the rest is excreted by the kidney in
unchanged form
▪ Adverse effects
▪ Digoxin is know itself to cause arrhythmias
▪ Digoxin has a very narrow therapeutic window.
▪ GIT symptoms such as diarrhea, nausea, anorexia, vomiting;
followed by neurologic symptoms such as delirium, visual
disturbance; and cardiac symptoms such as atrial tachycardia, AV
block, SA-nodal dysfunction and life threatening ventricular
arrhythmias can occur
▪ Hypoxia and electrolyte imbalance, specifically hypokalemia,
hypomagnesaemia and hypocalcaemia, increase the risk of the
arrhythmias induced by digoxin

60. ADENOSINE

61. ADENOSINE
▪ Adenosine is a naturally occurring purine nucleoside that forms
from the breakdown of adenosine triphosphate (ATP)
▪ Mechanism of action
▪ In cardiac tissue, Adenosine binds to type 1 (A1) receptors, which are
coupled to Gi-proteins
▪ Activation of this pathway opens potassium channels, which
hyperpolarizes the cell
▪ Activation of the Gi-protein also decreases cAMP, which inhibits L-
type calcium channels and therefore calcium entry into the cell
▪ In cardiac pacemaker cells located in the sinoatrial node, adenosine
acting through A1 receptors inhibits the pacemaker current, which
thereby decreasing its spontaneous firing rate (negative
chronotropic)
▪ Inhibition of L-type calcium channels also decreases conduction
velocity (negative dromotropic effect) particularly at the
atrioventricular (AV) nodes

62. ADENOSINE
▪ Therapeutic use
▪ Adenosine is used for the rapid treatment of supraventricular
tachycardias.
▪ Its suppression of atrioventricular conduction makes it very useful in
treating paroxysmal supraventricular tachycardia in which the AV node is
part of the reentry pathway (as in Wolff-Parkinson-White Syndrome)
▪ Pharmacokinetics
▪ Adenosine is only available for intravenous application and achieves its
maximal effect after 20 to 30 seconds.
▪ The drug has a very short half-life of about 10 seconds
▪ It is metabolized in erythrocytes and endothelial cells either by converting
to inosine through adenosine deaminase, or it can be converted to AMP
by adenosine kinase

63. ADENOSINE
▪ Adverse effects
▪ The most common adverse effects are flush, dyspnea, chest fullness,
bronchoconstriction, shortness of breath, nausea and headache
▪ High doses may lead to high degree of AV block resulting in asystole and
hypotension

64. MAGNESIUM SULFATE
▪ Magnesium is necessary for the transport of sodium, calcium, and
potassium across cell membranes
▪ It slows the rate of SA node impulse formation and prolongs
conduction time along the myocardial tissue
▪ Intravenous magnesium sulfate is the salt used to treat arrhythmias,
as oral magnesium is not effective in the setting of arrhythmia
▪ Most notably, magnesium is the drug of choice for treating the
potentially fatal arrhythmia Torsades de pointes and digoxin-induced
arrhythmias.

65. References
▪ ^_'Rhythmical Excitation of the Heart', in Arthur C. Guyton and
John E. Hall TEXTBOOK of Medical Physiology. : , pp. 116-121
▪ ^_’Anti-Arrhythmic Drugs’ in Goodman and Gillman’s
Pharmacological basis of therapeutics. : , pp. 816-846
▪ ^_’Antiarrhythmic’ in Lippincott Illustrated Reviews: Pharmacology.
: , pp. 269-280