PDF version of all drugs in Cardiac Arrythmia

1. Seminar on
Cardiac Arrhythmia and its treatment
Submitted by
Souvik Pal
Roll No: 17401913054
Reg. No: 131740210056
S_ID: B13017
B.Pharm, 3rd Year, 6th Semester
Netaji Subhas Chandra Bose Institute of Pharmacy
Tatla, Roypara, Chakdaha, Dist-Nadia, Pin- 741222
Affiliated to
Maulana Abul Kalam Azad University of Technology
BF-142, Sector 1, Saltlake City, Kolkata-700064, West Bengal

2. Reference
1. KD TRIPATHI MD (Ex-Director-Professor and Head of
Pharmacology Maulana Azad Medical College and associated
LN and GB Pant Hospitals New Delhi), Essentials of Medical
Pharmacology, 6th Edition, 2010: 508 , 509, 510-520
2. http://en.wikipedia.org/wiki/Cardiac_arrhythmia
3. http://www.mayoclinic.org/diseases-conditions/heart-
arrhythmia/symptoms-causes/dxc-20188128
4. http://www.healthline.com/health/cardiac-arrhythmia
5.http://www.medicinenet.com/cardiac_arrhythmia_overview/
article.htm
6. http://emedicine.medscape.com/article/163062-treatment

3. Contents:- Page No.
1. Introduction………………………………………………….......1
2. Epidemiology……………………………………………………2
3. Genetics involved in Cardiac Arrhythmia…………………..3
4. Pathophysiology………………………………………………...4
5. Sign and symptoms of Cardiac Arrhythmia………………...5
6. Drugs Treatment for Cardiac Arrhythmia…………………..6
6. a. Classification of drug for cardiac Arrhythmia……………………..7
6. b. Class Ia drugs…………………………………………………………..8-9
6. b. i. Quinidine…………………………………………………………………………..8
6. b. ii. Disopyramide……………………………………………………………………..9
6. c. Class Ib drugs…………………………………………………………..10
6. c. i. Lidocaine……………………………………………………………………………10
6. d. Class Ic drugs…………………………………………………………..11
6. d. i. Flecainide…………………………………………………………………………...11
6. d. ii. Propafenone……………………………………………………………………….11
6. e. Class II drugs…………………………………………………………...12-13
6. e. i. Propanolol…………………………………………………………………………..12
6. e. ii. Solatolol…………………………………………………………………………….13
6. f. Class III drugs…………………………………………………………...14-16
6. f. i. Amiodarone…………………………………………………………………………14
6. f. ii. Ibutilide…………………………………………………………………………….15
6. f. iii. Dofetilide………………………………………………………………………….15
6. f. iv. Dronedarone………………………………………………………………………16

4. ACKNOWLEDGEMENT
This seminar report entitled “Cardiac Arrhythmia and its treatment”
is by far the most significant scientific accomplishment in my life and I
was inspired to work in front of my supervisor Asst. Prof. Mrs. Saswati
Ghosh. I take this opportunity to humble acknowledge the contribution
my supervisor, her philosophy to venture into unknown field sciences
opened up new avenues and horizons before me while pursuing the
investigation. Without her constant encouragement, motivation, fruitful
suggestions and inspiration my review work would not have been
materialized.
Next I thank and express my sincere gratitude to the Principal Dr. Arnab
Samanta and I wish to pay my humble respect to all of my teachers who
have nurtured and developed the loyal spirit of education in me for the
facilities has provided.
I am also expressing the thanks to review papers which I consulted
during my review work, I have acknowledged them in reference section
of this report.
Last but not the least; I dedicate the pleasure of presenting this report at
the lotus feet of the Almighty.
Souvik Pal
(6th Semester, 3rd Year)

5. NETAJI SUBHAS CHANDRA BOSE
INSTITUTE OF PHARMACY
TATLA, ROYPARA, CHAKDAHA, NADIA, PIN 741222.
Estd. 2004
CERTIFICATE
This is to certify that the report entitled, Cardiac Arrhythmia and its
treatment submitted by Mr. SOUVIK PAL, 3rdYear, 6thSemester
under guidance of Mrs. Saswati Ghosh in partial fulfilment for the
award of degree of B.Pharm under MAKAUT.
Dr. Arnab Samanta Mrs. Saswati Ghosh
Principal of NSCBIP Asst. Prof. of NSCBIP

6. 1 | P a g e
INTRODUCTION:
Broadly defined, cardiac arrhythmias are any abnormality or perturbation in the
normal activation sequence of the myocardium. The rhythm of the heart is normally
generated and regulated by pacemaker cells within the sinoatrial (SA) node, which is
located within the wall of the right atrium. SA nodal pacemaker activity normally
governs the rhythm of the atria and ventricles. The sinus node, displaying properties of
automaticity, spontaneously depolarizes, sending a depolarization wave over the
atrium, depolarizing the atrio ventricular (AV) node, propagating over the His-Purkinje
system, and depolarizing the ventricle in systematic fashion. There are hundreds of
different types of cardiac arrhythmias. The normal rhythm of the heart, so-called
normal sinus rhythm, can be disturbed through failure of automaticity, such as sick
sinus syndrome, or through overactivity, such as inappropriate sinus tachycardia.
Ectopic foci prematurely exciting the myocardium on a single or continuous basis
results in premature atrial contractions (PACs) and premature ventricular contractions
(PVCs). Sustained tachyarrhythmias in the atria, such as atrial fibrillation, paroxysmal
atrial tachycardia (PAT), and supraventricular tachycardia (SVT), originate because of
micro- or macro re-entry. In general, the seriousness of cardiac arrhythmias depends on
the presence or absence of structural heart disease. . Normal rhythm is very regular,
with minimal cyclical fluctuation. Furthermore, atrial contraction is always followed
by ventricular contraction in the normal heart. When this rhythm becomes irregular,
too fast (tachycardia) or too slow (bradycardia), or the frequency of the atrial and
ventricular beats are different, this is called an arrhythmia. The term "dysrhythmia" is
sometimes used and has a similar meaning.

7. 2 | P a g e
Epidemology
Cardiac arrhythmia generally refers to an unexpected death from a cardiovascular cause in a
person with or without preexisting heart disease. The specificity of this definition varies
depending on whether the event was witnessed; however, most studies include cases that are
associated with a witnessed collapse, death occurring within 1 hour of an acute change in
clinical status, or an unexpected death that occurred within the previous 24 hours. Further,
sudden cardiac arrest describes cardiac arrhythmia cases with resuscitation records or aborted
cardiac arrhythmia cases in which the individual survived the cardiac arrest.
The incidence of cardiac arrhythmia in the United States ranges between 180 000 and 450 000
cases annually. These estimates vary owing to differences in SCD definitions and surveillance
methods for case ascertainment. In recent prospective studies using multiple sources in the
United States, Netherlands, Ireland, and China, SCD rates range from 50 to 100 per 100 000 in
the general population.
Fig—1
Fig-2
 Coronary artery disease was
the principal diagnosis in the
majority of men. In contrast,
women had more heart
disease than men, including
dilated cardiomyopathy
(19%) and valvular heart
disease (13%).
CAD indicates coronary
artery disease; DCM, dilated
cardiomyopathy; VHD,
valvular heart disease;
SPASM, coronary vasospasm;
and RV, right ventricular.
Fig-1
 Relative risk of cardiac arrest
in blacks in comparison with
whites by age group. The bars
represent 95% confidence
intervals. Fig-2

8. 3 | P a g e
Genetics of cardiac Arrhythmia-------
Over the last decade, we have witnessed a revolution in the understanding of primary
cardiac arrhythmia syndromes. These remarkable advances stemmed from the
discovery of mutations, primarily in ion channel genes, underlying a number of these
disorders. Only 10 years ago the long QT syndrome (LQTS) was considered one disease
entity, the Brugada syndrome had just been described and the short QT syndrome
(SQTS) had never been heard of. Moreover, it immediately became obvious that genetic
heterogeneity in these disorders is not the exception but the rule.
The recognition of the genetic substrate underlying the inherited arrhythmia
syndromes has provided remarkable insight into the molecular basis of cardiac
electrophysiology, including the role of the various ion channels and mechanism of
arrhythmias. The availability of a genetic diagnostic test has added an important
diagnostic tool, providing new opportunities for patient management such as early
identification and treatment of individuals at risk of developing fatal arrhythmias.
Herein review these developments at large,
Long QT Syndrome ------
The long QT syndrome, estimated to affect 1 per 5000 individuals, is a repolarization
disorder identified by prolongation of the QT interval on the ECG. It has long been
recognized as a familial disorder, frequently presenting in childhood with syncopal
episodes which occur in a significant proportion. Repolarization is a delicate process
depending on the intricate balance between inward currents (sodium, Na+, or calcium,
Ca2+) and outward current (Potassium, K+). Shifts in the balance of inward and
outward currents can increase or decrease the action potential duration with QT
interval prolongation.
Short QT Syndrome ------
The short QT syndrome is a recently described clinical entity that presents with a high
rate of sudden death and exceptionally short QT intervals. Contrary to the LQTS,
repolarization. Gain of the gene KCNQ1 gene, leading to an increase in outward K+

9. 4 | P a g e
current through the respectively K+ channel, were identified in patients with the
disorder.
Brugada Syndrome ----------
The Brugada syndrome was first described in 1992 and it is characterised by ST
segment elevation in the right precordial leads with or without conduction
abnormalities and a significant risk of sudden cardiac death in the absence of structural
heart disease. The electrocardiographic appearance may be variable and is under the
influence of body temperature, autonomic transmitters and drugs. The disorder is
endemic in East and Southeast Asia, where it underlies the sudden unexpected death
syndrome. The functional effects of Brugada syndrome causing SCN5A mutations are
opposite to those found in LQTS.
Genetics of Primary Cardiac Arrhythmia Syndrome -------
 Several cardiac arrhythmia syndromes that for long were considered idiopathic
are now known to have a genetic basis. They are caused by mutations in ion
channel.
 The genetic basis for most arrhythmia syndrome is heterogeneous ---- that is a
given disorder may be caused by mutations in different genes and evidences for
further genetic heterogenetic exits.
 It is becoming increasingly clear that treatment should take the type of gene
affected consideration.
 In the long QT syndrome information on ECG morphology and triggers for
arrhythmia the proband as well as family.

10. 5 | P a g e
Pathophysiology
Regardless of the specific arrhythmia, the pathogenesis of the arrhythmias falls into one
of four basic mechanisms: enhanced or suppressed automaticity, re-entry , triggered
activity, . Automaticity is a natural property of all myocytes. Ischemia, scarring,
electrolyte disturbances, medications, advancing age, and other factors may suppress
or enhance automaticity in various areas. Suppression of automaticity of the sinoatrial
(SA) node can result in sinus node dysfunction and in sick sinus syndrome (SSS), which
is still the most common indication for permanent pacemaker implantation (Fig. 1). In
contrast to suppressed automaticity, enhanced automaticity can result in multiple
arrhythmias, both atrial and ventricular. Triggered activity occurs when early after
depolarizations and delayed after depolarizations initiate spontaneous multiple
depolarizations, precipitating ventricular arrhythmias. Examples include torsades de
pointes (Fig. 2) and ventricular arrhythmias caused by digitalis toxicity. Probably the
most common mechanism of arrhythmogenesis results from re-entry. Requisites for re-
entry include bidirectional conduction and unidirectional block. Micro level re-entry
occurs with VT from conduction around the scar of myocardial infarction (MI), and
macro level re-entry occurs via conduction through (Wolff-Parkinson-White [WPW]
syndrome) concealed accessory pathways.
Fig 1 Fig 2

11. 6 | P a g e
Sign and Symptoms
The term cardiac arrhythmia covers a very large number of very different conditions.
The most common symptom of arrhythmia is an abnormal awareness of heartbeat,
called palpitations. These may be infrequent, frequent, or continuous. Some of these
arrhythmias are harmless (though distracting for patients) but many of them predispose to
adverse outcomes.
Some arrhythmias do not cause symptoms, and are not associated with increased mortality.
However, some asymptomatic arrhythmias are associated with adverse events. Examples
include a higher risk of blood clotting within the heart and a higher risk of insufficient blood
being transported to the heart because of weak heartbeat. Other increased risks are of
embolisation and stroke, heart failure and sudden cardiac death.
If an arrhythmia results in a heartbeat that is too fast, too slow or too weak to supply the body's
needs, this manifests as a lower blood pressure and may cause lightheadedness or dizziness, or
syncope (fainting).
Some types of arrhythmia result in cardiac arrest, or sudden death.
Medical assessment of the abnormality using an electrocardiogram is one way to diagnose and
assess the risk of any given arrhythmia.
Noticeable arrhythmia symptoms may include:
 A fluttering in your chest
 A racing heartbeat (tachycardia)
 A slow heartbeat (bradycardia)
 Chest pain
 Shortness of breath
 Lightheadedness or dizziness
 Sweating
 Fainting (syncope) or near fainting

12. 7 | P a g e
Antiarrhythmatic Drugs Classification
Class Known as Examples Mechanism
Ia
Membrane
stabilizing
agents
(Na+ Channel
blockers)
A Moderately
decrease dv/dt
of 0 phase
 Quinidine
 Disopyramide
(Na+) channel block (intermediate
association/dissociation) and K+ channel
blocking effect.
Ib
Little decrease
in dv/dt of 0
phase
 Lidocaine
 Tocainide
(Na+) channel block (fast
association/dissociation)
Ic
Marked
decrease in
dv/dt of 0
phase
 Flecainide
 Propafenone
(Na+) channel block (slow
association/dissociation)
II
Antiadrenergic
Agents (Beta-
blockers)
 Propranolol
 Solatolol
beta blocking
Propranolol also shows some class I action
III
Agents
widening AP
 Amiodarone
 Ibutilide
 Dofetilide
 Dronedarone

K+ channel blocker
Sotalol is also a beta blocker Amiodarone has
Class I, II, III & IV activity
IV
Calcium
channel
blockers
 Verapamil
 Diltiazem Ca2+ channel blocker

13. 8 | P a g e
Quindine
Drug Interactions
 Rise in blood levels and toxicity of digoxin due to displacement from tissue binding and
inhibition of P-Glycoprotein mediated renal and biliary clearance of digoxin.
 Marked fall in BP in patients receiving vasodilators.
 Risk of torsades de pointes is increased by hypokalaemia caused by diuretics.
 Synergic cardiac depression with blockers, verapamil, k+ salts.
 Quinidine inhibits CYP2D6; prolongs t half of popaferone and inhibits conversion of
codeine to morphine.
Mechanism of Action
Like all other class I Antiarrthymatic agents , quinidine primarily works by blocking the fast
inward sodium current (INa). Quinidine's effect on INa is known as a 'use dependent block'. The
effect of blocking the fast inward sodium current causes the phase 0 depolarization of
the cardiac action potential to decrease (decreased Vmax).
Quinidine also blocks the slowly inactivating, tetrodotoxin-sensitive Na current, the slow
inward calcium current (ICa), the rapid (IKr) and slow (IKs) components of the delayed potassium
rectifier current,
At micromolar concentrations, quinidine inhibits Na⁺/K⁺-ATPase by binding to the same
receptor sites as the digitalis glycosides such as ouabain.
The effect of quinidine on the ion channels is to prolong the cardiac action potential, thereby
prolonging the QT interval on the surface ECG.
Adverse Effect
Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6, and can lead to increased
blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also
inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs
such as loperamide to have central nervous system side effects, such as respiratory depression,
if the two drugs are coadministered.
Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis,
and torsades de pointes, so is not used much today. Torsades can occur after the first dose.
Quinidine-induced thrombocytopenia (low platelet count) is mediated by the immune system,
and may lead to thrombocytic purpura.
Quinidine intoxication can lead to a collection of symptoms collectively known as cinchonism,
with tinnitus (ringing in the ears).

14. 9 | P a g e
Disopyramide
Drug Interactions
Mechanism of action
Disopyramide’s class 1a activity is similar to that of quinidine in that it targets sodium channels
to inhibit conduction. Disopyramide depresses the increase in sodium permeability of the
cardiac Myocyte during phase 0 of the cardiac action potential, in turn decreasing the inward
sodium current. This results in an increased threshold for excitation and a decreased upstroke
velocity. Disopyramide prolongs the PR interval by lengthening both the QRS and P wave
duration. This effect is particularly well suited in the treatment of ventricular tachycardia as its
slows the action potential propagation through the atria to the ventricles. Disopyramide does
not act as a blocking agent for beta or alpha adrenergic receptors. As a result, the use of
Disopyramide may reduce the contractile force up to 42% at low dose and up to 100% in higher
doses leading to heart failure. Disopyramide decreases the chance of re-entry depolarization,
because signals are more likely to encounter tissue in a refractory period whichn can’t be a
excited state. This provides a possible treatment for atrial and ventricular fibrillation, as it
restores pacemaker control of the tissue to the SA and AV nodes.
Adverse Effects
 Acute heart failure
Disopyramide should not be given to patients with impaired LV systolic function and low
ejection fraction. Heart failure is not seen when Disopyramideis used in patient with normal or
supernormal LV systolic function.
 Severe hypotension Disopyramide should not be given to patients with impaired LV
systolic function and low ejection fraction. Hypotension is not seen in patient with
normal and supernormal LV systolic function.
Extracardiac effects
 Dry mouth
 Constipation
 Urinary retention Disopyramide should not be given to patients with symptomatic prostatism.
 Glaucoma
 Rash
 Blurred Vision

15. 10 | P a g e
Lidocaine
Drug Interactions
Any drugs that are also ligands of CYP3A4 and CYP1A2 can potentially increase serum levels
and potential for toxicity or decrease serum levels and the efficacy, depending on whether they
induce or inhibit the enzymes, respectively. Drugs that may increase the chance
of methemoglobinemia should also be considered
carefully. Dronedarone andliposomal morphine are both absolutely contraindicated, as they
may increase the serum levels, but hundreds of other drugs require monitoring for interaction.
Mechanism of Action
Lidocaine alters signal conduction in neurons by blocking the fast voltage-gated
Na+ channels in the neuronal cell membrane responsible for signal propagation.[33] With
sufficient blockage, the membrane of the postsynaptic neuron will not depolarize and will thus
fail to transmit an action potential. This creates the anaesthetic effect by not merely preventing
pain signals from propagating to the brain, but by stopping them before they begin. Careful
titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas
higher concentrations also affect other modalities of neuron signaling.
The same principle applies for this drug's actions in the heart. Blocking sodium channels in the
conduction system, as well as the muscle cells of the heart, raises the depolarization threshold,
making the heart less likely to initiate or conduct early action potentials that may cause an
arrhythmia.
Adverse Effect
The main toxicity is dose related neurological effects:
Drowsiness, nausea, vomiting, paresthesias, blurred vision, disorientation, nystagmus,
twitchings and fits.
Lidocaine gas practically no proarrythmatic potential and is the least cardiotoxic
antiarrthymatic. Only excessive doses cause cardiac depression and hypotension.

16. 11 | P a g e
Flecainide
Mechanism of Action
Flecainide works by blocking the Nav1.5 sodium channel in the heart, slowing the upstroke of
the cardiac action potential. This thereby slows conduction of the electrical impulse within the
heart, i.e. it "reduces excitability". The greatest effect is on the His-Purkinje system and
ventricular myocardium. The effect of flecainide on the ventricular myocardium causes
decreased contractility of the muscle, which leads to a decrease in the ejection fraction.
The effect of flecainide on the sodium channels of the heart increases as the heart rate increases;
This is known as use-dependence and is why that flecainide is useful to break
a tachyarrhythmia. It can reduce calcium sparks and thus arrhythmogenic calcium waves in the
heart.[24] While Flecainide therapy has been shown to suppress ventricular arrhythmias in
patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).
Adverse Effect
In patients with these kinds of heart diseases, flecainide actually increases the chance of
suffering a fatal arrhythmia.
The dose may need to be adjusted in certain clinical scenarios. As with all other antiarrhythmic
agents, there is a risk of proarrhythmia associated with the use of flecainide. This risk is
probably increased when flecainide is co-administered with other class Ic antiarrhythmics, such
as encainide. The risk of proarrhythmia may also be increased byhypokalemia.
As with all class I antiarrhythmic agents, Flecainide increases the capture thresholds
of pacemakers. Therefore, capture thresholds should be remeasured in individuals with
pacemakers after the steady-state flecainide dose is changed.
Propafenone
Mechanism of Action
Propafenone works by slowing the influx of sodium ions into the cardiac muscle cells, causing
a decrease in excitability of the cells. Propafenone is more selective for cells with a high rate,
but also blocks normal cells more than class Ia or Ib. Propafenone differs from the prototypical
class Ic antiarrhythmic in that it has additional activity as a beta-adrenergic blocker which can
cause bradycardia and bronchospasm. Pukinje as well as accessory pathway conduction.
Propaferone is absorbed orally and undergoes variable first pass metabolism; there being
extensive or poor metabolizes because the major metabolic isoenzyme CYP2D6 is deficient in
poor metabolizers. CYP2D6 inhibitors like fluoxetine increase its bioavailability and plasma
concentration.
Adverse Effects
Side effects attributed to propafenone include hypersensitivity reactions, lupus-like
syndrome, agranulocytosis, CNS disturbances such as dizziness, lightheadedness,
gastrointestinal upset, a metallic taste and bronchospasm. About 20% of patients discontinued
the drug due to side effects.

17. 12 | P a g e
Propranolol
Drug Interactions
Since beta blockers are known to relax the cardiac muscle and to constrict the smooth muscle,
these beta-adrenergic antagonists, including propranolol, have an additive effect with other
drugs which decrease blood pressure or which decrease cardiac conductivity. Clinically
significant interactions particularly occur with:
 Verapamil
 Epinephrine (adrenalin) 2-adrenergic receptor agonists
 Salbutamol, levosalbutamol, formoterol, salmeterol, clenbuterol etc.
 Clonidine
 Nonsteroidal anti-inflammatory drugs (NSAIDs)
 Quinidine
 Cimetidine
 Lidocaine
Mechanism of Action
Propranolol is a nonselective beta blocker; that is, it blocks the action
of epinephrine and norepinephrine on both 1- and 2-adrenergic receptors. It has little intrinsic
sympathomimetic activity, but has strong membrane stabilizing activity (only at high blood
concentrations, e.g. overdosage). Propranolol has inhibitory effects on thenorepinephrine
transporter (NET) and/or stimulates norepinephrine release (the concentration of
norepinephrine is increased in the synapse). Therefore, it can be looked upon as an indirect
1 agonist, as well as a antagonist. In addition, some evidence suggests propranolol may
function as an antagonist at certain serotonin receptors, namely 5-HT1A and 5-HT1B receptors.
Few studies have demonstrated propranolol's ability to block cardiac, neuronal, and skeletal
voltage-gated sodium channels, accounting for its known "membrane stabilizing effect" and
antiarrhythmic and other central nervous system effects.
Adverse Effect
 slow or uneven heartbeats;
 shortness of breath (even with mild exertion), swelling, rapid weight gain;
 sudden weakness, vision problems, or loss of coordination (especially in a child with
hemangioma that affects the face or head);
 Depression, confusion, hallucinations;
 liver problems - nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark
urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
 low blood sugar - headache, hunger, weakness, sweating, confusion, irritability,
dizziness, fast heart rate, or feeling jittery;

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Solatolol
Mechanism of Action
 Beta-blocker action
Sotalol non-selectively binds to both 1- and 2-adrenergic receptors preventing
activation of the receptors by their stimulatory ligand.[2] Without the binding of this ligand to
the receptor, the G-protein complex associated with the receptor cannot activate production of
cyclic AMP. A decrease in activation of calcium channels will therefore result in a decrease in
intracellular calcium. In cardiac cells, calcium is important in generating electrical signals for
contraction, as well as generating force for contraction. Firstly, with less calcium in the cell,
there is a decrease in electrical signals for contraction. Secondly, lower calcium means a
decrease in strength and rate of the contractions.
 Type III antiarrhythmic action
Sotalol also acts on potassium channels and causes a delay in relaxation of the ventricles. By
blocking these potassium channels, sotalol inhibits efflux of K+ ions, which results in an
increase in the time before another electrical signal can be generated in ventricular myocytes.
This increase in the period before a new signal for contraction is generated, helps to correct
arrhythmias by reducing the potential for premature or abnormal contraction of the ventricles.
Adverse Effect
Over 10% of oral sotalol users
experience fatigue, dizziness, lightheadedness, headache, weakness, nausea, shortness of
breath,bradycardia (slow heart rate), palpitations, or chest pain. Risk for all of these effects
increases with dosage. In rare cases, the QT prolongation caused by sotalol can lead to the
development of life-threatening torsade de pointes (TdP) ventricular tachycardia.
Due to this risk, the U.S. Food and Drug Administration requires patients to be hospitalized for
at least three days in a facility that can provide cardiac resuscitation and continuous
electrocardiographic monitoring upon starting or restarting sotalol.

19. 14 | P a g e
Amiodarone
Drug Interactions
The pharmacokinetics of numerous drugs including many that are commonly administered to
individuals with heart diseases, are affected by Amiodarone. Particularly doses of digoxin
should be halved in individuals taking Amiodarone.
Amiodarone potentiates the action of Warfarin by inhibiting the clearance of both (S) and (R)
warfarin. Individuals taking both of these medications should have their warfarin doses
adjusted based off their dosing of amiodarone and have their dosing of Amiodarone and have
their anticoagulation status as prothombin time (PT), international normalized ratio (INR)
measured more frequently. Dose reduction as follows: 40% reduction if Amiodarone dose is
400 mg daily, 35% reduction if Amiodarone dose is 300 mg daily, and 25% reduction if
Amidarone dose is 100 mg daily. The interaction may not peak for up to seven weeks.
Mechanism of Action
Amiodarone is caractarized as a class III antiarrhythmic drug. The repolarization phase where
there is normally decreased calcium permeability and increased potassium permeability.
Amiodarone shows beta blocker like actions on the SA and AV nodes, increases the refractory
period via Sodium and Potassium channel effects and shows intra cardiac conduction of the
cardiac action potential, via Sodium potassium channel effects.
Adverse Effects
Amiodarone has numerous adverse effects. Most individuals administered Amiodarone on a
chronic basis will experience at least one side effect.
Lung
Side effects of Amiodarone include various pulmonary effects. The most serious reaction that is
due to Amiodarone is interstitial lung disease. Risk factor include high cumulative dose, more
than 400 mg per day, duration over two months increased age and preexisting pulmonary
disease. Some individuals were noted to develop Pulmonary Fibrosis after a week of treatment.
Thyroid
Induced abnormalities in thyroid function are common. Amiodarone is structurally similar to
Thyroxine which contributes to the effects of Amiodarone on thyroid function. Both under and
overactivity of thyroid may occour on Amiodarone treatment.
Eye
Corneal micro deposits also called vortex or whorl keratopathy are almost universally present
in individuals taking Amiodarone longer than 6 months, especially doses greater than 400
mg/day. These deposits typically do not cause any symptoms. About 1 in 10 individuals may
complain of a bluish halo. Bilateral optic disc swelling and mild and reversible visual field
defects can also occur.

20. 15 | P a g e
Liver
Abnormal liver enzyme results are common in patients on Amiodarone. Much rare are
Jaundice, hepatomegaly, and hepatitis (inflammation of the liver). Low dose Amiodarone has
been reported to a
Cancer
A study between Amiodarone and an increased risk of cancer, especially in males, with a dose-
dependent effect.
Ibutilide
Mechanism of Action
Unlike most other Class III antiarrhythmic drugs, ibutilide does not produce its prolongation of
action potential via blockade of cardiac delayed rectifier of potassium current nor does it have a
sodium-blocking, antiadrenergic, and calcium blocking activity that other Class III agents
possess. Thus it is often referred as a “pure” Class III antiarrhythmic drug. Ibutilide’s unique
mechanism works by an activation of a specific inward sodium current, thus producing its
therapeutic response in which a prolonged action potential increases ‘myocytes’ cardiac
refractoriness in case of atrial fibrillation and flutter.
Adverse Effect
Like other antiarrhythmics, ibutilide can lead to abnormal heart rhythms due to its ability to
prolong the QT interval, which can lead to the potentially fatal abnormal heart rhythm known
as torsades de pointes. Consequently, the drug is contraindicated in patients that are likely to
develop abnormal heart rhythms; this includes persons that have hadpolymorphic ventricular
tachycardia in the past, have a long QT interval, sick sinus syndrome, or a recent myocardial
infarction, among others.

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Dofetilide
Drug Interaction
Dofetilide is well absorbed in its oral form with a bioavailability of >90%
The elimination half life of Dofetilide isroughly10 hours ; however this varies based on many
physiologically factors (most significantly Creatinine clearance), and ranges from 4.8 to 13.5
hours. Due to the significant level of renal elimination (80% unchanged, 20% metabolites), the
dose of Dofetilide must be adjusted to prevent toxicity due to impaired renal function.
Mechanism of Action
Dofetilide works by selectively blocking the rapid component of the delayed rectifier outward
potassium current.
This causes the refractory period of atrial tissue to increase, hence its effectiveness in the
treatment of atrial fibrillation and atrial flutter.
Dofetilide does not effect Vmax conduction velocity, or the resting membrane potential.
There is a dose dependent increase in the QT interval and the corrected QT interval (QTc).
Because of this , many practitioner will initiate Dofetilide therapy only on individuals under
telemetry monitoring can be performed. Dofetilide is blockade of the cardiac ion channel
carrying the rapid component of the potassium channels. This inhibition of the potassium
channels results in a prolongation of action potential duration and the effective refractory
period of accessory pathways (both anterograde and retrograde conduction in the accessory
pathway).
Adverse Effect
Torsades de pointes is the most serious side effects of Dofetilide therapy. The incidence of
torsades de pointes is 0.3-10.5% and is dose related, with increased incidence associated with
higher dose.
The risk of inducing Torsades de pointes can be decreased by taking precautions when
initiating therapy, such as hospitalizing individuals for a minimum of three days for serial
creatinine measurement, continuous telemetry monitoring and availability of cardiac
resuscitation.

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Dronedarone
Drug Interaction
Dronedarone is less lipophilic than Amiodarone has a much smaller volume of distribution,
and has an elimination half life of 13-19 hours. This stands in contrast to amiodarone’s half life
of several weeks. As a result of these pharmacokinetic characteristics, Dronedarone dosing may
be less complicated than Amiodarone.
Mechanism of Action
Dronedarone has been termed as “multichannel blocker” however it is under which channel
play a pivotal role in its success. Thus Dronedarone’s action at the cellular level are
controversial with most studies suggesting an inhibition in multiple outward potassium
currents including rapid delayed rectifier, and Ach activated inward rectifier. It is also believed
to reduce inward rapid Na current and L type Ca channels. The reduction in K current in some
studies was shown to be due to the inhibition of k-Ach channel associated GTP-binding
proteins. Reduction of K+ current by 69% led to increased AP duration and increased effective
refractory periods, thus shown to suppress pacemaker potential of the SA node and return
patients to a normal heart rhythm.
Adverse Effect
 Permanent AF (Patients in whom normal sinus rhythm will not or can’t be restored)
 Recently decompensated heart failure requiring hospitalization or class IV heart failure.
 Second or third degree AV block or sick sinus syndrome (expect when used in
conjunction with a functioning pacemaker)
 Bradycardia
 Liver or lungs toxicity
 Hypersensitivity to Dronedarone
 PR interval exceeding 280ms