ANTI ARRHYTHMIC DRUGS

Dr uzma riaz
 Rhythm
• Regular reccurring motion is termed as
rhythm
• Normal H.R-60-100bpm
• 100-150 simple tachycardia
• 150-250 paroxysmal tachycardia
• 250-350 flutter
• 350-450 fibrillation
 Normal cardiac impulse
• Originates in S.A node at frequency of 60-
100bpm
• Spreads through atria
• Enters A.V node(delay of 0.15secs)
• Impulse propagates to His-Purkinjie system
and invades all parts of the ventricles
dia
 Arrhythmias
• Irregular heartbeat
• Too fast(tachycardia)
• Too slow(bradycardia)
• Too early(premature contraction)
• Toorapidly(fibrillation)
 Cont…
• Arrhythmias consists of cardiac
depolarization that deviate from the normal
conducting pathway in one or more aspects.
• Abnormality in the site of origin of impulse
• Rate or regularity
• conduction
 Mechanism of arrhythmias

• Abnormalities in impulse formation

• Abnormalities of impulse conduction

 CLASSIFICATION
• There are four classes of antiarrthmic drugs:
• Class1 (1a,1b,1c)
• Class2
• Class3
• Class3
• Class4
• Misc
ANTI ARRTHYMIC DRUGS.
 Specific antiarrhythmic drugs
• 1. Class 1:Na Channel blockers:
• action is sodium channel blockade.
• Subclasses of this action reflect effects on the action
potential duration (APD) and the kinetics of sodium channel
blockade.
• Drugs with class 1A action prolong the APD and dissociate
from the channel with intermediate kinetics
• Drugs with class 1B action shorten the APD in some tissues of
the heart and dissociate from the channel with rapid kinetics
• Drugs with class 1C action have minimal effects on the APD
and dissociate from the channel with slow kinetics.
 Cont…
• 2. Class 2:SYMPATHOLYTICS:
mode of action is sympatholytic.
• Drugs with this action reduce -adrenergic activity
in the heart.
• 3. Class 3: action is manifest by prolongation of
the APD.
• Most drugs with this action block the rapid
component of the delayed rectifier potassium
current, IKr.
 Cont…
• 4. Class 4 Drugs: action is blockade of the
cardiac calcium current.
• This action slows conduction in regions where
the action potential upstroke is calcium
dependent, eg, the sinoatrial and
atrioventricular nodes
 PROCAINAMIDE (SUBGROUP 1A)

• Cardiac Effects
• Blocks sodium channels
• Slows the upstroke of the action potential
• Slows conduction
• Prolongs QRS duration of the ECG.
• Prolongs action potential duration by
nonspecific blockade of K channels.
 Cont…
• Less effective than quinidine in suppressing
abnormal ectopic pacemaker activity
• More effective in blocking sodium channels in
depolarized cells.
• Direct depressant actions on SA and AV nodes
that are only slightly counterbalanced by
drug-induced vagal block.
 Extracardiac Effects

• Ganglion-blocking properties.
• This action reduces peripheral vascular resistance
hypotension, with intravenous use.
• Less peripheral vascular effects than quinidine.
• Hypotension is associated with excessively rapid
procainamide infusion or the presence of severe
underlying left ventricular dysfunction
 Toxicity
• Excessive action potential prolongation
• QT interval prolongation
• Induction of torsade de pointes arrhythmia
and syncope.
• Excessive slowing of conduction.
• New arrhythmias can be precipitated.
 Cont…
• Lupus like syndrome(arthralgia and arthritis).
• Pleuritis
• Pericarditis.
• Renal lupus
• Serologic abnormalities (eg, increased
antinuclear antibody titer)
 Cont…
• Nausea
• Diarrhea
• Rash
• Fever
• Hepatitis
• Agranulocytosis
 Therapeutic Use
• Effective against most atrial and ventricular
arrhythmias.

• Procainamide is the drug of second or third

choice (after lidocaine or amiodarone) in most
coronary care units for the treatment of
sustained ventricular arrhythmias associated
with acute myocardial infarction.
 Quinidine (Subgroup 1A)
• Cardiac Effects
• Actions similar to those of procainamide
• Slows upstroke of action potential and
conduction
• Prolongs QRS duration by blockade of Na
channels.
• Prolongs action potential duration by
blockade of several K channels.
 Cont…
• Toxic cardiac effects include excessive QT
interval prolongation and induction of torsade
de pointes arrhythmia.

• Toxic concentrations produce excessive Na

channel blockade with slowed conduction
throughout the heart.
 Extracardiac Effects
• Diarrhea, nausea, and vomiting.
• A syndrome of headache, dizziness, and tinnitus
(cinchonism) is observed at toxic drug
concentrations.
• Idiosyncratic or immunologic reactions:
• thrombocytopenia
• hepatitis
• angioneurotic edema
• fever
 DISOPYRAMIDE (SUBGROUP IA)
• Cardiac Effects
• Effects similar to those of procainamide and
quinidine.
• Its cardiac antimuscarinic effects are even more
marked than those of quinidine.
• Therefore, a drug that slows atrioventricular
conduction should be administered with
disopyramide when treating atrial flutter or
fibrillation.
 Therapeutic Use
• Effective in a variety of supraventricular
arrhythmias.

• It is approved only for the treatment of

ventricular arrhythmias.
 Toxicity
• Due to its negative inotropic effect,
disopyramide may precipitate heart failure de
novo or in patients with preexisting
depression of left ventricular function.

• It should not be used in patients with heart

failure.
 Cont…
• Disopyramide's atropine-like activity accounts
for most of its symptomatic adverse effects:
• Urinary retention in male patients with BPH
• Dry mouth
• Blurred vision
• Constipation
• Worsening of preexisting glaucoma.
 LIDOCAINE (SUBGROUP 1B)
• Has a low incidence of toxicity
• High degree of effectiveness in arrhythmias
associated with acute MI.
• It is used only by the intravenous route.
 Cardiac Effects
• Lidocaine blocks activated and inactivated
sodium channels with rapid kinetics.

• Inactivated state block ensures greater effects

on cells with long action potentials:Purkinje
and ventricular cells, compared with atrial
cells.
 Cont…
• The rapid kinetics at normal resting potentials
result in recovery from block between action
potentials and no effect on conduction.
• The increased inactivation and slower
unbinding kinetics result in the selective
depression of conduction in depolarized cells.
• Little effect on ECG in normal sinus rhythm
 Therapeutic Use
• Ventricular tachycardia
• Prevention of ventricular fibrillation after
cardioversion in the setting of acute ischemia.
 Toxicity
• Least cardiotoxic of the currently used Na
channel blockers.
• In large doses,in patients with preexisting
heart failure, lidocaine may cause
hypotension—partly by depressing myocardial
contractility.
 Cont…
• Neurologic:
• Paresthesia
• Tremor
• Nausea of central origin
• Lightheadedness
• Hearing disturbances
• Slurred speech
• Convulsions( elderly, increase dose).
 MEXILETINE (SUBGROUP 1B)
• Orally active congener of lidocaine.
• Electrophysiologic and antiarrhythmic actions
are similar to those of lidocaine.
 Cont…
• Used in the treatment of ventricular
arrhythmias
• Significant efficacy in relieving chronic pain,
especially pain due to diabetic neuropathy
and nerve injury.
 Adverse effects
• Neurologic:
• Tremors
• Blurred vision
• Lethargy
• Nausea
 Flecainide (Subgroup 1C )
• Flecainide is a potent blocker of Na and K
channels with slow unblocking kinetics.
• It does block certain K channels, it does not
prolong the action potential or the QT
interval.
• Used in supraventricular arrhythmias.
• Effective in suppressing premature ventricular
contractions
 Adverse effects
• May cause severe exacerbation of arrhythmia
even to normal doses in pts. with prexisting
ventricular tachyarrhythmais,MI,ventricular
ectopy
 PROPAFENONE (SUBGROUP 1C)
• Structural similarity to propanolol
• Has weak beta blocking activity
• Action is similar to quinidine,but not prolong
action potential
• Adverse effects are :
• metallic taste
• Constipation
• Arrhythmia exacerbation can also occur.
Beta-Adrenoceptor–Blocking Drugs (Class 2)

• Cardiac Effects
• Propranolol and similar drugs have
antiarrhythmic properties by virtue of their -
receptor–blocking action.

• These agents can prevent recurrent

infarction,sudden death in patients recovering
from acute MI
 Cont…
• Esmolol is a short-acting blocker used
primarily as an antiarrhythmic drug for
intraoperative and other acute arrhythmias.
 AMIODARONE(CLASS 3)
• Oral and intravenous use to treat serious
ventricular arrhythmias.

• Highly effective for the treatment of

supraventricular arrhythmias such as atrial
fibrillation.
 Cardiac Effects
• Prolongs APD (and the QT interval on the ECG).

• Its action potential-prolonging action reinforces

this effect.

• Amiodarone also has weak adrenergic and calcium

channel blocking actions.
• Consequences of these actions include slowing of
the heart rate and AV nodal conduction.
 Extracardiac effects
• Peripheral vasodilation(prominent after I.V
administration)
 Toxicity
• Symptomatic bradycardia
• Heart block in patients with preexisting sinus
or atrioventricular node disease.
• Dose-related pulmonary toxicity.
• Abnormal LFTs and hepatitis.
 Therapeutic Use
• Effective in maintaining normal sinus rhythm
in patients with atrial fibrillation.

• Prevention of recurrent ventricular

tachycardia.

• As adjuvant therapy to decrease the

frequency of uncomfortable cardioverter-
defibrillator discharges
 Toxicity
• Tissue deposits in heart,lungs
• Skin deposits photodermatitis ,gray-blue
skin discoloration in sun-exposed areas, eg,
the malar regions
• optic neuritis
• Amiodarone blocks the peripheral
conversion of (T4 ) to (T3).
• Hypothyroidism or hyperthyroidism.
 Cont…
• Inhibits several cytochrome
enzymestoxicity of statins,digoxin and
warfarin
 SOTALOL
• Adrenergic receptor-blocking (class 2) and
action potential prolonging (class 3) actions .

• Approved for treatment of life-threatening

ventricular arrhythmias and maintenance of
sinus rhythm in patients with atril fibrillation.
 Cont…
• Approved for treatment of supraventricular
and ventricular arrhythmias in the pediatric
age group.
 Calcium Channel-Blocking Drugs (Class 4)

• VERAPAMIL
• Cardiac Effects
• Verapamil blocks both activated and
inactivated L-type calcium channels.

• Effect is more marked on sinoatrial and

atrioventricular nodes.
 Cont…
• Extracardiac Effects

• Verapamil causes peripheral vasodilation,

which may be beneficial in hypertension and
peripheral vasospastic disorders.
 Therapeutic Use
• Supraventricular tachycardia
• Occasionally useful in ventricular arrhythmias
 Toxicity
• Atrioventricular block
• Constipation
• lassitude
• Nervousness
• peripheral edema.
 DILTIAZEM
• Diltiazem has efficacy in the management of
supraventricular arrhythmias, including rate
control in atrial fibrillation.

• A/E:

• hypotension or bradyarrhythmias.
 Miscellaneous Antiarrhythmic
Agents
• ADENOSINE
• Mechanism & Clinical Use
• Its mechanism of action involves activation of
an inward rectifier K+ current and inhibition of
calcium current.

• Results of these actions are marked

hyperpolarization and suppression of calcium-
dependent action potentials.
 Toxicity
• Flushing
• Headache,
• Hypotension
• Nausea
• Paresthesias.
 MAGNESIUM
• Used for patients with digitalis-induced
arrhythmias who were hypomagnesemic,
magnesium infusion has been found to have
antiarrhythmic effects in some patients with
normal serum magnesium levels.
 Cont…
• Magnesium is recognized to influence Na+,K+
ATPase, sodium channels, certain potassium
channels, and calcium channels.
• Magnesium therapy appears to be indicated in
patients with digitalis-induced arrhythmias if
hypomagnesemia is present.
• It is also indicated in some patients with torsade de
pointes even if serum magnesium is normal.
 POTASSIUM
• Effects of increasing serum K+ can be
• (1) a resting potential depolarizing action
• (2) a membrane potential stabilizing action
• the latter caused by increased potassium
permeability.
• Hypokalemia results in an increased risk of early
and delayed afterdepolarizations, and ectopic
pacemaker activity, especially in the presence of
digitalis.
• Hyperkalemia depresses ectopic pacemakers
(severe hyperkalemia is required to suppress
the sinoatrial node) and slows conduction.