Antidysrhythmics

Dysrhythmia

 Any deviation from the normal rhythm of

the heart

Antidysrhythmics

 Drugs used for the treatment and

prevention of disturbances in cardiac
rhythm
Resting Membrane Potential:
RMP
 This difference in the electronegative
charge.
 Results from an uneven distribution of ions
(sodium, potassium, calcium) across the cell
membrane.
 An energy-requiring pump is needed to
maintain this uneven distribution of ions.
 Sodium-potassium ATPase pump
Heart and Conduction System
Resting Membrane Potential
of a Cardiac Cell
The Active Membrane cell
Action Potential

 A change in the distribution of ions causes cardiac

cells to become excited.

 The movement of ions across the cardiac cell’s

membrane results in the propagation
of an electrical impulse.

 This electrical impulse leads to contraction

of the myocardial muscle.

Four Phases
 The SA node and the Purkinje cells each have
separate action potentials.
Action Potentials: Phases
(SA Node)
Action Potentials: Purkinje Fiber

Non-pacemaker action potential

Phase 1: partial
repolarization
Due to rapid efflux of
K+

Phase 2: plateu
Phase 0: fast Due to Ca++
upstroke influx
Due to Na+
influx
Phase 3:
repolarization
Due to K+ efflux

Phase 4: resting
membrane
potential

NThe slope of phase 0 = conduction velocity

Also the peak of phase 0 = Vmax
Action Potentials: Intervals

 It is also called absolute

refractory period (ARP) :

 In this period the cell can’t

be excited

 Takes place between phase

0 and 3
 Arrhythmia

If the arrhythmia
arises from atria,
SA node, or AV
node it is called
supraventricular
arrhythmia

If the arrhythmia
arises from the
ventricles it is
called ventricular
arrhythmia
Factors precipitate
arrhythmias
• May includes :
• Ischemia, hypoxia, electrolytes
disturbance, excessive
catecholamines exposure , drug
toxicity.
Mechanisms of
arrhythmias

1- Disturbances in impulse formation.

• Vagal stimulation or β- receptor blocking

drugs slow normal pacemaker .

• Acceleration of pacemaker by
hypokalemia or β- adrenoceptor stimulants.

• Development of ectopic pacemakers.-­ 

2- Disturbances in impulse conduction

• May result from block ( nodal block or

bundle branch block .
• Reentry :
• circus movement
In which one impulse reenters and
excites areas of the heart more than
ones.
• Some forms of reentry are anatomical
in shape as in Wolff- Parkinson –White
syndrome.
 Abnormal Heart Rhythms
Arrhythmia BPM
tachycardia 150-250
bradycardia <60
atrial flutter 200-350
atrial fibrilation >350
prem. atrial cont. variable
prem. vent. cont. variable
vent. fibrilation variable
Premature
Ventricular
Contraction
Pharmaceutical Treatment
Pharmacologic Rationale & Goals

 Aimed at preventing life-threatening conditions by

The ultimate
restoring goal of antiarrhythmic drug
normal rhythm
therapy:
oActs on the normal
Restore myocardium where
sinus the impulses
rhythm are
and conduction
conducted
o Prevent more serious and possibly lethal
arrhythmias
 Some fromheart
drugs influence occurring.
rate, others influence
Antiarrhythmic
movement of ions (Nadrugs are used to:
and Ca)
decrease conduction velocity
change the duration of the effective refractory
period (ERP)
suppress abnormal automaticity
Vaughan Williams Classification

 Class 1
 Class Ia
 Class Ib
 Class Ic

 Class II
 Class III
 Class IV
 Other
Vaughan Williams Classification

Class I
 Membrane-stabilizing agents
 Fast sodium channel blockers
 Divided into Ia, Ib, and Ic agents, according
to effects
Vaughan Williams Classification

Class I
moricizine
 General Class I agent
 Has characteristics of all three subclasses
 Used for symptomatic ventricular and life-
threatening dysrhythmias
 Vaughan Williams Classification
Class Ia
quinidine, procainamide, disopyramide
 Block sodium channels
 Delay repolarization
 Increase the APD
 Used for atrial fibrillation, premature atrial
contractions, premature ventricular contractions,
ventricular tachycardia, Wolff-Parkinson-White syndrome
 Vaughan Williams Classification

Class Ib
tocainide, mexiletine, phenytoin, lidocaine
 Block sodium channels
 Accelerate repolarization
 Decrease the APD
 Used for ventricular dysrhythmias only
(premature ventricular contractions, ventricular
tachycardia, ventricular fibrillation)
Vaughan Williams Classification

Class Ic
encainide, flecainide, propafenone
 Block sodium channels (more pronounced
effect)
 Little effect on APD or repolarization
 Used for severe ventricular dysrhythmias

 May be used in atrial fibrillation/flutter

Vaughan Williams Classification
Class II
Beta blockers: atenolol, esmolol, petaprolol,
propranolol
 Reduce or block sympathetic nervous system
stimulation, thus reducing transmission of impulses in
the heart’s conduction system
 Depress phase 4 depolarization
 General myocardial depressants for both
supraventricular and ventricular dysrhythmias
 Vaughan Williams Classification
Class III (potassium channe;l blocker): amiodarone, bretylium, sotalol,
ibutilide

 Increase APD

 Prolong repolarization in phase 3

 Used for dysrhythmias that are difficult to treat

 Life-threatening ventricular tachycardia or fibrillation, atrial fibrillation or

flutter—resistant to other drugs

 Sustained ventricular tachycardia

 Ibutilide is specifically indicated only for treatment of recent-onset atrial

fibrillation and flutter.

 Patients taking amiodarone must have baseline and serial pulmonary

function tests in order to monitor for potential pulmonary toxicity.
Vaughan Williams Classification

Class IV
verapamil, diltiazem
 Calcium channel blockers
 Depress phase 4 depolarization
 Used for paroxysmal supraventricular
tachycardia; rate control for atrial
fibrillation and flutter
 Vaughan Williams Classification

Other Antidysrhythmics
digoxin, adenosine
 Have properties of several classes and are
not placed into one particular class
 Antidysrhythmics
Digoxin

 Cardiac glycoside

 Inhibits the sodium-potassium ATPase pump

 Positive inotrope—improves the strength of cardiac contraction

 Allows more calcium to be available for contraction

 Used for CHF and atrial dysrhythmias

 Monitor potassium levels, drug levels, and

for toxicity
 Antidysrhythmics

adenosine (Adenocard)
 Slows conduction through the AV node
 Used to convert paroxysmal supraventricular tachycardia to
sinus rhythm
 Very short half-life
 Only administered as fast IV push
 May cause asystole for a few seconds
 Other side effects minimal
Antidysrhythmics: Side Effects

ALL antidysrhythmics can cause dysrhythmias!!

 Hypersensitivity reactions
 Nausea
 Vomiting
 Diarrhea
 Dizziness
 Blurred vision
 Headache
 Principles in the clinical use of
ANTIARRHYTHMIC AGENTS
 Eliminate the cause. Precipitating factors must be
recognized and eliminated if possible (hypoxia or
electrolyte abnormalities (especially hypokalemia or
hypomagnesemia), hyperthyroidism or cardiac disease

 Make a firm diagnosis. A firm arrhythmia diagnosis

should be established. For example, the misuse of
verapamil in patients with ventricular tachycardia
mistakenly diagnosed as supraven- tricular tachycardia
can lead to catastrophic hypotension and cardiac arrest.
 Principles in the clinical use of
ANTIARRHYTHMIC AGENTS
 Determine the baseline condition. Underlying heart
disease is a critical determinant of drug selection for a
particular arrhythmia in a particular patient.

 Question the need for therapy. The mere identification

of an abnormality of cardiac rhythm does not
necessarily require that the arrhythmia be treated.

 consider benefit & risk : reduction of arrhythmia-

related symptoms vs he risk of an adverse reaction is
clearly related to high dosages or plasma
concentrations.
 1st: Reduce thrombus formation by using anticoagulant warfarin

2nd: Prevent the arrhythmia from converting to ventricular arrhythmia:

First choice: class II drugs:
•After MI or surgery
•Avoid in case of heart failure

Second choice: class IV

Third choice: digoxin

•Only in heart failure of left ventricular dysfunction

3rd: Conversion of the arrhythmia into normal sinus rhythm:

Class III:
IV ibutilide, IV/oral amiodarone, or oral sotalol

Class IA:
Oral quinidine + digoxin (or any drug from the 2nd step)
Use direct current in
Class IC: case of unstable
Oral propaphenone or IV/oral flecainide hemodynamic patient
 Premature ventricular beat (PVB)
First choice: class II
•IV followed by oral
•Early after MI Avoid
using
Second choice: amiodarone class IC
after MI
↑
mortality

First choice: Lidocaine IV

•Repeat injection

Second choice: procainamide IV

•Adjust the dose in case of renal failure

Third choice: class III drugs

•Especially amiodarone and sotalol
 (IA, IC, class III) torsades de pointes.

Classes II and IV bradycardia (don’t combine the two)

In atrial flutter use (1st ↓impulses from atria to ventricular to

prevent ventricular tachycardia)
1. Class II
2. Class IV
3. Digoxin.
2nd convert atrial flutter to normal sinus rhythm use:
1. Ibutilide
2. Sotalol
3. IA or IC.
If you use quinidine combine it with digoxin or β blocker
(because of its anti muscarinic effect)

Avoid IC in myocardial infarction because it ↑ mortality