CARDIAC

ARRYTHMIAS

Definition

 Cardiac arrythmias results from alterations in the orderly

sequence of depolarisation followed by repolarization in the heart.

 Cardiac arrythmias may result in alterations in heart rate or

rhythm and arise from alterations in simple generation or
conduction.
ELECTROPHYSIOLOGY – CARDIAC RHYTHM
 Cardiac Action Potential

• Divided into five phases (0,1,2,3,4) in non nodal

tissues

• Phase 0 – rapid depolarization

• Phase 1 – early repolarization

• Phase 2 – plateau phase

• Phase 3 – rapid repolarization

• Phase 4 – resting phase, diastolic depolarization

 Contraction of
ventricles

Repolarization
Contraction of ventricles
of atria
MECHANISM OF ARRHYTHMIAS
 Abnormal impulse
generation

• Depressed automaticity of SA node

• Enhanced automaticity of SA node

• Impulse from ectopic loci

– Ischemia, digitalis, catecholamine's, acidosis,

hypokalaemia

– Less (-) resting membrane potential

– More (-) TP
 Triggered Activity

• Extra abnormal depolarisation

- Due to abnormal intracellular Ca2+ regulation

- During or immediately after phase 3

- After depolarisation may be categorized in to

- Early after depolarisation

- Delay after depolarisation

 Conduction Block

• Due to depression of impulse conduction at AV node & bundle

of His, due to vagal influence or ischemia.

• Types :

– 1st degree heart block – slowed conduction

– 2nd degree block – some supraventricular complex not

conducted

– 3rd degree block – no supraventricular complex are

conducted
 Important cardiac arrhythmias

– premature beats

– Due to abnormal automaticity or impulse arising from

ectopic focus.

– Sudden onset of AT 150-200/min

– Due to circus movement type of Re-entry or accessory

pathway

– 200-300 / min

– Due to re entry circuit in right atrium

 Atrial fibrillation

• 350-550/min
• Due to electrophysiological inhomogenesity
of atrial fibers.
 – 4 or more consecutive ventricular extrasystoles

– Due to either discharge from ectopic focus or reentry

circuits

– Polymorphic VT with rapid asynchronous complex,

twisting along the baseline on ECG with long QT interval

• Grossly irregular, rapid & fractionated action of ventricles –

resulting in incoordinated contraction of ventricles with loss
of pumping function.
 Possible mechanisms of antiarrhythmic drugs

1. Suppressing the Automaticity

– ↓ Rate of phase 0

– ↓ Slope of phase 0

– Duration ERP ↑

– TP less negative

– Resting membrane potential more negative

2. Abolishing reentry

– Slow conduction

– ↑ ERP
 Pharmacological
goals

 The ultimate goal of antiarrhythmic drug therapy:

o Restore normal sinus rhythm and conduction

o Prevent more serious and possibly lethal arrhythmias from

occurring.

 Antiarrhythmic drugs are used to:

o Decrease conduction velocity

o Change the duration of the effective refractory period (ERP)

o Suppress abnormal automaticity

Have moderate K+ channel
blockade
Class I

IA IB IC

They act on open Na+ They ↓ automaticity in non-nodal

channels or tissues (atria, ventricles, and purkinje
inactivated only fibers)

Use dependence
 IA

Quinidine Procainamide Disopyramide Moricizine

 Slowing the rate of rise in phase 0

 They prolong action potential & ERP
 ↓ the slope of Phase 4 spontaneous depolarization
 ↑ QRS & QT interval
 QUINIDINE
 Antimalarial, antipyretic, skeletal muscle relaxant and atropine like
action.

Mechanism of action

• Quinidine binds to open and inactivated sodium channels

and prevents sodium influx, slowing the rapid upstroke during
phase 0.
• It also decreases the slope of phase 4 spontaneous
depolarization and inhibits potassium channels.
 C/I
A/E
AV block
• Diarrhoea

• “Cinchonism” – tinnitus, QT prolongation

- Torsades de pointes
vertigo,

headache, nausea & blurred

Digoxin, enzyme
vision. inducer

• 200-400 mg orally tds

Myasthenia gravis
 Uses

• Ventricular tachyarrythmias
• Used in the termination of ventricular tachycardia

Drug interactions

• Quinidine can interact the plasma concentration of digoxin,

which may in turn lead to signs and symptoms of digitalis
toxicity.
• Cimitidine increases hepatic metabolism of quinidine
 PROCAINAMIDE

 Procaine derivative, quinidine like action

Mechanism of action

 Procainamide binds to open and inactivated Na+ channels and

prevents sodium influx, slowing the rapid upstroke during
phase 0

A/E  Hypotension
 Hypersensitivity reaction
  Premature atrial contractions
Uses  Paroxysmal atrial tachycardia

Dose: 1-1.5g rate of 20-50mg/min

C/I Drug Interactions

• Procainamide • Cimitidine inhibits the

hypersensitivity metabolism of procainamide
• Bronchial asthma
 DISOPYRAMIDE

Mechanism of action

Disopyramide produces a negative ionotropic effects

that is greater than weak effect exerted by quinidine and
procainamide, and unlike the latter drugs, disopyramide
causes peripheral vasoconstriction.

• Myocardial depression
A/E
• Urinary retention
• Constipation
 Uses
• ventricular tachycardia
• AF & AFI

C/I - CHF

Disopyramide
Drug Interactions

 In the presence of phenytoin, the metabolism of disopyramide

is increased and the accumulation of its metabolite is also
increased, there by increasing the probability of
anticholinergic properties.
 IB

Lidocaine Mexiletine Phenytoin

 They shorten Phase 3 repolarization

 ↓ the duration of the cardiac action potential
 Prolong phase 4
 LIDOCAINE

the duration of action potential decreases

Mechanism of action

 It shorten phase 3 repolarization and decreases the

duration of action potential

A/E
Uses

• Drowsiness
• VA
• Slurred speech
• Digitalis toxicity
• Confusion and convulsions
C/I
Drug interactions
 Lidocaine is contraindicated
in the presence of second and
• Proponolol increases its
third degree heart block, since
toxicity.
it may increase the degree of
• The myocardial depressant
block and can abolish the effect of lidocaine is enhanced
idioventricular Pacemaker by phenytoin administration.
responsible for maintaining
the cardiac rhythm.
 IC

flecainide Encainide Propafenone moricizine

 Markedly slow phase 0 depolarization

 Slow conduction in the myocardial tissue
 Minor effects on the duration of action potential
and ERP
 Reduce automaticity by increasing threshold potential
rather than decreasing slope of Phase 4 depolarization.
 FLECAINIDE &
ENCAINIDE

Mechanism of action

 Flecainide suppresses phase 0 upstroke in purkinje

and myocardial fibers.
 This causes marked slowing of conduction in all cardiac
tissues, with a minor effect on the duration of the action
potential and refractoriness.
 Automaticity is reduced by an increase in the threshold
potential rather than a decrease in the slope of phase
4 depolarization
 Proarrhythmogenic efffect on patients with
coronary artery disease

 Use- ventricular arrhythmia

 A/E – torsades de point, visual disturbances &

headache

 Digoxin toxicity

 C/I- cardiogenic shock

 PROPAFENONE

 Structural similarities with propranolol

 C/I – Heart failure

 A/E – proarrhythmogenic effect, metallic

taste & constipation

 150-200mg at 8 hourly

 Uses – VT & supra ventricular arrhythmias.

 MORICIZINE

 Has all three subclass properties

 Less proarrhythmogenic effect
 Used in ventricular arrhythmias
 200-400mg orally at 8hourly
 Class II drugs – Propranolol, Metoprolol, Esmolol,
Acebutolol

Depress phase 4 depolarization

depress automaticity

prolong AV conduction

↑ ERP

Prolong PR interval

 HR

 contractility
 PROPRANOLOL
A/E
Mechanism of action
Hypoglycemia
 Propanolol decreases the slope of (infants)
Asthma
phase 4 depolarization and Branchospasm
other ectopic foci.
Prolong the ERP of A-V node. C/I
Uses Asthma
 AF Bradycardia
Digitalis-induced arrythmias Severe CHF
 ESMOLOL
 Esmolol is a short-acting i.v administered β1-selective
adrenoreceptor blocking agent.
 It doesn’t posses membrane-stabilizing activity.

C/I
Uses
A/E  Asthma
 Hypotension  Supraventricular
 Sinus bradycardia
 Nausea tachyarrythmias
 A-V block
 Headache  Severe CHF
 Dyspnea
 Uses

Sympathetically mediated
arrhythmia Sinus tachycardia

Supraventricular arrhythmia –
Ventricular arrhythmia – QT
AF / PSVT
 Class III

Amiodarone Bretylium Sotalol

• K+ channel blockers
• AP / ERP without affecting
phase 0 / 4
• Prolong QT & PR
 Amiodarone

LD-150mg slow
Iodine –  Arrhythmic IV
containing death in post MI MD-1mg/min
for 6hrs

A/E – heart block,

Block K+ Na+ , Uses =VF, VT pulmonary,
hepatitis, dermatitis,
Ca++ & β & AF corneal deposits &
thyroidism

Interaction –
HR & AV digoxin,
nodal QT prolongation
diltiazem &
conduction quinidine
 Sotalol Like – Amiodarone

• Non cardioselective blocker

• Has both class II & class III
actions  Arrhythmic
death in post MI
• Oral dose 80mg twice daily
• Proarrhythmic effect
• C/I - hypokalaemia
Uses =VF, VT &
AF
Drug interactions
Drug with inherent
QT-Interval prolonging activity may A/E= fatigue,
enhance the class 3 effects of sotalol. Headache, chest
pain
 Class IV

Verapamil Diltiazem

 Mechanism

• Block L-type calcium channels.

•  Rate of phase 4 in SA / AV node

• Slow conduction – prolong ERP

• Phase 0 upstroke 
Verapamil

• Stronger action on heart than smooth muscle

• Used in supraventricular arrhythmia

• 80-120mg three times a day

• A/E – ankle oedema, constipation

• C/I – AV block, LVF, hypotention & WPW

• It  digoxin toxicity

Diltiazem

• Mixed action
• Oral dose 30-90mg 6hourly
Adenosine

Naturally occurring nucleoside

Adenosine receptors – open GP-K+ & inhibits nodal

conduction

Used in Reentry circuit, PSVTs & SVT

Ultra short t1/2 (10-20 sec)

A/E – facial flushing, short breath, bronchospasm, metallic

taste

Dipyridamole  it’s action

3mg IV bolus
Magnesium

Na+/K+ATPase, Na+, K+ & Ca++

VT, digitalis-induced & torsades de point

Potassium

Normal –  conduction,  ERP &  automaticity

Hypokalaemia – EAD & DAD

 Drugs that prolong QT interval

Antiarrhythimcs Quinidine
Procainamide
Disopyramide
Propafenone
Amiodarone
Antimicrobials Quinine
Mefloquine
Artemisinin
Sparfloxacin & gatifloxacin
Antihistaminics Terfenadine
Astemizole
Ebastine
Antidepressants Amitryptylline
Antipsychotics Thioridazine
Risperidone
Prokinetics Cisapride