CARDIAC ARRHYTHMIAS

Disordered Cardiac Rhythm

Can be precipitated by several factors including:
3. Hypoxia
4. Electrolyte imbalance
5. Acidosis or alkalosis
6. Autonomic stimulation
7. Drug toxicity (eg. Cardiac glycosides)
8. Myocardial infarction
A. Disturbances of impulse formation
 The main problem is the development of an
ectopic focus. They are usually classified
according to the location.
• Supraventricular arrhythmias
ii. Atrial flutter:
iii. Atrial fibrillation:
iv. Supra ventricular paroxysmal
tachycardia

2. Ventricular arrhythmias:
viii. Ventricular fibrillation
ix. Paroxysmal tachycardia
B. Disturbance of impulse conduction

i. Heart block  conduction block in the AV node

and the bundle of His.

ii. Re-entrant arrhythmias – occurring in damaged

portions of the myocardium.
Functionally Defined Reentry
Conditions for re-entry:
2. there must be an obstacle to conduction
3. conduction block must be unidirectional
4. conduction time must exceed the effective
refractory period
Aim of therapy
 Reduce pacemaker activity.
 Modify critically impaired conductions.
ANTIARRHYTHMIC DRUGS
Drugs used in the treatment of arrhythmias
Class I: Drugs that block sodium channels
 reduce excitability of the non-nodal regions.

Class II: β-adrenoceptor antagonists (would also

include drugs that interfere with adrenergic
neurotransmission eg. neurone blockers).

Class III: Drugs that prolong the effective refractory period.

Class IV: Calcium channel antagonists.

Four Ways by Which Antiarrhythmic Drugs Reduce
Spontaneous Discharge in Autonomic Tissues
Class 1A. QUINIDINE Procainamide

 Drugs in this class combine with sodium

channels in the activated state.

 Reduce rate of rise of phase O depolarization.

 ↓Automaticity
 Antivagal activity  which can increase the
sinus rate.
 Reduce slope of phase 4 depolarization.
 ↓Excitability, responsiveness and conduction in
cardiac tissue.
 Increase action potential duration.
 Prolongs effective refractory period.
 α- adrenergic blocking effects  hypotension.
Pharmacokinetics
Very well absorbed after oral administration
90% bound to plasma protein metabolized in the
liver and excreted in the urine.
(Procainamide 20% bound protein and
minimally metabolized).
Uses
 All forms of atria and ventricular arrhythmias.
 Re-entrant arrhythmias.
 Digitalis-induced arrhythmias.
Side Effects
 Cardiotoxicity, Hypotension
 GIT symptoms  nausea, vomitting, diarrhoea.
 Hypersensitivity reactions – namely
anaphylactic reactions, thrombocytopenia,
rashes, systematic lupus erythematosus
(Procainamide).
CLASS 1B
Eg. Lidocaine, Phenytoin, Mexiletine

 Combines with Na+ channels in open and

refractory state.

 Reduce rate of rise of phase O depolarization.

 ↓Automaticity
 Reduce slope of phase 4 depolarization.
 ↓Excitability, responsiveness and conduction
in cardiac tissue.
 No significant action on the duration of AP
in atrial fibres.
 Shortens the duration of AP in Purkinje fibres
and ventricular muscle.
Pharmacokinetics
 Lidocaine is administered intravenously and
intramuscularly (significant 1st – pass
metabolism in the liver, so not effective orally)
others effective orally.

 Metabolized in the liver and excreted in the urine.

USES
 Lidocaine is used almost exclusively for
ventricular arrhythmias.

 Re-entrant arrhythmias.

 To prevent (or counteract) digitalis-induced

tachyarrhythmias.
Side Effects
Lidocaine

 CNS at high concentration – drowsiness

 Decreased hearing.
 Disorientations
 Muscle twitching
 Convulsion of respiratory arrest
 Nausea, ataxia, vomiting and anorexia
 Agranulocytosis, bone marrow depression.
CLASS 1C
Eg. Flecainide, Propafenone
 High affinity for Na+ channels, dissociate very slowly.
 ↓Automaticity
 Reduce slope of phase 4 depolarization.
 ↓Excitability, responsiveness and conduction
in cardiac tissue.
 No effect on the duration of AP
 Prolongs effective refractory period.
 Negative inotropic effect.
 Increase threshold potential thus reducing automaticity.
Pharmacokinetics
 Flecainide can be administered i.v. or orally.
No first-pass metabolism in the liver. Bound to
plasma-proteins (>75%). Excreted partly
metabolised and partly unchanged.
 Highly concentrated in the cardiac tissue
(about 10 times the plasma concentration).
Therapeutic Uses
 Life threatening ventricular arrhythmias.
 Re-entrant arrhythmias.
 Reserved for patients in whom other
antiarrhythmic agents are poorly tolerated
or not effective.
Side Effects
 Cardiac arrest
 Dizziness
 Visual disturbances
 Granulocytopenia
CLASS II
These are drugs that interfere with
sympathetic stimulation of the heart.
β-adrenoceptor antagonists
eg. Propranolol atenolol etc.
 Reduce slope of phase 4-depolarization.
 Increase effective refractory period.
 Decrease conduction velocity through the
AV node at high concentrations.
 Local anaesthetic action (Class I) – membrane
stabilizing effect.
 Inhibits Ca++ translocation (Class IV).
Adverse effects
 Bradycardia
AV Block
 Vasodilatation (rapid infusion)
 Withdrawal symptoms
(sudden withdrawal following chronic
administration).
Class III
Eg. Bretylium, Amiodarone, Sotalol.
 Decrease slope of phase 4 depolarization.
 They prolong the duration of the membrane
action potential (no effect on phase O or
resting membrane potential).
 Act by blocking K+ channels
(reduce K+ conductance).
 Amiodarone relaxes smooth muscle.
Used in
2) Supraventricular tachycardia.
3) Preventing ventricular tachyarrhythmias
refractory to conventional antiarrhythmic therapy.
3) Re-entry arrhythmias.
PHARMACOKINETICS
 Slowly absorbed after oral administration.
 Highly bound to plasma proteins.
 Slow onset (2-3 days).
 Metabolized into desethylamiodarone
(antiarrhythmic).
 Enterohepatic circulation
Toxicity
 Hepatitis, pneumotitis, corneal deposits
photosensitization, tremors,
insomnia ataxia.
Class IV
These are Ca++ channel inhibitors
eg. Verapamil, diltiazem, nifedipine.
Block the slow inward current (Ca++) in cardiac tissue.
↓ Slope of phase 4-depolarizations.
↓ Rate of rise of phase O in the SA-node and
AV node (upstroke due to Ca++ influx).
↓ Conduction through the AV node and increases
the AV node refractory period (depolarizations
in the AV node is dependent on an increaseed
slow Ca++ channel).
Uses
 Drug of choice in paroxysmal supraventricular
tachycardia
 Re-entry arrhythmias
 To decrease ventricular response to
atria flutter or fibrillation.
Adverse effects
 Bradycardia
 Constipation
 Hypotension
 Headache
 Dizziness
 Nausea
 Skin reactions.
 ADENOSINE
 Activates K+ channels to reduce
effective refractory period
 Blocks Calcium channels at the AV
node
 Can be used for supraventricular
tachycardia
 CARDIAC GLYCOSIDES
 Increase vagal activity to reduce
conduction through the AV-node
 Used to control ventericular
response rate in patients with
atrial fibrillation
 Classification of Antiarrhythmic Drugs

CLASS ACTION DRUGS

I. Sodium Channel
1A. Blockers
Moderate phase 0 Quinidine,
depression and slowed Procainamide,
conduction (2+); prolong Disopyramide
repolarization
1B. Minimal phase 0
depression and slow Lidocaine
conduction (0-1+);
1C. shorten repolarization
Marked phase 0
depression and slow Flecainide
conduction (4+); little
II. effect on repolarization
Beta-Adrenergic Blockers Atenolol
III. K+ Channel Blockers Amiodarone,
(prolong repolarization) Sotalol
IV. Calcium Channel Verapamil,Diltiaze
 Class 1: Sodium Channel
Blockers
 Act on fast response cells
 Reduce membrane responsiveness
 Reduce Phase 4 diastolic
depolarization
 Depress conduction velocity
 Prolong effective refractory period