Transcript Cardiac Arrhythmia

Cardiac Arrhythmias
Types of cardiac arrhythmias:
•Bradyarrhythmias
•Tachyarrhythmias
•Bradyarrhythmias: treat with atropine, pacing
•Tachyarrhythmias can occur due to:
Enhanced automaticity
Afterdepolarization and triggered activity
Re-entry
Tachyarrhythmias:
•Enhanced automaticity:
In tissues undergoing spontaneous depolarization
-stimulation, hypokalemia, mechanical stretch of cardiac muscle
Automatic behaviour in tissues that normally lack spontaneous
pacemaker activity e.g. ventricular ischaemia depolarizes ventricular
cells and can cause abnormal rhythm
•Afterdepolarization:
EAD: when APD is markedly prolonged
Occur in phase 3
May be due to inwards Na+ or Ca2+ current
Excessive prolongation of APD- torsades de pointes syndrome
EAD
DAD
Torsades de pointes: polymorphic ventricular tachycardia along
with prolonged QT interval
DAD: precipitating conditions are intracellular or sarcoplasmic
Ca2+ overload, adrenergic stress, digitalis intoxication, heart
failure
If afterdepolarizations reach a threshold, an AP is genererated
which is called ‘triggered beat’
DAD occur when the HR is fast, EAD occur when the HR is
slow
•Re-entry: when a cardiac impulse travels in a path such as to
return to and reactivate its original site and self perpetuate rapid
reactivation independent of normal sinus node conduction
Requirements for re-entry rhythm:
slowing or conduction failure due to either an anatomic or
functional barrier
Anatomic barrier- Wolff-Parkinson-White syndrome
Functional barrier- ischaemia, differences in refractoriness
Presence of an anatomically defined circuit
Heterogenecity in refractoriness among regions in the circuit
Slow conduction in one part of the circuit
•What are channels? – they are macromolecular complexes
consisting of a pore forming  subunit,  subunits and accessory
proteins
•They are:
Transmembrane proteins
Consist of a voltage sensitive domain
A selectivity filter
A conducting pore and,
An inactivating particle
•In response to changes in membrane voltage, the channel changes
conformation so as to allow or prevent the flow of ions through it
along their concentration gradient
K+ (Transient)
K+ (delayed rectifier)
Ca2+
Na+
Ca2+
Na+
Na+K+ATPase
K+
K+ channel blocker
-blocker, CCB
Na+ channel blocker
Ca2+ channel blocker
& -blocker
How can drugs slow the cardiac rhythm?
Decreasing phase 4 slope
Increase in threshold potential for excitation
Increase in maximum diastolic potential
Increase in APD
•Fast response tissues
•Slow response tissues
Na+ channel blocker:
•Na+ channel block depends on:
HR
Membrane potential
Drug specific physiochemical characteristic-  recovery
•Blockade of Na+ channels results in:
Threshold for excitability is increased (more current)
Increase in pacing and defibrillation threshold
Decrease conduction velocity in fast response tissues
Increase QRS interval
Some drugs tend to prolong PR interval- flecainide (possibly
Ca2+ channel blockade)
•Some sodium channel blockers shorten the PR interval (quinidine;
vagolytic effect)
•APD unaffected or shortened
•Increase in threshold for excitation also decreases automaticity
•Can also inhibit DAD/EAD
•Delays conduction so can block re-entry
•In some cases, it can exacerbate re-entry by delaying conduction
•Shift voltage dependence of recovery of sodium channels from
inactivated state to more negative potentials and so increases
refractoriness
•Net effect- whether it will suppress or exacerbate re-entry
arrhythmia depends on its effect on both factors- conduction velocity
and refractoriness
•Most Na+ channel blockers bind to either open or inactivated state
and have very little affinity for channels in closed state, drug binds to
channels during systole & dissociates during diastole
•ADRs:
Decrease in conduction rate in atrial flutter- slows rate of flutter
and increases HR due to decrease in AV blockade
Especially common with quinidine due to its vagolytic property;
also seen with flecainide and propafenone
Cases of ventricular tachycardia due to re-entrant rhythm following
MI may worsen due to slowing of conduction rate
Slowing of conduction allows the re-entrant rhythm to persist
within the circuit so that complicated arrhythmias can occur
Several Na+ channel blockers have been reported to exacerbate
neuromuscular paralysis by d-tubocurarine
•K+ Channel blockers:
Prolong APD (QT interval) and reduces automaticity
Increase in APD also increases refractoriness
Effective in treating re-entrant arrhythmias
Reduce energy requirement for defibrillation
Inhibit ventricular arrhythmias in cases of myocardial ischemia
Many K+ channel blockers also have  blocking activity also like
sotalol
Disproportionate prolongation of APD can result in torsaides de
pointes, specially when basal HR is slow
•CCBs:
Major effect on nodal tissues
Verapamil, diltiazem and bepridil cause slowing of HR, nifedipine
and other dihydropyridines reflexly increase HR
Decrease AV nodal conduction so PR interval increases
AV nodal block occurs due to decremental conduction and increase
in AV nodal refractoriness
DAD leading to ventricular tachycardia respond to verapamil
Verapamil and diltiazem are recommended for treatment of PSVT
Bepridil increases APD in many tissues and can exert
antiarrhythmic action in atria and ventricles but it use is associated
with increased incidence of torsades de pointes- rarely used