Cardiac Arrhythmias

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Cardiac Arrhythmias
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• Types of cardiac arrhythmias
• Bradyarrhythmias
• Tachyarrhythmias
• Bradyarrhythmias treat with atropine, pacing
• Tachyarrhythmias can occur due to
• Enhanced automaticity
• Afterdepolarization and triggered activity
• Re-entry

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• 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

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EAD
DAD
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• 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

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• 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

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• 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

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(No Transcript)
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K (Transient)
K (delayed rectifier)
Ca2
Ca2
Na
Na
NaKATPase
K
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K channel blocker
?-blocker, CCB
Na channel blocker
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Ca2 channel blocker ?-blocker
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• 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

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• 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)

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• 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

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• 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

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• 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

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• 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