CVS: Arrhythmias and Anti-arrhythmic drugs

Question 1

Briefly outline electrophysiology of the heart

Answer 1

Built upon 2 types of APs present in nodal (SAN, AVN) and non-nodal (contractile) cells

Question 2

Compare nodal APs to non-nodal APs

Answer 2

• Nodal - non-contractile tissues, no phase 1
• Nodal - contractile - Has phase 1 which relates to contraction-relaxation phase (QT of ECG)

Question 3

Define arrhythmia, its symptoms, causes, origin and effect

Answer 3

Arrhythmia - Abnormalities in rate + heart rhythm

Symptoms:

• Palpitations
• Dizziness
• Fainting
• Fatigue
• Loss of consciousness
• Cardiac arrest
• Blood coagulation (Stroke, MI)

Causes:

• Cardiac ischemia (MI, angina), heart failure, hypertension, coronary vasospasm, heart block, excess sympathetic stimulation

Origin:

• Supraventricular - above the ventricles → SAN, atria, AVN
• Ventricular

Effect:

• Tachycardia (>100bpm) or Bradycardia (<60bpm)

Arrhythmias lead to incorrect filling and ejection = incorrect cardiac output

Question 4

Describe atrial fibrilation (AF)

Answer 4

• Quivering atrial activity (no discrete P waves)
• Irregular ventricular contraction
• ‘Clot-producing’ - Increased stroke risk

Question 5

Describe supraventricular tachycardia (SVT)

Answer 5

• P wave buried in T wave
• Fast ventricular contractions

Question 6

Describe Heart block

Answer 6

Failure of conduction system (e.g., SAN, AVN, bundle of His)

Uncoordinated atria/ventricular contractions

Question 7

Describe ventricular tachycardia (VT) and describe ventricular fibrilation (VF)

Answer 7

VT

• Fast, regular

VF

• Fast irregular

Both limit CO and can result in no CO

Question 8

What are 2 mechanisms of arrhythmogenesis?

Answer 8

Abnormal impulse may arise due to:

• Automatic rhythms - Increased SAN activity, ectopic activity
• Triggered rhythms - Early- after depolarisations (EADs), delayed-after depolarisations (DADs)

Abnormal contraction due to:

• Re-entry electrical circuits in heart
• Conduction block

Question 9

Describe ectopic activity

Answer 9

Pacemaker activity initiated in SAN but other areas can have pacemaker activity to ‘safeguard’ if SAN becomes damaged

SAN = 60-70/s - Most powerful pacemaker (AVN - 40-60/s, Bundle of His= 30/40/s, purkinje fibres = 15/25/s

Other low freq pacemakers greatly enhanced by SNS activity:

• Increase HR
• Increase AVN conduction
• Increase excitability of ventricular tissue

Hence continuous/enhanced stimulation of SNS (stress, heart failure) can lead to arrhythmias → Increase risk of ectopic activity

Question 10

Describe EAD and DAD

Answer 10

EAD:

• Altered ion channel activity
• E.g. abnormal increase in Na or Ca channel activity
• Na+ influx leads to depolarisation

DAD:

• Abnormal levels of Ca2+ in SR
• Ca2+ leaks out from RyR into cytosol
• Stimulate Na/Ca exchanger (3:1 ratio)
• Na+ influx leads to depolarisation

Question 11

Describe re-entry

Answer 11

Basis for SAN → ventricles ‘wave’ of conduction pathway of heart is:

• APs stop conducting bcs surrounding tissue refractory ∴ cannot conduct anymore APs

Myocardial damage means some areas of heart more conductive than others → Produces re-entry pathways

Question 12

Describe Heart block

Answer 12

Can develop due to fibrosis/ ischaemic damage of conducting pathway (often AVN issue)

First degree: PR interval >0.2 seconds

Second degree: >1 atria impulses fail to stimulate ventricles

Third degree (complete block): Atria and ventricles beat independently of one another

Ventricles contract at slow rate, depending on what ectopic pacemaker sets the rate (e.g., Bundle of His, ventricular tissue)

Can cause loss of consciousness, Adams-Stokes attacks = syncope (fainting)

Question 13

What are the goals and rationale of anti-arrhythmia medications?

Answer 13

Goal:

• Restore sinus rhythm and normal conduction
• Prevent more serious and possibly fatal arrhythmia occurring

Rationale:

• Reduce conduction velocity
• Alter refractory period of cardiac APs
• Reduce automaticity (decrease EADs, DADs, ectopic beats)

Question 14

Describe the Vaughan Williams classification system for anti-arrhythmic drugs

Answer 14

Class I: Na+ channel blockers (non-nodal tissue)

Class II: B-blockers (nodal + non-nodal tissue)

Class III: K+ channel blockers (non-nodal tissue)

Class IV: Ca2+ channel blockers (nodal + non-nodal tissue)

Question 15

Describe class I anti-arrhythmic medication

Answer 15

Na+ channel blockers

• Block Na+ channels in non-nodal tissue (e.g. atria/ventricles)
• Block Na+ channels in activated state
• Have property of Use-dependence & fast dissociating
• Only block Na+ channels in high frequency firing tissue e.g. ventricular tachycardia/fibrillation

Question 16

Describe class II anti-arrhythmic medication

Answer 16

Increased SNS activity associated with arrhythmias

Stimulation of sympathetic nerves leads to activation of B1 receptors in heart causing:

• Increase in SAN and AVN firing rate
• Increase ventricular excitability
  
  • Both of these are pro-arrhythmic

B1-selective blockers, e.g. atenolol, bisoprolol

• Reduce VT after myocardial infarctions caused by increase in sympathetic nerve activity
• Slows initiation of pacemaker potentials in SAN, and slows conduction through AVN to reduce ventricular firing rate in SVT
  
  • Useful for all types (SVT) and reduces heart work (less O2 consumption)

Question 17

Describe class III anti-arrhythmic medication

Answer 17

Increasing length of AP increases refractory period of heart (cannot fire another AP)

Inhibit K= channels responsible for repolarisation in atria/ventricles (not K+ channels in SAN/AVN)

Class III e.g. amiodarone - Used for SVT and VT

Rationale:

• Block repolarisation channels - maintain depolarisation (muscle more refractory)
• Na+ channels in-activated - reduce inappropriate AP firing - prevent arrhythmias

Question 18

Describe class IV anti-arrhythmic medication

Answer 18

Ca2+ channel antagonists

• Block of L-type VgCa channels, mainly affects firing of SA and AV nodes - reduces ventricular firing
  
  • Also block phase 2 so inappropriate in heart failure
• L-type Ca2+ channels also found on vascular smooth muscle and involved in vasoconstriction
• Blocker will relax blood vessels + decrease blood pressure
• Class IV, e.g., Verapamil (more cardiac specific), diltiazem (cardiac and vascular smooth muscle)
• Used to control ventricular response rate in SVT

Question 19

What are some non-classified drugs used to treat arrhythmias?

Answer 19

Adenosine - Decreases activity in SAN + AVN, used for SVT

Atropine - Muscarinic antagonist - Reduce parasympathetic activity - May be used to treat sinus bradycardia (V-low HR) after MI

Digoxin (cardiac glycoside)- Central effects - increases vagus nerve activity - Decrease HR + conduction, used for AF

Question 23

How can arrhythmias arise from the use of anti-arrhythmic drugs?

Answer 23

E.g. Class III drugs:

• Increase QT duration
• Long QT syndrome = Arrhythmia
• Due to EADs & DADs generation

Class I, II and IV can increase refractory period (less SA, AV, atria/ventricular firing) and reduce conduction time → Potentially pro-arrhythmic

Class IV may also reduce contractility

Question 24

How can sinus tachycardia be treated?

Answer 24

• Slow down SAN
• Class II, III, IV

Question 25

How can AF be treated?

Answer 25

• Reduce atria activity, return of atria output, prevent clot formation
• Use II, III, IV, digoxin, anticoagulants

Question 26

How can SVT be treated?

Answer 26

• Reduce ventricular response rate
• Use II, III, IV, adenosine

Question 27

How can heart block be treated?

Answer 27

• Coordinate atria/ventricular contractions
• Insert pacemaker

Question 28

How can VT/VF be treated?

Answer 28

• Reduce ventricular activity
  
  • Return ventricular output
  • Use I, II, III