CVS: Arrhythmias and Anti-arrhythmic drugs Flashcards
Briefly outline electrophysiology of the heart
Built upon 2 types of APs present in nodal (SAN, AVN) and non-nodal (contractile) cells
Compare nodal APs to non-nodal APs
- Nodal - non-contractile tissues, no phase 1
- Nodal - contractile - Has phase 1 which relates to contraction-relaxation phase (QT of ECG)
Define arrhythmia, its symptoms, causes, origin and effect
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
Describe atrial fibrilation (AF)
- Quivering atrial activity (no discrete P waves)
- Irregular ventricular contraction
- ‘Clot-producing’ - Increased stroke risk
Describe supraventricular tachycardia (SVT)
- P wave buried in T wave
- Fast ventricular contractions
Describe Heart block
Failure of conduction system (e.g., SAN, AVN, bundle of His)
Uncoordinated atria/ventricular contractions
Describe ventricular tachycardia (VT) and describe ventricular fibrilation (VF)
VT
- Fast, regular
VF
- Fast irregular
Both limit CO and can result in no CO
What are 2 mechanisms of arrhythmogenesis?
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
Describe ectopic activity
Pacemaker activity initiated in SAN but other areas can have pacemaker activity to ‘safeguard’ if SAN becomes damaged
SAN = 60-70/s - Most powerfulpacemaker (AVN - 40-60/s, Bundle of His= 30/40/s, purkinje fibres
So pacemakers are produced from other areas of the heart
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
Describe EAD and DAD
EAD (Early-after depolarisation):
- Altered ion channel activity
- E.g. abnormal increase in Na or Ca channel activity
- Na+ influx leads to depolarisation
DAD (Delayed-after depolarisation):
- 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
Describe re-entry
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
Describe causes and consequences of Heart block
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)
What are the goals and rationale of anti-arrhythmia medications?
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)
Describe the Vaughan Williams classification system for anti-arrhythmic drugs
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)
Describe class I anti-arrhythmic medication
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
Describe class II anti-arrhythmic medication
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)
Describe class III anti-arrhythmic medication
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
Describe class IV anti-arrhythmic medication
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
What are some non-classified drugs used to treat arrhythmias?
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
How can arrhythmias arise from the use of anti-arrhythmic drugs?
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
How can sinus tachycardia be treated?
- Slow down SAN
- Class II, III, IV
How can AF be treated?
- Reduce atria activity, return of atria output, prevent clot formation
- Use II, III, IV, digoxin, anticoagulants
How can SVT be treated?
- Reduce ventricular response rate
- Use II, III, IV, adenosine
How can heart block be treated?
- Coordinate atria/ventricular contractions
- Insert pacemaker
How can VT/VF be treated?
- Reduce ventricular activity
- Return ventricular output
- Use I, II, III
