Arrhythmias and antiarrhythmic drugs Flashcards
What is the definition of arrhythmias?
Abnormalities in heart rhythm
What are the symptoms of arrhythmias?
Palpitations, dizziness, fainting, fatigue, loss of conscious, cardiac arrest, blood coagulation (e.g. stroke, MI)
What are the causes of arrhythmias?
Cardiac ischemia (MI, angina), heart failure, hypertension,
coronary vasospasm, heart block, excess sympathetic stimulation
What is the origin of arrhythmias?
- Supraventricular(above the ventricles - SA node, atria, AV node)
- Ventricular
What are the effects of arrhythmias?
Tachycardia (>100 bpm) or Bradycardia (<60 bpm)
What happens in atrial fibrillation and how does it show on the ECG?
Quivering atria activity (no discrete P waves)
Irregular ventricular contraction
‘Clot-producing’ – risk of stroke
What happens in supraventricular tachycardia(SVT) and how does it show on the ECG?
P wave buried in T wave
Fast ventricular contractions
What happens in heart block and how does this show on ECG?
Failure of the conduction system
(e.g. SAN, AVN, or bundle of his)
Uncoordinated atria/ventricular
contractions
-P waves and QRS complexes are independent of each other. P waves and R waves are regular
What happens in ventricular tachycardia(VT)?
Fast, regular
What happens in ventricular fibrillation?
Fast, irregular
What are the mechanisms of arrhhythmogenesis?
- Abnormal impulse generation due to
-Automatic rhythms - increased SA node activity, ectopic activity
-Triggered rhythms - Early afterdepolarizations(EADs), Delayed-afterdepolarizations (DADs) - Abnormal conduction due to
-Re-entry electrical circuits in heart
-Conduction block
Where is pacemaker activity initiated?
Pacemaker activity is initiated in SAN but other areas of the heart can have
pacemaker activity to ‘safeguard’ if SAN becomes damaged
What is the frequency of the SA node?
60-70/s
What is the frequency of the AV node?
40-60/s
What is the frequency of the bundle of His?
30-40/s
What is the frequency of purkinje fibres?
15-25/s
What are the low frequency pacemaker areas enhanced by?
These other low frequency ‘pacemaker’ areas are greatly enhanced by sympathetic nerve activity:
-Increase heart rate
-Increasing AVN conduction
-Increase excitability of ventricular tissue
What can the continuous/enhanced stimulation of sympathetic nervous system lead to and what does this increase the risk of?
Continuous/enhanced stimulation of sympathetic nervous system
(stress, heart failure) can lead to arrhythmias
- increase risk of ectropic pacemaker activity -
Whats early afterdepolarization and what does it involve?
Altered ion channel activity
e.g. Abnormal increase
in Na or Ca channel activity
What is delayed afterdepolarization and what does it involve?
Abnormal levels of Ca2+ in SR
Ca2+ leaks out from RyR into cytosol
Stimulate Na/Ca exchanger (NCX)
Na+ influx – depolarisation
What is the basis for the SAN to ventricles ‘wave’ of conduction pathway of the heart/
Basis for the SAN to ventricles ‘wave’ of conduction pathway of the heart is:
Action potentials stop conducting because surrounding tissue is refractory
Cannot conduct anymore APs
What happens to conduction when there’s damage to the myocardium?
Damage to myocardium means that some areas of the heart are more
conductive than others – produces RE-ENTRY pathways
What happens in normal impulse conduction?
Impulses down 1 and 2 cancel each
other out in branch 3
- consistent depolarising wave front
followed by refractory tissue -
What happens in abnormal impulse conduction, in particular re-entry?
Branch 2 has impaired unidirectional conduction
Slows/Stops conduction of impulses down 2
Allows conduction of impulses from 3 to 2
When refractory period is over in 1 this causes
premature impulses to go from 2 to 1
Inappropriate action potential generated
What is heart block due to?
Due to fibrosis / ischaemic damage
of conducting pathway
Often AV node issue
how does the ECG look like in a first degree heart block?
P-R interval >0.2 s
How does the ECG look like in a second degree heart block?
> 1 atria impulses fail to stimulate ventricles
What happens in a third degree(complete block) heart block?
atria and ventricles beat independently of one another
How do the ventricles contract in a third degree(complete block)?
Ventricles contract at slow rate, depending on
what ectopic pacemaker sets the rate
(e.g., Bundle of his, ventricular tissue)
What is the goal when treating arrhythmias?
-Restore sinus rhythm and normal conduction
-Prevent more serious and possibly fatal arrhythmia occurring
What are the 3 things that anti-arrhythmic drugs do?
-Reduce conduction velocity
-Alter refractory period of cardiac action potentials
-Reduce automaticity (decrease EADs, DADs, Ectopic beats)
What are Class I antiarrhythmic drugs?
Na+ channel blockers (non-nodal tissue)
What are class II antiarrhythmic drugs?
β blockers (nodal and non-nodal tissue)
What are class III antiarrhythmic drugs?
K+ channel blockers (non-nodal tissue)
What are Class IV antiarrhythmic drugs?
Ca2+ channel blockers (nodal and non-nodal tissue)
When phase do class IV antiarrhythmic drugs act?
Act during phase 2 on non nodal tissues
Act during phase 0 on nodal tissue
What phase do class I antiarrhythmic drugs act on in non-nodal tissue?
Act during phase 0 on non-nodal tissue
What phase do class IV antiarrhythmic drugs act on in non-nodal tissue?
Act during phase 2 on non-nodal tissue
What phase do Class III antiarrhythmic drugs act on in non-nodal tissue?
Act during phase 3 on non-nodal tissue
What do class II antiarrhythmic drugs act on?
Class II act at SAN & AVN and Atria/Ventricles
to reduce excitability of cardiac tissue
What do Class I antiarrhythmic drugs do?
Block Na+ channels in non-nodal tissue, e.g. atria/ventricles
Block Na+ channels in their in-activated state
What property do class I drugs have?
Have property of Use-dependence
Only block Na+ channels in high frequency firing tissue
e.g., ventricular tachycardia/fibrillation
How do Class I drugs work?
- Drugs bind to inactivated state
- Fast dissociating drug
-Turns Off channels in <0.5s
- Drug comes off channel in inactivated state before next impulse so there’s no effect on normal firing - The fast dissociating drug is still bound to inactivate site when next impulse arrives
-Inhibits high frequencies
How do Class II drugs work?
β1 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
What does increasing the length of action potential increase and therefore what can’t be done?
Increasing the length of the action potential increases refractory period of
heart (can not fire another action potential)
What do class III drugs do?
Inhibit K+ channels responsible for repolarisation in atria/ventricles
(not K+ channels in SAN/AVN)
How do the Class III drugs work?
- Block K+ channels that are involved in repolarization
- Maintain depolarisation
- Na+ channels are in-activated
- This reduces inappropriate actional potential firing
- Therefore prevent arrhythmias
For what conditions are class III drugs used for?
Used for SVT and VT
What do class IV drugs do?
Block of L-type voltage-gated Ca2+ channels mainly affects firing of SA and
AV nodes - reduces ventricular firing
Where are L-type Ca2+ channels found and therefore what other effect can class IV drugs have?
L-type Ca2+ channels also found on vascular smooth muscle and are
involved in vasoconstriction – so blockers can produce relaxation of blood
vessels and decrease in blood pressure
What are class IV drugs used to control?
Used to control ventricular response rate in SVT
What does the adenosine drug do and what is it used for?
Decreases activity in SAN and AVN
Used for SVT
What does atropine do and what is it used for?
-Muscarinic antagonist
-Reduce parasympathetic activity
-May be used to treat sinus bradycardia(very low HR) after MI
What does digoxin do and what is it used for?
-Central effects, increases vagus nerve activity,
decrease heart rate, and conduction
-Used for AF
What is the paradox with anti-arrhythmic drugs?
Anti-arrhythmic drugs can be pro-arrhythmic
How can class III drugs actually be pro-arrhythmic?
Class III drugs increases QT duration
Long QT syndrome - arrhythmia –
due to EADs and DADs generation
