Antiarrhythmics

Question 1

Which cardiac cells are latent pacemakers?

Answer 1

• AV node - Bundle of His - Purkinje fibres

Question 2

What are the 3 basic mechanisms responsible for the initiation of tachyarrhythmias?

Answer 2

1) Enhanced automaticity - the cell is more permeable to Na in phase 4 -> increased slope in phase 4
- other cells are capable of generating impulses faster than the SA node
2) Triggered activity - leakage of cations into the cell, resulting in an afterdepolarisation
- these can occur in phases 2, 3 or 4
- if the afterdepolarisation is strong enough it can trigger premature complexes
3) Re-entry - e.g Wolff-Parkinson White (WPW)
- the re-entrant mechanism causes premature atrial contraction (i.e. prior to the next sinus impulse)
- AVNRT is another example
- there is a fast and a slow pathway in the AV node, normally the fast pathway will terminate the slow pathway
- the fast pathway has fast conduction but slow repolarisation, whereas the slow pathway has slow conduction but fast repolarisation
- usually the fast pathway spreads quickly down to the ventricles and also loops up to intercept the slow pathway and terminate it
- if there is a premature beat when the fast pathway is in its refractory period, it can stimulate the slow pathway, which depolarises the ventricles and then spreads up into the fast pathway. Because the slow pathway has a short refractory period it is stimulated again, leading to a loop which results in tachycardia.

Question 3

Discuss class I antiarrhythmics

Answer 3

Vaughan-Williams classification of antiarrhythmics NB: class 1 antiarrhythmics can be arrhythmogenic! Class I: Na channel blockers, slow conduction of Na in phase 0 of the action potential - Class Ia - prolong phase 0 and phase 3 - prolong action potential + refractory period - may be used for AF, VT - procainamide, quinidine, disopyramide - Class 1b - shorten repolarisation; minimal effect on phase 0 - shorten action potential & refractory period - mainly used for ventricular arrhythmias - e.g. lidocaine, mexiletine - Class 1c - strong effect on phase 0 (Na channels), inhibit His-Purkinje conduction system - refractory ventricular arrhythmias, AF - e.g. flecainide, propafenone