Antiarrhythmic agents

Antiarrhythmic agents are usually classified according to their effect on the electrophysiology of cardiac myofibrils. Figure CV1 shows the different sites in the heart on which these drugs act. There are four basic classes of antiarrhythmic agent, with considerable variation in the chemical structure of the drugs within each functional class (Vaughan Williams 1970). Examples of the drugs by class are shown in Figure CV2.

Class I

Class I drugs work in a similar way to local anaesthetic agents (lidocaine is used for both roles). They act by slowing sodium entry into cells through the fast, voltage-gated sodium channels that primarily affect the non-nodal areas characterised by a fast depolarisation action potential. They reduce the maximum rate of rise of phase 0 depolarisation. The rate of phase 4 sinoatrial node depolarisation may also be reduced, and with it spontaneous automaticity.

Fast, voltage-gated sodium channels may exist in three states – resting, open and refractory. In normal myocardium their state switches between resting and open, but ischaemia results in prolonged depolarisation and the channel becomes refractory. The class I antiarrhythmics block open channels so that the more frequent the action potentials the more ionophores become blocked. The first action potential shows a slight reduction in phase 0 depolarisation. Subsequent action potentials show a progressive reduction in the rate of depolarisation as more channels are blocked. The block is therefore usedependent.

Class I has three subdivisions, based on the effect on the action potential duration.