Class I antiarrhythmic drugs

Class I antiarrhythmic drugs

General information

Class I drugs have defined therapeutic ranges and generally dose-dependent toxicity. As a general principle therapeutic drug monitoring is required and should be based on predose trough levels after allowing five half-lives to achieve steady state (where a loading dose is not required). These drugs are toxic and require specialist supervision.

Class IA drugs

Class IA drugs include disopyramide. These drugs have anticholinergic and negative inotropic activity. There is wide interpatient variability in the dose required to achieve therapeutic plasma concentrations. They can produce proarrhythmic complications by slowing conduction and by promoting oscillatory behaviour of the action potential associated with delayed repolarisation, giving rise to a form of polymorphic ventricular tachycardia referred to as torsades de pointes. This is particularly of concern with disopyramide, where the tendency to produce this effect may be more marked at lower rather than higher concentrations, with clinical reports occurring below or at the lower end of the therapeutic range. Torsades de pointes is therefore seen most commonly in susceptible individuals at the commencement of therapy or after therapy has been ceased and the blood level is falling.

Class IB drugs

Class IB drugs include lignocaine and mexiletine.

Lignocaine has a short half-life of approximately 2 hours and is given intravenously. It has two active metabolites that contribute to the central nervous system toxicity seen with lignocaine (headache, dizziness, drowsiness, mental changes, paraesthesia [often perioral] and visual disturbances). Toxicity increases in patients with reduced liver blood flow due to heart failure or to other drug therapy such as the beta blockers.

Lignocaine is also used in the management of neuropathic pain and as a local anaesthetic 

Mexiletine is structurally similar to lignocaine but can be given orally. It shares a similar adverse effect profile to lignocaine but also has gastrointestinal effects.

Mexiletine is also used in the management of neuropathic pain

Both drugs are capable of producing proarrhythmic complications.

Class IC drugs

Flecainide is a class IC drug. It causes marked depression of cardiac conduction and contractility and is proarrhythmic. It should not be used in the presence of significant left ventricular dysfunction or myocardial ischaemia.

Flecainide is also used in the management of neuropathic pain. Consultation with a palliative care specialist, a pain physician, or a pain clinic is strongly recommended before using antiarrhythmic drugs for pain management.