24th April 2024

Vaughan-Williams Classification

This classification was introduced in 1970 by a pharmacology tutor at Oxford, Miles Vaugh Williams and groups antiarrhythmic medications according to their primary mechanism of action. It was traditionally broken down into four main categories: class I-IV. The updated Vaughan-Williams classification includes Class 0: hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ivabradine, used in chronic heart failure and stable angina where the heart rate is ≥70 bpm.

Antiarrhythmic medications

The development of new medications to treat arrhythmias and a greater understanding of the underlying mechanisms of current medicines, means there is often an overlap between categories. Amiodarone for example, is a class III antiarrhythmic that blocks potassium channels but also sodium and calcium channels (see Table 1). 

Table 1: Vaugh-Williams classification of antiarrhythmic medicines.

Physiology

An understanding of the cardiac action potential and its different phases will help clarify the mechanisms of different antiarrhythmic medications (see image and table below). Cardiac myocytes have a resting membrane potential of -90mV, like skeletal muscle but lower than that of neurons (-70mV) and smooth muscle (between -50mV and -60mV).

Medications affecting the cardiac action potential. Depolarisation phase 0, is due to a net flow of positive charge into the cell from sodium ions. Dips 1 and 3 occur when sodium channels are inactivated and there is an efflux of potassium ions, restoring the negative potential of the cardiac myocyte (repolarisation). The plateau phase 2, results from inward movement of calcium ions. 

Image Source: Wikimedia Commons (2021). Cardiac action potential, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Cardiac_action_potential (Accessed: 23 April 2024).

Table 2: Cardiac action potential 

Amiodarone

Amiodarone is a class III antiarrhythmic drug which is used to treat atrial, nodal, and ventricular tachycardias. It primarily inhibits potassium channels preventing repolarisation, prolonging the action potential and refractory period in cardiac myocytes. Additional actions include inhibition of beta-adrenergic receptors, calcium and sodium channels which contributes to the large side effect profile. 

Side effects include thyroid dysfunction, corneal deposits, pulmonary and hepatotoxicity, peripheral neuropathy, photosensitivity, hypokalaemia, a ‘slate-grey’ appearance, bradycardia, QT interval prolongation and torsades de pointes. Amiodarone can cause thrombophlebitis and should ideally be given via central veins. The half-life is long, over several weeks, and loading doses are often used. It can take up to six weeks to see clinical effects following oral therapy and after discontinuation, effects can persist for 1-3 months. 

Prior to initiation, patients should have thyroid function, liver function, renal function and a chest x-ray. Thereafter, thyroid and liver function should be repeated six monthly. ECG monitoring is required for intravenous infusions. 

References

• NICE/BNF. Arrhythmias. Accessed 1 February 2024. From: https://bnf.nice.org.uk/treatment-summaries/arrhythmias 
• NICE/BNF. Amiodarone. Accessed 1 February 2024. From:  https://bnf.nice.org.uk/drugs/amiodarone-hydrochloride