Classification, mechanism of action and usage of antiarrhythmic drugs
Drugs have been the main means of preventing and treating tachyarrhythmias. quinidine has been used for nearly a century and procainamide for 50 years. in the 1960s, lidocaine was widely used in myocardial infarction ventricular arrhythmias. By the 1980s, the application of propafenone and flecainide brought the development of class I drugs to its peak. in the early 1990s, CAST results were published, and it was noticed that in patients with ventricular asystole after myocardial infarction, the application of class I drugs led to a decrease in ventricular asystole but an increase in overall mortality. This drew attention to the benefit-risk relationship of antiarrhythmic drug therapy and to the development of class III drugs.
Classification of antiarrhythmic drugs
Antiarrhythmic drugs are now widely used in the modified VaughanWilams classification, which divides drugs into four classes according to their different electrophysiological effects (Table 1). The effect of an antiarrhythmic drug may not be single, for example, sotalol has both β receptor blocking (class II) effect and QT interval prolonging (class III) effect; amiodarone shows the effect of class I, II, III and IV at the same time, and also blocks α and β receptors; procainamide belongs to class Ia, but its active metabolite N-acetyl procainamide (NAPA) has class III effect; quinidine has both I, Ⅲ class of action. It can be seen that the above classification seems too simple, and there are some other antiarrhythmic drugs not included.
Therefore, in 1991, foreign arrhythmia experts in Sicily, Italy, developed a new classification called Siciliangambit. This classification breaks with the traditional classification and incorporates a new concept of arrhythmia drug action in relation to arrhythmia mechanisms. “The Siciliangambit classification expresses the channel, receptor and ion pump of each drug according to the target of drug action, and facilitates the selection of appropriate drugs according to the different ion flow bases of arrhythmias and the vulnerable links of their formation. In this classification, some drugs that could not be categorized have also found their corresponding place. This classification helps to understand the mechanism of action of antiarrhythmic drugs, but the complexity of the arrhythmia mechanism makes the Sicilian classification difficult to apply in practice, and the VaughanWilams classification is still customarily used in clinical practice. The channels, receptors and main electrophysiological effects of drug actions are shown in Table 1.
Table 1 Classification of antiarrhythmic drugs
Category
Channels and receptors of action
APD or QT interval
Commonly used representative drugs
Ⅰa
Blocking ⅠNa+ +
Prolongation of +
Quinidine, propiamine, procainamide
Ⅰb
BlockingⅠNa
Shortening +
Lidocaine, phenytoin, mexiletine, tocainide
Ⅰc
BlockingⅠNa+ + +
Unchanged
flecainide, propafenone, morethizine
Ⅱ
Blocking β1
Unchanged
Atenolol, metoprolol, esmolol
Blocking β1, β2
Unchanged
Nadolol, propranolol, sotalol
III
Blockade ⅠKr
Prolongation + + +
Dofetilide, sotalol, (simeprilide, amorant )
BlockingⅠKr.Ⅰto
Prolongation + + +
Tidisamide, (amobarbital )
Blocking ⅠKr activation ⅠNaS
Prolongation + + +
Ibutilide
BlockingⅠKr,ⅠKs
Prolongation + + +
Amiodarone, azimilide
Blocking IK, sympathetic endings
Prolongation + + +
Evacuation of norepinephrine
bromobenzylamine
IV
Blockade I Ca l
Unchanged
Verapamil, diltiazem
Others
OpenⅠK
Shortening + +
Adenosine
Blocking M2
Shortening + +
Atropine
Blocking Na/K pump
Shortening + +
Digoxin