Antidysrhythmic actions

Moracizine (moricizine) has Class I antidysrhythmic actions that cannot be easily further subclassified. Its pharmacology, clinical pharmacology, clinical uses, adverse effects and interactions have been reviewed (1-3). 

Phenytoin possesses anticonvulsant activity without significant central nervous system (CNS) depression. At various concentrations, phenytoin has been shown to inhibit inward Na currents, outward K currents, and Ca -mediated action potentials. The ability to inhibit sodium channels is responsible for the antidysrhythmic action (class II-B) of phenytoin. Phenytoin can induce enzymes of the hepatic cytochrome P450 system. 

Walker DK, Alabaster CT, Congrave GS, et al. Significance of metabolism in the disposition and action of the antidysrhythmic drug, dofetilide. In vitro studies and correlation with in vivo data. Drug Metab Dispos 1996 24 447-455. 

Acecainide (A-acetylprocainamide) is the main metabolite of procainamide, and it has antidysrhythmic activity (1). However, in contrast to procainamide, which has Class Ib activity, the main action of acecainide is that of Class III. 

Several reviews of the clinical pharmacology, actions, therapeutic uses, and adverse reactions and interactions of adenosine and ATP have appeared (1-4). After intravenous administration adenosine enters cells, disappearing from the blood with a half-life of less than 10 seconds intracellularly it is phosphorylated to cyclic AMP. Its mechanism of action as an antidysrhythmic drug is not known, but it may act by an effect at adenosine receptors on the cell membrane. Its electrophysiological effects are to prolong AV nodal conduction time by prolonging the AH interval, without an effect on the HV interval. The pharmacological and adverse effects of adenosine triphosphate are similar to those of adenosine. 

Antidysrhythmic drugs with Class I activity reduce the rate of the fast inward sodium current during Phase I of the action potential and increase the duration of the effective refractory period expressed as a proportion of the total action potential duration. The action potential duration is itself affected in different ways by subgroups of the Class I drugs ... 

Antidysrhythmic drugs with class IV activity prolong total action potential duration by prolonging the plateau phase (phase III) of the action potential via calcium channel blockade. 

Table 2 Classification of antidysrhythmic drugs by their actions in different parts of the heart...

The most common mechanism of dysrhythmias at the molecular level is by inhibition of the potassium channels known as IK, which are encoded by the human ether-a-go-go-related gene (HERG). The antidysrhythmic drugs that affect these channels include almokalant, amiodar-one, azimilide, bretylium, dofetilide, ibutilide, sematilide, D-sotalol, and tedisamil (all drugs with Class III actions) and bepridil, disopyramide, prenylamine, procainamide, propafenone, quinidine, and terodiline (all drugs with Qass I actions). Other drugs that affect these channels but are not used to treat cardiac dysrhythmias include astemizole and terfenadine (antihistamines), cisapride, erythromycin, haloperidol, sertindole, and thioridazine. 

Hjrpokalemia due to diuretics potentiates the dysrhyth-mogenic actions of antidysrhythmic drugs that prolong the QT interval, such as Class I and Qass III antidysrhythmic drugs, increasing the risk of torsade de pointes (164). This can also happen with other drugs that prolong the QT interval, such as phenothiazines (165). 

Mexiletine is a class Ib antidysrhythmic drug, similar in action to lidocaine, but it can be given orally. Its adverse effects occur in up to 50% of patients (1) and withdrawal is often necessary (2). The most common adverse effects are on the cardiovascular and central nervous systems. The pharmacokinetics, clinical use, and adverse effects and interactions of mexiletine have been reviewed widely (3-8). 

The effects of procainamide on the QT interval can be potentiated by other drugs with this action, for example other class I antidysrhythmic drugs (62). 

Quinidine is a class I antidysrhythmic drug. Its actions, clinical use, interactions, and adverse effects have been reviewed (1). 

Table 19.2 lists the actions of Antidysthythmics and Table 19.3 describes classes of Antidysthythmics. There are four classes of Antidysrhythmics. These are ... 

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