Antiarrhythmic drugs class II

Blockers are antiarrhythmics of class II according to the Vaughan-Williams classification, effective in the treatment of both supraventricular and ventricular tachyarrhythmias. These drugs can also reduce ectopic beats, especially if they are a result of sympathetic activity. Sotalol is a racemic mixture of the -blocking L-isomer and the class III antiarrhythmic D-isomer. This racemic mixture as well as D-sotalol are used as class Ill-antiarrhythmic. 

Activity mimics all antiarrhythmic drug classes (I, II, III, and IV) blocks Na, Ca, and K channels and beta adrenoceptors. 

Class II antiarrhythmic drugs are (3-adrenoceptor antagonists such as propranolol, metoprolol or atenolol. (3-adrenoceptor antagonists slow sinus rate and atrioventricular conduction and exert negative inotropic effects. 

Class II antiarrhythmic drugs include beta (( -adrenergic blocking drugs, such as acebutolol (Sectral), esmolol (Brevibloc), and propranolol (Inderal). These drugp also decrease myocardial response to epinephrine and norepinephrine (adrenergic neurohormones) because of their ability to block stimulation of p receptors of the... 

The Vaughan-Williams classification of antiarrhythmic drugs has been criticized for a number of reasons. The classification is based on the effects of drugs on normal, rather than diseased, myocardium. In addition, many of the drugs may be placed into more than one class. For example, the class IA drugs prolong repolarization/refractoriness, either via the parent drug8,9 or an active metabolite,10 and therefore also maybe placed in class III. Sotalol is also a 3-blocker, and therefore fits into class II. Amiodarone inhibits sodium and potassium channels, is a non-competitive inhibitor of 3-receptors, and inhibits calcium... 

Class II antiarrhythmic drugs competitively inhibit /3-adrenoceptors and inhibit catecholamine-induced stimulation of cardiac 15-receptors. In addition, some members of the group (e.g., propranolol and acebutolol) cause electrophysiological alterations in Purkinje fibers that resemble those produced by class I antiarrhythmic drugs. The latter actions have been called membrane-stabilizing effects. 

Fig. 24.1 The action potential of a cardiac cell that is capable of spontaneous depolarisation (SA or AV nodal, or His-PurkInje) indicating phases 0-4 the figure illustrates the gradual increase in transmembrane potential (mV) during phase 4 cells that are not capable of spontaneous depolarisation do not exhibit increase in voltage during this phase (see text).The modes of action of antiarrhythmic drugs of classes I, II, III and IV are indicated in relation to these phases...

Although officially classified as a class III antiarrhythmic, amiodarone possesses electrophysiologic characteristics of all four Vaughn Williams classifications. Acutely, intravenous amiodarone displays mainly antiadrenergic (class II) and calcium channel blocking (class TV) properties. Consequently, hypotension, which occurs in roughly 20% of clinical trials, is a concern. This hypotension is more dependent on the rate of administration than on the amount of drug... 

Class II and IV antiarrhythmic drugs can slow phase 4 in pacemaker fibers. 

Furthermore, the antiarrhythmic (class II) and antiangi-nal effects of these drugs make them especially valuable in hypertensive patients with coexisting coronary disease. 

I Repolarization (phase 3) in all cardiac cells is due to K efflux (delayed rectifier current) and this is I blocked by class lA and class III antiarrhythmic drugs. Pacemaker currents (phase 4) are blocked by class II and class IV drugs. 

I Class II antiarrhythmic drugs are beta-blockers that decrease SA and AV nodal activity, decrease the I phase 4 slope, and prevent p, adrenoceptor activation, thereby circumventing the normal increase in I cAMR Propranolol is nonselective acebutolol and esmolol are selective. Their antiarrhythmic use is I discussed. 

Class 1, II, III, and IV drugs A method for classifying antiarrhythmic drugs, sometimes called the Vaughan-Williams classification based loosely on the channel or receptor affected... 

A. Prototypes, Mechanisms, and Effects Beta-blockers are discussed in more detail in Chapter 10. Propranolol and esmolol are the prototype antiarrhythmic beta-blockers. Their mechanism in arrhythmias is primarily cardiac beta blockade and reduction in cAMP, which results in the reduction of both sodium and calcium currents and the suppression of abnormal pacemakers. The AV node is particularly sensitive to beta-blockers the PR interval is usually prolonged by class II drugs (Table 14-2). Under some conditions, these dmgs may have some direct local anesthetic (sodium channel-blocking) effect in the heart, but this is probably rare at the concentrations achieved clinically. 

Guamieri T, Datorre SD, Bondke H, Brinker J, Myers S, Levine JH. Increased pacing threshold after an automatic defibrillator shock in dogs effect of class I and class II antiarrhythmic drugs. Pacing Clin Electrophysiol 1988 11 1324-1330. 

PVC s alone with Class IC drugs was not sufficient to reduce mortality in the specific post-infarction population chosen for the CAST study. The failure of Class IC agents in the CAST study and their low efficacy in preventing induction of SVT during electrophysiological testing has increased the interest in alternative approaches to antiarrhythmic therapy, particularly towards Class III agents, a number of which are in Phase II clinical evaluation. 

Dolasetron Hypersensitivity to the drug or components of the product markedly prolonged QTc or atrioventricular block II to III patients receiving class I or III antiarrhythmic agents. 

The polypeptide ATX II has been found to have class III antiarrhythmic activity, indicating its potential in the management of cardiac arrhythmias [32]. A positive inotropic drug that was also effective as an antiarrhythmic might offer significant advantages therapeutically [33,34]. 

---