Cardiac electrophysiologic effects

TABLE 16.2 Cardiac Electrophysiological Effects of Class I Antiarrhythmic Drugs... 

Table 16.3 summarizes the cardiac electrophysiological effects of class II, III, and IV agents, and Table 16.4 summarizes the actions of the (3-receptor blocking agents... 

Ibutilide (Corvert) is a structural analog of sotalol and produces cardiac electrophysiological effects similar to those of the antiarrhythmic agents in class III. 

In neonates, hypotension can occur (SEDA-16,80), and respiratory arrest in a child and sudden cardiac arrest have been reported (SEDA-16, 80). However, in one study there were no cardiac electrophysiological effects of midazolam combined with fentanyl in subjects undergoing cardiac electrophysiological studies (SEDA-18, 80). 

CLASSICAL IN VITRO/EX VIVO ASSESSMENT OF CARDIAC ELECTROPHYSIOLOGIC EFFECTS... 

Wit, A. L., Hoffman, B. F. and Rosen, M. R.(1975) Electrophysiology and pharmacology of cardiac arrhythmias. IX. Cardiac electrophysiology effects of beta adrenergic receptor stimuiation and biockade. Part B. Amer. Heart J., 90, 665. 

The Class I agents decrease excitability, slow conduction velocity, inhibit diastoHc depolarization (decrease automaticity), and prolong the refractory period of cardiac tissues (1,2). These agents have anticholinergic effects that may contribute to the observed electrophysiologic effects. Heart rates may become faster by increasing phase 4 diastoHc depolarization in SA and AV nodal cells. This results from inhibition of the action of vagaHy released acetylcholine [S1-84-3] which, allows sympathetically released norepinephrine [51-41-2] (NE) to act on these stmctures (1,2). 

While most -blocking agents on acute administration have little direct electrophysiological effects, studies in rabbits [94] and man [95] have shown that chronic administration of y -blockers increases APD. This increase in APD (and hence refractory period) has been postulated to contribute to the effectiveness of -receptor blocking agents in the prevention of sudden cardiac death [94]. Direct Class III action has been claimed for the y -blockers oxprenolol (30) [96,97], nadolol (31) [96] and atenolol (10) [98] in addition... 

Class rv drugs block the slow inward Ca current (L-type calcium channel) in cardiac tissue. The most pronounced electrophysiological effects are exerted on cardiac cells that depend on the Ca" " channel for initiating the action potential, such as those found in the sinoatrial and A-V nodes. The administration of class IV drugs slows conduction velocity and increases refractoriness in the A-V node, thereby reducing the ability of the A-V node to conduct rapid impulses to the ventricle. This action may terminate supraventricular tachycardias and can slow conduction during atrial flutter or fibrillation. 

The primary electrophysiological effects of moricizine relate to its inhibition of the fast inward sodium channel. Moricizine reduces the maximal upstroke of phase 0 and shortens the cardiac transmembrane action potential. The sodium channel blocking effect of moricizine is more significant at faster stimulation rates an action referred to as use dependence. This phenomenon may explain the efficacy of moricizine in suppressing rapid ectopic activity. An interesting effect of moricizine is its depressant effect on automaticity in ischemic... 

The most notable electrophysiological effect of amiodarone after long-term administration is prolongation of repolarization and refractoriness in all cardiac tissues, an action that is characteristic of class III antiarrhythmic agents. 

Drugs with membrane-stabilizing activity reduce the rate of rise of the cardiac action potential and have other electrophysiological effects. Membrane-stabilizing activity has only been shown in human cardiac muscle in vitro in concentrations 100 times greater than those produced by therapeutic doses (23). It is therefore likely to be of clinical relevance only if large overdoses are taken. 

Fenici RR, Melillo G. Effects of nicorandil on human cardiac electrophysiological parameters. Cardiovasc Drugs Ther 1991 5(Suppl 3) 367. 

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