Nifedipine antiarrhythmic activity

The class IV-antiarrhythmics are the calcium antagonists, but remain limited to verapamil and possibly also diltiazem. The dihydropyridines (nifedipine and related compounds) are unsuitable for antiarrhythmic therapy. The antiarrhythmic activity of verapamil and diltiazem is based upon the impairment of AV conduction and heart rate. A few compounds may be considered to act as antiarrhyth-mics, but they are not included in the Vaughan-Williams classification. 

It is noteworthy that calcium inhibitory compounds with the ability to inhibit %a+ possess the most potent antiarrhythmic activity against both experimental and clinical arrhythmias (126). For example, nifedipine exerts minimal, if any, antiarrhythmic effect against ischemic induced arrhythmias in intact animals (6, 87, 131). Diltiazem and perhexiline, on the other hand, demonstrate variable antiarrhythmic effects dependent upon their dose and the mechanism responsible for arrhythmia production (ischemia, hypoxia, digitalis, aconitine) (102, 126, 151, 152). Only verapamil, which has been investigated in the largest number of experimental and clinical trials, has demonstrated consistent antiarrhythmic activity against cardiac arrhythmias regardless of cause (155) ... 

Calcium channel blockers inhibit the passage of calcium through the membrane charmels the result in myocardial cells is to depress contractility, and in pacemaker cells to suppress their automatic activity. Members of the group therefore may have negative cardiac inotropic and chronotropic actions. These actions can be separated nifedipine, at therapeutic concentrations, acts almost exclusively on noncardiac ion charmels and has no clinically useful anti-arrhythmic activity whilst verapamil is a useful antiarrhythmic. 

The Ca +-channel antagonists, the 1,4-dihydropyridines (DHPs), represent a remarkably successful group of cardiovascular drugs that have antihypertensive, antiangi-nal, and antiarrhythmic properties (167). Nifedipine (Fig. 10.8) was the first member of the DHP family a structure that embraces both Ca -channel antagonists and activators (168), which was followed by the synthesis of a number of analogs with a prolonged duration cf action and enhanced vascular selectivity (167). 

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