Antiarrhythmics, specific agents

Type III antiarrhythmics include agents that specifically prolong refractoriness in atrial and ventricular tissue. This class includes very different drugs bretylium, amiodarone, sotalol, ibutilide, and recently, dofetilide they share the common effect of delaying repolarization by blocking potassium channels. The electrophysiologic actions of bretylium are related to its multifaceted pharmacology. 

Other Glass III Antiarrhythmic Agents. Clofihum phosphate is a benzene-butanaminium derivative that has highly specific Class III antiarrhythmic activity. It is orahy active, has a rapid onset of action, and a reasonably long duration of antiarrhythmic activity. In preliminary clinical studies, clofihum has shown efficacy against spontaneous ventricular tachycardias (69). 

Jurkiewicz, N.K. and Sanguinetti, M.C., Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide, Circ. Res., 72, 75-83, 1993. 

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. 

As our data show, the activity seems to be of a very broad range and is not specific for one organism, which would be a desirable trait if we think of exploiting natural products as plant-protection substances or therapeutic agents. It should be recalled that QA are useful in medicine as antiarrhythmic and obstetric drugs ( ). These observations also hold true for most other natural products. We would stress that natural products form a preselected reservoir of bioactive compounds, useful for further chemical manipulation. 

All SSRIs (e.g., Feonard et ah, 1997) and in particular fluoxetine, Fluvosamine and paroxetine are metabolized by hepatic cytochrome P450 enzymes. Therefore, it is important to be aware of the possibility that the therapeutic or toxic effects of other medications metabolized by the cytochrome P450 isoenzyme system can be increased. Substantial inhibition of these isoenzymes converts a normal metabolizer into a slow metabolizer with regard to this specific pathway. Inhibition of the hepatic oxidative isoenzymes has been associated with a reduction, to a varying extent, in the clearance of many therapeutic agents, including the TCAs, several neuroleptics, antiarrhythmics, theophy-lene, terfenadine, benzodiazepines, carbamazepine, and warfarin (for a complete list, see Nemeroff et ak, 1996). 

Ibutilide. Ibutilidc, A - 4- 4-(cthylheptylaminoH-hy-droxybutyllphenyllmethanesulfonamidc (Corvert), a class III antiarrhythmic belonging to the mcthancsulfonanilidc class of agents, is indicated for rapid conversion of atrial Hbrillation or atrial flutter to normal sinus rhythm. Unlike dofetilide, it is not highly. specific for the delayed a clificr potassium currents (Ikr) and does have some affinity for. sodium channels. 

A recommendation for a specific antiarrhythmic agent of first choice does not exist. Amiodarone, lidocaine, and procainamide are the available options. 

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