[Pharmacogenetic aspects of antiarrhythmic drug therapy].

It is known for a long time that individuals vary widely in their responses to therapy with different drugs. Variability in drug response may be due to variability in the relationship between drug dose and concentrations of the drug at target sites (pharmacokinetic variability). Another mechanism is that individuals vary in their response to identical exposures to a drug due to variability in the target molecule with which a drug interacts or in biological microenvironment in which the "drug-target" interaction occurs (pharmacodynamic variability). Variants (polymorphisms and mutations) of genes that encode proteins important for pharmacokinetics or for pharmacodynamics are described as important contributors to variable drug actions. In this article pharmacogenetic and pharmacogenomic aspects of antiarrhythmic drug therapy and genetic factors contributing to proarrhythmia are reviewed.

[Novel class III antiarrhythmic agent niferidile: review of experimental and clinical studies].

This article reviews experimental and clinical studies of a novel antiarrhythmic agent niferidile. Niferidile, a class III antiarrhythmic agent, blocks potassium outward currents, prolongs repolarization and refractory periods predominantly in atria than in ventricles. Intravenous Niferidile was efficient for interruption of AV-nodal and orthodromic re-entrant tachycardias with rates of 75% to 80%. Niferidile had a conversion rate of up to 87.3% in persistent atrial fibrillation and up to 100% in persistent atrial flutter. Proarrhythmic action of niferidil administration manifested as nonsustained torsade de pointes and monomorphic ventricular tachycardia in 1.2 and 3.7% of cases, respectively. Niferidile can be used for pharmacological cardioversion of persistent atrial fibrillation and flutter as an alternative to electrical cardioversion.

[Cardiac potassium channels: molecular structure, physiology, pathophysiology and therapeutic implications].

Potassium channels and currents play essential roles in cardiac repolarization. Potassium channel blockade by class III antiarrhythmic drugs prolongs cardiac repolarization and results in termination and prevention of cardiac arrhythmias. Excessive inhomogeneous repolarization prolongation may lead to electrical instability and proarrhythmia (Torsade de Pointes tachycardia). This review focuses on molecular structure, physiology, pathophysiology and therapeutic potential of potassium channels of cardiac conduction system and myocardium providing information on recent findings in pathogenesis of cardiac arrhythmias, including inherited genetic abnormalities, and future perspectives.

[Electrophysiological effects and antiarrhythmic activity of novel domestic class III antiarrhythmogenic drug niferidil administered in patients with paroxismal supraventricular tachycardia].

Intracardiac electrophysiological effects and antiarrhythmic activity of novel domestic class III antiarrhythmogenic drug niferidil has been studied in a group of 25 patients with paroxismal supraventricular tachycardia (PSVT) diagnosis. The drug was administered in a dose of 20 mg/kg (i.v.). Niferidil injections increased the refractory periods in both right and left atrium (by 22 and 20%, respectively, p < 0.001), right ventricle (12%, p < 0.01), and the His-Purkinje system (34%, p < 0.001) and improved additional anterograde and retrograde conduction (by 22 and 31%, respectively, p < 0.001), while not influencing the conduction via excitable cardiac tissues. Elongation of the QTc interval (22%, p <0.05) in one case was accompanied by an arrythmogenic effect (induction of short-term polymorphous ventricular tachycardia of the "torsade de pointes" type. Niferidil arrested PSVT in 78% cases and prevented PSVT development in response to endocardial stimulation in 86% of patients.

[Vanilloid receptors: structure, regulatory functions, pharmacology, therapeutic potential].

Transient receptor potential vanilloid (TRPV1), representing ion channel family, is activated in human and animal organism by capsaicin and some other factors such as heat, acidosis, and ion dysbalance. TRPV1 is a component of the endogenous system regulating various functions and participating in some pathologic processes. The structure, regulatory functions, mechanisms of activation, and chemistry of vanilloid receptors are reviewed and the mechanisms of their agonists and antagonists (including endogenous ligands) are considered. The results of experiments and clinical tests showing the therapeutic potential of vanilloids are considered.