Antiarrhythmics pharmacodynamics

Sedgwick M, Rasmussen HS, Walker D, Cobbe SM. Pharmacokinetic and pharmacodynamic effects of UK-68,798, a new potential class III antiarrhythmic drug. Br J Clin Pharmacol 1991 31(5) 515-19. 

Tham TC, MacLennan BA, Burke MT, Harron DW. Pharmacodynamics and pharmacokinetics of the class III antiarrhythmic agent dofetilide (UK-68,798) in humans. J Cardiovasc Pharmacol 1993 21(3) 507-12. 

With warfarin, one is always concerned about pharmacodynamic and pharmacokinetic drug interactions. None of the antiarrhythmic drugs mentioned above are likely to cause a pharmacodynamic interaction with warfarin. However, amiodarone is a cytochrome P450 enzyme inhibitor and increases warfarin s antithrombotic effects. Patients taking both drugs usually need to decrease their dose of warfarin. 

In addition, a common contaminant in quinidine preparations, dihydroquinidine, which is derived from reduction of the quinuclidine vinyl group at C-3 to an ethyl group, also may contribute to its activity (32). Although similar to quinidine in pharmacodynamic and pharmacokinetic behavior, this contaminant is both more potent as an antiarrhythmic and more toxic. Thus, levels of this contaminant may contribute to variability between commercial preparations. The most frequent adverse effects associated with quinidine therapy are gastrointestinal ... 

Woosley, R. L., Pharmacokinetics and pharmacodynamics of antiarrhythmic agents in patients with congestive heart failure. Am. Heart J., 114 1280-1291, 1987. 

The pharmacodynamics and pharmacokinetics of ( )-flecainide acetate have been studied extensively in animal models and in humans. This drug exhibits potent antiarrhythmic effects... 

Although the chiral antiarrhythmic agents possess some similarities, they also display a number of features that make them unique. From the perspective of stereoselectivity, a range of differences between the enantiomers of each of these drugs exists in their metabolism, excretion, degree of plasma protein binding and volume of distribution, and pharmacodynamic properties. 

Probably because of its withrawal from the market in 1991, prompted by its adverse safety profile, only limited information is available for the stereoselective pharmacokinetics or pharmacodynamics of encainide in humans. The antiarrhythmic effects of the drug are not stereoselective [80] (Table 8), and the metabolites are also potent antiarrhythmic agents [128]. Turgeon et al. [80] monitored the steady-state urinary recovery of encainide and its metabolites ODE and MODE in 7 EMs and 3 PMs after... 

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