ABSTRACT
Nifedipine can enhance the cytotoxicity of antineoplastic drugs. The present paper describes characteristics of sensitive and acquired resistant cells prior to and after transplantation into nude mice and experiments to reverse the acquired resistance to Daunorubicin (DR) by Nifedipine. Resistant cells (HT/DR+) are characterized by prolonged doubling time and diminished drug sensitivity and drug uptake. HT/DR+ cells show a slightly increased number of polyploid cells. These characteristics are not changed after nude mouse transplantation. Nifedipine enhances the intracellular level of Daunorubicin and cytotoxicity in vitro and in vivo in case of HT/DR+ cells. But Nifedipine acts both in vitro and in vivo also on sensitive cells (HT). This could support the hypothesis that Nifedipine increases the toxicity, which could be confirmed by experiments on mice (B6D2F1 strain). But probably the increased incidence of toxic deaths is not due to increased cardiac toxicity. This increase of toxicity could limit the clinical usefulness of the combination of antineoplastic drugs with calcium channel blockers.
Subject(s)
Antineoplastic Agents/pharmacology , Heart/drug effects , Mammary Neoplasms, Experimental/drug therapy , Nifedipine/pharmacology , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Cell Count , Cell Line , Clone Cells , DNA, Neoplasm/metabolism , Daunorubicin/administration & dosage , Daunorubicin/metabolism , Daunorubicin/pharmacology , Drug Combinations , Drug Resistance , Female , Male , Mice , Mice, Nude , Neoplasm Transplantation , Nifedipine/administration & dosage , Nifedipine/adverse effects , RatsABSTRACT
This is a first review of lorcainide hydrochloride, a new antiarrhythmic agent with local anaesthetic activity. The antiarrhythmic actions of lorcainide are mediated by an impairment of fast sodium conductance. Pharmacologically, this drug appears effective in suppressing reentry phenomena and ectopic pacemaker activity, especially in the ventricles. Lorcainide has only negligible depressant effects on important haemodynamic parameters and its toxicity is minimal. The drug is well absorbed by the oral route and its elimination half-life is long when compared with other substances. Lorcainide-induced QRS widening is directly correlated with the plasma levels of the drug. Preliminary experience in supraventricular arrhythmias is promising but pre-excitation syndromes and the ventricular arrhythmias are the main indications for this drug since a very high response rate has been observed in these conditions. Side effects are harmless and dose-dependent, but may be clinically troublesome.
