Document Detail

Reversal of the electrocardiographic effects of cocaine by lidocaine. Part 2. Concentration-effect relationships.
MedLine Citation:
PMID:  7885974     Owner:  NLM     Status:  MEDLINE    
Ventricular arrhythmias due to cocaine may be related to its ability to slow ventricular conduction or prolong repolarization. We previously showed that lidocaine reversed QRS prolongation due to cocaine. The purposes of these experiments were to characterize cocaine's concentration-effect relationship on both ventricular conduction and repolarization, and to determine the effects of lidocaine on these relationships. The effects of lidocaine on cocaine-induced electrocardiographic changes were studied in 20 isolated, Tyrode-perfused guinea pig hearts. Variables at cocaine concentrations ranging from 3-195 microM were measured and repeated in the presence of a fixed concentration of lidocaine 30 microM. Using nonlinear regression analysis, the sigmoid Emax and simple Emax models were fit to cocaine concentration versus percentage change in QRS plots. Measures of best fit indicated that this relationship was best described by the sigmoid Emax model. Compared with cocaine alone, the curve for cocaine with lidocaine showed a greater EC50 (concentration at 50% of maximum effect) (59 vs 100 microM) but similar Emax (371 vs 367%), consistent with competition. Similar values were obtained from the linear transformation of the data. Cocaine concentration versus percentage change in the JTc interval showed a biphasic effect: concentrations below 65 microM prolonged JTc, but those above 65 microM had no effect or decreased JTc. In contrast to changes in QRS, addition of lidocaine increased the effects of cocaine on JTc: area under the concentration-effect curve for cocaine alone was 720 versus 859 microM% for cocaine with lidocaine. Lidocaine reverses cocaine-induced slowed ventricular conduction through competition for binding, but it appeared to increase cocaine-induced prolongation of repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
J J Grawe; R J Hariman; A P Winecoff; J H Fischer; J L Bauman
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacotherapy     Volume:  14     ISSN:  0277-0008     ISO Abbreviation:  Pharmacotherapy     Publication Date:    1994 Nov-Dec
Date Detail:
Created Date:  1995-04-07     Completed Date:  1995-04-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8111305     Medline TA:  Pharmacotherapy     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  704-11     Citation Subset:  IM    
Department of Pharmacy Practice, University of Illinois at Chicago 60612.
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MeSH Terms
Arrhythmias, Cardiac / chemically induced
Cocaine / adverse effects,  antagonists & inhibitors*
Electrocardiography / drug effects*
Guinea Pigs
Heart Ventricles
Lidocaine / pharmacology*
Reg. No./Substance:
137-58-6/Lidocaine; 50-36-2/Cocaine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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