Electrophysiologic and electrocardiographic pharmacodynamics of cocaine.
To determine and describe relationships between plasma cocaine concentrations and electrophysiologic and electrocardiographic effects, 10 anesthetized dogs with normal intact hearts received a continuous 3-hour infusion of cocaine 0.11 mg/kg/minute (total dose 20 mg/kg). Data were collected as part of a randomized, blinded, placebo-controlled study investigating the effects of cocaine on ventricular fibrillation threshold. Every 30 minutes during infusion of cocaine or placebo and for 3 hours after discontinuation of the infusion, heart rate and mean arterial pressure were determined, effective refractory period (ERP) was measured, and QRS duration and PR, QTc, and JTc intervals were recorded. At the time of each 30-minute measurement, arterial blood was obtained to determine plasma cocaine concentrations. Hysteresis curves were observed for cocaine-induced increases in ERP and PR interval. The effects of cocaine on QRS duration and QTc and JTc intervals were not well described by tested models. Pharmacodynamic modeling techniques may be used to describe relationships between plasma cocaine concentrations and specific cardiovascular effects of cocaine. Further study is required to determine applicability of this model for prediction of cocaine's cardiovascular effects in humans.
Tisdale
J E
JE
College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
Ducharme
M P
MP
Shimoyama
H
H
Webb
C R
CR
Sabbah
H N
HN
Edwards
D J
DJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects*; D009294:Narcotics / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D009294:Narcotics; D003042:Cocaine