Reversal of the electrocardiographic effects of cocaine by lidocaine. Part 1. Comparison with sodium bicarbonate and quinidine.
Based on modulated receptor concepts, an agent with fast on-off sodium channel binding properties (e.g., lidocaine) may reverse the effects of a drug with slow on-off kinetics (e.g., cocaine) through competition for a single receptor site on the sodium channel. We compared the effects of two drugs with different sodium channel-binding kinetics with those of sodium bicarbonate, a known antidote, on cocaine-induced slowing of ventricular conduction. Electrocardiographic (ECG) intervals were recorded before and after the addition of cocaine 30 microM in 26 isolated, Tyrode-perfused guinea pig hearts. The effects of the three potential antidotes were then analyzed: equimolar lidocaine (8 hearts), equimolar quinidine (6), and sodium bicarbonate (8). Cocaine significantly increased all ECG intervals. The addition of lidocaine to cocaine-containing perfusate decreased QRS duration from 42 +/- 3 to 29 +/- 3 msec (p < 0.01), a 60% reversal. Addition of sodium bicarbonate to increase the pH of the perfusate from 7.37 +/- 0.09 to 7.52 +/- 0.08 (p < 0.01) decreased the QRS duration from 38 +/- 4 to 30 +/- 6 msec (p < 0.01), a 47% reversal. Addition of quinidine 30 microM augmented the effects of cocaine: QRS increased from 40 +/- 6 msec to 54 +/- 9 msec (p < 0.01). Consistent with modulated receptor concepts, lidocaine reverses slowed ventricular conduction due to cocaine. The magnitude of this reversal is similar to that due to sodium bicarbonate. The potential of fast on-off agents to serve as antidotes for cocaine-induced arrhythmias requires further study.
Winecoff
A P
AP
Department of Pharmacy Practice, University of Illinois at Chicago 60612.
Hariman
R J
RJ
Grawe
J J
JJ
Wang
Y
Y
Bauman
J L
JL
D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors*; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D011802:Quinidine / Q000494:pharmacology*; D017693:Sodium Bicarbonate / Q000494:pharmacology*
D017693:Sodium Bicarbonate; D008012:Lidocaine; D003042:Cocaine; D011802:Quinidine