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Reversal of the Electrocardiographic Effects of Cocaine by Lidocaine. Part 1. Comparison With Sodium Bicarbonate and Quinidine
Author(s) -
Winecoff Allison P.,
Hariman Robert J.,
Grawe Jeffrey J.,
Wang Yanggao,
Bauman Jerry L.
Publication year - 1994
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1994.tb04162.x
Subject(s) - quinidine , sodium bicarbonate , lidocaine , sodium channel , chemistry , sodium , bicarbonate , pharmacology , qrs complex , anesthesia , medicine , organic chemistry
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 μM 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 pM 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.