Tolerance develops to the sympathomimetic but not the local anesthetic effects of cocaine

Objectives: The cardiovascular effects of cocaine are complex and include s ympathomimetic as well as local anesthetic effects. The aim of the present study was to delineate cocaine toxicity in a model simulating cocaine bingi ng patterns. Design: Prospective laboratory investigation. Twelve dogs were randomized to receive 6 intravenous boluses of cocaine 5.25 mg/kg (high do se, n = 5), 3.5 mg/kg (low dose, n = 4), or placebo (n = 3) at 15-minute in tervals. Arterial pressure, electrocardiogram, and serum cocaine were measu red at control, then at fixed time intervals after each bolus of cocaine or placebo. Statistical significance was determined by ANOVA. Results: Peak s erum cocaine concentrations were 3500 ng/mL and 2167 ng/mL in the high- and low-dose groups. There were progressive decreases in mean arterial pressur e in the high-dose cocaine group by as much as 32% (p = .003) after each co caine bolus. However, in the low-dose group, increases in mean arterial pre ssure were observed after the initial cocaine boluses by as much as 31% (p = .013). Significant QRS prolongation was observed in both the high- and lo w-dose cocaine groups by as much as 65% (p < .001) and 10% (p < .03), respe ctively. However, the prolongation observed in the high-dose group was more pronounced and cumulative, while in the low-dose group the prolongation wa s transient. Conclusions: At low doses, cocaine's sympathominetic propertie s predominate but tolerance develops. At high doses, cocaine's local anesth etic properties predominate, become more pronounced,vith repeated administr ation, and may have implications for cocaine-related dysrhythmias, cardiova scular collapse, and sudden death.