title: Tolerance develops to the sympathomimetic but not the local anesthetic effects of cocaine.
abstract: OBJECTIVE
  The cardiovascular effects of cocaine are complex and include sympathomimetic as well as local anesthetic effects. The aim of the present study was to delineate cocaine toxicity in a model simulating cocaine binging patterns.
  
  
  METHODS
  Prospective laboratory investigation. Twelve dogs were randomized to receive 6 intravenous boluses of cocaine 5.25 mg/kg (high dose, n = 5), 3.5 mg/kg (low dose, n = 4), or placebo (n = 3) at 15-minute intervals. Arterial pressure, electrocardiogram, and serum cocaine were measured at control, then at fixed time intervals after each bolus of cocaine or placebo. Statistical significance was determined by ANOVA.
  
  
  RESULTS
  Peak serum cocaine concentrations were 3500 ng/mL and 2167 ng/mL in the high- and low-dose groups. There were progressive decreases in mean arterial pressure in the high-dose cocaine group by as much as 32% (p = .003) after each cocaine bolus. However, in the low-dose group, increases in mean arterial pressure were observed after the initial cocaine boluses by as much as 31% (p = .013). Significant QRS prolongation was observed in both the high- and low-dose cocaine groups by as much as 65% (p < .001) and 10% (p < .03), respectively. However, the prolongation observed in the high-dose group was more pronounced and cumulative, while in the low-dose group the prolongation was transient.
  
  
  CONCLUSIONS
  At low doses, cocaine's sympathomimetic properties predominate but tolerance develops. At high doses, cocaine's local anesthetic properties predominate, become more pronounced with repeated administration, and may have implications for cocaine-related dysrhythmias, cardiovascular collapse, and sudden death.
authors.affiliation: Department of Emergency Medicine, MetroHealth Medical Center, Cleveland, Ohio 44109, USA. LDWilson@pol.net
authors.forename: L D
authors.initials: LD
authors.lastname: Wilson
authors.forename: G
authors.initials: G
authors.lastname: Jeromin
authors.forename: C
authors.initials: C
authors.lastname: Shelat
authors.forename: B
authors.initials: B
authors.lastname: Huettl
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D004361:Drug Tolerance / Q000502:physiology*; D004562:Electrocardiography; D005260:Female; D008297:Male; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D013566:Sympathomimetics; D003042:Cocaine