Tolerance Develops to the Sympathomimetic But Not the Local Anesthetic Effects of Cocaine

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Wilson, Lance. et al. 000. Tolerance Develops to the Sympathomimetic But Not the Local Anesthetic Effects of Cocaine. Journal of Toxicity Clinical Toxicology. Vol 8 (7) 71.

The objective of this study was to obtain the effects of cocaine in the tolerance development of the sympathomimetic and the tolerance development to the local anesthetic. Twelve mixed-sex mongrel dogs, with the mean body weight of 17.7 kg were randomized to receive six, 5.5 mg/kg doses of cocaine. Arterial pressure, electrocardiogram, and serum cocaine were measured at control group, then at fixed time intervals of 15 minutes after each doses of cocaine or placebo. Each dog was given an intramuscular injection of morphine sulfate, 1.5 mg/kg, for sedation and anesthetized with an intravenous injection of alpha-chloralose, 100mg/kg, dissolved in polyethylene glycol. Each dog was then randomized in to one of three groups. Each dog in the low-dose group received .5 mg/kg of cocaine in ten cc saline. Each dog in the high-dose group received 5. mg/kg of cocaine in ten cc saline. The dogs in the control group received ten cc of normal saline. All dogs were given six total doses of cocaine at 15-minute intervals. Just before each injection, blood samples were drawn from each dog and immediately placed in a chilled glass tube containing potassium oxalate and sodium fluoride. Blood concentrations were acquainted using capillary gas chromatography with a mass spectrometer using electron ionization in a selected ion-monitoring mode as a detector. The major observed changes in mean arterial pressure were significant decrease in the high cocaine dose group lasting one to two minutes after each cocaine dose. After the third dosage, the maximal decrease of % in mean arterial pressure occurred two minutes. After the initial increase, there was a no significant increase in the mean arterial pressure. In the low cocaine dose group, there was a significant increase in the mean arterial pressure six minutes after the fourth cocaine injection. The mean arterial pressure increased 1% compared to the control group. There were no significant changes in mean arterial pressure in the control group. Both high-dose and low-dose cocaine caused prolongation of the intervals of the surface electrocardiogram. The sympathomimetic effects of cocaine include positive ionotropic, chronotropic, and hypertensive responses to cocaine and have been attributed to increased tissue catecholamine level

Wilson, Lance. et al. 000. Tolerance Develops to the Sympathomimetic But Not the Local Anesthetic Effects of Cocaine. Journal of Toxicity Clinical Toxicology. Vol 8 (7) 71.

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