Faculty Bibliography

STUDY OBJECTIVE: To determine whether plasma cholinesterase (pseudocholinesterase) activity is a marker for severe cocaine toxicity. DESIGN: A prevalence study in a cohort of cocaine users. SETTING: A large urban emergency department. PARTICIPANTS: During a three-month period in 1989, 187 patients who presented to the ED on 191 consecutive occasions with signs and symptoms consistent with cocaine intoxication were prospectively enrolled in the study protocol. METHODS AND MEASUREMENTS: All patients had plasma cholinesterase activity determined by the electrometric method. The patients who were cocaine positive were stratified into one of two groups: life-threatening toxicity (LT) and non-life-threatening toxicity (NLT), based on a predetermined set of criteria. Cocaine-negative patients served as controls for the LT group if criteria were otherwise met. RESULTS: Mean (+/- SD) plasma cholinesterase activities for the LT, NLT, and control groups were 682 +/- 277, 904 +/- 279, and 1,058 +/- 385 Michel units/L, respectively. All three groups were significantly different from each other (P less than .05 by analysis of variance). CONCLUSION: The data suggest that decreased plasma cholinesterase activity is associated with increased risk of life-threatening cocaine toxicity

The effect of buprenorphine pretreatment on the acute cocaine toxicity was assessed in male Swiss Webster mice. Buprenorphine pretreatment (0.15 or 0.30 mg/kg ip, 30 mins before) significantly attenuated the lethal effects of cocaine (60-140 mg/kg ip). The dose of cocaine which resulted in 50% mortality (LD50) in saline pretreated group was 100.61 mg/kg while the LD50 of cocaine in buprenorphine (0.15 and 0.3 mg/kg) pretreated groups were 113.57 and 118.16 mg/kg respectively. There was no significant change in the ratio of brain/plasma levels of cocaine in buprenorphine pretreated group when compared to the ratio from saline treated controls. Furthermore, neither naloxone (10 mg/kg ip, 15 mins before) nor naltrexone (3 mg/kg ip, 15 mins before) pretreatment affected the LD50 of cocaine. When tested 0.5, 1, 2, 4, 8 and 24 hrs after cocaine administration, sublethal dose of cocaine (80 mg/kg ip) injection resulted in significant increase in the plasma lactate dehydrogenase (LDH) levels. Buprenorphine pretreatment significantly attenuated cocaine-induced release of LDH. These results suggest that buprenorphine could be of potential advantage over naloxone in the management of cocaine and heroin ('speed ball') toxicity and in studies on the pharmacotherapy of cocaine-induced toxicity, LDH levels may be used as a biochemical marker to assess the protective effects of drugs

1. The interaction between ethanol and morphine on core temperature was investigated in Swiss Webster mice. 2. Morphine (2.5-30 mg/kg) and ethanol (0.5-3.0 mg/g) administered individually resulted in a dose dependent decrease in body temperature. 3. When both drugs were injected simultaneously, body temperature decreased less than it would be expected to if the effects were additive. 4. Naloxone antagonized the hypothermic effect of morphine, but the hypothermic effect of ethanol and that of the combination of morphine plus ethanol was only reversed with high doses of naloxone (10 mg/kg). 5. Individual morphine and ethanol plasma levels were not significantly altered by their concomitant administration. 6. Binding of tritiated naloxone to opiate receptors in mouse brain membrane preparations was unchanged by pretreatment with ethanol (0.5 and 2 mg/g). 7. The interaction between morphine and ethanol was found to be less than additive and not related to pharmacokinetic changes of either drug