Cocaine fatality: An unexplained blood concentration in a fatal overdose

Peretti, Frank J.; Isenschmid, Daniel S.; Levine, Barry; Caplan, Yale H.; Smialek, John E.

doi:10.1016/0379-0738(90)90105-8

Cited by 42 publications

(18 citation statements)

References 10 publications

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“…Multiple dosing is particularly relevant because recreational cocaine is often associated with binge use (Levine et al 1987;Ward et al 1997;Fischman and Schuster 1982). Toxic/lethal plasma cocaine concentrations average ∼20 µmol/L with an upper range of ∼80 µmol/L as determined in admitted patients (Winek et al 1987;Peretti et al 1990). Because these toxic/lethal plasma samples are obtained at times distant to the actual time of cocaine administration, and with a cocaine half-life of ∼40 min (Barnett et al 1981), much higher peak cocaine concentrations would be expected.…”

Section: Discussionmentioning

confidence: 99%

Acute Cocaine Induces Endothelin-1–Dependent Constriction of Rabbit Basilar Artery

2007

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It has been postulated that ischemic stroke due to acute cocaine usage involves constriction of the cerebral vasculature. However, the mechanism underlying the constriction remains unclear. This study tested whether cocaine constriction was mediated via endothelin-1. Cocaine suffusion induced maintained constriction in the rabbit basilar artery in situ. The constriction was relaxed by PD145065, an endothelin A and B receptor antagonist. These results support the hypothesis that constriction of the cerebral vasculature due to acute cocaine exposure is via endothelin-1 release. Endothelin receptor antagonists may be of therapeutic benefit in cerebrovascular pathophysiologies involving cocaine constriction.

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Section: Discussionmentioning

confidence: 99%

Acute Cocaine Induces Endothelin-1–Dependent Constriction of Rabbit Basilar Artery

2007

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“…Earlier reports have indicated mean plasma cocaine concentration of 0.26±0.5 μM from a group of 111 cocaine users even though it could be as high as 120 μM [41] In another report Patel showed in 1996, that in a fatal case because of overdosing blood cocaine concentration was found to be 0.31 mM [42]. In yet another report of fatal case, >1mM cocaine was found to be present in blood [43]. Based on earlier studies, cocaine it is also known that CNS concentration could be as high as up to 155 times higher than that present in blood [44].…”

Section: Discussionmentioning

confidence: 99%

Cocaine-Mediated Autophagy in Astrocytes Involves Sigma 1 Receptor, PI3K, mTOR, Atg5/7, Beclin-1 and Induces Type II Programed Cell Death

et al. 2015

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Cocaine, a commonly used drug of abuse, has been shown to cause neuropathological dysfunction and damage in the human brain. However, the role of autophagy in this process is not defined. Autophagy generally protective in nature, can also be destructive leading to autophagic cell death. This study was designed to investigate whether cocaine induces autophagy in the cells of CNS origin. We employed astrocyte, the most abundant cell in the CNS, to define the effects of cocaine on autophagy. We measured levels of the autophagic marker protein LC3II in SVGA astrocytes after exposure with cocaine. The results showed that cocaine caused an increase in LC3II level in a dose- and time-dependent manner, with the peak observed at 1 mM cocaine after 6 hours exposure. This result was also confirmed by detecting LC3II in SVGA astrocytes using confocal microscopy and transmission electron microscopy. Next, we sought to explore the mechanism by which cocaine induces the autophagic response. We found that cocaine-induced autophagy was mediated by sigma 1 receptor, and autophagy signaling proteins p-mTOR, Atg5, Atg7 and p-Bcl-2/Beclin-1 were also involved and this was confirmed by using selective inhibitors and siRNAs. In addition, we found that chronic treatment with cocaine resulted in cell death, which is caspase-3 independent, and can be ameliorated by autophagy inhibitor. Therefore, this study demonstrated that cocaine induces autophagy in astrocytes and is associated with autophagic cell death.

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“…It is likely that many reported concentrations do not accurately reflect concentrations at the time of death [10]. Serum cocaine concentrations exceeding 1000 microM [11] have been reported following acute fatal overdose, although one series of 26 cases reported a mean concentration of 21 microM (range 0.3 to 70 microM) in deaths where cocaine was the only drug detected [12]. A second series compared cocaine concentrations of patients who died from trauma (and incidentally used cocaine) to cocaine concentrations of patients who died from cocaine poisoning.…”

Section: Cocaine Concentrations and Clinical Effectsmentioning

confidence: 99%

Mechanisms of Acute Cocaine Toxicity

Heard¹,

Palmer²,

Zahniser³

2008

TOPHARMJ

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Abstract:Patients with acute cocaine poisoning present with life-threatening symptoms involving several organ systems. While the effects of cocaine are myriad, they are the result of a limited number of cocaine-protein interactions, including monoamine transporter, neurotransmitter receptor and voltage-gated ion channels. These primary interactions trigger a cascade of events that ultimately produce the clinical effects. The purpose of this article is to review the primary interactions of cocaine and the effects that these interactions trigger. We also describe the progression of symptoms observed in cocaine poisoning as they relate to serum cocaine concentrations.

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Cocaine fatality: An unexplained blood concentration in a fatal overdose

Cited by 42 publications

References 10 publications

Acute Cocaine Induces Endothelin-1–Dependent Constriction of Rabbit Basilar Artery

Acute Cocaine Induces Endothelin-1–Dependent Constriction of Rabbit Basilar Artery

Cocaine-Mediated Autophagy in Astrocytes Involves Sigma 1 Receptor, PI3K, mTOR, Atg5/7, Beclin-1 and Induces Type II Programed Cell Death

Mechanisms of Acute Cocaine Toxicity

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