Overdose cocaine

Figure 5.1 Visualization of the distribution of the DA transporter, D3 receptor, and K2-opioid receptor in the human brain of a drug-free control subject and a representative cocaine overdose victim. (A, B) The DA transporter was measured using [3H]WIN 35,428 (2 nM) as described previously. (C, D) The D3 receptor was measured using [3H]-(+)-7-OH-DPAT (1 nM) in the presence of GTP (300 m/W) to enhance the selective labeling of the D3 receptor subtype over the D2 receptor subtype as described previously. (E, F) The K2-opioid receptor subtype was measured using [125l]IOXY on tissue sections pretreated with BIT and FIT to occlude binding to the p- and 8-opioid receptors, respectively.

Staley J., Basile M., Wetli C. et al. Differential regulation of the dopamine transporter in cocaine overdose deaths. Natl. Inst. Drug Abuse Res. Monogr. 32, 1994. 

Staley J., Hearn W., Ruttenber A., Weth C., Mash D. High affinity cocaine recognition sites on the dopamine transporter are elevated in fatal cocaine overdose victims. Pharmacol. Exp. Ther. 271 1678, 1994. 

Mash D.C., Staley J.K. D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims. Ann. N.Y. Acad. Sci. 877 507, 1999. 

Figure 6.1 Tracking the incidence of cocaine overdose deaths in Dade County, FL. Medicolegal investigations of the deaths were conducted by forensic pathologists. Forensic pathologists evaluated the scene environment and circumstances of death and autopsied the victim in order to determine the cause and manner of death. The circumstances of death and toxicology results were reviewed before classifying a death due to cocaine toxicity with or without preterminal delirium. There was a sharp increase in the incidence of cocaine-related and cocaine overdose cases with the arrival of crack cocaine in Dade County. The incidence of cocaine delirium victims is shown by year, from the first report in 1982.

In the epidemiological tracking of agitated delirium victims in Metropolitan Dade County, men with preterminal delirium comprised approximately 10% of the annual number of cocaine overdose deaths. The demographic trends show that the proportion of these cases remains consistent throughout the epidemic of cocaine abuse and tends to track the annual frequency of cocaine-related sudden deaths. This observation suggests that a certain percentage of cocaine addicts may be at risk for cocaine delirium with chronic abuse. 

Physical effects of high doses of ketamine include decreased respiration and heart rate, increased blood pressure, and the possibility of vomiting and convulsions. These can lead to cardiac and respiratory arrest, coma, and death. The risk of ketamine overdose is much greater when it is mixed with other drugs such as alcohol, Ecstasy, caffeine, or cocaine. Overdoses of ketamine have been reported when people boost the drug (take another dose before the first dose wears off) to prolong its psychedelic effects. 

June 19 College basketball star Len Bias dies from a cocaine overdose. The death of an apparently healthy athlete highlights the potential dangers of the drug. 

Cocaine is a central nervous system (CNS) stimulant that causes a significant increase in heart rate, respiration, blood pressure, and body temperature. According to DAWN, one in thirteen cocaine users go to the hospital to be treated for severe reactions that could be life-threatening. Sudden death can result from heart failure, respiratory failure, seizures, strokes, and cerebral hemorrhage. There is no antidote for cocaine overdose. Even if the adverse reactions do not result in death, they can do permanent damage to the body. 

No changes (Meador-Woodruff et al., 1995) or an increase in striatal D3 mRNA expression levels (Segal et al., 1997) have been reported in human cocaine abusers. The increase in the D3 mRNA was most evident in the nucleus accumbens of cocaine overdose victims who did not present a preterminal excited delirium (Segal et al., 1997) and there was a complementary increase in the striatal D3 binding in the cocaine fatalities (Staley and Mash, 1996). Only one study has examined the D4 receptor with regard to stimulant abuse no alterations were evident in the striatum of human cocaine users (Meador-Woodruff et al., 1995). 

Staley JK, Talbot JZ, Ciliax BJ, Miller GW, Levey AI, Kung M-P, Kung HF, Mash DC (1997) Radioligand binding and immunoautoradiographic evidence for a lack of toxicity to dopaminergic nerve terminals in human cocaine overdose victims. Brain Res 747 219-229. 

Q4 Yes. Rob has used both atropine and phenylephrine this afternoon. Muscarinic antagonists such as atropine, tropicamide and cyclopentolate cause dilation of the pupils. The a-adrenoceptor agonists, such as phenylephrine, also produce my driasis. Mydriasis may cause acute closed-angle glaucoma in some patients. It is unlikely that a very small amount of cocaine in the eye would cause problems, but in cocaine overdose pupils become widely dilated. This is due to blockade of uptake 1, a process normally involved in terminating the effects of noradrenaline. In the presence of cocaine the effects of sympathetic stimulation on the eye would be prolonged and the pupil would dilate. Morphine causes constriction of the pupils via opiate receptors. 

Aspects of non-fatal cocaine overdose among cocaine users have been studied in Australia in 200 current cocaine users (120 injecting users and 80 non-injecting users), who volunteered for a structured interview 13% had overdosed on cocaine, 7% in the preceding 12 months (379). Those who had overdosed were more likely to inject cocaine, to be female, to have longer cocaine habits,... 

Marzuk PM, Tardiff K, Leon AC, Hirsch CS, Portera L, Iqbal MI, Nock MK, Hartwell N. Ambient temperature and mortality from unintentional cocaine overdose. JAMA 1998 279(22) 1795-800. 

Kaye S, Darke S. Non-fatal cocaine overdose among injecting and non-injecting cocaine users in Sydney, Australia. Addiction 2004 99 1315-22. 

Martz, R., Donnelly, B., Fetterolf, D., Lasswell, L., Flime, G. W., Hearn, W. L., The Use of Hair Analysis to Document a Cocaine Overdose Following a Sustained Survival Period Before Death, /. Anal. Toxicol., 15, 279,1991. 

Generally, the samples tested were head hair obtained from expertises or from subjects deceased from fatal heroin or cocaine overdose. Collection procedures have not been standardized, but hair is often collected from the area at the back of the head (vertex posterior), cut as close as possible to the scalp and stored in dry tubes. In this area, there is less variability in hair growth rate, the number of hairs in the growing phase is more constant, and the hair is less subject to age and sex-related influences. Occasionally, axiUaty or pubic hair have also been tested for cannabinoids. 

Zheng, F., Zhang, C.-G. (2008). Structure-and-mechanism-based design and discovery of therapeutics for cocaine overdose and addiction. Org. Biomol. Chem. 6 836-43. 

Of course, the risk of overdose death always accompanies high doses of cocaine or amphetamines. Specifying the dose that places the user at risk is difficult. With cocaine in particular, when we speak of low to moderate doses, we refer to 15-60 milligrams (a typical line contains 10-20 mg). Rut cocaine overdose deaths have been reported in individuals who were given as little as 20 milligrams as a local anesthetic, apparently because they suffered from a rare deficiency in the enzyme that breaks down cocaine in the blood and liver (Weiss Mirin, 1987). Such cases are certainly exceptional, and generally much higher doses are taken before either... 

Cocaine and other stimulant drugs are often taken in combination with other drugs, particularly alcohol and opiates. Laboratory studies in humans have shown that alcohol can enhance and prolong the subjective pleasure associated with cocaine, and this is likely the basis for their frequent association. Recent studies have revealed that when cocaine is taken with alcohol, a new compound called cocaethylene is formed in the body. Cocaethylene has pharmacological properties similar to cocaine, but it may be more toxic. Many cases of cocaine overdose may in fact involve cocaethylene toxicity caused by combining cocaine and alcohol (Raven, Necessary, Danluck, Ettenberg,... 

Metabolism also plays a critical role in the pharmacology of cocaine. The rapid hydrolysis of cocaine via two different pathways leads to its rapid inactivation/detoxification. This rapid metabolism has been a major determinant in the methods and modes of cocaine abuse. Identification and characterization of these hydrolytic enzymes would be useful in that selective induction of these enzymes offers a potential treatment strategy for dealing with cocaine overdose. It is conceivable that long-term elevation of the enzyme or enzymatic activity could be used in conjunction with maintenance therapy for cocaine addicts. Hydrolases or esterases are also responsible for the transesterfication of cocaine. The pharmacological effect of cocaine is prolonged and enhanced when cocaine is used in conjunction with ethanol. A carboxylesterase catalyzes an ethyl transeterification of cocaine to cocaethylene, which is biologically active. 

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