Toxicity cocaine

Hoffman RS, Henry GC, Howland MA, et al. 1992. Association between life-threatening cocaine toxicity and plasma cholinesterase activity. Ann Emerg Med 21 248-253... 

Shimosato K., Marley R., Saito T. Differential effects of NMDA receptor and dopamine receptor antagonists on cocaine toxicities. Pharmacol. Biochem. Behav. 51, 1995. 

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.

Ruttenber, A.J., Lawler-Haevener, J., Wetli, C.V., Hearn, W.L., and Mash, D.C. Fatal excited delirium following cocaine use epidemiologic findings provide evidence for new mechanisms of cocaine toxicity. J. Forensic Toxicol. 42 25, 1997. 

In a review of 114 cases, coronary anatomy, defined either by angiography or autopsy, was normal in 38% of chronic cocaine users who had had a myocardial infarction (23). The authors of another review concluded that the vast majority of patients dying with cocaine toxicity, either have no pathological changes in the heart, or only minimal changes (24). There can be a delay between the... 

Dysrhythmias seem to be the most likely cause of sudden death from cocaine, but cardiac conduction disorders are more common in patients with acute cocaine toxicity. Severe cocaine toxicity also causes acidemia and cardiac dysfunction (96). Four patients developed seizures, psychomotor agitation, and cardiopulmonary arrest two of these are briefly summarized here. 

Myocardial ischemia was reported in a fit 29-year-old patient after the nasal application of cocaine for surgery. No relief was gained from vasodilators or intracoronary verapamil, and there were no other signs of cocaine toxicity. Although coronary vasoconstriction and platelet activation are systemic effects of cocaine, pre-existing thrombus may also have played a part (SEDA-22,142). 

The grafts took in all three cases. Myoglobinuric acute renal insufficiency in the donor did not affect immediate, short-term, or long-term graft function. In their review of the literature, the authors found one report of eight transplants from three donors. There were no effects attributable to cocaine in any of the recipients in the immediate post-transplantation period. They concluded that organ donation is safe after brain death caused by cocaine toxicity, probably because of the characteristics of the cocaine, such as a short half life. 

Stark TW, Pruet CW, Stark DU. Cocaine toxicity. Ear Nose Throat J 1983 62(3) 155-8. 

Acute systemic cocaine toxicity may result from as little as 20 mg (10 drops of a 4% solution) of drug. The total dose of cocaine should not exceed 3 mgAg of... 

In a review of 114 cases, coronary anatomy, defined either by angiography or autopsy, was normal in 38% of chronic cocaine users who had had a myocardial infarction (20). The authors of another review concluded that the vast majority of patients dying with cocaine toxicity, either have no pathological changes in the heart, or only minimal changes (21). There can be a delay between the use of cocaine and the development of chest pain (44). The results of a study of 101 consecutive patients admitted with acute chest pain related to cocaine suggested that it commonly causes chest pain that may not be secondary to myocardial ischemia (45). The use of intranasal cocaine for therapeutic purposes (to treat epistaxis) was associated with myocardial infarction in a 57-year-old man with hypertension and stable angina (46). 

Glauser J and Queen JR. An overview of non-cardiac cocaine toxicity. J Emer Med. 2007 32 181-186... 

Lombard J,Wong B,YoungJH. Acute renal failure due to rhabdomyolysis associated with cocaine toxicity. West J Med 1988 148 ... 

Cocaine toxicity is primarily secondary to its ability to prevent the reuptake of neurotransmitters including serotonin, dopamine, and norepinephrine. Direct cardie toxicity may be due to inhibition of... 

Animal models have demonstrated acute toxicity similar to that present in humans. Dogs develop toxicity at lower doses than rats, and death appears to be associated with the development of hyperthermia. The functional status of organ enervation and the presence of anesthetics may alter cocaine toxicity in animal models. 

For recreational use, cocaine (hydrochloride salt) is often administered by nasal insufflation ( snorting ) or less frequently, intravenously. Cocaine is more volatile when converted from the salt to the freebase therefore freebase cocaine may be inhaled by smoking. This latter route of administration results in a rapid onset of action. It has gained increased popularity owing to the ready availabihty of the freebase cocaine form known as crack. Consequently the number of emergency room admissions related to cocaine toxicity has increased. 

Acute cocaine toxicity produces a sympathomimetic response that may result in mydriasis, diaphoresis, hyperactive bowel sounds, tachycardia, hypertension, hyperthermia, hyperactivity agitation, seizures, or coma. Sudden death due to cardiotoxicity may occur following cocaine use. Death may also occur following the sequential development of hyperthermia, agitated delirium, and respiratory arrest. Excited delirium and extreme physical activity may lead to rhabdomyolysis, acute renal failure, and disseminated intravascular coagulopathy. 

Powerful selective antidotes or antagonists to treat cocaine abuse are necessary to offset the increased cocaine toxicity currently observed in the United States. The use of catalytic antibodies in the creation of selective binding agents and detoxication catalysts of cocaine could represent a novel approach that may result in significant advances in the field of detoxication of drugs of abuse. An anti-cocaine catalytic antibody directed to hydrolyze the benzoyl ester could in principle catalyze the formation of ecgonine and benzoic acid, hydrolysis products of cocaine that do not possess the reinforcing or CNS stimulation properties of cocaine (Spealman et al. 1989). 

The short MRT of rHu BChE in animals has precluded the testing of its protective properties against OP agents. Using tetrameric rHu BChE in mice, which has an MRT of 16 h, Duysen et al. (2002) demonstrated that it conferred 50% protection from cocaine toxicity. Because rHu BChE protects against cocaine toxicity by hydrolyzing cocaine, the improvement in its MRT from 2 min to 16 h was sufficient to protect mice. However, the circulatory stability and bioavailability of tetrameric rHu BChE were still not comparable to that for Hu BChE (Table 7.3), which... 

Duysen, E.G., Bartels, C.F. and Lockridge, O. Wild-type and A328W mutant human butyrylcholinesterase tetramers expressed in Chinese hamster ovary cells have a 16-hour half-life in the circulation and protect mice from cocaine toxicity, J. Pharmacol. Exp. Ther., 302, 751, 2002. 

Cocaine toxicity has both somatic and psychiatric manifestations. Somatic effects include myocardial depression, malignant dysrhythmias, stroke, and sudden death, partially due to cocaine-related myocardial sodium channel blockade and coronary and cerebral vasoconstriction. Such life-threatening conditions occur mainly when cocaine is combined with other abused drugs. Psychiatric effects can mimic the positive and negative symptoms of schizophrenia. 

Derlet, R. W., and T. E. Albertson. 1990a. Acute cocaine toxicity antagonism by agents interacting with adrenoceptors. Pharmacol Biochem. Behav. 36(2) 225-31. 

Cocaine has a half-life of 0.5-1.5 h but its metabolites such as benzoylecgonine and cocaethylene have much longer half-lives. The authors report that the clinical use of ILE in the treatment of local-anaesthetic-associated cardiac toxicity was first reported in 2006. This helped to move treatment from supportive management to more specific intervention. Now, ILE is incorporated into current guidelines for management of local anaesthetic toxicity. This treatment is hypothesised to work by absorbing the circulating toxins. There are other hypotheses too about how this may work. The authors report that other case reports have also documented the benefits of ILE in treatment of cocaine toxicity and have the potential to prevent mortality. 

Gao, Y, Geng, L., Orson, R, et al., 2013. Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage. Chem. Biol. Interact. 203, 208-211. 

---