With cocaine toxicity

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... 

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). 

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

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.

Amphetamines are often combined with cocaine to extend the high. Cocaine creates a rush but it is short-lived. Adding amphetamines extends the high for up to ten hours. Using these drugs together increases the chances of an overdose and increases toxic effects. 

Cocaine also blocks the reuptake of norepinephrine in the PNS the combination of central and peripheral actions leads to a high probability of toxicity. The cardiovascular system is particularly sensitive to the actions of cocaine, and cardiac arrhythmias, marked increases in blood pressure, cerebral hemorrhage, myocardial ischemia, and outright heart failure are not uncommon with cocaine use. Even young, otherwise healthy individuals with normal coronary and cerebral arteries have died suddenly after cocaine use from cerebral hemorrhage or ventricular fibrillation. There have been several deaths of famous athletes attributed to cocaine cardiotoxicity. These cardiotoxic effects may be related to increased intracellular calcium levels and involve both cardiac and vascular actions of the drug. 

Therapeutic uses Factors that limit the therapeutic usefulness of amphetamine include psychological and physiological dependence similar to those with cocaine, and the development of tolerance to the euphoric and anorectic effects with chronic use. [Note Less tolerance to the toxic CNS effects (for example, convulsions) develops.]... 

Cocaine was also the first aminoester local anesthetic, and its adverse effects differ from those of other local anesthetics. Owing to its rapid absorption by mucous membranes, cocaine applied topically can cause systemic toxic effects. There is a wide variation in the rate and amount of cocaine that is systemically absorbed. This variability can be affected by the type and concentration of vasoconstrictor used with cocaine and also accounts for the differences in cocaine pharmacokinetics in cocaine abusers (SEDA-20,128). 

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. 

Cocaine has been associated with liver toxicity (SEDA-14, 32 SEDA-13, 27). 

Amphetamines are more toxic than cocaine and, when abused, cause worse problems. The body has a great capacity to metabolize and eliminate cocaine the liver can detoxify a lethal dose of cocaine every thirty minutes. It cannot handle amphetamines as efficiently. At the same time, people can establish stable relationships with amphetamines more easily than they can with cocaine, probably because the intensely pleasureful but very short effect of cocaine is more seductive and invites repetitive dosing. 

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,... 

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. 

This chapter addresses the toxic effects of the mixtures of two recreational toxins, ethanol and tobacco. These are the most abused chemicals in the world and both are used recreationally worldwide. There are many other recreational drugs in use. These include marijuana, cocaine, heroin, and methamphetamines for example. These other recreational drugs are not addressed here, except where they are components of xenobiotic mixtures that produce unanticipated toxic effects. At this time there is a substantial volume of information that describes unanticipated toxic effects of ethanol and tobacco when used in conjunction with other toxicants. That information is the subject of this chapter. 

Cocaine Metabolism. Because cocaine (3)has two ester functions, both can be hydrolyzed in vivo to generate metabolites. Hydrolysis of the methyl ester leads to benzo-ylecgonine (12), and hydrolysis of the benzoyl ester leads to ecgonine methyl ester (13).Tro-pan-3j3-ol-2j8-carboxylic acid is known as ecgonine (14). In cocaine users who also consume significant amounts of ethanol, a transesterification product (cocaethylene, 15) is also detected. Cocaethylene is also a potent psychostimulant, with about four times higher potency as a local anesthetic than that of cocaine itself (69), and can enhance the cardio-toxicity associated with cocaine use. 

Cocaine is a psychotomimetic drug, sometimes even at system-ically nontoxic doses. A kindling phenomenon has been described with cocaine in which neuronal function becomes altered with each dose of the drug. This causes a type of reverse tolerance with increased receptor sensitivity to cocaine, and psychosis may be caused by doses that formerly did not cause psychosis. The toxic psychosis is characterized by auditory, visual, and frequently tactile hallucinations, paranoid thinking, and looseness of associations. The psychosis is qualitatively very similar to a paranoid schizophrenic psychosis. ... 

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. 

If a 1 % solution is injected intravenously into rabbits at the rate of 1 cc. in 18 sec., the toxicity is about twice that of cocaine. By subcutaneous injection the toxicity appeared to be about five times cocaine. A 2% solution applied to a rabbit s cornea did not produce complete anesthesia. Moreover, the solution appeared to be distinctly more irritating than a similar solution of cocaine hydrochloride although it was only faintly acid in reaction. There was no sign of dilation of the pupil as is noticed with cocaine hydrochloride. 

The toxicity of ethanol is enhanced in the presence of compounds such as barbiturates, carbon monoxide, and methyl mercury. With the latter compound, ethanol enhanced the retention of mercnry in the kidney of rats and thns increased nephrotoxicity (McNeil et al. 1988). When combined with cocaine and fed to rats, increased maternal and fetal toxicity was observed (Chnrch et al. 1988). Ethanol is reported to be synergistically toxic with caffeine (Pollard 1988) and with n-bntanol and isoamyl alcohol. Prior ethanol consnmption increased the toxicity... 

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

Alcohol increases cocaine levels and the active metabolite coca-ethylene. Subjective effects such as euphoria are enhanced and some of the CNS-depressant effects of alcohol, such as sedation, are attenuated by cocaine. The combination may be potentially more toxic, with increased cardiovascular effects particularly heart rate. The use of alcohol with cocaine may increase violent behaviour. 

Limited evidence su ests intravenous lidocaine use in patients with cocaine-associated myocardial infarction is not associated with significant toxicity. 

Infectious disease A 48 year-old female presented with streptococcal toxic shock syndrome Streptococcus pyogenes) and was found to have ingested levamisole-adulterated cocaine [53 ]. 

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