Half-life of cocaine

The half-life of cocaine in plasma is about 50 min, but inhalant (crack) users typically desire more cocaine after 10 to 30 min. Intranasal and intravenous uses also result in a high of shorter... 

The stimulant properties of cocaine are similar to those of amphetamines, although the differences are notable, in part because of the very short half-life of cocaine. However, cocaine has the same problem of abuse potential as other stimulants, and at high doses causes stimulant psychosis (10). In addition, even when it is used as a local nasopharyngeal anesthetic, it has toxic, even fatal, effects in high doses. 

Cocaine is metabolized and eliminated rapidly. The elimination half-life of cocaine is approximately 1 hour, and the duration of effect is very short. The short duration of effect provides a powerful incentive for repeated use of the drug. Many users experience intense drug use cycling, sometimes lasting days, characterized by rapidly repeating doses of cocaine until their supply is exhausted. Laboratory monkeys, given a choice between food and cocaine around the clock for 8 days, consistently choose cocaine. ... 

Once in the blood stream, cocaine levels quickly rise in the brain, faster than plasma levels, which then redistribute to other tissues. Cocaine is rapidly metabolized in the blood and liver, with a half-life of 30 to 90 minutes. The major metabolites have a half-life of approximately 8 hours. Although cocaine itself is detected in urine for only 12 hours, the metabolite benzoylecgonine can be detected in urine for at least 48 hours and sometimes up to 2 weeks. Concurrent use of cocaine and ethanol produces an ethyl ester of benzoylecgonine called cocaethylene. Cocaethylene is an active metabolite, blocking dopamine reuptake, and potentiating the effect of cocaine. Thus, concurrent use of cocaine and ethanol can further increase the additional effects of the drugs and the risk of dependency. 

The main difference between cocaine and the amphetamine-like drugs lies in its shorter duration of action, the half-life for cocaine being about 50 minutes while that of amphetamine is 10 hours. 

Cocaine acts as a potent local anesthetic and is a strong CNS stimulant it extends and intensifies the effects of dopamine, norepinephrine, serotonin neurotransmitters [3], The effects of cocaine can vary in relation to the individual characteristics, the administered dose, frequency of use, and route of administration. The intranasal administration causes plasma peak concentrations after 5-20 min, the euphoric effect in 15-20 min with a half-life of 40 min. The oral route involves a slow and low absorption with plasma peak concentrations after approximately 90 min and euphoric effect in 15-20 min. Intravenous plasma peak is immediate, euphoric effect occurs after 4-8 min with a half-life of about 40 min. Finally it may be administered through inhalation of combustion products or crack vapors, with great absorption speed. 

The elimination half-life for cocaine ranges from 0.5 to 1.5 hours, for ecgonine methyl ester from 3 to 4 hours, and for benzoylecgonine from 4 to 7 hours. The principal urinary metabolites are benzoylecgonine and ecgonine methyl ester. Only small amounts of cocaine are excreted in urine. The elimination half-life for cocaethylene is 2.5 to 6 hours, considerably longer than that for cocaine. This longer elimination half-life may contribute to cocaethylene s toxicity. 

C. Pharmacokinetics. Cocaine Is well absorbed from all routes, and toxicity has been described after mucosal application as a local anesthetic. Smoking and intravenous Injection produce maximum effects within 1-2 minutes, while oral or mucosal absorption may take up to 20-30 minutes. Once absorbed, cocaine is eliminated by metabolism and hydrolysis with a half-life of about 60 minutes. In the presence of ethanol, cocaine Is transesterified to cocaethyl-ene, which has similar pharmacologic effects and a longer half-life than cocaine. (See also Table 11-59.)... 

It has been suggested that the enhaneed psyehological effects associated with alcohol and cocaine may lead to the use of larger amounts of the combination with an increased risk for toxic effects, such as cardiotoxicity. It has been reported that users of aleohol and eoeaine who also have coronary artery disease have 21.5 times the risk for sudden death than users of eoeaine alone. The longer half-life of the metabolite cocaethylene explains why many people who experienee eoeaine-related heart attacks and strokes do so when the eoeaine levels in their blood are low, as cocaethylene ean remain active in the body for 7 hours after cocaine has disappeared. Patients with eoronaiy artery disease or alcoholics may be particularly vulnerable to the eombined toxie effects of alcohol and cocaine. 

However, contamination of cocaine with levamisole can be hard to prove, because testing is not routinely available and levamisole has a short half-life of a few hours. 

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. 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

Racemic f/zreo-methylphenidate was approved for the treatment of fatigue, nausea, and depression in 1955 under the brand name Ritalin , and was first used in children in 1958 with an approval for hyperkinetic disorder (ADHD) in 1960. Methylphenidate has an even shorter half-life than amphetamine, and its use in treating ADHD was limited by the fact that schoolchildren would need to visit a nurse during the day to take a second dose of this scheduled drug (in order to maintain efficacy throughout the entire school day). In humans, injecting methylphenidate produces effects similar to intravenous cocaine, but oral methylphenidate is adsorbed very slowly from the gut into the blood and takes an unusually long time (estimated 2.5 h) to reach a peak concentration... 

Cocaine is a local vasoconstrictor, and snorting of cocaine intra-nasally reduces the amount of blood flow to the area, resulting in a reduced rate of drug absorption and slower onset of action. Often in cocaine abusers, the reduced blood supply to the nasal septum leads to the development of a perforation between the nasal passages. The effects of cocaine last approximately 40 minutes, while the effects of other stimulants usually last several hours, as each has a different half-life. 

The highest levels of cocaine use in Canada are found along the Pacific coast in the province of British Colombia (16.7% life-time prevalence in 2004). The four Canadian provinces along the Atlantic show rates of cocaine use that are just half or less (3.7%-7.1%) the levels reported from British Colombia. Life-time prevalence rates of cocaine use in British Colombia are also higher than those reported for the USA as a whole. 

A two-compartment open linear model has been described for the pharmacokinetic profile of cocaine after intravenous administration.14 The distribution phase after cocaine administration is rapid and the elimination half-life estimated as 31 to 82 min.14 Cone9 fitted data to a two-compartment model with bolus input and first-order elimination for the intravenous and smoked routes. For the intranasal route, data were fitted to a two-compartment model with first-order absorption and first-order elimination. The average elimination half-life (tx 2 3) was 244 min after intravenous administration, 272 min after smoked administration, and 299 min after intranasal administration. 

Cocaine easily passes the blood brain barrier and the plasma levels are detectable for about 4-6 h after nasal ingestion it is rapidly metabolized into inactive metabolites benzoylecgonine (BEG), ecgonine methyl ester (EME), and ecgonine [12], These molecules are biomarkers for the identification of cocaine abuse due to their higher biological half-life with respect to cocaine (about fivefold). 

The criteria for the interpretation of cocaine concentrations in biological samples and their relation to the cause of death has been comprehensively reviewed (234). The importance of scene investigation, forensic autopsy, and forensic sampling for drug analysis has been discussed, with particular emphasis on the need to use appropriate blood preservatives and interpretation of the half-life and concentrations of cocaine and its metabolites, benzylec-gonine and ethylcocaine, in combined cocaine + alcohol abuse. 

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. 

Dose/concentration relation could only be found for some legal drugs, for example, methadone by Moeller et al. and meprobamate by Kintz et al. For illegal drugs it will probably not be possible to perform studies to answer this question, because even in countries where such studies are allowed, it is not permitted to administer levels used by drug addicts. An additional difficulty is that most drugs, heroin, cocaine, THC metabolite having a short half-life, and a number of metabolites are detected in the hair. 

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