Blood ethanol concentrations

The best-known exception to exponential kinetics is the elimination of alcohol (ethanol), which obeys a linear time course (zero-order kinetics), at least at blood concentrations > 0.02 %. It does so because the rate-limiting enzyme, alcohol dehydrogenase, achieves half-saturation at very low substrate concentrations, i.e at about 80 mg/L (0.008 %). Thus, reaction velocity reaches a plateau at blood ethanol concentrations of about 0.02 %, and the amount of drug eliminated per unit of time remains constant at concentrations above this level. 

The metabolism of most drugs or chemicals is proportional to the concentration in the blood, which allows a half-life to be calculated. Ethanol is different its metabolism is relatively constant over time and does not increase with rising blood ethanol concentrations. Metabolism is proportional to body weight thus the bigger you are, the higher the rate of ethanol metabolism, but on average ethanol is metabolized at a rate of 120 mg/kg per hour or about 1 oz (30 ml) in 3 hours. 

Management of methanol and ethylene glycol poisoning is similar. Symptomatic support of respiration and circulation is augmented by correction of metabolic acidosis with intravenous bicarbonate infusion, and control of seizures with diazepam. Ethanol inhibits the metabolism of methanol and ethylene glycol to the toxic metabolites, and can give time for further treatment. The goal is to maintain blood ethanol concentrations between 100 and 150 mg per decilitre, sufficient to saturate alcohol... 

In fact, small amounts of morphine, 6-acetylmorphine, codeine, and thebaine, all opiate compounds, have been found in mammalian brain877 878 and have presumably arisen by the same pathway observed in plants (Fig. 25-10). However, there is no cross reactivity between morphine and alcohol in addicted mice,879 and acetaldehyde is probably not the addictive agent. Acetaldehyde is very reactive and may be responsible for much of the damage caused by ethanol.880 At a blood ethanol concentration of 20 mm a person is legally intoxicated, and large amounts of acetaldehyde may be formed and react with many amines, nucleotides, proteins, etc. Ethanol blocks glutamatergic NMDA receptors and... 

Alcohol clearly affects eye movement. Both smooth pursuit movements and saccades are impaired when blood ethanol concentrations reach the range of 60 to 100 mg/dl. There is a direct linear relationship between blood alcohol concentration and a reduction in smooth-pursuit movement velocity. At a blood ethanol concentration of 80 mg/dl, the capacity of the eyes to track objects moving across the visual fields is impaired by 25%. 

Alcohol distributes into the aqueous compartments of blood, and because the water content of serum ( 98%) is greater than that of whole blood ( 86%), results indicating higher alcohol levels are obtained with serum. Experimentally the serum whole blood ethanol ratio is 1.14 (1.09 to 1,18) and varies slightly with hematocrit.Several states have enacted laws that define intoxication while driving a motor vehicle under the influence of alcohol based on whole blood ethanol concentrations. Some states do not specify the specimen type. Therefore laboratories that perform alcohol determinations should make clear the choice of specimen. 

Winek CL, Carfagna M. Comparison of plasma, serum, and whole blood ethanol concentrations. J Anal Toxicol 1987 11 267-8. 

Third, for forensic cases in which there is a question of poisoning with ethanol, a sample of blood could be analyzed for FAEE quantitation to assess prior ethanol administration. It is not yet known if there are any causes for a false-positive FAEE test or a false-negative FAEE value. It is possible that ingestion of certain medications or foodstuffs will make the FAEE test falsely positive, and it is also possible that interferences exist that block the detection of FAEE. No causes of false-positive or falsenegative tests have been yet identified, but there is always a possibility that one will appear as more research is done in the field. In addition, one cannot use the level of blood FAEE 24 h after drinking alcohol to predict the peak blood ethanol concentration much earlier. 

A positive blood ethanol concentration and/or positive urine drug screen indicates that drug intoxication may be affecting the patient s mental status in addition to the TBI. 

Figure E7-7.3 gives the predicted blood ethanol concentration trajectories and experimentally measured trajectories. The different curves are for different initial doses of ethanol. Note that the highest initial dose of ethanol reaches a maximum concentration of 16.5 raM of alcohol and that it takes between 5 and 6 hours to reach a level where it is safe to drive. A comparison of the model and experimental data of Jones et al. for the acetaldehyde concentration is shown in Figure E7-7.4, Because the acetaldehyde concentrations are three orders of magnitude smaller and more difficult to measure, there is a wide range of error bars. The model can predict both the alcohol and acetaldehyde concenu-ation trajectories without adjusting any parameters.

As blood ethanol concentration rises above 18 mM (the legal intoxication limit is now defined as 0.08% in most states of the United States, which is approximately 18 mM), the brain and central nervous system are affected. Induction of CYP2E1 increases the rate of ethanol clearance from the blood, thereby contributing to increased alcohol tolerance. However, the apparent ability of a chronic alcoholic to drink without appearing inebriated is partly a learned behavior. 

II. Toxic dose. Generally, 0.7 g/kg pure ethanol (approximately 3- drinks) will produce a blood ethanol concentration of 100 mg/dL (0.1 g/dL), legally considered... 

Brown ASJM, James OFW. Omeprazole, ranitidine and cimetidine have no effect on peak blood ethanol concentrations, first pass metabolism or area under the time-ethanol curve under real-life drinking cor i or)s.AUmentPhcuinacolTher 99Z) 12,141-5. 

Congener analysis is a modification of the conventional headspace gas chromatography analysis for measuring blood ethanol concentration However, the sensitivity of the method must be increased to allow measuring much lower concentrations (Iffland Jones, 2003)... 

Gas-liquid chromatography (GLC) is the most commonly used method for the forensic and clinical analysis of ethanol. Cadman and Johns in 1958 first reported a GLC method for determining blood ethanol concentrations. They extracted ethanol from samples prior to analysis by adding equal volume of n-propyl acetate (1ml) to a blood sample (1ml) to extract ethanol. No internal standard was used. A fixed volume of extract (35 pi) was injected into a GL chromatograph equipped with a thermal... 

Table 3 Blood ethanol concentrations and clinical signs/symp-toms...

Since the effects of ethanol on a person s mental and physical condition are correlated with its blood concentrations, intoxication is based on blood ethanol concentrations (Table 3). However, some... 

Adverse effects on the central nervous system are already evident at blood ethanol concentrations of 10 mg/100 mL in children. Higher peak ethanol blood concentrations are also observed in children than in adults for a similar intake [15]. 

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