After oral administration, ethanol is almost completely absorbed throughout the gastrointestinal tract. The rate of absorption is largely determined by the quantity consumed, the concentration in the beverage, the rate of consumption, and the composition of the gastric contents. Eating food before or during drinking retards absorption, especially if the food has a high lipid content.
After absorption, ethanol is distributed throughout body water. In organs with high blood flow, such as the brain, liver, lungs, and kidney, equilibrium occurs rapidly. Conversely, in organs with low blood flow, such as muscle, equilibrium occurs more slowly. Ethanol readily passes through the blood-placenta barrier into the fetal circulation. Although the concentration of ethanol in the blood can be quite predictable, measurements of blood ethanol, especially when the concentrations are rising, may lead to erroneous conclusions, since the values obtained can underestimate the concentration of ethanol in the brain. This fact can confound legal proceedings in drunk-driving cases where blood ethanol concentrations are considered an accurate and legally acceptable determinant of the amount of ethanol consumed.
Ethanol is metabolized primarily in the liver by at least two enzyme systems. The best-studied and most important enzyme is zinc dependent: alcohol dehydro-genase. Salient features of the reaction can be seen in Fig. 35.1. The rate of metabolism catalyzed by alcohol dehydrogenase is generally linear with time except at low ethanol concentrations and is relatively independent of the ethanol concentration (i.e., zero-order kinetics). The rate of metabolism after ingestion of different amounts of ethanol is illustrated in Fig. 35.2.
In adults, ethanol is metabolized at about 10 to 15 mL/hour. Since metabolism of ethanol is slow, ingestion must be controlled to prevent accumulation and intoxication. There is little evidence that chronic ingestion of ethanol leads to a significant induction of alcohol de-hydrogenase, even in heavy drinkers.
Some populations, most notably East Asians, exhibit an unusual response after drinking ethanol. The symptoms include facial flushing, vasodilation, and tachycardia. These individuals apparently have a genetic deficiency of the enzyme aldehyde dehydrogenase, which leads to an accumulation of acetaldehyde even after they drink relatively small amounts of ethanol. If drugs such as metronidazole, griseofulvin, quinacrine, the hypoglycemic sulfonylureas, phenothiazines, and phenylbutazone are coadministered with ethanol, a similar accumulation of acetaldehyde may occur.
In addition to alcohol dehydrogenase, ethanol can be oxidized to acetaldehyde by the microsomal mixed-function oxidase system (cytochrome P450 2 EI), as illustrated in Figure 35.1. Although this microsomal ethanol-oxidizing system probably has minor impor-
2-10% expired unchanged in air and urine
Zero-order kinetics Alcohol
Major metabolic route Dehydrogenase Not induced
Liver Mixed function oxidase (90-98%) (P450 2EI)
First-order kinetics Minor metabolic pathway Induced by ethanol Interferes with metabolism of other drugs
Vasodilation Headache Nausea Vomiting
Respiratory difficulties Chest pains
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