Pathophysiology

Ethanol is a central nervous system depressant which inhibits neuronal activity, probably through its effects on cell membranes. Behavioral stimulation is often observed at low blood concentrations. Cross-tolerance exists between ethanol and other sedative-hypnotic agents, including benzodiazepines and barbiturates. Absorption occurs from the mouth and esophagus to a small extent, from the stomach and large bowel to a moderate extent, but chiefly from the proximal portion of the small bowel.

Gender-related differences in the metabolism of ethanol explain the considerably higher blood ethanol levels in women versus men after similar dosing on a gram-per-kilogram basis. Women have a smaller volume of distribution (0.6 L/kg) for ethanol than men (0.7 L/kg) and have decreased first-pass metabolism of ethanol because their gastric walls contain less alcohol dehydrogenase than do those of men. 4

Approximately 2 to 10 percent of ethanol may be excreted by the lungs, in urine, or in sweat, the proportion being dependent on blood concentration. The remainder is metabolized to acetaldehyde in the liver by one of two pathways. In the cell, cytosol alcohol dehydrogenase with nicotinamide adenine dinucleotide as a cofactor produces acetaldehyde, which in turn is metabolized by aldehyde dehydrogenase. The second pathway, which is clinically significant at high blood ethanol concentrations and has increased activity with repeated exposures to ethanol, is a microsomal alcohol oxidizing system.

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