1In many parts of the United States, a blood level above 80–100 mg/dL for adults or 5–20 mg/dL for persons under 21 is sufficient for conviction of driving while “under the influence.” intoxicated with a blood alcohol concentration of 300–400 mg/dL (0.30-0.40%), whereas this level is associated with marked intoxication or even coma in a nontolerant individual. The propensity of moderate doses of alcohol to inhibit the attention and information-processing skills as well as the motor skills required for operation of motor vehicles has profound effects. Approximately 30–40% of all traffic accidents resulting in a fatality in the United States involve at least one person with blood alcohol near or above the legal level of intoxication, and drunken driving is a leading cause of death in young adults.
Like other sedative-hypnotic drugs, alcohol is a CNS depressant. At high blood concentrations, it induces coma, respiratory depression, and death.
Ethanol affects a large number of membrane proteins that participate in signaling pathways, including neurotransmitter receptors for amines, amino acids, opioids, and neuropeptides; enzymes such as Na+/K+-ATPase, adenylyl cyclase, phosphoinositide-specific phospholipase C; a nucleoside transporter; and ion channels. Much attention has focused on alcohol’s effects on neurotransmission by glutamate and γ-aminobutyric acid (GABA), the main excitatory and inhibitory neurotransmitters in the CNS. Acute ethanol exposure enhances the action of GABA at GABAA receptors, which is consistent with the ability of GABA-mimetics to intensify many of the acute effects of alcohol and of GABAA antagonists to attenuate some of the actions of ethanol. Ethanol inhibits the ability of glutamate to open the cation channel associated with the N-methyld-aspartate (NMDA) subtype of glutamate receptors. The NMDA receptor is implicated in many aspects of cognitive function, including learning and memory. “Blackouts”—periods of memory loss that occur with high levels of alcohol—may result from inhibition of NMDA receptor activation. Experiments that use modern genetic approaches eventually will yield a more precise definition of ethanol’s direct and indirect targets. In recent years, experiments with mutant strains of mice, worms, and flies have reinforced the importance of previously identified targets and helped identify new candidates, including a calcium-regulated and voltage-gated potassium channel that may be one of ethanol’s direct targets (see Box: What Can Drunken Worms, Flies, and Mice Tell Us about Alcohol?).
B. Heart
Significant depression of myocardial contractility has been observed in individuals who acutely consume moderate amounts of alcohol, ie, at a blood concentration above 100 mg/dL.
C. Smooth Muscle
Ethanol is a vasodilator, probably as a result of both CNS effects (depression of the vasomotor center) and direct smooth muscle relaxation caused by its metabolite, acetaldehyde. In cases of severe overdose, hypothermia—caused by vasodilation—may be marked in cold environments. Preliminary evidence indicates that flibanserin augments the hypotensive effects of ethanol and may cause severe orthostatic hypotension and syncope (see Chapter 16). Ethanol also relaxes the uterus and—before the introduction of more effective and safer uterine relaxants (eg, calcium channel antagonists)—was used intravenously for the suppression of premature labor.
Consequences of Chronic Alcohol Consumption