The molecular mechanisms involved in alcohol intoxication and tolerance are obviously more complex than the foregoing remarks would indicate (see reviews by Charness and by Samson and Harris). There is now a vast literature on this subject, much of it contradictory, and a unified concept of the role of neurotransmitters and their receptors and modulators in the production of alcohol intoxication and tolerance has yet to emerge. The part played by internal cellular messengers, which have attracted much attention in the field of addiction, is also currently under investigation.
Alcohol tolerance A scale of blood concentrations such as the one previously described has virtually no value in the chronic alcoholic patient, as it does not take into account the phenomenon of tolerance. It is common knowledge that a habituated person can drink more and show fewer effects than the moderate drinker or abstainer. This phenomenon accounts for the surprisingly large amounts of alcohol that the chronic drinker can consume without showing significant signs of drunkenness. Sober-appearing alcoholics may have blood alcohol levels of 400 to 500 mg/dL. This aspect of tolerance must be considered in judging the significance of a single estimation of the blood alcohol concentration as an index of functional capacity. The mechanisms that underlie tolerance and addiction are just beginning to be understood. There is little evidence that an enhanced rate of alcohol metabolism can adequately account for the degree of tolerance observed in alcoholics. An increase of neuronal adaptation to alcohol is a more likely explanation. Theoretically, the factors that are operative in this adaptation are the increasing resistance of neuronal membranes to the effects of alcohol and an increase in the number of neuronal calcium channels in the cell membrane.
Clinical Effects of Alcohol on the
Alcohol functions as a central nervous system (CNS) depressant. Some of the early effects of alcohol, such as garrulousness, aggressiveness, excessive activity, and increased electrical excitability of the cerebral cortex—all of them suggestive of cerebral stimulation—are thought to be caused by the inhibition of certain subcortical structures (possibly the high brainstem reticular formation) that ordinarily modulate cerebrocortical activity. Similarly, the initial hyperactivity of tendon reflexes may represent a transitory escape of spinal motor neurons from higher inhibitory centers. With increasing amounts of alcohol, however, the depressant action involves the cortical as well as other brainstem and spinal neurons. All motor functions—whether the simple maintenance of a standing posture, the control of speech and eye movements, or highly organized and complex motor skills—are adversely affected by alcohol. The movements involved in these acts are not only slower than normal but also more inaccurate and random in character and therefore less well adapted to the accomplishment of specific ends.
Alcohol also impairs the efficiency of mental function by interfering with the speed of perception and the ability to persist in mental processing. The learning process is slowed and rendered less effective. Facility in forming associations, whether of words or of figures, and the ability to focus, sustain attention, and concentrate are reduced. Finally, alcohol impairs the faculties of judgment and discrimination and, all in all, the ability to think and reason clearly.
A number of neurologic disorders are characteristically associated with alcoholism. The factor common to all of them, of course, is the abuse of alcohol, but the mechanism by which alcohol produces its effects varies widely from one group of disorders to another and in many cases, the essential problem is one of nutritional deficiency as discussed in the preceding chapter. The classification that follows is based for the most part on known mechanisms.
I. Alcohol intoxication—drunkenness, coma, paradoxical excitement (“pathologic intoxication”), “blackouts”
II. Abstinence or withdrawal syndrome—tremulousness, hallucinosis, seizures, delirium tremens
III. Nutritional diseases of the nervous system accompanying alcoholism (see Chap. 40)
A. Wernicke-Korsakoff syndrome
B. Polyneuropathy
C. Optic neuropathy (“tobacco-alcohol amblyopia”)