Chapter 143 Alcohol Dependence
• Psychological/social signs of excess alcohol consumption: depression, loss of friends, arrest for driving while intoxicated, surreptitious drinking, drinking before breakfast, frequent accidents, unexplained work absences
Alcohol dependence, alcohol-use disorder, or, as it was formerly known, alcoholism, is a disabling addictive disorder characterized by alcohol consumption that exceeds acceptable cultural limits or injures health or social relationships. Estimates are that the prevalence of lifetime and 12-month alcohol dependence in the United States is 12.5% and 3.8%, respectively.1 Alcohol dependence is significantly more prevalent among men, whites, Native Americans, younger and unmarried adults, and those with lower incomes. Alcohol dependence affects over 18 million Americans, making it one of the most serious health problems facing physicians today.1 The total number of Americans affected, either directly or indirectly, is much greater when one considers disruption of family life, automobile accidents, crime, decreased productivity, and mental and physical diseases. With more than 100,000 deaths annually attributed to alcohol misuse, alcohol-related problems are a cause of considerable mortality.2 As indicated in Box 143-1, the health, social, and economic consequences of alcohol dependence are alarming.
BOX 143-1 Consequences of Alcohol Dependence
Modified from Hyman SE, Cassem NH. Alcoholism. In Dale DC, Federman DD, eds. Scientific American medicine. New York: Scientific American 1997;III:1-12, 13.
Physicians should consider alcohol dependence when the information provided by the patient and the doctor’s own analysis seems to indicate a missing factor. Often, alcohol dependence is a “hidden” disease. The natural consequences of the alcoholic’s behavior may be disguised by sympathetic family and friends. This allows the alcoholic to target other factors as the “real problem” without identifying his or her drinking behavior. Table 143-1 provides an alcohol dependence screening questionnaire.
|1. Do you feel you are a normal drinker?||Yes (0)||No (2)|
|2. Do friends or relatives think you are a normal drinker?||Yes (0)||No (2)|
|3. Have you ever attended a meeting of Alcoholics Anonymous (AA)?||Yes (5)||No (0)|
|4. Have you ever lost friends or girlfriends or boyfriends because of drinking?||Yes (2)||No (0)|
|5. Have you ever gotten into trouble at work because of drinking?||Yes (2)||No (0)|
|6. Have you ever neglected your obligations, your family, or your work for 2 or more days in a row because you were drinking?||Yes (2)||No (0)|
|7. Have you ever had delirium tremens (DTs), severe shaking, heard voices, or seen things that were not there after heavy drinking?||Yes (2)||No (0)|
|8. Have you ever gone to anyone for help about your drinking?||Yes (5)||No (0)|
|9. Have you ever been in a hospital because of drinking?||Yes (5)||No (0)|
|10. Have you ever been arrested for drunk driving or driving after drinking?||Yes (2)||No (0)|
Alcohol dependence is indicated by a score above 5.
Modified from Hyman SE, Cassem NH. Alcoholism. In Dale DC, Federman DD, eds. Scientific American medicine. New York: Scientific American, 1997:III, 1-12, 13
The etiology of alcohol dependence remains obscure. It represents a multifactorial condition involving genetic, physiologic, psychological, and social factors, each of which seems to be important. Serious drinking often starts in younger people; approximately 35% of alcoholics develop their first symptoms between 15 and 19 years of age, and more than 80% develop their first symptoms before age 30.3
Although alcohol dependence is most common in men, the incidence has been increasing in women. Although the figures were once more disparate, the female- to-male ratio for alcohol dependence has tapered to 1:2.1,2 Women generally seem to develop disease at a lower level of intake than men do. This may be partially because of women’s lower volume of distribution for alcohol and may also be related to increased gut permeability to endotoxins.4
Research indicates that genetic factors may be particularly important.5 The finding of a genetic marker for alcohol dependence could result in the diagnosis of the disease in its initial and most reversible stage. Some case-control studies suggest that non–gender-based gene polymorphisms encoding cytokines and other immune modulators may play a role in the predisposition to alcoholism. The gene patterns associated with risk reveal that antibody-mediated mechanisms may play a role in disease pathogenesis.4 The genetic basis of alcohol dependence has also been supported by the following:
A number of studies have shown that the incidence of alcohol dependence is four to five times more common in the biological children of alcoholic parents than those of nonalcoholic parents.5 Although it would be ultimately useful, knowledge of family history suggests that clear evidence of a biological marker may not be necessary for the implementation of a relatively innocuous primary prevention program.
The signs of alcoholic intoxication are typical of a central nervous system depressant: drowsiness, errors of commission, disinhibition, dysarthria, ataxia, and nystagmus. Fifteen milliliters of pure alcohol (the equivalent of 1 oz of whiskey, 4 oz of wine, or 10 oz of beer) raise the blood level of alcohol by 25 mg/dL in a 70-kg person. Table 143-2 shows the effects of varying blood levels of alcohol.
|BLOOD LEVEL (MG/DL)||EFFECT|
|<50||No significant motor dysfunction|
|100||Mild intoxication—decreased inhibitions, slight visual impairment, slight muscular incoordination, slowing of reaction time|
|Legally intoxicated in most jurisdictions|
|150||Ataxia, dysarthria, slurring of speech, nausea and vomiting|
|350||Marked muscular incoordination, blurred vision, approaching stupor|
|500||Coma and death|
Withdrawal symptoms usually occur 1 to 3 days after the last drink. They typically range from anxiety and tremulousness to mental confusion, tremor, sensory hyperactivity, visual hallucinations, autonomic hyperactivity, diaphoresis, dehydration, electrolyte disturbances, seizures, and cardiovascular abnormalities.
It is generally accepted that the availability and regeneration of NAD+ are the dominant rate-limiting factors for ethanol oxidation.7 Ethanol is converted to acetaldehyde by ADH, with NAD+ as a necessary cofactor.
The aldehyde product of ethanol metabolism is believed to be responsible both for many of the harmful effects of alcohol consumption and for the addictive process itself. Higher than normal blood aldehyde levels have been found in alcoholics and their relatives after alcohol consumption.7 This suggests either increased ADH activity or depressed ALDH activity in people susceptible to alcohol dependence. Acetaldehyde is converted by ALDH to acetate, with little entering the Krebs cycle; most is converted to long-chain fatty acids.6
All active alcoholics display fatty infiltration of the liver, with the severity roughly proportional to the duration and degree of alcohol excess. Even moderate doses of ethanol may produce both acute and chronic fatty liver infiltrates. The pathogenesis is due to the following6,8:
Leptin is a peptide hormone involved in the regulation of appetite and energy metabolism. It is most likely directly related to liver pathology in alcoholics. High levels of leptin are known to contribute to liver pathology, including increased rates of fibrosis, a known factor in liver steatosis.9 Research has demonstrated increased circulating leptin levels in a dose-dependent manner in chronic alcohol dependence regardless of nutritional status.10
Alcohol induces reactive hypoglycemia. The resultant drop in blood sugar produces a craving for food, particularly foods that quickly elevate blood sugar (i.e., sugar and alcohol). Increased sugar consumption aggravates the reactive hypoglycemia, particularly in the presence of alcohol, owing to alcohol-induced impairment of gluconeogenesis.6 Hypoglycemia aggravates the mental and emotional problems of the alcoholic and the withdrawing alcoholic with such symptoms as the following:
Although many of the nutritional problems of alcoholics relate directly to the effects of alcohol, a major contributing factor is that alcoholics tend not to eat, substituting alcohol for food. As a result, the alcoholic has to deal not only with nutritional deficiencies caused by excessive alcohol consumption but also true nutritional deficiencies due to inadequate intake.
One of the key nutrients involved in the metabolic handling of alcohol is zinc, as both ADH and ALDH are zinc-dependent enzymes, with the latter being more sensitive to deficiency.11 Both acute and chronic alcohol consumption result in zinc deficiency.11,12 Several factors contribute to the development of zinc deficiency in alcoholics: