For benefits of chronic alcohol consumption, see page 187.
Central nervous system. The development of dependence on alcohol appears to involve alterations in central nervous system neurotransmission. The acute effect of alcohol is to block NMDA receptors for which the normal agonist is glutamate, the main excitatory transmitter in the brain. Chronic exposure increases the number of NMDA receptors and also 'L type' calcium channels, while the action of the (inhibitory) GAB A neurotransmitter is reduced. The resulting excitatory effects may explain the anxiety, insomnia and craving that accompanies sudden withdrawal of alcohol (and may explain why resumption of drinking brings about relief, perpetuating dependence).
Malnutrition. With heavy continuous drinking, subjects take all the calories they need from alcohol, cease to eat adequately and develop deficiency of B group vitamins particularly. The malnutrition complicates the long-term effects of alcohol itself.
Organ damage. Chronic heavy alcohol use is associated with: hepatic cirrhosis, deteriorating brain function (psychotic states, dementia, seizures, Wernicke's encephalopathy, episodes of loss of memory); peripheral neuropathy and, separately, myopathy (including cardiomyopathy); cancer of the upper alimentary and respiratory tracts (many alcoholics also smoke heavily, and this contributes), hepatic carcinoma and breast cancer in women; chronic pancreatitis; cardiomyopathy; bone marrow depression, including megaloblastosis (due to the alcohol and to alcohol-induced folate deficiency); deficiency of vitamin K-dependent blood clotting factors (due to liver injury); psoriasis; multiple effects on the hypothalamic/pituitary/ endocrine system (endocrine investigations should be interpreted cautiously); Dupuytren's contracture.
Hypertension. Heavy chronic use of alcohol is an important cause of hypertension and this should always be considered in both diagnosis and management. Cessation of use may be sufficient to eliminate or reduce the need for drug therapy. But even social drinking can raise blood pressure, and hypertensives should be told this.
In general, reversal of all or most of the above effects is usual in early cases if alcohol is abandoned. In more advanced cases, the disease may be halted (except cancer) but in severe cases it may continue to progress. When wine rationing was introduced in Paris, France, in the 1939-45 war, deaths from hepatic cirrhosis dropped to about one-sixth the previous level; 5 years after the war they had regained their former level.
Blood lipoproteins. Moderate intake of alcoholic drinks may increase high density lipoprotein and diminish low density lipoprotein, which may account for the observed protective effect against ischaemic heart disease (see below).
General aspects of dependence are discussed earlier in this chapter. Dependence (chronic alcoholism) varies from social drinkers for whom companionship is the principal factor, through individuals who take a drink at the end of a working (or indeed any) day, who feel a need and who would be reluctant to give it up, to the person who is overcome by need, who cannot resist and whose whole life is dominated by the quest for alcohol. The major factors determining physical dependence are dose, frequency of dosing, and duration of abuse.
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