Alcohol (beverage ethanol) distributes throughout the body, affecting almost all systems and altering nearly every neurochemical process in the brain. This drug is likely to exacerbate most medical conditions, affect almost any medication metabolized in the liver, and temporarily mimic many medical (e.g., diabetes) and psychiatric (e.g., depression) conditions. Because ∼80% of people in Western countries have consumed alcohol, and two-thirds have been drunk in the prior year, the lifetime risk for serious, repetitive alcohol problems is almost 20% for men and 10% for women, regardless of a person's education or income. While low doses of alcohol have some healthful benefits, the intake of more than three standard drinks per day on a regular basis enhances the risk for cancer and vascular disease, and alcohol use disorders decrease the life span by about 10 years. Unfortunately, most clinicians have had only limited education regarding these conditions. This chapter presents a brief overview of clinically useful information about alcohol use, abuse, and dependence.
Pharmacology and Nutritional Impact of Ethanol
Blood levels of ethanol are expressed as milligrams or grams of ethanol per deciliter (e.g., 100 mg/dL = 0.10 g/dL), with values of ∼0.02 g/dL resulting from the ingestion of one typical drink. In round figures, 340 mL (12 oz) of beer, 115 mL (4 oz) of nonfortified wine, and 43 mL (1.5 oz) (a shot) of 80-proof beverage such as whisky, gin, or vodka each contain ∼10–15 g of ethanol and represent a standard drink;0.5 L (1 pint) of 80-proof beverage contains ∼160 g (about 16 standard drinks), and 750 mL of wine contains ∼60 g of ethanol. These beverages also have additional components known as congeners that affect the drink's taste and might contribute to adverse effects on the body. Congeners include methanol, butanol, acetaldehyde, histamine, tannins, iron, and lead. Alcohol acutely decreases neuronal activity and has similar behavioral effects and cross-tolerance with other depressants, including benzodiazepines and barbiturates.
Alcohol is absorbed from mucous membranes of the mouth and esophagus (in small amounts), from the stomach and large bowel (in modest amounts), and from the proximal portion of the small intestine (the major site). The rate of absorption is increased by rapid gastric emptying (as can be induced by carbonated beverages); by the absence of proteins, fats, or carbohydrates (which interfere with absorption); and by dilution to a modest percentage of ethanol (maximum at ∼20% by volume).
Between 2% (at low blood alcohol concentrations) and 10% (at high blood alcohol concentrations) of ethanol is excreted directly through the lungs, urine, or sweat, but the greater part is metabolized to acetaldehyde, primarily in the liver. The most important pathway occurs in the cell cytosol where alcohol dehydrogenase (ADH) produces acetaldehyde, which is then rapidly destroyed by aldehyde dehydrogenase (ALDH) in the cytosol and mitochondria (Fig. 392-1). A second pathway in the microsomes of the smooth endoplasmic reticulum (the microsomal ethanol-oxidizing system, or MEOS) is responsible for ≥10% of ethanol oxidation at high blood alcohol concentrations.
The metabolism of alcohol. MEOS, microsomal ethanol-oxidizing system.
While alcohol supplies calories (a drink contains ∼300 kJ, or 70–100 kcal), these are devoid of nutrients such as minerals, proteins, and vitamins. In addition, alcohol can also interfere with absorption of vitamins in the small intestine and decreases their storage in the liver with modest effects on folate (folacin or folic acid), pyridoxine (B6), thiamine (B1), nicotinic acid (niacin, B3), and vitamin A.
A heavy ethanol load in a fasting, healthy individual is likely to produce transient hypoglycemia within 6–36 h, secondary to the acute actions of ethanol on gluconeogenesis. This can result in temporary abnormal glucose tolerance tests (with a resulting erroneous diagnosis of diabetes mellitus) until the alcoholic has abstained for 2–4 weeks. Alcohol ketoacidosis, probably reflecting a decrease in fatty acid oxidation coupled with poor diet or recurrent vomiting, can be misdiagnosed as diabetic ketosis. With the former, patients show an increase in serum ketones along with a mild increase in glucose but a large anion gap, a mild to moderate increase in serum lactate, and a β-hydroxybutyrate/lactate ratio of between 2:1 and 9:1 (with normal being 1:1).
In the brain, alcohol affects almost all neurotransmitter systems, with acute actions that are often the opposite of those seen following desistance after a period of heavy drinking. The most prominent actions relate to boosting gamma aminobutyric acid (GABA) activity, especially in GABAA receptors. Enhancement of this complex chloride channel system contributes to anticonvulsant, sleep-inducing, antianxiety, and muscle relaxation effects of all GABA-boosting drugs. Acutely administered alcohol produces a release of GABA, and continued use of this drug increases density of GABAA receptors, while alcohol withdrawal states are characterized by decreases in GABA-related activity. Equally important is the ability of acute alcohol to inhibit postsynaptic N-methyl-d-aspartate (NMDA) excitatory glutamate receptors, while chronic drinking and desistance are associated with an upregulation of these excitatory receptor subunits. The relationships between greater GABA and diminished NMDA receptor activity during acute intoxication and diminished GABA with enhanced NMDA actions during alcohol withdrawal explain much of intoxication and withdrawal phenomena.
As with all pleasurable activities, drinking alcohol acutely increases dopamine levels in the brain, especially in the ventral tegmentum and related brain regions, and this effect plays an important role in continued alcohol use, craving, and relapse. The changes in dopamine pathways are also linked to increases in “stress hormones,” including cortisol and adrenocorticotropic hormone (ACTH) during intoxication and decreases in these hormones during withdrawal. Such alterations are likely to contribute to both feelings of reward during intoxication and depression during falling blood alcohol concentrations. Also closely linked to ...