Alcohol and Alcoholism: Introduction

Alcohol, a drug, is consumed at some time by up to 80% of the population. At low doses alcohol can have some beneficial effects such as decreased rates of myocardial infarction, stroke, gallstones, and possibly vascular or Alzheimer’s dementias, but the consumption of more than two standard drinks per day increases the risk for health problems in many organ systems. Heavy repetitive drinking, as is seen in alcohol abuse and dependence, cuts short the life span by an estimated decade in both genders, all cultural groups, and all socioeconomic strata. Even low doses of alcohol have a significant effect on many organ systems, adversely affecting most preexisting disease states and altering the effectiveness or blood levels of most over-the-counter and prescribed medications.

Pharmacology and Nutritional Impact of Ethanol
Ethanol is a weakly charged molecule that moves easily through cell membranes, rapidly equilibrating between blood and tissues. The level of alcohol in the blood is expressed as milligrams or grams of ethanol per deciliter (e.g., 100 mg/dL or 0.10 g/dL); a level of 0.02 to 0.03 results from the ingestion of one to two typical drinks. 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 each contain 10 to 15 g of ethanol; 0.5 L (1 pint) of 86-proof beverage contains 160 g (about 16 standard drinks), and 1 L of wine contains 80 g of ethanol. Congeners found in alcoholic beverages, including low-molecular-weight alcohols (e.g., methanol and butanol), aldehydes, esters, histamine, phenols, tannins, iron, lead, and cobalt, may contribute to the adverse health consequences associated with heavy drinking.

Ethanol is a central nervous system (CNS) depressant that decreases neuronal activity, although some behavioral stimulation is observed at low blood levels. This drug has cross-tolerance with other depressants, including benzodiazepines and barbiturates, and all produce similar behavioral alterations. 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; by the absence of proteins, fats, or carbohydrates (which interfere with absorption); by the absence of congeners; by dilution to a modest percentage of ethanol (maximum at about 20% by volume); and by carbonation (e.g., champagne).

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. 372-1). 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.
Figure 372-1 The metabolism of alcohol. javascript:windowReference(‘Reference’,%20’popup.aspx?aID=109575’);

While alcohol supplies calories (a drink contains 300 kJ, or 70 to 100 kcal), these are devoid of nutrients such as minerals, proteins, and vitamins. Alcohol can also interfere with absorption of vitamins in the small intestine and decreases their storage in the liver with effects on folate (folacin or folic acid), pyridoxine (B6), thiamine (B1), Nicotinic Acid (niacin, B3), and vitamin A.

An ethanol load in a fasting, healthy individual is likely to produce transient hypoglycemia within 6 to 36 h, secondary to the acute actions of ethanol on gluconeogenesis. This can result in glucose intolerance until the alcoholic has abstained for 2 to 4 weeks. Alcohol ketoacidosis, probably reflecting a decrease in fatty acid oxidation coupled with poor diet or recurrent vomiting, should not 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 -hydroxybutyrate/lactate ratio of between 2:1 and 9:1 (with normal being 1:1).

Behavioral Effects, Tolerance, and Dependence
The effects of any drug depend on the dose, the rate of increase in plasma, the concomitant presence of other drugs, and the past experience with the agent. With alcohol, an additional factor is whether blood alcohol levels are rising or falling; the effects are more intense during the former period.

Even though “legal intoxication” requires a blood alcohol concentration of at least 80 to 100 mg/dL, behavioral, psychomotor, and cognitive changes are seen at levels as low as 20 to 30 mg/dL (i.e., after one to two drinks) (Table 372-1). Deep but disturbed sleep can be seen at twice the legal intoxication level, and death can occur with levels between 300 and 400 mg/dL. Beverage alcohol is probably responsible for more overdose deaths than any other drug.

The intoxicating effects of alcohol appear to be due to actions at a number of neurotransmitter receptors and transporters. Alcohol enhances -aminobutyric acid A (GABAA) receptors and inhibits N-methyl-D-aspartate (NMDA) receptors. In vitro studies suggest that additional effects involve inhibition of adenosine uptake and a translocation of the cyclic AMP–dependent protein kinase catalytic subunit from the cytoplasm to the nucleus. Neurons adapt quickly to these actions, and thus different effects may be present during chronic administration and withdrawal.

At least three types of compensatory changes develop after repeated exposure to the drug, producing tolerance of higher ethanol levels. First, after 1 to 2 weeks of daily drinking, metabolic or pharmacokinetic tolerance can be seen, with a 30% increase in the rate of hepatic ethanol metabolism. This alteration disappears almost as rapidly as it develops. Second, cellular or pharmacodynamic tolerance develops through neurochemical changes that may also contribute to physical dependence. Third, individuals can learn to adapt their behavior so that they can function better than expected under drug influence (behavioral tolerance).

The cellular changes caused by chronic ethanol exposure may not resolve for several weeks or longer following cessation of drinking. In the interim, the neurons require ethanol to function optimally, and the individual can be said to be physically dependent. This is distinct from psychological dependence, a concept indicating that the person is psychologically uncomfortable without the drug.

Alcohol and Alcoholism

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Revision date: July 8, 2011
Last revised: by Janet A. Staessen, MD, PhD