INTRODUCTION

The two-carbon alcohol ethanol, CH3CH2OH, is a CNS depressant that is widely available to adults; its use is legal and accepted in many societies, and its abuse is a societal problem. The relevant pharmacological properties of ethanol include effects on the gastrointestinal, cardiovascular, and central nervous systems, effects on disease processes, and effects on prenatal development. Ethanol disturbs the fine balance between excitatory and inhibitory influences in the brain, producing disinhibition, ataxia, and sedation. Tolerance to ethanol develops after chronic use, and physical dependence is demonstrated on alcohol withdrawal. Understanding the cellular and molecular mechanisms of these myriad effects of ethanol in vivo requires an integration of knowledge from multiple biomedical sciences.

HISTORY AND OVERVIEW

Alcoholic beverages are so strongly associated with human society that fermentation is said to have developed in parallel with civilization. Indeed, there is speculation that human alcohol use is linked evolutionarily to a preference for fermenting fruit, where the presence of ethanol signals that the fruit is ripe but not yet rotten (Dudley, 2000) (the terms ethanol and alcohol are used interchangeably).

The Arabs developed distillation about 800 C.E., and the word alcohol is derived from the Arabic for “something subtle.” Alchemists of the Middle Ages were captivated by the invisible “spirit” that was distilled from wine and thought it to be a remedy for practically all diseases. The term whiskey is derived from usquebaugh, Gaelic for “water of life,” and alcohol became the major ingredient of widely marketed “tonics” and “elixirs.”

Although alcohol abuse and alcoholism are major health problems in many countries, the medical and social impacts of alcohol abuse have not always been appreciated. The economic burden to the U.S. economy is about $185 billion each year, and alcohol is responsible for more than 100,000 deaths annually. At least 14 million Americans meet the criteria for alcohol abuse or alcoholism, but medical diagnosis and treatment often are delayed until the disease is advanced and complicated by multiple social and health problems, making treatment difficult. Biological and genetic studies clearly place alcoholism among diseases with both genetic and environmental influences, but persistent stigmas and attribution to moral failure have impeded recognition and treatment of alcohol problems. A major challenge for physicians and researchers is to devise diagnostic and therapeutic approaches aimed at this major health problem.

Compared with other drugs, surprisingly large amounts of alcohol are required for physiological effects, resulting in its consumption more as a food than a drug. The alcohol content of beverages typically ranges from 4% to 6% (volume/volume) for beer, 10% to 15% for wine, and 40% and higher for distilled spirits (the “proof” of an alcoholic beverage is twice its percentage of alcohol; e.g., 40% alcohol is 80 proof). A glass of beer or wine, a mixed drink, or a shot of spirits contains about 14 g alcohol, or about 0.3 mol ethanol. Consumption of 1 to 2 mol over a few hours is not uncommon. Thus, alcohol is consumed in gram quantities, whereas most other drugs are taken in milligram or microgram doses. Since the ratio of ethanol in end-expiratory alveolar air and ethanol in the blood is relatively consistent, blood alcohol levels (BALs) in human beings can be estimated readily by the measurement of alcohol levels in expired air; the partition coefficient for ethanol between blood and alveolar air is approximately 2000:1. Because of the causal relationship between excessive alcohol consumption and vehicular accidents, there has been a near-universal adoption of laws attempting to limit the operation of vehicles while under the influence of alcohol. Legally allowed BALs typically are set at or below 80 mg% (80 mg ethanol per 100 ml blood; 0.08% w/v), which is equivalent to a concentration of 17 mM ethanol in blood. A 12-oz bottle of beer, a 5-oz glass of wine, and a 1.5-oz “shot” of 40% liquor each contains approximately 14 g ethanol, and the consumption of one of these beverages by a 70-kg person would produce a BAL of approximately 30 mg%. However, it is important to note that this is approximate because the BAL is determined by a number of factors, including the rate of drinking, sex, body weight and water percentage, and the rates of metabolism and stomach emptying.

Source: GOODMAN & GILMAN’S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS

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