Alcohol has been described as the “universal solvent.” It is readily miscible in water (meaning that it forms a homogeneous solution) and has significant lipid solubility. Therefore, alcohol readily crosses cell membranes. Alcohol is absorbed in the stomach (20%) and small intestine (80%). In normal adults, 80–90% of absorption occurs within 30–60 min. The absorption of alcohol is delayed by up to 4–6 h if food is present in the stomach, and the total amount of alcohol absorbed is reduced (Figure 6.3). The “absorption” of a drug means the movement of the drug into the blood stream. Blood alcohol levels have become the standard by which to assess the absorption of alcohol and make comparisons between animals and humans, and between experimental conditions (Table 6.3).

Alcohol is largely eliminated through catabolism in the liver by three enzymatic pathways. Only 5–10% of alcohol is excreted unchanged from the lungs or urine. A factor of 2100 will convert breath alcohol concentration to arterial blood concentration, which is the basis of the “Breathalyzer” test. Alcohol is broken down to acetaldehyde in the liver by the enzyme alcohol dehydrogenase, which is responsible for a large part of its oxidation (Figure 6.4). Acetaldehyde is then broken down to acetic acid by acetaldehyde dehydrogenase and then further broken down to water and carbon dioxide in some organs. Allelic (genetic) variations in this pathway are responsible for the differential alcohol elimination rates in the human population. Inactivation of acetaldehyde dehydrogenase-2 (ALDH2) provides the basis for the alcohol-induced flush reaction seen in many individuals with Asian heritage. The flush reaction is characterized by facial flushing, tachycardia (increased heart rate), hypotension, elevated skin temperature, increased body sway, and nystagmus and is attributable to the buildup of acetaldehyde caused by a lack of acetaldehyde dehydrogenase activity. Initially, the surge in acetaldehyde produces more intense feelings of intoxication, but with increased drinking, the flush reaction produces nausea, vomiting, and an aversive reaction. Disulfiram (Antabuse) inhibits acetaldehyde dehydrogenase and produces an identical flush reaction. This is extremely aversive and forms the basis of its use in the treatment of alcoholism (see Medications for the Treatment).


Blood Alcohol Level (gm%) Estimations for Men and Women

Subtract 0.01 gm% for each 40 min of drinking.

1 drink = 1.25 ounce 80 Proof liquor, 12 ounce beer, or 5 ounce wine.

In certain ethnic groups, a mutation in two nucleotides of the ALDH2 gene produces complete inactivation of acetaldehyde dehydrogenase if a person is homozygous for both alleles and partial inactivation in heterozygous individuals. Forty to 50% of the Japanese, Chinese, and Vietnamese populations are heterozygous for the ALDH2 gene mutation, and the Japanese are approximately 7% homozygous for the mutation. Europeans show virtually 0% of the population with the mutation, Koreans are 30% heterozygous and 3% homozygous for the mutation, and Native North Americans also show a very low incidence of the ALDH2 mutation (Table 6.4).

In a 150 lb person, the average rate of metabolism of pure alcohol is approximately 7–9 ml/h (0.3 ounces/h). This converts to approximately 0.01–0.015 g% per hour or approximately half of a standard drink per hour. Individuals with alcoholism can double this rate of metabolism through the mechanism of metabolic tolerance, which has been theorized to be largely attributable to the induction of the liver enzyme cytochrome P4502E1 (although some have argued for increased activity of alcohol dehydrogenase as well). P4502E1 was found to be increased by four to 10-fold in liver biopsies of recently drinking humans and can contribute to the production of highly toxic metabolites in the liver in individuals with alcoholism. Importantly, this type of tolerance results in lower blood alcohol levels for the tolerant individual than the nontolerant individual for the same dosing at the same body weight. Pharmacodynamic tolerance results from changes in the response to the drug when the blood alcohol levels are the same (see History of Alcohol Use).

BOX 6.3


Blood alcohol levels are measured in gram%. The degree of intoxication throughout the United States is measured by a blood alcohol level, and the legal limit is 0.08 gram%. For example, 0.08 grams alcohol/100 ml = 0.08 gram% = 17 mM. Generally, for a male who weighs 150 lbs, 4 ounces of spirits (100 proof = 50% alcohol), four glasses of wine, or four beers will result in a blood alcohol level of approximately 0.10 gram%. For a female who weighs 150 lbs, these same amounts of alcohol will result in a blood alcohol level of 0.12 gram%. The difference in blood alcohol levels in males and females has been attributed to differences in the distribution of body fat, with more fat per kilogram (thus less water) for females, and lower gastric levels of the alcohol-metabolizing enzyme alcohol dehydrogenase in females.

BOX 6.4


ORLAND PARK, Ill. – A high school cheerleader who downed a quart of 107-proof liquor on a dare passed out and died after she was dropped off at a friend’s house to sleep it off.

Authorities said 16-year-old Elizabeth Wakulich might have been saved if someone had taken her to a hospital sooner. Wakulich was out with friends early Monday when she answered a challenge to drink a bottle of schnapps with an alcohol content of more than 53 percent. Wakulich was pronounced dead with a blood alcohol level of .38 percent, nearly four times the legal limit for driving in Illinois. The medical examiner estimated her level was closer to .60 shortly after the binge. A level of .40 to .50 can kill.

Associated Press

From: San Diego Union Tribune, Thursday, June 19, 1997. © The Associated Press, 2013.

A third pathway for alcohol metabolism is a non-oxidative pathway catalyzed by fatty acid ethyl ester (FAEE) synthase, which leads to the formation of fatty acid esters, which in turn produce mono-, di-, and triglycerides. FAEEs are found in the highest concentrations in the liver, adipose tissue, and the heart and are hypothesized to contribute to the toxic effects of alcohol.

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