Despite all the attention given to illegal drugs, alcohol abuse is a more widespread hazard and claims many more lives. Fifty percent of adults in the Western world drink alcohol, and approximately 5% to 10% have chronic alcoholism. It is estimated that there are more than 10 million chronic alcoholics in the United States and that alcohol consumption is responsible for more than 100,000 deaths annually. Almost 50% of these deaths result from accidents caused by drunken driving and alcohol-related homicides and suicides, and about 15% are a consequence of cirrhosis of the liver.
After consumption, ethanol is absorbed unaltered in the stomach and small intestine and then distributes to all of the tissues and fluids of the body in direct proportion to the blood level. Less than 10% is excreted unchanged in the urine, sweat, and breath. The amount exhaled is proportional to the blood level and forms the basis for the breath test used by law enforcement agencies. A concentration of 80 mg/dL in the blood constitutes the legal definition of drunk driving in most states. For an average individual, this alcohol concentration may be reached after consumption of three standard drinks, about three (12 ounce) bottles of beer, 15 ounces of wine, or 4 to 5 ounces of 80-proof distilled spirits. Drowsiness occurs at 200 mg/dL, stupor at 300 mg/dL, and coma, with possible respiratory arrest, at higher levels. The rate of metabolism affects the blood alcohol level. Chronic alcoholics develop tolerance to alcohol. They metabolize alcohol at a higher rate than normal and hence show lower peak levels of alcohol than average for the same about of alcohol consumed. Most of the alcohol in the blood is metabolized to acetaldehyde in the liver by three enzyme systems: alcohol dehydrogenase; cytochrome P-450 isoenzymes; and catalase (
Fig. 8.10 ). Of these, the main enzyme involved in alcohol metabolism is alcohol dehydrogenase, located in the cytosol of hepatocytes. At high blood alcohol levels, however, the microsomal ethanol-oxidizing system also plays an important role. This system involves cytochrome P-450 enzymes, particularly the CYP2E1 isoform, located in the smooth ER. Induction of P-450 enzymes by alcohol explains the increased susceptibility of alcoholics to other compounds metabolized by the same enzyme system, which include drugs (acetaminophen, cocaine), anesthetics, carcinogens, and industrial solvents. Of note, however, when alcohol is present in the blood at high concentrations, it competes with other CYP2E1 substrates and may delay the catabolism of other drugs, thereby potentiating their effects. Catalase is of minor importance, being responsible for only about 5% of alcohol metabolism. Acetaldehyde produced by these systems is in turn converted by acetaldehyde dehydrogenase to acetate, which is used in the mitochondrial respiratory chain.
Several toxic effects result from ethanol metabolism. Listed here are only the most important of these: • Alcohol oxidation by alcohol dehydrogenase causes a decrease in nicotinamide adenine dinucleotide (NAD+) and an increase in NADH (the reduced form of NAD+). NAD+ is required for fatty acid oxidation in the liver. Its deficiency is a main cause of fat accumulation in the liver of alcoholics. The increase in the NADH/NAD+ ratio in alcoholics also causes lactic acidosis.
http://ebooksmedicine.net