Metabolism alcohol tolerance

Finally, some people metabolize alcohol more rapidly than others and so can handle larger doses. This may be genetically determined if so, some people could inherit a tendency to become alcoholic. People who drink alcohol regularly metabolize it faster than people who do not, and won t be affected by doses that nondrinkers would certainly feel. This is tolerance, and it develops quickly to alcohol and other sedative-hypnotics. Alcoholics show very high tolerance to the drug they can even survive doses of alcohol that would kill nondrinkers. Other people may have lower than normal abilities to metabolize alcohol. Some Japanese, for example, have an inborn biochemical quirk that causes them to get drunk on doses of wine or liquor that would hardly affect most Americans or Europeans. 

A variety of factors can affect a person s sensitivity and tolerance to heat, such as age, gender, ethnicity, body dimensions, weight, physical fitness, acclimatization, metabolism, alcohol or drug use, and medical conditions such as obesity, hypertension, and history or predisposition to heat injuries. Individuals with degenerative cardiovascular system diseases, diabetes, and/or malnutrition are at increased risk when exposed to heat and when stress is placed on the cardiovascular system (Ogawa 1998 NIOSH 1986). 

Yeast (qv) metabolize maltose and glucose sugars via the Embden-Meyerhof pathway to pymvate, and via acetaldehyde to ethanol. AH distiUers yeast strains can be expected to produce 6% (v/v) ethanol from a mash containing 11% (w/v) starch. Ethanol concentration up to 18% can be tolerated by some yeasts. Secondary products (congeners) arise during fermentation and are retained in the distiUation of whiskey. These include aldehydes, esters, and higher alcohols (fusel oHs). NaturaHy occurring lactic acid bacteria may simultaneously ferment within the mash and contribute to the whiskey flavor profile. 

As regards toxicity, pyrazole itself induced hyperplasia of the thyroid, hepatomegaly, atrophy of the testis, anemia and bone marrow depression in rats and mice (72E1198). The 4-methyl derivative is well tolerated and may be more useful than pyrazole for pharmacological and metabolic studies of inhibition of ethanol metabolism. It has been shown (79MI40404) that administration of pyrazole or ethanol to rats had only moderate effects on the liver, but combined treatment resulted in severe hepatotoxic effects with liver necrosis. The fact that pyrazole strongly intensified the toxic effects of ethanol is due to inhibition of the enzymes involved in alcohol oxidation (Section 4.04.4.1.1). 

It is generally recognized that workers exposed to either NG or EGDN have reduced tolerance for alcohol. Animal studies suggest that NG may decrease the activity of alcohol dehydrogenase, thereby decreasing the rate of alcohol metabolism. ... 

Ethanol. As with morphine addiction, tolerance to alcohol is developed, and a lack of ethanol produces withdrawal symptoms. Tire principal route of metabolism of ethanol (both ingested and the small amount of endogenous alcohol) is believed to be oxidation in the liver to the chemically reactive acetaldehyde (p. 774),874/875 which is further oxidized to acetate. Some theories of alcoholism assume that addiction, and possibly also the euphoric feeling experienced by some drinkers, results from a metabolite of ethanol in the brain. For example, acetaldehyde could form alkaloids (Eq. 30-5).876... 

With benzaldehyde 144 or halogenated derivatives (Cl, F) as acceptors the yeast-PDC-catalyzed addition proceeds with almost complete stereoselectivity to furnish the corresponding (R)-configurated 1-hydroxy-1-phenylpropanones 145 [447]. For practical reasons, whole yeast cells are most often used as the catalyst, with only small loss of enantioselectivity [423,424]. The conversion of benzaldehyde in particular has gained industrial importance because the acyloin is an important precursor for the synthesis of L-(-)-ephedrine [448]. Otherwise, the substrate tolerance is remarkably broad for aromatic aldehydes on the laboratory scale, however, yields of acyloins are usually low because of the prior or consequent reductive metabolism of aldehyde substrate and product, giving rise to considerable quantities of alcohol 146 and vicinol diols 147, respectively [423,424,449], The range of structural variability covers both higher a-oxo-acids (e.g. -butyrate, -valerate) as the donor component, as well as a,/J-un-saturated aldehydes (e.g. cinnamaldehyde 148) as the acceptor [450]. 

Repeated exposure to ethyl alcohol results in the development of a tolerance as evidenced by decreasing symptomatic reactions. It has been demonstrated that the symptoms of exposure are less clear and the time required to produce them is greater in subjects accustomed to alcohol. There is no proof, however, of physiological adaptation in humans in terms of metabolic changes or resistance to cellular injuries. The subject of the interaction of alcohol with other drugs has received much attention (277). 

Tolerance—decreased responsiveness to a drug following repeated exposure—is a common feature of sedative-hypnotic use. It may result in an increase in the dose needed to maintain symptomatic improvement or to promote sleep. It is important to recognize that partial cross-tolerance occurs between the sedative-hypnotics described here and also with ethanol (Chapter 23 The Alcohols)—a feature of some clinical importance, as explained below. The mechanisms responsible for tolerance to sedative-hypnotics are not well understood. An increase in the rate of drug metabolism (metabolic tolerance) may be partly responsible in the case of chronic administration of barbiturates, but changes in responsiveness of the central nervous system (pharmacodynamic tolerance) are of greater importance for most sedative-hypnotics. In the case of benzodiazepines, the development of tolerance in animals is associated with down-regulation of brain benzodiazepine receptors. 

Psychological tolerance to alcohol develops at a faster rate than metabolic tolerance. Thus death from alcohol overdose can occur in a psychologically tolerant person following only a moderate increase in alcohol intake above that normally consumed. 

A "reverse tolerance" has also been described, whereby an alcoholic taking a small quantity of alcohol may become intoxicated, aggressive, and antisocial. This occurs in those who have brain or liver damage and therefore show an enhanced sensitivity to the disinhibiting actions of the drug or a decreased metabolism. 

Increased metabolism as a result of enzyme induction (see p. 113) also leads to tolerance, as experience shows with alcohol, taken regularly as opposed to sporadically. There is commonly crosstolerance between drugs of similar structure. 

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