Tolerance with ethanol

The clinical consequences of the currently used benzodiazepines range from sedation, muscle relaxation, seizure reduction, anxiolysis, and hypnosis. Clearly, it would be highly desirable to be able to separate some of these effects. In addition, it would be useful to reduce other undesirable consequences such as development of tolerance and dependence, abuse, synergistic interaction with ethanol, and memory impairment (for a comprehensive review see [22]). Animal models for some of the aforementioned conditions, in combination with transgenic mouse technology, have recently led to a deeper understanding of the contribution some of the individual a subunits make to these behaviors. 

Tolerance—decreased responsiveness to a drug following repeated exposure—is a common feature of sedative-hypnotic use. It may result in the need for an increase in the dose required 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 (see Chapter 23)—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 has been associated with down-regulation of brain benzodiazepine receptors. Tolerance has been reported to occur with the extended use of zolpidem. Minimal tolerance was observed with the use of zaleplon over a 5-week period and eszopiclone over a 6-month period. 

Patients with ethanol or sedative-hypnotic overdose may be euphoric and rowdy ("drunk") or in a state of stupor or coma ("dead drunk"). Comatose patients often have depressed respiratory drive. Depression of protective airway reflexes may result in aspiration of gastric contents. Hypothermia may be present because of environmental exposure and depressed shivering. Ethanol blood levels greater than 300 mg/dL usually cause deep coma, but regular users are often tolerant to the effects of ethanol and may be ambulatory despite even higher levels. Patients with GHB overdose are often deeply comatose for 3-4 hours and then awaken fully in a matter of minutes. 

Little is known about fuel transfer hose compatibility with ethanol. Some of the hoses used for gasoline may be adequate. Experience has demonstrated that dispensing hose made for gasoline will tolerate gasoline that has 10 volume percent ethanol [3.10]. Suppliers of fuel hose should be consulted when choosing hose that will be used for transferring ethanol. 

Ethanol is to be pumped with an oil-sealed rotary pump with an exhaust pressure of 1.3 bar. Calculate the vapour tolerance to ethanol if the pump temperature is about 60 °C and atmospheric pressure is 1000 mbar. 

Palladium-catalyzed cyclization-carboalkoxylation of alkenyl indoles tolerated substitution along the alkenyl chain and at the internal and tfr-terminal olefinic position. In addition to 2-(4-alkenyl)indoles, 2-(3-alkenyl)-, 2-(5-hexenyl)-, 3-(3-butenyl)-, and 3-(4-pentenyl)indoles also underwent efficient palladium-catalyzed cyclization-carboalkoxylation to form the corresponding tricyclic indole derivatives in moderate to good yield with excellent regioselectivity. By employing this procedure, efficient palladium-catalyzed cyclization-carboalkoxylation of 2-(4-pentenyl)indole with ethanol, 1-octanol, 2-propanol, and cyclohexanol was achieved. 

Wine with an increased viscosity and a siimy appearance is called ropy . This aspect is due to the production of dextrane or glucane produced by Leuconostoc and Pediococcus (Fugelsang 1997 Lonvaud-Funel 1999). These polysaccharides are mainly produced by P. damnosus and their production is linked to a plasmid of approximately 5500 bp the ropy phenotype disappears when the plasmid is lost. These ropy strains are much more tolerant to ethanol than others. Concentrations of glucane around 100 mg/L are high enough to give the wine this abnormal viscosity. 

Some authors have found the transition from a fermentative status to a film forming status in the yeasts to occur simultaneously with an increased saturation in long-chained fatty acids and, especially, an increased C18 l/C18 0 ratio (Aguilera et al. 1997 Farris et al. 1993 Valero et al. 2002) this probably increases the tolerance to ethanol of the yeasts (Aguilera et al. 2006) and their hydrophobicity, thereby facilitating flotation of cells and the formation of a stable film. 

Torulaspora delbrueckii (anamorp Candida colliculosa formerly Saccharomyces rosei) has a moderate tolerance to ethanol (<12.5 vol.% Table 8D.6) and produces wines which resemble those made with Saccharomyces cerevisiae. Production of higher alcohols is however highly variable and strain dependent. Because this yeast produces comparatively low concentrations of acetic acid, ethyl acetate, acetaldehyde and acetoin, its potential suitability for wine production has been suggested by several studies (Cabrera et al. 1988 Ciani and Ferraro 1998 Herraiz et al. 1990 ... 

Hanseniaspora uvarum (anamorph Kloeckera apiculata) is commonly the major yeast present on the grape berry and in musts and juices, but due to low tolerance to ethanol, populations decline quickly in the presence of Saccharomyces cerevisiae. Strains are typically characterised by low fermentative ability and high production of acetic acid, ethyl acetate and acetaldehyde, which render such strains more suitable to vinegar production. Nevertheless, Ciani and Maccarelli (1998) surveyed 37 isolates and found considerable variability, with some strains producing concentrations of these compounds approaching concentrations present in wines made with Saccharomyces cerevisiae (Table 8D.6). Cofermentation fermentation with Saccharomyces cerevisiae can produce wines with an acceptable balance of volatile and non-volatile compounds and sensory scores (Ciani et al. 2006 Jemec and Raspor 2005 Jolly et al. 2003b Zohre and Erten 2002). 

Chronic use leads to tolerance (cross with other S-H drugs), possibly via down-regulation of BZ receptors. Psychological and physical dependence occurs, but abuse liability and withdrawal signs are less intense than with ethanol or barbiturates. Rebound REM sleep, insomnia, and anxiety are common on discontinuance. 

The treatment of anxiety throughout human history has involved a variety of natural agents which were administered to relieve tension and induce a state of altered consciousness, with ethanol in its various forms the most widely used [4]. Within the last century, general CNS depressants such as barbiturates, bromide salts, and ethanol surrogates such as chloral hydrate and paraldehyde have been employed to treat anxiety. Because of side-effects of the other drugs, barbiturates were used predominantly in the first half of this century as anxiolytics, but their clinical utility was limited by tolerance and dependence liability. Propanediolcarbamates such as meprobamate were also used to treat anxiety but displayed many of the barbiturate side-effects. 

Alcohol inhibits the release of vasopressin (antidiuretic hormone see Chapter 29) from the posterior pituitary gland, resulting in enhanced diuresis. The volume loading that accompanies imbibing complements the diuresis that occurs as a result of reduced vasopressin secretion. Alcoholics have less urine output than do control subjects in response to a challenge dose with ethanol, suggesting that tolerance develops to the diuretic effects of ethanol. Alcoholics withdrawing from alcohol exhibit increased vasopressin release and a consequent retention of water, as well as dilutional hyponatremia. 

Benzodiazepines produce little respiratory depression. Dosages of >2000 mg produce lethargy, drowsiness, confusion, and ataxia. However, the effect of CNS depression is additive when taken with ethanol, barbiturates, or other sedative-hypnotics. Also, the euphoric effects are lower than those experienced with most other sedative-hypnotics. Tolerance, risk of dependence, or addiction is relatively low. Tolerance can still... 

B. The level sufficient to cause deep coma or respiratory depression is highly variable, depending on the individual s degree of tolerance to ethanol. /M-though levels above 300 mg/dL usually cause coma in novice drinkers, chronic alcoholics may be awake with levels of 500-600 mg/dL or higher. 

Most bacteria convert malic acid to lactic acid with an intermediate formation of pyruvic acid, while Oenococcus oeni (previously classified as Leuconostoc oenos) expresses the malolactic enzyme to directly convert malic acid in one-step reaction. O. oeni has been extensively studied for controlled MLF of wine due to its higher tolerance to ethanol, low pH, and Yeasts like Schizosaccharomyces pombe and Saccharomyces strains can also convert malic acid through a maloethanolic-type fermentation. Lactic acid is less acidic than malic acid, and as a conseqnence, MLF leads to improvement of the sensory properties and biological stability of the wines. Additionally, the production of various other by-products of the MLF reaction may affect wine flavor positively. 

In the case of DEFC, Piipadchev and co-authors [28] developed platinum-based (Pt/C) cathode catalysts modified with S, P, and Bi that were highly tolerant to ethanol crossover into the cathode compartment of the fuel cell. In the case of doping Pt/C with these elements, the researchers used ttiphenylphosphine, bismuth nitrate, and thiourea as dopant sources. The catalysts were synthesized by high-temperature treatment of the catalyst-dopant element mixture in an inert atmosphere (further details see Ref. [28]). 

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