ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04784.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

The pharmacokinetics of ethanol in man are reviewed from a historical perspective from the earliest attempts at kinetic analysis of urinary data in 1899 to the present nonlinear analysis of blood alcohol concentration (BAC) and time data. Review of the various kinetic theories that have been utilized to describe the kinetics of alcohol metabolism is provided. Extensive review is made of recent investigations supporting the application of Michaelis‐Menten enzyme kinetics to describe alcohol metabolism. Results of direct, nonlinear least‐squares computer fitting of BAC following intravenous and oral feeding of alcohol both in the fasting and fed states are presented with appropriate theory. The kinetics of the oral absorption of alcohol and the relationship among stomach emptying rate, the apparent absorption rate, and the area under the BAC‐time curve are discussed and data presented. The kinetics of multiple Michaelis‐Menten pathways are discussed with application to the (potential) contributions of the MEOS and/or ADH systems to the observed BAC curve and resultant kinetic parameters. Several methods of obtaining pharmacokinetic (Michaelis‐Menten) parameters from BAC curves and their interpretation and usage in comparative studies are

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04785.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

The determination of acetaldehyde in biologic samples is complicated by a variety of formation and disappearance reactions occurring in the present methods of acetaldehyde analyses. The acetaldehyde formation (ethanol oxidation) in deproteinized supernatant of tissue preparations is prevented by the use of thiourea. During deproteinization, however, it is not inhibited by thiourea, and this remains the main problem in blood acetaldehyde determinations. To circumvent this problem, the use of a correction curve is proposed which is generated by adding control blood samples to the deproteinizing agent such that the blood dilution, temperature, and the ethanol concentrations (the main factors affecting the artifactual acetaldehyde formation) in the controls are identical to those of the samples. Disappearance reactions mainly include loss of acetaldehyde due to binding and/or metabolism. The problem seems to be pronounced with human blood samples, and it is recommended that they be rapidly (<5 sec) deproteinized.

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04786.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Acetaldehyde infusions inhibit albumin synthesis in the liver from fed donors but not in the livers from fasted donors. The inhibition of acetaldehyde metabolism with 4‐MP and disulfiram reverses this finding, suggesting that acetaldehyde per se is not the toxic agent. Disulfiram stimulates albumin synthesis in livers from fasted donors, and the presence of acetaldehyde does not prevent this process. The effects of ethanol infusions cannot be explained as due to the presence of acetaldehyde; some intermediate metabolic step may be the basis of the inhibition of albumin production and polysome disaggregation in the presence of ethano

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04787.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

We studied the effect of prior narcotic addiction on response to treatment of alcoholism. Patients in the Elmhurst Alcoholism Treatment Program are offered medical care, counseling, disulfiram, and close affiliation with Alcoholics Anonymous. We compared 85 alcoholics who had a history of narcotic use with a control group of 85 alcoholics matched for age, sex, and race who had never used narcotics. Among controls, 30 (35%) became abstinent from alcohol for at least half the time that they were known to us. Of the former narcotic users, only 8 (9%) became abstinent for at least half the time they were known to us. Former narcotic users did poorly in alcoholism treatment, whether or not they had ever been treated with methadone maintenance. Alcohol use. often heavy, began before heroin use in at least half the narcotic group. We conclude that a history of narcotic use reduces markedly the chance of success in conventional alcoholism treatment, and that alcoholism and narcotic addiction develop independently.

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04788.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Ethanol elimination rates were measured in 7 baboons fed alcohol for 2–7 yr (and their controls) by using a constant ethanol infusion to maintain blood ethanol at three different levels; 5, 10, and 50 mM. Ethanol elimination rates were significantly faster at a blood ethanol level of 50 mMthan at 10 or 5 mMin both alcohol‐fed and control animals. The difference between 50 mMand 5 mMconcentration was 36% in alcohol‐fed and 25% in control animals. In baboons fed ethanol chronically, the ethanol elimination rates were significantly faster than in pair‐fed controls at 50 mM(179 ± 10.0 mg/kg/hr versus 144 ± 9.8) and at 10 mM(148 ± 4.1 versus 114 ± 8.2), but not at 5 mM. Even if one takes into account the extrahepatic losses, these differences cannot be explained solely by the elimination of ethanol through the lowKmalcohol dehydrogenase pathway, and these observations indicate that a non‐ADH system significantly contributes to ethanol elimination in vivo, especially in alcoho

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04789.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04790.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Studies in man on the effect of ethanol on growth hormone (GH) release have been inconclusive. In order to investigate the effect of ethanol on spontaneous episodic secretion of GH, rats were implanted with chronic carotid catheters to permit frequent sampling in unanesthetized rats. Secretion during the 3 hr before (0–180 min) and after (181–360 min) ethanol or saline was assessed by means of samples drawn every 15 min. Secretion patterns after saline or ethanol 0.5 and 2 g/kg were indistinguishable, but ethanol in doses of 3 and 4 g/kg abolished rat GH (rGH) secretion in a majority of animals. Mean rGH after saline injection for the period 181–360 min was 62 ± 9 ng/ml. When ethanol was given, mean rGH values for this time period were 0.5 g/kg, 63 ± 6 ng/ml; 2.0 g/kg, 47 ± 7 ng/ml; 3 g/kg. 28 ± 3 ng/ml; and 4 g/kg, 23 ± 2 ng/ml. Differences were not statistically significant between saline and 0.5 or 2 g/kg ethanol, but were significant (p<0.01) for 3 or 4 g/kg ethanol. Thus, a single dose of ethanol can abolish spontaneous rGH secretion, but it must be a high dose. The effect of chronic ethanol administration remains to be in

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04791.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Maternal ethanol consumption was associated with reduced levels of dihydrotestosterone in the brains of 1–2‐day‐old male rats when compared to those of sex‐matched pups obtained from dames that were fed sucrose. In contrast, brain levels of corticosterone were increased significantly in the pups of ethanol‐fed animals when compared to those from sucrose‐fed controls. Brain and plasma estradiol did not differ between groups. These results suggest that maternal ethanol consumption may influence the central nervous system and plasma levels6000 of certain steroidal hormones in th

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04792.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Rats were maintained on liquid diets containing ethanol (6.8% v/v) or sucrose (controls) for periods of 2 and 6 wk to determine whether excised aortic or venous (portal vein) smooth muscle would exhibit any change in tone or reactivity when exposed to vasoactive agonists or to added ethanol (ETOH) in vitro. The results indicate that portal veins (PV) from the 2‐wk ETOH group show marked attenuation of (A) spontaneous tone, (B) angiotensin and K+‐induced contractions, and (C) Ca2+‐induced contractions. In contrast, PV from rats on ETOH for 6 wk only show depression of tone and Ca2+‐induced responses when compared to sucrose‐fed controls. Exposure of the PV to ethanol in vitro inhibits spontaneous tone of control sucrose‐fed animals but exerts little action on PV obtained from ETOH‐maintained rats. Although the addition of a high bathing concentration of ETOH (430 m/W) can evoke potent contractions in normal aorta, it fails to exert such action in most aortas obtained from rats maintained on ETOH. In vitro ETOH also dose‐dependently inhibited all drug‐induced contractions of blood vessels from control rats, but exerted little inhibition on PV and aortas obtained from ETOH‐maintained rats. These data indicate (1) chronic ETOH ingestion can directly influence vasomotor tone, reactivity of vascular muscle, and permeability of vascular membranes to Ca2+; (2) chronic ETOH treatment can induce a progressive “tolerance” in vascular tissue; and (3) the development of tolerance in vascular smooth muscle to ETOH may aid in explaining why long‐term alcoholic animals and man do not dev

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1980.tb04793.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY