d-Amphetamine and ethanol: A drug-drug interaction study

MESSIHA, F. S. d-Amphetamine and ethanol: A drug-drug interaction study. BRAIN RES. BULL. 3(6) 595–599, 1978.—The in vivo and in vitro effects of d-amphetamine on the specific activities of endogenous liver alcohol-(L-ADH) and aldehyde dehydrogenase (L-ADH) were studied using rat and mouse liver enzyme preparations. d-Amphetamine, 10^?4M, noncompetitively inhibited rat and mouse L-ALDH in vitro. Mitochondrial L-ALDH was not affected by d-amphetamine invivo and in vitro in both species studied. A noncompetitive inhibition of mouse L-ADH, occurred in vivo 16 hr after administration of d-amphetamine, 4 mg/kg, IP. A moderate, but not significant decline in specific activity of rat L-ADH was determined after injection of d-amphetamine, 4 mg/kg IP. Mice pretreated with d-amphetamine, 3.5 mg/kg, IP, 30 min prior to a single injection of 25% (w/w) ethanol solution, 2.5 g/kg, IP, showed a significant decrease in their blood and brain content of exogenously administered ethanol from corresponding saline-treated controls for the 60 min and 90 min periods after ethanol administration, respectively. The results show species differences in d-amphetamine action on liver enzymes studied and indicate that d-amphetamine can interfere in the metabolism of ethanol.     

Interaction toxicity between ethanol and narcotics in mice with reference to alpha-l-acetylmethadol (LAAM)

Interactions between narcotics, especially alpha-l-acetylmethadol (LAAM) and ethanol were studied in mice. Co-administration of LAAM either at 18 or 36 mg/kg significantly potentiated ethanol lethality, the LD₅₀ due to ethanol was lowered by 21% and 36%, respectively. At low doses of ethanol (0.5 and 1.0 g/kg), toxicity due to LAAM was decreased; the LD₅₀ was increased significantly (p<0.006?0.05) to 76 and 64 mg/kg, respectively, compared with 56 mg/kg for LAAM alone. At 4 g/kg of ethanol, the LD₅₀ due to LAAM was decreased to 43.9 mg/kg, showing a significant (p<0.002) potentiation of interaction toxicity between the two compounds. Chronic pretreatment of LAAM for 7 days produced no significant alteration in ethanol lethality. Treatment with various narcotic agonists (morphine, LAAM, methadone, and levorphanol) and ethanol, the rate of disappearance of ethanol was decreased significantly in the blood and brain whereas naloxone and dextrorphan, an inactive stereoisomer of levorphanol, produced a small but significant increase. Ethanol pretreatment produced no significant alteration on the brain and blood levels of morphine with the exception of 4g/kg at 150 min after treatment. Increase in toxicity with the combined administration of LAAM and ethanol was attributed in part to the retention of ethanol.     

Distribution of ethanol between saliva and blood in man

1. Forty-eight male subjects drank ethanol (0.72 g/kg) as neat whisky on a fasting stomach within 20 min and the ethanol concentrations in saliva and capillary blood were determined at 30-60 min intervals for the next 7 h. 2. The concentration of ethanol in saliva was generally slightly higher than in capillary blood, as expected from their relative water contents. The mean saliva/ blood ethanol ratio between 60 and 360 min from the start of drinking was 1.082 (s.e.m. = 0.0059), (n= 336). Moreover, the saliva/blood ethanol ratio was remarkably constant throughout the absorption, distribution and elimination phases of ethanol metabolism. 3. The saliva (y) and blood ethanol (x) concentrations (mmol/1) were highly correlated (r= 0.976, standard error = 0.011, P < 0.001). The regression equation was y = 0.109 + 1.071x. The saliva and blood ethanol concentrations reached zero nearly simultaneously, there being no appreciable time lag in the saliva. 4. The results indicate that saliva is a practical medium for ethanol determinations and that blood ethanol can be reliably estimated from analysis of a saliva specimen. Saliva ethanol analysis could well serve as supporting evidence in clinical and medico-legal diagnosis of ethanol intoxication.     

Increased sensitivity to chronic ethanol in isolated mice

Isolated C57BL/10 mice fed liquid diet as their only nutritional supply consumed 44% more diet than did groupedhoused mice. A similar increase due to isolation of 36% for C57BL/10 mice and of 89% for DBA/1 mice was demonstrated when the sucrose in the liquid diet was replaced by an equicaloric (6% v/v) amount of ethanol. The ethanol-drinking isolated mice suffered a higher mortality rate than the grouped mice. When isolated mice were given a restricted amount of ethanol diet to match the consumption of the grouped mice, their death rate still remained higher. It was concluded that isolation increased the sensitivity to ethanol effects. The observed changes in the sensitivity to ethanol effects may have been mediated by the known isolation-induced changes in the levels of brain amines and corticosterone. Generally, DBA/1 mice were more susceptible to chronic ethanol than C57BL/10, and the young more susceptible than the adults.     

FOLIC ACID, ETHANOL AND JEJUNAL GLYCOLYSIS

Jejunal glycolysis is affected by specific substrate, oral folic acid and ethanol. The relationship of jejunal glycolysis to intestinal absorption and nutrition requires further definition.     

Cardiovascular collapse during ethanol sclerotherapy in a pediatric patient

Ethanol sclerotherapy is a first line management therapy for low flow vascular malformations. It is usually performed under general anesthesia because of the pain associated with ethanol injection. Ethanol sclerotherapy frequently produces minor local complications but may rarely produce catastrophic cardiopulmonary complications. This report describes the cardiovascular collapse associated with an ethanol sclerotherapy procedure in an 11-year- old child. The evidence for ethanol-induced cardiovascular derangements is discussed.     

Is using ethanol–glycine irrigating fluid monitoring and ‘good surgical practice’ enough to prevent harmful absorption during transurethral resection of the prostate?

OBJECTIVE: To evaluate the utility of using a tracer of 1% ethanol in 1.5% glycine for the early detection of irrigation fluid absorption during transurethral resection of the prostate (TURP). PATIENTS AND METHODS: In all, 126 men undergoing TURP were irrigated with a solution of 1% ethanol and 1.5% glycine; their expired air was tested for ethanol every 20 min, and again at the end of the procedure. Maximum absorption by the breath-ethanol reading was compared with the serum concentration of absorbed glycine (analysed by anion-exchange chromatography). RESULTS: Complete data on 120 men were assessed; 75% of the men absorbed irrigation fluid, with glycine levels above the normal range. The sodium levels tended to decrease with increasing glycine levels (Spearman's rank correlation coefficient, - 0.57; 120 men) and five men (4%) developed clinical features of the TUR syndrome. There was a weak correlation between breath-ethanol levels and serum glycine levels (Spearman's rank correlation coefficient, 0.54). The experience of the surgeon, the weight of the resected chips, and the operative duration were not significantly predictive of irrigation fluid absorption. CONCLUSIONS: A rising breath-ethanol level indicates irrigation fluid absorption. However, irrigating fluid absorption is unpredictable, supporting the case for alternative, potentially safer irrigants.     

白藜芦醇和乙醇对内毒素诱导小鼠腹腔巨噬细胞炎性因子产生的作用

目的:研究白藜芦醇和乙醇对细菌内毒素活化的小鼠腹腔巨噬细胞炎性因子产生的相互作用.方法:Griess试剂法检测NO产生;小鼠胸腺细胞增殖法检测IL-1的产生;ELISA检测IL-6,TNF-α的生成.结果:自藜芦醇(6.25,12.5,25 μmol/L)和乙醇(0.2％,0.8％)剂量依赖性和协同性地抑制24小时LPS(1 mg/L)和IFN-γ(5 kU/L)刺激的NO的产生;25μmol/L的白黎芦醇还抑制IL-6的产生,此作用可被乙醇加强;乙醇单独对24小时IL-1的产生无影响,但可提高自藜芦醇促进IL-1产生的作用;低剂量乙醇抑制巨噬细胞TNF-α产生,但两种浓度的乙醇与白黎芦醇共用时均增强白黎芦醇对TNF-α的产生的促进作用.结论:白黎芦醇和乙醇对巨噬细胞功能分子的产生有调控作用.     

LPO and ethanol biotransformation systems in the liver as markers of predisposition to ethanol hepatotoxicity

An original experimental model for detecting organ-specific markers of predisposition to ethanol hepatotoxicity is proposed. A relationship between congenital activity of LPO processes in rat liver (before ethanol intoxication) and the type and severity of ethanol-induced damage to the liver was demonstrated using methods of mathematical modeling. It was proven that intact rats with genetically high MDA levels in the liver and more active systems of MDA generation in ascorbate- and NADPH-dependent reactions are prone to ethanol-induced damage to the liver.     

Diazoxide, a K(ATP) opener, accelerates restitution of ethanol or indomethacin-induced gastric ulceration in rats independent of polyamines

BACKGROUND AND AIMS: Experimental acute gastric ulcerations (EAGU) are healed very rapidly. This healing process has two steps; mucosal restitution and delayed repair. Adenosine 5'-triphosphate (ATP)-dependent potassium channels (K(ATP)) have a regulatory role in the gastrointestinal physiology. In the present study, the effects of K(ATP) channel modulators; diazoxide (channel opener) and glibenclamide (channel antagonist) on the healing of EAGU were investigated. The effect of polyamine (mediators presumably responsible for restitution) biosynthesis by difluoromethylornithine (DFMO) on diazoxide-induced alterations, and the effects of acid secretion inhibitors (cimetidine, omeprazole and atropine) on the mucosal restitution of EAGU were also studied. METHODS: Groups of 10 male rats were starved for 24 h and EAGU was induced by oral administration of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin. Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg) and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine, omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and 1 mg/kg, respectively, after EAGU induction. Animals were killed and their gastric mucosa was examined for ulcerations. RESULTS: Diazoxide accelerated the healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant administration of glibenclamide antagonized the diaoxide effect. Diazoxide-induced acceleration of mucosal restitution was not abolished by DFMO. Cimetidine, omeprazole and atropine had no effect on the healing of EAGU. CONCLUSION: The K(ATP) channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU.