Barbiturates Ethanol

Horizontal-gaze nystagmus is common with a variety of dmgs and toxins, including barbiturates, ethanol, carbamazepine, phenytoin, and scorpion envenomation. Phencyclidine (PGP) may cause horizontal, vertical, and even rotatory nystagmus. 

Opioids (especially methadone and heroin) are the most common cause of serious neonatal drug withdrawal symptoms. Other dmgs for which a withdrawal syndrome has been reported include phencyclidine (POP), cocaine, amphetamines, tricyclic antidepressants, phenothiazines, benzodiazepines, barbiturates, ethanol, clonidine, diphenhydramine, lithium, meprobamate, and theophylline. A careful dmg history from the mother should include illicit drugs, alcohol, and prescription and over-the-counter medications, and whether she is breast-feeding. 

Preparation of 1-Methyl-5-Allyl-5-( 1-Methyl-2-Pentynyl) Barbituric Acid A solution of 23.8 g of sodium in 360 ml of absolute alcohol was prepared and thereto were added 38.3 g of methyl urea and 96.8 g of diethyl allyl (1-methyl-2-pentynyl) malonate. The mixture was refluxed for about 20 hours, cooled, and the ethanol was removed by distillation in vacuo. The residue was dissolved in about 300 ml of water and the aqueous solution was washed with ether, and the washings were discarded. The aqueous solution was then acidified with acetic acid, and extracted with three 150 ml of portions of ether. 

The combined ether extracts were washed with 5% aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate, and fractionally distilled in vacuo. The fraction boiling at about 145° to 150°C at the pressure of 0.5 mm of mercury, weighing 61 g and consisting of 1-methyl-5-allyl-5-(1-methyl-2-pentynyl) barbituric acid, was collected. The only distillate was substantially pure, and could be used as such In pharmaceutical preparation or a salt could be prepared therefrom according to the procedures disclosed hereinafter. On standing, the oil crystallized. The crystalline 1-methyl-5-allyl-5-( 1-methyl-2-pentynyl) barbituric acid melted at about 60° to 64°C after recrystallization from dilute ethanol. 

The thus-washed crude product is dissolved in a mixture of 12 parts of ethanol and 20 parts of benzene, with mild warming if necessary. 1 Part of sodium chloride and 1.5 parts of saturated aqueous sodium chloride solution are added to the obtained solution in ethanol-benzene, and whole thoroughly admixed. When the brine layer has settled. It is separated and the afore-described washing repeated. The clear solution is concentrated under reduced pressure until incipient formation of crystals and is then poured into 30 parts of benzene, whereupon a thick crystalline pulp is forthwith formed which, after being cooled to room temperature, is centrifuged off. The so-obtained 5-allyl-5-( 3-hydroxypropyl)-barbituric acid is dried at 70°C under reduced pressure and can be used for therapeutic purposes without further purification. Melting point 164 °C to 165°C. Yield 5 parts. 

The higher than expected frequency of alcohol PCP -, and heroin PCP-rel ated deaths may be the result of an interaction of the combined substances. Balster (this volume) anticipated an interaction of the combined substances when he reported "PCP very markedly enhances the effects of classical depressant drugs, including barbiturates and ethanol."... 

The GABA-gated chloride ion channel is modulated by several classes of drugs that bind to allosteric sites on the receptor complex the benzodiazepines, barbiturates and related intravenous general anesthetics such as etomidate and propofol, as well as anesthetic steroids and endogenous neurosteroids. It appears that some types of GABAa receptor are directly enhanced by ethanol and volatile general anesthetics (Fig. 16-2) [7,8,20]. 

Barbiturates Carbamazepine Ethanol, chronic ingestion Phenytoin... 

Many CNS depressants have some liability for dependence. This is typically greater with barbiturates, but lesser with benzodiazepines, and perhaps nonexistent in many antiseizure medications. CNS depressants produce tolerance when administered chronically, where increasingly larger doses are required to sustain the same level of effect. Further, a cross-tolerance often develops, where the tolerance is generalized to other CNS depressants. For example, a person with an ethanol tolerance will also display some tolerance to barbiturates. The therapeutic index tends to decrease as tolerance increases, so that the difference between an effective and toxic dose diminishes. Thus, tolerance to CNS depressants is accompanied by a smaller safety margin. 

Several animal studies indicate that chloroform interacts with other chemicals within the organism. The lethal and hepatotoxic effects of chloroform were increased by dicophane (DDT) (McLean 1970) and phenobarbital (a long-acting barbiturate) in rats (Ekstrom et al. 1988 McLean 1970 Scholler 1970). Increased hepatotoxic and nephrotoxic effects were observed after interaction with ketonic solvents and ketonic chemicals in rats (Hewitt and Brown 1984 Hewitt et al. 1990) and in mice (Cianflone et al. 1980 Hewitt et al. 1979). The hepatotoxicity of chloroform was also enhanced by co-exposure to carbon tetrachloride in rats (Harris et al. 1982) and by co-exposure to ethanol in mice (Kutob and Plaa 1962). Furthermore, ethanol pretreatment in rats enhanced chloroform-induced hepatotoxicity (Wang et al. 1994) and increased the in vitro metabolism of chloroform (Sato et al. 1981). 

Changes have also been reported to occur in the sub-unit composition of the GABA-A receptor following chronic exposure to barbiturates, neurosteroids, ethanol and benzodiazepine agonists. These changes may underlie the development of tolerance, physical dependence and the problems which are associated with the abrupt withdrawal of such drugs. 

Another Methodfor 5 5-Diethyl Barbituric Acid. (This is a scaled down version.) 16 g of clean sodium is dissolved in 300 g of absolute ethanol. To this cooled solution is added 20 g of dry urea and 50 g of diethyl malonic ester (diethyl diethyl malonate). The mixture is heated in an autoclave (pressure cooker, very strong) for 4 to 5 hours at 100-110°. After removing from the autoclave, the mixture is cooled. Upon cooling, the sodium salt of diethyl barbituric acid separates, is filtered off, dissolved in water, and the free acid precipitated by the addition of hydrochloric acid. The acid is filtered and recrystallized from water, using decolorizing carbon, if necessary. Yield Depends on your ability to exclude H2O from the beginning of reaction. 

In higher doses, ethanol and barbiturates also depress the thermoregulatory center (Bl), thereby permitting cooling of the body to the point of death, given a sufficiently low ambient temperature (freezing to death in drunkenness). 

With any hypnotic, the risk of suicidal overdosage cannot be ignored. Since benzodiazepine intoxication may become life-threatening only when other central nervous depressants (ethanol) are taken simultaneously and can, moreover, be treated with specific benzodiazepine antagonists, the benzodiazepines should be given preference as sleep remedies over the all but obsolete barbiturates. 

An interesting entry to functionalized dihydropyrans has been intensively studied by Tietze in the 1990s using a three-component domino-Knoevenagel Hetero-Diels-Alder sequence. The overall transformation involves the transient formation of an activated heterodienophile by condensation of simple aldehydes with 1,3-dicarbonyls such as barbituric acids [127], Meldrum s acid [128], or activated carbonyls. In situ cycloaddition with electron-rich alkenes furnished the expected functionalized dihydropyrans. Two recent examples concern the reactivity of 1,4-benzoquinones and pyrazolones as 1,3-dicarbonyl equivalents under microwave irradiation. In the first case, a new three-component catalyst-free efficient one-pot transformation was proposed for the synthesis of pyrano-1,4-benzoquinone scaffolds [129]. In this synthetic method, 2,5-dihydroxy-3-undecyl-1,4-benzoquinone, paraformaldehyde, and alkenes were suspended in ethanol and placed under microwave irradiations to lead regioselectively the corresponding pyrano-l,4-benzoquinone derivatives (Scheme 38). The total regioselectivity was... 

Drugs that may affect sulfonylureas include androgens, anticoagulants, azole antifungals, barbiturates, beta blockers, calcium channel blockers, charcoal, chloramphenicol, cholestyramine, ciprofloxacin, clofibrate, corticosteroids, diazoxide, estrogens, ethanol, fluconazole, gemfibrozil, histamine H2 antagonists, hydantoins,... 

Drugs that may affect metronidazole include barbiturates and cimetidine. Drugs that may be affected by metronidazole include anticoagulants, disulfiram, ethanol, hydantoins, and lithium. 

Patients should avoid sunlight and drugs such as barbiturates and ethanol, which induce cytochromes in the liver, further reducing available heme and up-regulating ALA synthase expression. 

Bis(2-hydroperoxy-2,2-diphenylethyl)barbituric acid ethanol solvate (EACJIB) 1.450 1.446 102.1 92... 

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