Barbiturates interaction

FIG U RE 65.2 Schematic model of the GABAa receptor. The receptor spans the cell membrane. GABA binds to the outside of the receptor, causing an influx of Cl ions through the channel. Benzodiazepines and barbiturates interact with different recognition sites on the receptor and increase the effectiveness of GABA. 

For the reasons given in the Purpose/Rationale section above, barbiturate interaction tests yield useful information not readily provided by the other procedures in the core battery. Furthermore, the data obtained are highly correlated with results that could be expected in man. To our knowledge, no sleep enhancing agent used in man has been found inactive in a barbiturate interaction procedure. Conversely, no clinically known enhancer of wakefulness, for example caffeine, amphetamine and modafinil, has failed to reduce or abolish barbiturate-induced sleep. Potential to cause drowsiness, as is observed with many antihistamines, is also clearly picked up in barbiturate interaction procedures as are the potential sedative effects of a variety of neuroleptics. 

Although procedurally simple, barbiturate interaction procedures are extremely subject to small environmental changes (lighting, ambient noise and temperature, time of day) and therefore have to be performed under highly controlled conditions to yield reproducible results. 

Fig. 47 Assembly of calix[4]arenes via 2,4,6-triamino-triazine/barbiturate interactions. Reprinted with permission from [165]...

Barbiturates. Barbiturate interactions with the GABAa receptor complex have been reviewed (130,131). Barbiturate effects on receptor-mediated chloride ion flux have been extensively studied employing electrophysio-logical techniques either in vivo or in isolated... 

Table I. Association constants for the receptor-barbiturate interaction.

The proplnts described above are in the realm of prior art and depict those NC proplnts with low smoke potential that are used primarily as gun proplnts. Recent research and development work has been concentrated on creating both gun proplnts and rocket proplnts with reduced smoke output in order to foil countermeasures. Lavitt (Ref 76) found that the concurrent use of optimum proportions of lead stearate and sodium barbiturate in double-base proplnts resulted in a marked reduction in smoke output. This was attributed to the synergistic interaction of the two salts to produce more complete oxidation of the exhaust products. The importance of using the optimum ratio of the two catalysts is demonstrated by the higher smoke values shown in Table 4 for Propellants 105, 106 and 107, when compared to other... 

Discuss the uses, general drug actions, adverse reactions, contraindications, precautions, and interactions of the barbiturates and miscellaneous sedatives and hypnotics. 

Phenytoin interacts widi many different drugp. For example isoniazid, chloramphenicol, sulfonamides, benzodiazepines, succinimides, and cimetidine all increase phenytoin blood levels. The barbiturates, rifampin, theophylline, and warfarin decrease phenytoin blood levels. When administering the hydantoins with meperidine, die analgesic effect of meperidine is decreased. 

Valerian Valeriana officinalis Restlessness, sleep disorders Rare if used as directed. May interact with the barbiturates (eg, phenobarbital), the benzodiazepines (eg, diazepam) and the opiates, (eg, morphine). 

The most common unwanted effects of the barbiturates are oversedation and psychomotot impaitment, which may petsist well into the next day following a hypnotic dose. Patadoxical excitement, hypersensitivity reactions, and muscle or joint pain may occur in rare cases. Drug-drug interactions occur with the CNS sedatives, and a number of drugs have enhanced metabolism when co-administered with barbiturates (Barnhill et al. 1989). 

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."... 

Test for central interaction with barbiturates Anti/proconvulsant activity... 

Synthesis of Immunogen (Hapten) The barbiturate, 5-ally 1-5-(1-carboxyisopropyl) barbituric acid (I) is first converted to 5-allyl-5-(1 -p-n i trophenyloxycarbonylisopropyl) barbituric acid (II) by the interaction of the base with /7-nitrophenol in N, N-dimethylformamide (DMF) as shown below ... 

Noncovalent interactions in metal complexes of biomolecules may play an important role in the creation of supramolecular structures around the metal center. For instance, extensive three-dimensional hydrogen-bonded stmcmres grow around metal complexes of barbiturates, recognized as the most widely used drugs for the treatment of epilepsy.Electrostatic interactions between a cation and the Trring of an aromatic molecule (cation-tt interactions) are common motifs in protein structures. Little is known about alkali and alkali-earth cation-tt inter-... 

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). 

Valerian, ginger, goldenseal, and chamomile all interact with sedatives (such as barbiturates and alcohol) to increase sedative effects. 

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