Toxicology barbiturates

The effect of urinary pH on drug ionization also has toxicological implications. For example, in cases of phenobarbital (a weak acid barbiturate) overdose the urine can be alkalinized (the pH elevated) by administering sodium bicarbonate to the patient. The resultant increase in pH shifts the dissociation equilibrium for this weak acid to the right, producing an increase in the proportion of the ionized form, less reabsorption in the kidneys, and more rapid elimination. Conversely, acidifying the urine with ammonium chloride will increase the excretion rate of drugs that are weak bases since they will be more protonated (ionized) and less reabsorbed (more polar, less lipophilic). 

B. Widdop. Screening for Drugs of Abuse (II) Cannabinoids, Lysergic Acid Diethylamide, Buprenorphine, Methadone, Barbiturates, Benzodiazepines and Other Drugs. Annals of Clinical Biochemistry 34 (5) (1997) 460-510 Shannon, M. Toxicology Reviews Physostigmine. Pediatric Emergency Care 14 (3) (1998) 224-226. 

Fetal microcephaly has been attributed to cocaine abuse during pregnancy (323). Urine toxicology confirmed the presence of morphine, benzoylecgonine, barbiturates, paracetamol, and propoxyphene. Analyses of amniotic fluid, placenta, and fetal serum and urine were also positive for these substances. The authors suggested that vascular disruption was the likely major mechanism of anomalies, both behavioral and malformative, due to prolonged exposure to cocaine in utero. 

Elisabeth, I. Rene, S. Dieter, J. Screening for drugs in clinical toxicology hy high-performance liquid chromatography Identification of barbiturates by post-column ionization and detection by a multiplex photodiode array spectrophotometer. J. Chromatogr. 1988, 428, 369. 

A set of 25 barbiturates was analyzed using CZE and MEKC. Buffers consisting of 90 mM borate, pH 8.4 (CZE), and 20 mM phosphate, 50 mM sodium dodecylsulfate (SDS), pH 7.5 (MEKC). The methods were evaluated for their suitability in systematic toxicological analysis (STA), especially when a combination of methods having a low correlation is used (305). A solid-phase microextraction device in combination with CE for the determination of barbiturates was described (see 306 and Sec. VII). The detection limit for 10 barbiturates was 0.1 ppm in urine, while the limit of detection was about 3 times poorer in bovine serum (306). Polyacrylamide-coated columns have been used for barbiturates and benzodiazepines. Seven kinds of barbiturates were sucessfully separated with the coated columns without further additives (307). The benzodiazepines, which are electrically neutral solutes, were separated in the presence of SDS. The CE method offered fast and efficient separations of the more hydrophobic solutes. 

Fig. 3.1 Thalidomide was developed as a non-addictive sedative as an alternative to barbiturates. Following its administration to pregnant women, it was found that the babies were bom with truncated limbs (phocomeUa). At the time this was perceived as a classic case of the pharmacological activity residing in one enantiomer (R-) and the undesirable toxicological effect residing in the other enantiomer. The simation is now known to be much more complex than this (see text and reference cited therein).

A. Specific levels of phenobarbital are usually readily available from hospital clinical laboratories concentrations greater an 60-80 mg/L are usually associated with coma and those greater than 150-200 mg/L with severe hypotension. For short- and intermediate-acting barbiturates, coma is likely when the semm concentration exceeds 20-30 mg/L. Barbiturates are easily detected in routine urine toxicologic screening. 

Gupta RC, Kofoed J. Toxicological statistics for barbiturates, otiier sedatives, and tranquillizers in Ontario a 10-year survey. CanMed Assoc J (1966) 863-5. 

Toxicology S. is rapidly absorbed after oral uptake, is metabolized mainly in the liver, and rapidly eliminated. Symptoms of intoxication are initial restlessness, anxiety, vomiting, then convulsions of the extensor muscles (1 or more/minute), the convulsions are again triggered by external stimuli. Therapy for acute poisoning gastrolavage and administration of activated charcoal - for severe poisoning barbiturate narcosis and administration of muscle relaxants. 

CE is also useful in forensic toxicology laboratories to screen urine for drugs of abuse such as opiates, barbiturates, benzodiazepines, amphetamines, morphine, etc. and also for screening postmortem fluids for illicit drugs or elevated levels of legal drugs. When coupled to MS, CE is a powerful tool in the confirmation of positive results. 

Academic researchers have reported that barbituric acid and thiobarbituric acid can outperform many of the stabilisers currently in commercial use, at least in laboratory tests. Promising results have also been reported for N-substituted itaconimide derivatives, said to be more effective at stabilising phthalate-plasticised PVC than many of the stabilisers traditionally used in the industry. Commercialisation of academic developments would require extensive data about the effects of the stabilisers on processing and overall technical performance, as well as toxicological studies. 

Separation of Ten Barbiturates by Gas-Phase Chromatography. Application to Clinical Toxicology Bull. Soc. Pharm. Bordeaux 109(3) 132-144 (1970) CA 74 62775t... 

Difference spectroscopy was developed by Chance and Williams in course of their research on electron transport chain proteins in the mitochondria. TTie technique subsequently provided much needed information about the state and sequence of the electron transport proteins. Difference spectroscopy has also been utilized in toxicology laboratories for analysis of many toxic drugs. Example can be cited of barbiturates which show characteristic changes in absorption spectra between their keto and enol forms. Moreover, difference spectroscopy is a necessary tool to study globular protein conformation. 

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