Barbiturates in blood

For the preparation of derivatives on a micro scale (at the microgram and picogram levels) reaction with methyl iodide was recommended [510] 100—200 /il of an acetone solution of barbituric acids was mixed with a 3- to 1000-fold molar excess of methyl iodide and refluxed with 3—5 mg of potassium carbonate. After about 30 min, 0.2 /A of the supernatant was injected directly into a column with 3% of OV-225, with temperature programming at 8°C/min from 100 to 240°C. The advantage of the method is that no toxic and hazardous chemicals are used. The method was further modified for the micro-determination of barbiturates in blood [511]. Only 20-25 /d of blood were necessary for the determination, and with the use of a detector sensitive to nitrogen down to 1 ng of barbiturate could be determined in this sample. The derivatization reaction was performed in a micro-refluxer (see Fig. 2.6). 

For quantitation of barbiturates in blood, Walker et al.40 used dilutions of 12.5... 

Street, H. V., and McMartin, C., Quantitative estimation and identification of barbiturates in blood in emergency cases. Nature 199, 456-459 (1963). 

Gallaher, E. J., and Skinner, R. F. Rapid Assay of Barbiturates in Blood... 

The Determination of Pentobarbital and Other Barbiturates in Blood Plasma by Gas-Liquid Chromatography with On-Column and Pre-Column Butylation... 

Prognon, P., and Paris, M. Application of Gas Phase Chromatography to Determine Barbiturates in Blood... 

OWENS has prepared antibodies to PCP in goats. When administered to mice the PCP levels in blood rose tenfold as an antibody-bound form that was readily excreted in urine. BROWNE tested the selfadministration by rats of 1,000 compounds related (and not related) to PCP, some of which produced PCP-like effects. One compound that was self-administered prevented the entrance of PCP into brain. BALSTER gave a general review of the effects produced by PCP in laboratory animals and showed that some effects were similar to those produced by amphetamine, some to barbiturates, and some to antipsychotics. This response profile makes PCP a unique drug that stands alone in its complex effects and toxicity. 

The antagonistic effects of sodium pentothal on the blood pressure and the respiratory effects of chlordan are illustrated in Figure 1, C. The intermittent severe tremors with concomitant Cheyne-Stokes type of respiration produced by the injection of chlordan were decreased or entirely abolished, and both the respiratory rate and depth were restored to near normal. A dose of barbiturate sufficient to diminish the tremors appreciably and to restore the respiration to normal also produced a temporary drop of 10 to. 40 mm. of mercury in blood pressure. 

Lehane, D.P. et al. 1976. Therapeutic drug monitoring Measurements of antiepileptic and barbiturate drug levels in blood by gas chromatography with nitrogen-selective detector. Ann Clin Lab Sci. 6 404. 

Since GABA-ergic synapses are confined to neural tissues, specific inhibition of central nervous functions can be achieved for instance, there is little change in blood pressure, heart rate, and body temperature. The therapeutic index of benzodiazepines, calculated with reference to the toxic dose producing respiratory depression, is greater than 100 and thus exceeds that of barbiturates and other sedative-hypnotics by more than tenfold. Benzodiazepine intoxication can be treated with a specific antidote (see below). 

Branston NM, Hope DT, Symon L (1979) Barbiturates in focal ischemia of primate cortex effects on blood flow distribution, evoked potential and extracellular potassium. Stroke 10 647-653... 

Stage II—excitement The patient experiences delirium and violent combative behavior. There is a rise and irregularity in blood pressure. The respiratory rate may be increased. To avoid this stage of anesthesia, a short-acting barbiturate, such as sodium pentothal, is given intravenously before inhalation anesthesia is administered. 

The sorption efficiency of MC was determined as the ratio of the quantity of the adsorbed substance to its initial amount (w / w), expressed in % for a certain ratio (w / w) of adsorbent to substance. Optimal ratios of adsorbent to substance equal 15-20 for barbiturates, 20 - 25 for cyanocobalamin and bilirubin, and 40 - 50 for hemoglobin. The initial concentration of absorbed substances was 100 - 200 pg/ml. The substances were incubated for lmin with MC either in physiological solution or in donor plasma and donor blood at room temperature (pH 7.4). The concentration of substances in the solutions was measured by differential visual and UV-spectroscopy. Concentrations of substances in blood and plasma and adsorption of total plasma proteins was determined by thin-layer chromatography with a fluorescent label. 

All the barbiturates possess the properties of CNS depressants. Thus, in moderate doses they produce a drunken euphoric state. Similar to alcohol, barbiturates may produce a loss of motor coordination, a staggering gait, and slurred speech. Loss of emotional control and behavioral disinhibition arc also characteristic cfTccts. Sedation and sleep are produced by increased doses, and higher doses produce surgical anesthesia. Physiological effects include respiratory depression, which is responsible for most of the overdose deaths associated with barbiturates. In addition some depression of heart rate, blood pressure, and gastrointestinal activity is noted at higher doses. 

Thiocyanate is separated from cyanide by distilling off HCN from a weakly acid medium. With bromine and chloramine-T, thiocyanate is converted into cyanogen bromide and cyanogen chloride, respectively, and determined as a polymethine dye by the benzidine-pyridine method or pyridine—barbituric acid method [38—40]. The latter method has been applied for continuous determination of thiocyanate in blood plasma and in urine [40]. 

This short survey is intended only to outline major developments in the analysis of barbiturates. Methods are directed tbward better sensitivity, specificity, rapidity, and discriminating power to meet many demands, but mostly those of trace analysis in blood, urine, and other body fluids and tissues, often in postmortem material, and in combinations with other drugs... 

A chromatogram of the derivatives of barbiturates is shown in Fig. 1.4 [39]. The notation of the peaks corresponds to the numbers of the barbiturates in Table 1.2. The asterisk denotes the peak appearing in the analysis of blood plasma. The total concentration of barbiturates was 20 10" g/ml. 

Cardiovascular The anesthetic barbiturates produce dose-dependent decreases in blood pressure that are due primarily to vasodilation, particularly venodUation, and to a lesser degree to a direct decrease in cardiac contractility. Typically, heart rate increases as a compensatory response to a lower blood pressure, although barbiturates also blunt the baroreceptor reflex. 

Cardiovascular Cardiovascular stability after induction is a major advantage of etomidate over either barbiturates or propofol. Induction doses of etomidate typically produce a small increase in heart rate and little or no decrease in blood pressure or cardiac output. Etomidate has little effect on coronary perfusion pressure while reducing myocardial consumption. Thus, of all induction agents, etomidate is best suited to maintain cardiovascular stability in patients with coronary artery disease, cardiomyopathy, cerebral vascular disease, or hypovolemia. 

Barbiturates selectively depress transmission in autonomic ganglia and reduce nicotinic excitation by choline esters, an effect that may account for the fall in blood pressure produced by intravenous oxybarbiturates and by severe barbiturate intoxication. At skeletal neuromuscular junctions, the blocking effects of both tubocurarine and decamethonium are enhanced during barbiturate anesthesia. These actions probably result from the capacity of barbiturates at hypnotic or anesthetic concentrations to inhibit the passage of current through nicotinic cholinergic receptors. Several distinct mechanisms appear to be involved and little stereoselectivity is evident. 

When given orally in sedative or hypnotic doses, the barbiturates do not produce significant overt cardiovascular effects except for a slight decrease in blood pressure and heart rate such as occurs... 

Pharmacokinetics PO/PR/IM/IV. Well absorbed orally. Give IM only if patient cant take orally. Give IV slowly because of fall in blood pressure. Barbiturates vary markedly in lipid solubility and plasma protein binding (Table 3.86). Barbiturates induce P450 enzymes in the liver which T metabolism of phenytoin, digitoxin, coumadin and others. Pharmacokinetics Primary difference between various benzodiazepine agonists are their pharmacokinetic properties (Table 3.8C). 

---