Barbiturates disadvantages

The principal disadvantages of barbiturates as hypnotics include the development of physical dependence, a relatively low therapeutic index (and the potential of poisoning, as in suicide), suppression of REM sleep, and possible hangover effects. As mentioned above, benzodiazepines (e.g., flurazepam or brotizolam) are hypnotics as effective as barbiturates and are much safer in terms of their therapeutic index, addiction potential, and REM sleep-deprivation effects. Thus benzodiazepines have displaced barbiturates as sedative hypnotics. 

Humanity s centuries-old, avid search for substances that would relieve these conditions has resulted in a progression from alcohol to opiates to the synthesis of bromides and barbiturates. Each of these, however, shares treatment-limiting and potentially life-threatening disadvantages, including the following ... 

This involves considerable art, which must be learned in the clinic. It falls into two divisions (1) surface application to the mucous membranes, especially of the eye, nose, throat, and urethra and (2) injections about nerves, in different parts of their course and distribution, from their spinal roots to their ultimate fibrils. The advantages and disadvantages in comparison with general anesthesia and the selection of the local anesthetic agent also depend on clinical discrimination. Nervous, fearful, and excitable patients often suffer severely from apprehension, which also disposes toward accidents. They may be at least somewhat quieted by sedatives, morphine (0.015 g hypodermically) half an hour before the operation, or by barbiturates. The latter also tend to prevent convulsions. 

The rapid-acting barbiturates, such as methohexital (Brevital), are used as intravenous anesthetics/induction agents. Advantages are rapid anesthesia and short duration of action. A disadvantage is respiratory suppression with higher doses. 

The thermal decomposition of tetramethylammonium salts of barbiturates is a procedure used extensively for their methylation [512-515]. Decomposition is performed at 240°C (temperature of the injection port) with analysis on SE-30, QF-1 and similar stationary phases. The use of trimethylanilinium hydroxide leads to better reproducibility of the preparation of the phenobarbital derivatives and to an improvement in the quantitative results [516,517]. The disadvantage of this procedure is the dependence of the course of the reaction on several parameters, e.g., geometry of the injection port, temperature. 

Several presumptive tests are available for barbiturates and benzodiazepines. These are not as general as those used for other drug classes (for example, the Marquis test for opiates and amphetamines (including ring-substituted species)), but have the disadvantage that they do not discriminate between the drugs within the specific class. These tests are described in the following sections. 

It is of interest that those who inherited acute intermittent porphyria and variegate porphyria suffered no biological disadvantage from the natural environment and bred as well as the normal population until the introduction of barbiturates and sulphonamides. They are now at serious disadvantage, for many other drugs can precipitate fatal acute attacks. 

LC, GC, and CE are three typical analytical separation approaches used to determine barbiturates. The advantages and disadvantages of the three techniques are summarized in Table 3. 

The benzodiazepines overtook the barbiturates because of the following disadvantages of barbiturates ... 

Using the conventional diluent, stable optical density readings are attained in 15-25 min, which is a distinct disadvantage in clinical practice. Lowering the pH of the diluent to 7.2 yields a stable value for 2) within 5 minutes, irrespective of whether the pH is determined by borate, barbiturate, or phosphate buffers (V3). However, as in the observation of Chilcote and O Dea, the results are 2-3% too high. Addition of 0.5 ml Sterox SE per liter diluting solution appeared to suppress the development of turbidity completely, even at pH 7. 

N-Chloromethylphthalimide (ClMPI), N-chloromethyl-4-nitrophthalimide (ClMNPl) and N-chloromethylisatin (ClMIS) react quantitatively with fatty acids, dicarboxylic acids and barbiturates (Figure 11) [105]. The reactivity of these labels is due to the high mobility of the chlorine atom. This reaction is similar to those with phenacyl bromide. For a complete reaction it is necessary to convert the acids to alkali metal or ammonium salts. Triethylamine or a crown ether is used as catalyst. Aprotic solvents such as acetonitrile, methanol and diethyl ether are suitable reaction media. The reaction is complete within 30—40 min at 60 °C. The disadvantage of these labels is reactivity to alcohols and primary and secondary amines, and as a result the selectivity is limited. HPLC separation of phthalimidomethyl esters was performed on a reversed phase column (Cg) with acetonitrile/water in various proportions as the mobile phase. Detection was at 254 nm. 

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