Pentobarbital Alcohol

Pentobarbital withdrawal may involve a distal region of the chromosome 1 in the mouse (Buck et al. 1999), a site that may be identical to that associated with alcohol withdrawal. This finding suggests that common genes may be involved in both ethanol and pentobarbital dependence. 

Buck K, Metten P, Belknap J, et al Quantitative trait loci affecting risk for pentobarbital withdrawal map near alcohol withdrawal loci on mouse chromosomes 1, 4, and... 

Research in rodents has provided evidence of solvent withdrawal. Continuous exposure to toluene for 4 days and subsequent cessation produced an increase in handling-induced convulsions for at least 2 hours after cessation (Wiley et al. 2003). A similar pattern of trichloroethane administration to rodents produced pronounced withdrawal, which was worsened by the administration of the proconvulsant drug pentylenetetrazole and attenuated by reexposure to 2,000 ppm of toluene or the administration of alcohol, pentobarbital, or midazolam (Evans and Balster 1993). 

Barbiturates. The hrst barbiturate, barbital, was introduced in 1903 and was followed a few years later by phenobarbital. The barbiturates effectively relieve anxiety, but they are never used as anxiolytics today due to toxicity and abuse concerns. However, several barbiturates, including phenobarbital (Luminal), secobarbital (Seconal), and pentobarbital (Nembutal), remain available and are occasionally used to treat epilepsy and rarely to manage acute alcohol withdrawal. 

Barbiturates. The first barbiturate, barbital, was introduced at the turn of the 20th century. Hundreds of others, including phenobarbital and pentobarbital, were later developed. The barbiturates were a highly successful class of medications as it became clear that they treated not only alcohol withdrawal but seizure disorders, anxiety, and insomnia as well. By the 1960s, however, the barbiturates were largely surpassed by the benzodiazepines. The newer benzodiazepines act in a similar fashion and provide much the same therapeutic benefit but are significantly safer and easier to tolerate. 

Before the introduction of the benzodiazepines, a number of drugs from different chemical and pharmacological classes were used in the treatment of anxiety and insomnia. However, these drugs are more toxic and produce more serious side effects than do the benzodiazepines. Many also have signihcant abuse potential. Consequently, most of these compounds are no longer widely used. These drugs include the barbiturates (e.g., pentobarbital, amobarbital), carbamates (e.g., meprobamate), piperidinediones (e.g., glutethimide), and alcohols (e.g., ethchlorvynol). 

Pentobarbital Amobarbital lar to alcohol See alcohol Death from drug over-... 

Pentobarbital is biotransformed by oxidation of the penultimate carbon of the methyl butyl side-chain to produce a mixture of alcohols, and by iV -hydroxylation. The alcoholic metabolites of pentobarbital are pharmacologically inactive. Approximately 86% of a radioactive dose is excreted in the urine in 6 days, about 1% as unchanged drug and up to 73% as the L- and D-diastereoisomers of 3 -hydroxypentobarbital in a 5.4 1 ratio, and up to 15% as JV-hydroxypentobarbital.9 None of these metabolites is eliminated as a conjugate. 

The correct answer = B. It is important to treat the seizures associated with alcohol withdrawal. Benzodiazepines, such as chlordiazepoxide, diazepam or or the shorter-acting lorazepam, are effective in controlling this problem. They are less sedating than pentobarbital or phenytoin. 

After the last experiments, the rats are euthanized by injection of an overdose of pentobarbital and then perfused intracardially with a phosphate-buffered 2.0% paraformadehyde - 2.5% glutaraldehyde fixative. Methyl green solution was injected to confirm the location of the catheter after the perfusion. The spinal cord and nerve roots were dissected out and immersed in the same fixative for 4 h. Two specimens (10 mm rostral and caudal to the conus medullaris from each rat were postfixed with cacodylate-buffered 1 % osmium tetroxide dehydrated in a series of graded alcohol solutions, and embedded in epoxy resin. From the embedded tissue, 1-pm transverse sections were obtained and stained with toluidine blue dyes. Sections obtained from 10 mm rostral to the conus (caudal spinal cord) were used for qualitative evaluation. Quantitative analysis of nerve injury was performed using the sections obtained form 10 mm caudal to the conus. Each fascicle present in the cross section was assigned to an injury score 0 to 3. The injury score for each cross section was then calculated as the average score of all fascicles present in the cross section. 

Another group of barbiturates is more rapidly metabolized by the liver. Their effects last six or seven hours, and they are called short-acting. They include amobarbital (Amytal), pentobarbital (Nembutal), hexobarbital (Sombulex), and secobarbital (Seconal). These drugs behave very much like alcohol, giving pleasant feelings in low doses, especially as they begin to take effect. There fore, some people seek them out to change the way they feel, and... 

Several classes of pharmacologic agents are available for insomnia. Barbiturates are the oldest agents that have been used for insomnia and include pentobarbital, secobarbital, and amobarbital. Barbiturates are currently not recommended because of their high abuse potential (due to rapid development of tolerance) and lethal potential in overdose situations. Barbiturates potentiate the GABAergic-induced increase in chloride ion conductance at low doses, and at high doses they depress calcium-dependent action potentials. Caution should be exercised in patients with marked renal or liver dysfunction, severe respiratory disease, suicidal tendencies, or history of alcohol/drug abuse. 

Numerous barbiturates and oral hypoglycemic sulfonyl-ureas also have aliphatic side chains that arc su.sceptible to oxidation. Note that the sedative hypnotic amobarbital (Amytal) undergoes extensive to - I oxidation to the corresponding 3 -hydroxylated metabolite.Other barbiturates, such as pentobarbital, thiamylal,and secobarbital," reportedly are metabolized by way of a and to - I oxidation. The ri-propyl side chain attached to the oral hypoglycemic agent chlorpropamide (Diabinc.se) undergoes extensive to -I hydroxylation to yield the secondary alcohol 2 -hydroxy-chlorpropamide as a major urinary metabolite in humans. " ... 

Two alcoholic valerian extracts were found to potentiate pentobarbital sleeping time in mice (37), and Valdispert, an aqueous extract prepared from V. officinalis (L.), increased the thiopental sleeping time in a dose-dependent manner in rats (16). Based on these animal studies, in vitro studies of valerian s effect on GAB Anergic transmission, as well as the case series reported by Chan and colleagues, valerian would be expected to have at least an additive effect with barbiturates, alcohol, benzodiazepines, and other CNS depressants. 

Clinically important, potentially hazardous interactions with alcohol, anticholinergics, barbiturates, benzodiazepines, butabarbital, chloral hydrate, chlordiazepoxide, chlorpromazine, clonazepam, clorazepate, diazepam, ethchlorvynol, fluphenazine, flurazepam, hypnotics, lorazepam, MAO inhibitors, mephobarbital, mesoridazine, midazolam, narcotics, oxazepam, pentobarbital, phenobarbital, phenothiazines, phenylbutazone, primidone, prochlorperazine, promethazine, quazepam, secobarbital, sedatives, temazepam, thioridazine, tranquilizers, trifluoperazine, zolpidem... 

Clinically important, potentially hazardous interactions with adrenergic neurone blockers, alcohol, antihistamines, butalbital, hypnotics, isocarboxazid, pentobarbital, phenelzine, phenobarbital, primidone, sedatives, tranylcypromine, zolpidem... 

Oxidation of substituents attached to C5 is the most important pathway of metabolism for the barbiturates. The oxidative processes may yield alcohols, ketones, and carboxylic acids. For example, pentobarbital is oxidized to a hydroxy compound and a carboxylic acid (8) as shown in Fig. 5.2. The oxidative process may also yield phenols. If the barbiturate has a phenyl group attached to C5, by far the most important metabolic product is the p-hydroxyphenyl derivative, which has been shown to be formed through the intermediate epoxide (9). For example, phenobarbital is metabolized top-hydroxyphenobarbital (Fig. 5.3). The oxygenated metabolites (alcohols, phenols, ketones, and carboxylic acids) may be excreted in the urine in the free form or conjugated with glucuronic or sulfuric acid. 

Pentobarbital sodium Nembutal hypnotic drug (50 mg/mL), 40% propylene glycol, 10% alcohol, 10% pH 9.5 (approx.) 122-123 2.08 (Avdeef, 2003)... 

Both alcohol and the barbiturates are CNS depressants, and simple additive CNS depression provides part of the explanation. Acute alcohol ingestion may inhibit the liver enzymes concerned with the metabolism of barbiturates such as phenobarbital and pentobarbital, but chronic exposure to alcohol increases hepatic microsomal enzyme activity and may reduce sedation from barbiturates in patients without liver impairment. - Similarly, chronic exposure to a barbiturate such as phenobarbital may increase alcohol metabolism due to enzyme induction and consequently reduce blood-alcohol levels. ... 

Raskovic, A., O. Horvat, V. Jakovljevic, J. Sabo, and R. Vasic. 2007. Interaction of alcoholic extracts of hops with pentobarbital and diazepam in mice. Eur. f. Drug Metab. Pharmacokinet. 32(l) 45-49. 

A series of other barbiturates (phenobarbital, barbital, thiopental, pentobarbital at 1 mmol l i concentration inhibit the orotate uptake system without affecting the incorporation of uracil into cellular pyrimidines [287]. While barbituric acid and hexobarbital are less active, phenylethylhydan-toin, chlorpromazine and phenethyl alcohol are extremely active. Phenobarbital also depresses the utilization of orotic acid for the synthesis of cytidine nucleotides in the liver [288]. a-Hexachlorocyclohexane, an inhibitor of the phenobarbital type, was even more effective in depressing de novo cytidine nucleotide synthesis from orotic acid [289]. 

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