Phenobarbital Alcohol

Gastrointestinal Anticholinergic Combinations Antrocol Elixir—atropine sulfate, phenobarbital, alcohol Barbidonna—atropine, scopolamine HBr, hyoseyamine sulfate, phenobarbital... 

Bellacane Elixir—atropine, scopolamine HBr, hyoseyamine HBr or sulfate, phenobarbital, alcohol, tartrazine Bellacane SR Tablets—1-alkaloids of belladonna, phenobarbital, ergotamine tartrate Bellergal-S Tablets—1-alkaloids of belladonna, phenobarbital, ergotamine tartrate Butibel Elixir—belladonna extract, butabarbital sodium, alcohol, sucrose, saccharin Butibel Tablets—belladonna extract, butabarbitol Chardonna-2 Tablets—belladonna extract, phenobarbital Donnatal Elixir—atropine, scopolamine HBr, hyoseyamine HBr or sulfate, phenobarbital, alcohol, sucrose, saccharin... 

Miscellaneous Pharmaceutical Processes. Solvent extraction is used for the preparation of many products that ate either isolated from naturally occurring materials or purified during synthesis. Among these are sulfa dmgs, methaqualone [72-44-6] phenobarbital [50-06-6] antihistamines, cortisone [53-06-5] estrogens and other hormones (qv), and reserpine [50-55-5] and alkaloids (qv). Common solvents for these appHcations are chloroform, isoamyl alcohol, diethyl ether, and methylene chloride. Distribution coefficient data for dmg species are important for the design of solvent extraction procedures. These can be determined with a laboratory continuous extraction system (AKUEVE) (244). 

The barbiturates are contraindicated in patients with known hypersensitivity to the drugs. The barbiturates are used cautiously in patients with liver or kidney disease and those with neurological disorders. The barbiturates (eg, phenobarbital) are used with caution in patients with pulmonary disease and in hyperactive children. When barbiturates are used with other CNS depressants (eg, alcohol, narcotic analgesics, and antidepressants), an additive CNS depressant effect may occur. See Chapter 26 for additional information on the barbiturates. 

In rabbits under light amytal anesthesia, chlordan has no direcr effect on the blood pressure, but produces a type of respiration having many characteristics in common with Cheyne-Stokes type. The generalized tremors, opisthotonus, tonic and clonic convulsions, produced by chlordan were decreased or abolished and respiration restored to normal by suitable injections of the sodium salts of amytal, phenobarbital, and pentothal. The LD60 of chlordan, which was about 20 mg. per kg. on intravenous administration to intact rabbits, was increased to about 60 mg. per kg. through the antidotal action of the barbiturates. An unidentified chlorine-containing degradation product with acidic properties was recovered from the urine of rabbits treated with chlordan. Approximately one third of its chlorine content was set free on hydrolysis at 100° C. with sodium hydroxide in either absolute alcohol or in water. 

Fig. 2 Solubility of phenobarbital as a function of pH and alcohol concentration. (From Ref. 5).

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. 

When used for detoxification, phenobarbital is given in equal doses four times a day. The maximum daily dose of phenobarbital is 600 mg, but much lower doses are usually sufficient. The phenobarbital dose is lowered (i.e., tapered) by about 20% per day. If the patient is too drowsy, then a dose should be skipped. If breakthrough withdrawal symptoms continue to occur, then the pace of the detoxification should be slowed. Before using phenobarbital, liver function tests should be obtained. All barbiturates depend greatly on the liver to be metabolized. Alcoholics with cirrhosis or other forms of liver impairment may have difficulty clearing phenobarbital. Phenobarbital should not be used in patients with poor liver function. In addition, the barbiturates can worsen a medical condition known as porphyria and should be avoided in those with this disorder. Phenobarbital, as noted, is seldom used today for alcohol detoxification. 

Phenobarbitone is used to treat epilepsy, migraine headache, dental infections, pregnancy vomiting, tetanus, enuresis, chorea, pre and post operative sedation, hypertension, anxiety states, neurosis, and in the treatment of drug and alcohol addiction. This drug is also called phenobarbital. 

A number of substances including ethanol, isopropyl alcohol, polybrominated biphenyls, phenobarbital, and benzo( )pyrene have been shown to synergistically affect carbon tetrachloride toxicity." Alcohol has been a concomitant factor in many of the human cases of poisoning, especially in cases in which severe liver and kidney damage have occurred. Some substances such as chlordecone greatly potentiate the toxicity of carbon tetrachloride at... 

Conversely, certain drugs modify the effectiveness or side effects of aspirin. Phenobarbital, occasionally used for seizures, induces liver enzymes that increase the metabolism and excretion of aspirin, (3-adrenoceptorblocking drugs, such as propranolol, and decrease the antiinflammatory effects of aspirin, whereas reserpine decreases its analgesic effects. Antacids decrease the absorption of aspirin. Alcohol consumption in combination with aspirin increases the latter s ulcerogenic effects. 

Historically, alcohol has been used as an anxiety-reducing agent, both casually and in professional medical settings. In 1903, barbital was introduced as the first barbiturate to treat anxiety, and phenobarbital followed a few years later. Barbiturates have many side effects and addictive properties, and overdose can lead to coma and death. For these reasons, they are rarely used today, except to treat some forms of epilepsy. This class of drugs was eventually replaced by the benzodiazepines (see Chapter 4). 

Rosenthal RN, Perkel C, Singh P, et al. A pilot open randomized trial of valproate and phenobarbital in the treatment of acute alcohol withdrawal. Am J Addict 1998 7 189-197. 

Each 5 mL (teaspoonful) of elixir (23% alcohol) contains phenobarbital 16.2 mg, hyoscyamine sulfate 0.1037 mg, atropine sulfate 0.0194 mg, and scopolamine hydrobro-... 

In isolated rat hepatocytes obtained from acetone- or phenobarbital-treated rats, the metabolism of toluene at low (below 100 pM) or high (100-500 pM) concentration was increased, in particular after phenobarbital treatment. Ethanol (7 and 60 mM) inhibited the overall metabolism of toluene (sum of benzyl alcohol, benzaldehyde, benzoic acid and hippuric acid), leading to accumulation of benzyl alcohol (Smith-Kielland Ripel, 1993). 

Fusari and coworkers3 have developed a similar method for the assay of phenytoin and phenobarbital in dosage forms. They have used Silanized Celite 545 as the support material, 25% amyl alcohol in chloroform as the stationary phase and 0.05M borate buffer of pH 9.5 as the mobile phase. Phenobarbital was eluted with the mobile phase and phenytoin eluted with absolute ethanol. Ultraviolet absorption was used to quantitate the substances. 

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