Barbiturates dependence

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. 

The mental effects of barbiturates depend on the amount of the drug taken and the strength of the dosage. Generally, a person falls asleep when taking a prescribed dosage at bedtime. 

With aggressive treatment in the hospital and counseling, most people survive barbiturate abuse. However, even with aggressive therapy, some patients die. A person s outcome after abusing barbiturates depends on many factors, such as ... 

Meprobamate causes physical dependence similar to that seen with barbiturate dependence. No physical dependence on buspirone administration has been... 

Barbiturates. QSAR studies by Hansch presented evidence that the hypnotic activity of barbiturates depends largely on their relative lipophilic character as determined by octanol-water partition coefficients (102-104). Employing Equation 5.6, a QSAR analysis was conducted on over 100 barbiturates as well as a number of non-barbiturates having hypnotic activity. 

Near-UV absorption spectra of barbiturates depend on the type of substitution and the state of ionization of the molecule.52-54 Absorption bands at — 210 nm for undissociated compounds are shifted to 240-270 nm... 

Hansch and coworkers, in their continuing attempts to place the discussion of structure-activity relationships of biologically active compounds on a mathematic basis, have presented evidence that the hypnotic activity of groups of barbiturates depends almost entirely on their relative lipophilic character as defined by their octanol-water partition coefficients. Although hypnotic activity was the model, the principle should apply to other actions of drugs in the central nervous system. 

The various barbiturates differ m the time required for the onset of sleep and m the duration of their effects All the barbiturates must be used only m strict accordance with instructions to avoid potentially lethal overdoses Drug dependence m some mdi viduals IS also a problem... 

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

Sedatives and hypnotics may be divided into two classes barbiturates and miscellaneous sedatives and hypnotics. The barbiturates are divided into several groups, depending on tiieir duration of action ... 

All barbiturates have essentially die same mode of action. Depending on the dose given, tiiese drags are capable of producing central nervous system (CNS) depression and mood alteration ranging from mild excitation to mild sedation, hypnosis (sleep), and deep coma These drugs also are respiratory depressants the degree of depression... 

Like the barbiturates, the miscellaneous drugp sedative or hypnotic effects diminish after approximately 2 weeks. Ffersons taking these dragp for periods longer than 2 weeks may have a tendency to increase the dose to produce the desired effects (eg, sleep, sedation). Physical and psychological dependence may occur, especially after prolonged use of high doses. However, their addictive potential appears to be less than that of the... 

As with the barbiturates, the most common adverse reaction seen with the use of clonazepam (Klonopin), clorazepate (Tranxene), and diazepam (Valium) is sedation in varying degrees. Additional adverse effects may include anorexia, constipation, or diarrhea. Some adverse reactions are dose dependent, whereas others may diminish in intensity or cause few problems after several weeks of therapy. 

Dependence on barbiturates has declined in recent years as physicians have substituted benzodiazepines for the treatment of many of the conditions for which barbiturates were formerly used. Clinicians will still see cases of abuse and dependence among medical patients receiving barbiturates or barbirurate combination products (e.g., Fiorinal) and in substance abusers (Silberstein and McCrory 2001). 

Ibrahim RB, Wilson JG, Thorsby ME, et al Effect of buprenorphine on CYP3Aactivity in rat and human liver microsomes. Life Sci 66 1293—1298, 2000 Iguchi MY, Handelsman L, Bickel WK, et al Benzodiazepine and sedative use/abuse by methadone maintenance clients. Drug Alcohol Depend 32 257—266, 1993 Isbell H Manifestations and treatment of addiction to narcotic drugs and barbiturates. Med Clin North Am 34 423 38, 1950... 

Wilder A Diagnosis and treatment of drug dependence of the barbiturate type. Am J Psychiatry 125 758-765, 1968... 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

---