Addiction to barbiturates

The barbiturates also cause a physical dependence different from the opioid narcotics. In an individual addicted to barbiturates, the barbiturates should not be withdrawn abruptly but, rather, tapered slowly. Sudden withdrawal of the barbiturates can precipitate extreme agitation and grand mal seizures. This can lead to a spasm of the respiratory musculature, producing impaired respiration, cyanosis, and possibly, death (42). As a rule, drug dependence is followed by tolerance, in which increasing doses are required to obtain the same pharmacological effect. Because barbiturates cause tolerance and, often, dependence, their use as a hypnotic rarely is justified. 

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... 

The importance of producing pharmaceuticals in enantiomerically pure forms was brought to the public s attention with the thalidomide (Formula 4.2) tragedy in the early 1960s. Thalidomide, as a racemic mixture, was originally produced in 1953 as a sedative and a non-addictive alternative to barbiturates. It was later found that it alleviated many of the unpleasant symptoms of early pregnancy but by 1961 its use had been linked with an increase in the number of severe birth deformities and it was withdrawn. It... 

Barbiturate sensitivity manifest or latent porphyria marked impairment of liver function severe respiratory disease when dyspnea or obstruction is evident nephritic patients patients with respiratory disease where dyspnea or obstruction is present intra-arterial administration subcutaneous administration previous addiction to the sedative/hypnotic group. 

Naloxone (Narcan) and naltrexone hydrochloride (Trexan) reverse the respiratory depressant action of narcotics related to morphine, meperidine, and methadone. They differ from other narcotic analgesics in several respects. Naloxone does not cause respiratory depression, pupillary constriction, sedation, or analgesia. However, it does antagonize the actions of pentazocine. Naloxone neither antagonizes the respiratory depressant effects of barbiturates and other hypnotics nor aggravates their depressant effects on respiration. Similar to nalorphine, naloxone precipitates an abstinence syndrome when administered to patients addicted to opiate-like drugs. 

As access to barbiturates was limited, benzodiazepines were promoted as a safer alternative. Benzodiazepines went on the market during the 1960s and were thought to be less addictive than barbiturates. 

Furthermore, the late 1990s brought concerns about benzodiazepines, the drugs thought to be a safe alternative to barbiturates. Benzodiazepines produced side effects similar to those produced by barbiturates. These included the risk of addiction when high doses were taken. Benzodiazepines accounted for 30% of all prescriptions for controlled substance, according to the DEA. 

When actress Sheree North filmed the 1956 movie How to Be Very, Very Popular, she received metham-phetamine shots, bottles of Benzedrine (another amphetamine) for daytime use and the barbiturate Nembutal to sleep at night. The actress described that situation in the book Marilyn The Last Take. In the 1993 book written by Peter Harry Brown and Patte Barham about the late actress Marilyn Monroe, North said that people did not know the drugs were harmful. She became addicted to the drugs, as did Monroe. 

Benzodiazepines were first developed and marketed in the 1960s and touted as safer alternatives to barbiturates. They also were thought to be less addictive than barbiturates. Of all controlled substances for which prescriptions are written, benzodiazepines account for about 30%. One of the main uses of prescription Rohypnol is to reduce anxiety and insomnia and induce sleep. As a sedative, Rohypnol is reportedly about 10 times more powerful than Valium. 

All barbiturates have the potential to be abused and cause addiction. Different barbiturates are designated as schedule II, III, and IV drugs, which means that all barbiturates require a prescription from a doctor or health care provider and the prescription must contain the doctor s DEA number. Physicians must obtain a special license to get a DEA number in order to prescribe controlled or addictive substances such as barbiturates. Doctors are very cautious about prescribing barbiturates to patients who have a history of drug abuse. 

There are no drugs that can be used in the treatment of barbiturate abuse or addiction, but it is good to have some knowledge of those available to treat other addictions. For a friend or parent addicted to another drug, there may be legal drugs they can take to help them kick the habit. 

Medications can cross the placenta and have an adverse effect on the fetus. The fetus has an immature metabolism and a slow excretion rate that can cause a pooling of the medication. Depending on the physiological effect of the medication, the fetus can be addicted to the medication and go through withdrawal after birth. This can occur with alcohol, barbiturates, and narcotics. 

Glutethimide (250 to 500 mg at bedtime) is indicated in short-term (a few days) relief of insomnia. It exhibits pronounced atropine-like effects including mydriasis and inhibition of secretion and motility of the GI tract. Similar to barbiturates, glutethimide depresses the CNS and has addictive effects with alcohol and other CNS drugs. It depresses rapid-eye-movement (REM) sleep and is associated with REM rebound. Glutethimide induces the activity of hepatic microsomal enzyme and accelerates the metabolism of anticoagulants, and hence reduces their effectiveness, thus requiring dose adjustment. 

The names and formulae of some of the psycholeptic compounds which cannot be classified in the major chemical categories so far considered are set out in Table 5.3. Meprobamate VIII) was one of the earliest used tranquillizers. It was developed from mephenesin VII), which was introduced as a muscle relaxant and was soon seen to have a sedative action too. In small doses, meprobamate is a sedative. In larger doses, it causes muscle relaxation and has been classed, with similar compounds, as a tranquillo-sedative . Like the barbiturates, it produces no sign of extrapyramidal or central autonomic stimulation. Well-authenticated reports of addiction to meprobamate have appeared . Both mephenesin and meprobamate produce muscle relaxation by inhibiting interneurones—and hence polysynaptic reflexes—in the spinal cord. Though not described as a hypnotic, meprobamate has been successfully used in the treatment of insomnia, perhaps because it reduces tension. 

Addiction to one drug predisposes to addiction to another. Cocaine and marihuana users very often change to opiates. Alcoholics gravitate to the use of barbiturates and morphine. 

Fig. 3.1 Thalidomide was developed as a non-addictive sedative as an alternative to barbiturates. Following its administration to pregnant women, it was found that the babies were bom with truncated limbs (phocomeUa). At the time this was perceived as a classic case of the pharmacological activity residing in one enantiomer (R-) and the undesirable toxicological effect residing in the other enantiomer. The simation is now known to be much more complex than this (see text and reference cited therein).

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... 

Secobarbital exhibits the same pharmacologic properties as other members of the barbiturate class. Most nonmedical use is with short-acting barbiturates, such as secobarbital. Although there may be considerable tolerance to the sedative and intoxicating effects of the drug, the lethal dose is not much greater in addicted than in normal persons. Tolerance does not develop to the respiratory effect. The combination of alcohol and barbiturates may lead to fatalities because of their combined respiratory depressive effects. Similar outcomes may occur with the benzodiazepines. Severe withdrawal symptoms in epileptic patients may include grand mal seizures and delirium. 

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