Dependence with sedative-hypnotics

In subjects with sedative-hypnotic dependence who underwent detoxification in an addictions treatment unit, a significant association was not found between abstinence rate and either gender or psychiatric status (Charney et al. 2000). Patients dependent on benzodiazepines reported decreased anxiety during follow-up, even though their use of these agents had decreased. 

Detoxiflcation may be accomplished with phenobarbital (60 mg of phe-nobarbital for 500 mg of glutethimide). If concomitant codeine dependence is present (and this codependence should be strongly suspected), then methadone can be used adjunctively (10 mg of methadone for 120 mg of codeine) (Khajawall et al. 1982). Approximate sedative-hypnotic dosage equivalencies are listed in Table 3-5. 

Barbiturate The family name for a group of drugs with anticonvulsant, anaesthetic and sedative-hypnotic properties. Examples include amylobarbitone and pheno-barbitone. The problem of dependence and the introduction of safer benzodiazepine alternatives has resulted in a marked reduction in their clinical use. 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

Knowing the differential pharmacokinetics for a class of drugs allows the clinician to choose specific members to either achieve a faster onset or a delayed offset of action (13, 14, 17, 18). For example, lorazepam is rapidly absorbed from the gastrointestinal tract into the systemic circulation and from there distributed into the brain. In contrast, oxazepam, the most polar BZD, is slowly absorbed from the gastrointestinal tract. Even after oxazepam is in the systemic circulation, it slowly enters tissue compartments, including the brain, during the distribution phase. Unlike lorazepam, oxazepam is not available in either the intramuscular or intravenous formulations. Thus, lorazepam would be preferable to achieve acute control of alcohol withdrawal (e.g., delirium tremens), whereas oxazepam would better stabilize a dependency-prone patient on sedative-hypnotics, because it does not cause the euphoria seen with the more rapidly absorbed members of this class. 

Eight healthy male subjects with a mean age of 34.1 years volunteered for this study. During their participation in the study, they resided on a clinical research unit. The subjects had extensive histories of illicit drug use that included recent ingestion (within the past 2 years) of opiates, marijuana, stimulants, alcohol, and sedative-hypnotics, although they were not dependent on any drug (except nicotine). 

Actions at benzodiazepine receptors are thought to underlie virtually all the pharmacological actions of the benzodiazepines, those that are desirable as well as those that are undesirable. This includes the desirable therapeutic actions of benzodiazepines as anxiolytics and sedative-hypnotics, as well as anticonvulsants and muscle relaxants. It also includes their undesirable side effects as amnestic agents and as agents that cause adaptations at the benzodiazepine receptor with chronic administration, which are thought to underlie the production of dependence and withdrawal from these agents (see Chapter 13). 

Barbiturates (a class of drugs with more effective sedative-hypnotic effects) replaced bromides in 1903. Depending on the dose, frequency, and duration of use, however, tolerance, physical dependence, and psychological dependence on barbiturates can occur relatively rapidly. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that can produce coma and death. 

Flunitrazepam (Rohypnol), also known as roofies, is a benzodiazepine with physiological effects similar to diazepam (Valium), although it is about 10 times more potent. The drug produces sedative-hypnotic effects that include muscle relaxation and amnesia it can also produce physical and psychological dependence. It is illegal and not approved for use in the United States. 

Buspirone causes less psychomotor impairment than diazepam and does not affect driving skills. The drug does not potentiate the central nervous system depressant effects of conventional sedative-hypnotic drugs, ethanol, or tricyclic antidepressants, and elderly patients do not appear to be more sensitive to its actions. Tachycardia, palpitations, nervousness, gastrointestinal distress, and paresthesias may occur more frequently than with benzodiazepines. Buspirone also causes a dose-dependent pupillary constriction. Blood pressure may be elevated in patients receiving MAO inhibitors. A number of buspirone analogs have been developed (eg, ipsapirone, gepirone, tandospirone) and are under study. 

With the chronic use of sedative-hypnotics, especially if doses are increased, a state of physiologic dependence can occur. This may develop to a degree unparalleled by any other drug group,... 

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