Etiology and Pathophysiology, Epidemiology - Sedative, Hypnotic, or Anxiolytic Use Disorders

Etiology and Pathophysiology

Sedative–Hypnotics and GABA Receptors

Many neurons in the central nervous system (CNS) have recep-tors for the neurotransmitter gamma-aminobutyric acid (GABA). Benzodiazepines attach to receptors that are allosteric to the GABA_A receptor, that is, occupancy of the benzodiazepine re-ceptor potentiates GABA at the GABA_A receptor. The molecular pharmacology of the receptor is exceedingly complex. Chronic exposure to benzodiazepines may uncouple the benzodiazepine receptor from the GABA_A receptor. The uncoupling may explain in part why over time benzodiazepines appear to become less effective in controlling symptoms in some patients, which give them an impetus to increase dosage.

Epidemiology

The prevalence of sedative–hypnotic disorders is not known with precision. Unlike most drugs of abuse (e.g., cocaine or heroin) that are manufactured in clandestine laboratories and distrib-uted through the street-drug black markets, sedative–hypnotics are exclusively manufactured by pharmaceutical companies. Sedative–hypnotics that are used and abused by addicts are obtained either from the black market, where they have been di-verted from medical channels, or from physicians and pharma-cies under treatment subterfuge. Drug dependence may arise as an inadvertent consequence of medical treatment or through pa-tient’s self-administration of sedative–hypnotics obtained from illicit sources or sequential visits to different physicians. By some indicators, tranquilizer and sedative–hypnotic use is increasing.

Insomnia and anxiety disorders are common and sedative– hypnotics are among the most commonly prescribed medications worldwide. Sedative–hypnotic abuse and dependence disorders are common, but involve only a small percentage of the people who use these medications. Most people do not find the subjec-tive effects of sedative–hypnotics pleasant or appealing beyond their therapeutic effects (e.g., relief of anxiety or facilitation of sleep). Many addicts, on the other hand, have a subjectively dif-ferent response to sedative–hypnotics and like the subjective effects of sedative–hypnotics. The qualitative difference in sub-jective response to medications by addicts is one extremely im-portant factor in understanding why medications that are safe and efficacious for nonaddicts cannot be safely prescribed for addicts. In addition, addicts may take doses of medications far in excess of recommended dosage, take them by injection or means other than prescribed (e.g., dissolving tablets and injecting them, crushing tablets and snorting them), or take them in combination with other prescription medications or street drugs such as heroin or cocaine that are extremely likely to produce adverse consequences.