155 - Sedative-Hypnotic Agents

Barbiturates were formerly the primary sedative-hypnotic agents used clinically. Currently, they are most often encountered as anticonvulsants, induction agents for anesthesia, and agents used for procedural sedation. Because the barbiturates have largely been replaced clinically by benzodiazepines due to safety concerns, their prevalence in overdoses has drastically decreased when compared with previous decades. The reported use of barbiturates among high school seniors experienced a slow but steady surge throughout the 1990s and reached a peak in 2005, only to experience a decline since then. Barbiturates accounted for only two single-substance deaths reported to poison centers in 2009. Gamma-hydroxybutyrate (GHB) was synthesized in 1960 as an anesthetic agent. Although it found limited use in this arena, GHB gained widespread acceptance in the bodybuilding community in the 1990s as a purported anabolic agent. More recently, it has been used as a recreational drug for its euphoric and intoxicating effects. It has also been implicated in date rape because of its “knockout” and amnestic properties. Several nonbenzodiazepine sedatives have been introduced for sleep induction. Examples include zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). Cases of abuse and dependence have been reported, albeit with much less frequency compared with benzodiazepines. Nonbenzodiazepine sedatives have been implicated in cases of impaired driving. Chloral hydrate has been used as a sedative since the nineteenth century. In the early 1900s, chloral hydrate was used maliciously, added to alcoholic drinks consumed by unwary individuals to facilitate robberies. The drug-laced drink was referred to as a “Mickey Finn,” named after the owner of a Chicago bar who used these drinks to rob unsuspecting patrons. Currently, chloral hydrate is used primarily for procedural sedation. Propofol is a short-acting sedative-hypnotic that has become widely used clinically for induction of anesthesia and procedural sedation. Despite its abuse potential, the literature is limited to case reports of toxicity from recreational use because of its limited availability to the general public. Most reported cases involve self-administration by medical personnel. Propofol is covered in greater detail elsewhere in this text. • Benzodiazepines account for the majority of overdoses with sedative-hypnotic drugs. • Benzodiazepines can induce cardiovascular and pulmonary toxicity, but fatalities resulting from pure benzodiazepine overdoses are rare. • Central nervous system depression is the primary symptom of sedative-hypnotic toxicity. • Treatment should focus on supportive care, with particular attention to airway patency and respiratory function. • Urinary alkalinization and multiple doses of activated charcoal can enhance the elimination of phenobarbital. • Flumazenil is a reversal agent for benzodiazepine toxicity, but it should be used cautiously, to avoid the risk of seizures. • Other possible causes of altered mental status should always be considered. KEY POINTS