Intermediate-acting hypnotics

The benzodiazepine hypnotics midazolam, triazolam, and brotizolam, together with zopiclone, eszopiclone, zolpidem, and zaleplon are short-acting derivatives. The benzodiazepines flunitrazepam and temazepam are intermediate-acting hypnotics,... 

Similar to the BZD anxiolytics, BZD hypnotics can be classified by their elimination half-life into those that are long-acting, those that are intermediate-acting, and those that are short-acting (Table 12-5). The Physician s Desk Reference (PDR) (93) aptly calls attention to the postulated relationship... 

Short- to intermediate-acting BZD hypnotics may have some residual effects the next day due to accumulation on daily ingestion. These, with their elimination half-life, include the following ... 

FIGURE 8-30. The hypnotic agent zopiclone is an intermediate acting nonbenzodiazepine which binds to omega sites near benzodiazepine sites on GABA-A receptors. 

In summary, therefore, various studies suggest strongly that short-acting benzodiazepine hypnotics are much more likely than intermediate-acting and prolonged-acting hypnotics to induce rebound [21], Withdrawal studies have been much less consistently pursued but withdrawal potential tends to parallel rebound potential. 

The barbiturates have a low therapeutic index and a relatively high abuse potential. Because of their rapid onset and short duration of action, the short- to intermediate-acting barbiturates are used as sedative-hypnotics (amobarbitai, butabarbital, butalbital, pentobarbital, and secobarbital) and are those most commonly abused. The longer acting barbiturates (mephobarbital and phenobarbital), used primarily for their anticonvulsant properties, are rarely abused. 

The onset of action for intermediate acting barbiturates is 30 minutes and their hypnotic effect last for 2 to 6 hours. Most of them are first degraded by the liver and the metabolised product subsequently excreted by the kidney. They are generally used in insomnia and also as a pre-operative sedative. They also find their use in the treatment of convulsions when administered intravenously. 

Its hypnotic action is similar to the intermediate-acting barbiturate which may be enhanced when administered along with an antihistaminic agent like diphenylhydramine. It may be used as a sedative at lower dose levels. 

It is safely used for indueing sleep in all types of insomnia without causing depression of respiration. Its hypnotic action is parallel to intermediate-acting barbiturates. 

Short-acting sedative-hypnotics are ideal for patients who need assistance falling asleep but who must awaken early without experiencing a Kngering aftereffect from the medication. Intermediate-acting sedative-hypnotics are useful to sustain sleep. Patients may experience residual drowsiness (hangover) after awakening. 

Barbiturates are a type of sedative-hypnotic that is used to induce sleep, as an anesthetic, and in high doses to control epileptic seizures. Barbiturates are classified by duration of action referred to as ultrashort-acting, short-acting, intermediate acting, and long-acting. 

Intermediate- acting Amobarbital sodium (Amytal Sodium) Sleep sustainers PB 50-60% half life 20-40 hours Sedative PO 30-50 mg bid-tid Hypnotic PO/IM 65-200 mg h.s., IV 65-200 mg... 

The Summary Drug Table Sedatives and Hypnotics Barbiturates gives examples of the short-, intermediate-, and long-acting barbiturate sedatives and hypnotics. 

The ultra-short-acting barbiturates include methohexital sodium (Brevi-tal) and thiopental sodium (Pentothal). These agents are used as anesthetics and are administered intravenously. Barbiturates with short-to-intermediate duration of action are used for their sedative-hypnotic effect in the treatment of anxiety. These medications include amobarbital (Amytal), butabarbital (Butisol), sodium pentobarbital (Nembutal), and secobarbital (Seconal). 

Like the barbiturates, the benzodiazepines make it easier to fall asleep and to stay asleep through the night. However, they also suppress REM sleep, which can lead to REM rebound when they are discontinued. Tolerance to their sleep-promoting effects often develops after chronic use. Some long-acting benzodiazepines, such as flurazepam (Dalmane), are associated with pronounced hangover effects in the morning and are therefore problematic as sedative-hypnotics. Others, with a short-to-intermediate dnration of action, are more desirable as hypnotics. 

Most of the minor tranquilizers in the BZD exhibit similar clinical effects they differ primarily in their duration of action and in the dosage required to achieve the same effect. The BZDs are classified as short- (triazolam [Halcion]), intermediate- (alprazolam [Xanax] and lorazepam [Ativan]), and long-acting (chlordiazepoxide [Librium] and diazepam [Valium]). Of the various BZDs available in the United States in 2002, those primarily prescribed as anxiolytics and hypnotics include the intermediate- and long-acting variety. 

Presently available hypnotic drugs for the treatment of transient, short-term, or chronic insomnia differ significantly in pharmacokinetic properties, including elimination half-life and presence of active metabolites. On the other hand, they have in common short absorption and distribution times. As a result, in most circumstances they induce sleep rapidly. According to their elimination half-life, hypnotics can be divided into short-, intermediate-, or long-acting derivatives. 

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