Barbiturate sedative-hypnotics

Phenobarbitone A barbiturate sedative-hypnotic used to treat epilepsy. It is a potent inducer (stimulator) of cytochrome P-450 activity. 

CURRENT MEDICAL USES OF BARBITURATES Sedative/Hypnotics... 

Aprobarbital, a barbiturate sedative-hypnotic (40 to 80 mg p.o. h.s.), is indicated in the management of mild to severe insomnia (see also Barbiturates). 

Secobarbital, a barbiturate sedative-hypnotic and anticonvulsant (200 to 300 mg 1 to 2 hours before surgery), is... 

Barbituric acid was first pre pared in 1864 by Adolf von Baeyer (page 112) A histori cal account of his work and the later development of barbiturates as sedative-hypnotics appeared in the October 1951 issue of the Journal of Chemical Education (pp 524-526)... 

Barbituric acid is the parent of a group of compounds known as barbiturates The bar biturates are classified as sedative-hypnotic agents meaning that they decrease the responsiveness of the central nervous system and promote sleep Thousands of deriva lives of the parent ring system of barbituric acid have been tested for sedative-hypnotic activity the most useful are the 5 5 disubstituted derivatives... 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

Benzodiazepiaes have largely replaced barbiturates and barbiturate-like agents for use as anxiolytics and sedative—hypnotics. Because benzodiazepiaes rarely produce levels of CNS depression that require therapeutic iatervention, the need for analeptics has decreased considerably. 

The pseudo-barbiturate , 2-methyl-3-o-tolylquinazolin-4(3H)-one (methaqualone, Revonal 1017) has an even wider spectrum of activities than do the barbiturates proper it appears to be quite widely used as- a sedative, hypnotic, anticonvulsant, antispasmodic and local anaesthetic agent (63MI21301, b-75MI21301>. 

The continuing search for molecules that possess the sedative-hypnotic properties of the barbiturates but show a better pharmacologic ratio has, as shown above, taken many directions. To name only two variants, the ring has been contracted and even opened entirely in each case some activity of the parent was retained. Although at one time the acylurea functional array was thought necessary for activity, the work below shows that even... 

Cyclization of the two pendant alkyl side chains on barbiturates to form a spiran is consistent with sedative-hypnotic activity. The synthesis of this most complex barbiturate starts by alkylation of ethyl acetoacetate with 2-chloropentan-3-one to give 152. Hydrolysis and decarboxylation under acidic conditions gives the diketone, 153. This intermediate is then reduced to the diol (154), and that is converted to the dibromide (155) by means of hydrogen bromide. Double Internal alkylation of ethyl... 

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

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

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). 

Long-acting barbiturates used as sedative-hypnotics and also for their anticonvulsant effects include phenobarbital (Luminal) and mephobarbital (Mebaral). 

Respiratory drive and rhythm are depressed by barbiturates. Coughing, sneezing, hiccupping, and laryngospasm may occur during anesthesia with barbiturates. Sedative ot hypnotic doses of barbiturates teduce heatt tate and blood pressure to levels found in normal sleep. Anesthetic doses produce more pronounced effects. Barbiturates cross the placenta when used in labor, they can cause respiratoty depression in neonates. Anesthetic doses dectease force and frequency of uterine contractions among pregnant women. 

Other sedative-hypnotic medications, such as barbiturates, may play a useful role in severe withdrawal from this group of drugs. For example, in a case series of GBL withdrawal, use of intravenous pentobarbital in the range of 1-2 mg/kg/hour lowered the total requirement for intravenous lorazepam (Sivilotti et al. 2001). Antipsychotic medications are often used to reduce psychotic agitation. However, because antipsychotic medications lower the seizure threshold and may contribute to loss of central control of temperature leading to hyperthermia or neuroleptic malignant syndrome (NMS), they are not indicated as first-line medications for GHB withdrawal delirium (Dyer and Roth 2001 McDaniel and Miotto 2001 Sharma et al. 2001). If anti-... 

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. 

Sedatives/hypnotics (barbiturates, benzodiazepines, chloral hydrate)... 

Alcohol, barbiturates, and sedative-hypnotics (nonbenzodiazepines) Support vital functions None B3... 

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. 

Since GABA-ergic synapses are confined to neural tissues, specific inhibition of central nervous functions can be achieved for instance, there is little change in blood pressure, heart rate, and body temperature. The therapeutic index of benzodiazepines, calculated with reference to the toxic dose producing respiratory depression, is greater than 100 and thus exceeds that of barbiturates and other sedative-hypnotics by more than tenfold. Benzodiazepine intoxication can be treated with a specific antidote (see below). 

---