Sedative Hypnotics triazolam

For testing sedative hypnotic drugs of the triazolam type the preparation was undertaken of 8-chloro-6-(o-chlorophenyl)-4ff-.y-triazolo[4,3-a][l,4]benzodiazepin-1 -valeric acid methyl ester as an intermediate, with subsequent cyclization and amida-... 

The benzodiazepines that have been most commonly marketed as sedative-hypnotics include temazepam (Restoril), estazolam (ProSom), flurazepam (Dalmane), quazepam (Doral), and triazolam (Halcion). Of these five, temazepam is the most easily metabolized and eliminated. Therefore, temazepam is preferred for elderly and medically ill patients to minimize the risk of drug accumulation. 

Sedative/Hypnotics Midazolam, triazolam Gl motility agents Cisapride... 

Sedatives/Hypnotics Midazolam, triazolam Because of the required coadministration of tipranavir with ritonavir 200 mg, refer to... 

Triazolam is a triazolobenzodiazepine sedative-hypnotic that depresses the CNS at the limbic and subcortical levels of the brain. It potentiates the effect of GABA on its receptor, which increases inhibition and blocks cortical and limbic arousal. It is well absorbed through the gastrointestinal tract with peak levels in 1 to 2 hours. 

The benzodiazepines are widely used sedative-hypnotics. All of the structures shown in Figure 22-2 are 1,4-benzodiazepines, and most contain a carboxamide group in the 7-membered heterocyclic ring structure. A substituent in the 7 position, such as a halogen or a nitro group, is required for sedative-hypnotic activity. The structures of triazolam and alprazolam include the addition of a triazole ring at the 1,2-position. 

The rates of oral absorption of sedative-hypnotics differ depending on a number of factors, including lipophilicity. For example, the absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate, a prodrug, is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Most of the barbiturates and other older sedative-hypnotics, as well as the newer hypnotics (eszopiclone, zaleplon, zolpidem), are absorbed rapidly into the blood following oral administration. 

Lipid solubility plays a major role in determining the rate at which a particular sedative-hypnotic enters the central nervous system. This property is responsible for the rapid onset of central nervous system effects of triazolam, thiopental (see Chapter 25), and the newer hypnotics. 

Insomnia is a common comorbid condition with depression, and frequently is made worse by antidepressants, particularly the SSRIs. When insomnia persists despite adequate evaluation and attempts to reduce it by other approaches, it is often necessary to use a concomitant sedative-hypnotic, especially a short-acting nonbenzodiazepine with rapid onset such as zaleplon or zolpidem. At times a benzodiazepine sedative hypnotic such as triazolam or temazepam may be necessary. If anxiety persists during the day and cannot be otherwise managed, it may be necessary to add an anxiolytic benzodiazepine such as alprazolam or clonazepam. Use of sedative-hypnotics and anxiolytics should be short-term whenever possible. 

Benzodiazepines -epam or -olam Diazepam, temazepam, alprazolam, triazolam Sedative-hypnotic (6), antianxiety [6], antiseizure (9), anesthetic [11]... 

The extensive clinical use of triazolam has led to reports of serious central nervous system effects including behavioral disinhibition, delirium, aggression, and violence. While behavioral disinhibition may occur with sedative-hypnotic drugs, it does not appear to be more prevalent with triazolam than with other benzodiazepines. Disinhibitory reactions during benzodiazepine treatment are more clearly associated with the use of very high doses and the pretreatment level of patient hostility. 

Insomnia is a common complaint in the elderly. As people age they require less sleep, and a variety of physical ailments to which the elderly are subject can cause a change in the sleep pattern (e.g. cerebral atherosclerosis, heart disease, decreased pulmonary function), as can depression. Providing sedative hypnotics are warranted, the judicious use of short half-life benzodiazepines such as temazepam, triazolam, oxazepam and alprazolam for a period not exceeding 1-2 months may be appropriate. Because of their side effects, there would appear to be little merit in using chloral hydrate or related drugs in the treatment of insomnia in the elderly. It should be noted that even benzodiazepines which have a relatively short half-life are likely to cause excessive day-time sedation. The side effects and dependence potential of the anxiolytics and sedative hypnotics have been covered elsewhere in this volume (Chapter 9). 

Triazolam, USP. Triazolam. 8-chloro-6-(o-chlorophc-nyl)-l-methyl-4Ay-j-triaz.olol4.3-a f l,4 benzxxliazcpinc (Hal-cion). has all of the characteristic benzodiazepine pharmacological actions. It is marketed as a sedative-hypnotic drug said to impair little, if any. daytime function. It is rapidly metabolized to the I-methyl alcohol, which is then conjugated and excreted. 

Older drugs of the class (e.g., diazepam) have sedative, hypnotic, and muscle relaxant properties. This may be due primarily to the formation of active metabolites with various actions. Newer drugs, however, have been engineered to have increased activity in a specific area (e.g., triazolam as a hypnotic and alprazolam as an anxiolytic). 

Hypnotics fall into different categories, including the benzodiazepines (e.g., triazolam, temazepam, clotiaze-pam, nitrazepam), barbiturates (e.g., hexobarbital, pentobarbital), chloral hydrate, and Hi-antihistamines with sedative activity (p. 114). Benzodiazepines act at specific receptors (p. 226). The site and mechanism of action of barbiturates, antihistamines, and chloral hydrate are incompletely understood. 

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