Hypnotic drug

The lack of structural specificity among sedative-hypnotic drugs has been alluded to before. It is perhaps not too surprising that quinazolones, too, show this activity. The prototype, methaqualone (149), is obtained in a single step from the condensation of the"anthranilamide, 148, with o-toluidine.(The reaction may well involve first formation of the bisamide cycli-zation will then give the quinazolone ring system.) Condensation... 

Sedatives decrease activity, moderate excitement and calm the recipient. In contrast to hypnotic drugs, they do not produce drowsiness and do not facilitate the onset... 

Assessment of the patient receiving a sedative or hypnotic drug depends on die reason for administration and whether the drug is given routinely or as needed. 

Glutethimide (3-ethyl-3-phenyl-2,6-piperidinedione) is a sedative-hypnotic drug that is now rarely used therapeutically because of wide variation in gastrointestinal absorption, fast development of pharmacodynamic tolerance, a fairly severe discontinuation syndrome, and potential for abuse. Reports of... 

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-... 

Most hypnotic drugs act on GABA receptors. It is reasonable to hypothesize that hypnotic actions are mediated by the GABA receptors on wake-promoting neurons innervated by POA sleep-active neurons, but there is little study of this problem. However, there is evidence that GABAergic anesthetics induce c-Fos IR in the VLPO and suppress c-Fos IR in histaminergic neurons (Nelson et al, 2002). 

Barbiturates represent a class of sedative and hypnotic drugs employed extensively in medicine. RIA provides a rapid, sensitive specific and reliable means for their determination in plasma levels upto 5 ng without indulging in any type of extraction, filtration or evaporation as required for other conventional analytical methods. ... 

By far, the biggest class of hypnotic drugs are derivatives of barbituric acid. The action of barbiturates is reliable and reprodueible, they are easy to administer and offer a wide range of activity. 

Use of a hypnotic drug should not be extended beyond 4 wk, because tolerance may develop. The risk of a rebound decrease in sleep propensity after drug withdrawal may be avoided by tapering off the dose over 2 to 3 wk. 

B. Wake-sleep pattern, stress, and hypnotic drug action... 

The barbiturates were widely used as sedative-hypnotic drugs. Barbital was introduced as a drug in 1903. The method of synthesis for thousands of its analogs has undergone little change. Urea reacts with various derivatives of malonic acid, usually a diethyl ester of a dialkyl substituted malonic acid. This is a classic example of a nucleophilic acyl substitution. A derivative of ammonia reacts with esters to form an amide, only in this case a cyclization to a strainless six-membered ring results because of the proximity of the bifunctionality. 

Sedation is an intermediate degree of CNS depression, while hypnosis is a degree of CNS depression similar to natural sleep. From the chemical point of view, soporific, sedative, and hypnotic drugs are classified as barbiturates, benzodiazepine hypnotics, and so on. Except for a few rare exceptions, any one of these compounds can be used for acquiring a sedative effect or state of sleep. Presently, the less toxic benzodiazepines are edging out the class of barbiturates more and more because of the possibility of chronic dependence associated with the use of barbiturates. Drugs of both classes are primarily CNS depressants, and a few of their effects, if not all, are evidently linked to action on the GABA-receptor complex. 

CNS-depressant effects Zolpidem, like other sedative/hypnotic drugs, has CNS-depressant effects. Because of the rapid onset of action, only ingest immediately prior to going to bed. Zolpidem had additive effects when combined with alcohol therefore, do not take with alcohol. 

Elderly Closely monitor these patients. Impaired motor or cognitive performance after repeated exposure or unusual sensitivity to sedative/hypnotic drugs is a concern in the treatment of elderly or debilitated patients. 

Depression As with other sedative/hypnotic drugs, administer zolpidem with caution... 

Respiratory ejects Although preliminary studies did not reveal respiratory depressant effects at hypnotic doses of zaleplon in healthy subjects, observe caution if zaleplon is prescribed to patients with compromised respiratory function because sedatives/hypnotics have the capacity to depress respiratory drive. Depression As with other sedative/hypnotic drugs, administer zaleplon with caution to patients exhibiting signs or symptoms of depression. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdosage is more common in this group of patients therefore, prescribe the least amount of the drug that is feasible for the patient at any one time. 

Depression Administer with caution in severely depressed patients or in those in whom there is evidence of latent depression or suicidal tendencies. Signs or symptoms of depression may be intensified by hypnotic drugs. 

Depression - Administer sedative/hypnotic drugs with caution to patients exhibiting signs and symptoms of depression. 

Rudolph U, Crestani F, Mohler H (2001) GABAa receptor subtypes dissecting their pharmacological functions. Trends Pharmacol Sci 22 188-194 Sanger DJ, Morel E, Perrault G (1996) Comparison of the pharmacological profiles of the hypnotic drugs, zaleplon and Zolpidem. Eur J Pharmacol 313 35-42... 

Propofol is primarily a hypnotic drug with substantial cardiorespiratory depressant actions and with no ability to produce neuromuscular blockade. While propofol lacks analgesic properties, its use permits lower doses of opioids. Likewise, less propofol is required for adequate hypnosis when it is administered with opioids. Thus, it is said that propofol and opioids interact synergistically. 

Insomnia includes a wide variety of sleep disturbances, such as difficulty in falling asleep, early or frequent awakenings, and remaining unrefreshed after sleep. Use of sedative-hypnotic drugs is one approach to the therapy of insomnia. Other measures include advice to avoid stimulants before retiring, maintenance of a proper diet, initiation of an exercise program, and avoidance of stressful or anxiety-provoking situations. 

Most anxiolytic and sedative-hypnotic drugs produce dose-dependent depression of central nervous system function. The ideal anxiolytic drug should calm the patient without causing too much daytime sedation and drowsiness and without producing physical or psycho-... 

Buspirone is as effective as the benzodiazepines in the treatment of general anxiety. However, the full anxiolytic effect of buspirone takes several weeks to develop, whereas the anxiolytic effect of the benzodiazepines is maximal after a few days of therapy. In therapeutic doses, buspirone has little or no sedative effect and lacks the muscle relaxant and anticonvulsant properties of the benzodiazepines. In addition, buspirone does not potentiate the central nervous system depression caused by sedative-hypnotic drugs or by alcohol, and it does not prevent the symptoms associated with benzodiazepine withdrawal. 

Another chemical class of sedative-hypnotic drugs, the barbiturates, also binds to receptors associated with the GABA-chloride ionophore, but these drugs appear to prolong rather than intensify GABA s effects. Fig. 24.4 shows the presumed drug receptor-GABA-chloride ionophore relationship. 

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