Other Hypnotics

Thalidomide cannot be extracted from acid solution. A solution in N sodium hydroxide can be applied to the plate. TLC can be carried 

Solvent Petrol ether (BP 50—75°)-pyridine (75 + 15) silica gel G layer standard method (cf. p. 85). Testing soporifics and their metabolites in urine [43]. 

Solvent Chloroform-cyclohexane-pyridine (60 + 20 + 5) silica gel G layer standard method chamber saturation 10 cm run. Solvent removed after TLC by 15 min/150° C. Method for testing pharmaceutical preparations [63]. 

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Because individuals with a history of addiction to, or abuse of, drugs or alcohol are at risk of habituation and dependence, they should be under careful surveillance when receiving zolpidem or any other hypnotic. 

CNS depressants When barbiturates, narcotics, other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with magnesium, adjust their dosage with caution because of additive CNS depressant effects of magnesium. 

The data on zaleplon to date indicate that it has some advantages over other hypnotics, including a favorable safety profile, as indicated by the absence of rebound insomnia and withdrawal symptoms when zaleplon is discontinued (162). In addition, when taken by a nursing mother, zaleplon is transferred through breast milk to her infant in such very small quantities that this is unlikely to be important ( 163). 

Hindmarch, I., Sherwood, N., and Kerr, J.S., Amnestic effects of triazolam and other hypnotics, Prog. Neuropsychopharmcicol. Biol. Psychiatry, 17, 407, 1993. 

To review the drug treatments for insomnia, including newer nonbenzodiazepine hypnotics as well as benzodiazepine and other hypnotics. 

Naloxone (Narcan) and naltrexone hydrochloride (Trexan) reverse the respiratory depressant action of narcotics related to morphine, meperidine, and methadone. They differ from other narcotic analgesics in several respects. Naloxone does not cause respiratory depression, pupillary constriction, sedation, or analgesia. However, it does antagonize the actions of pentazocine. Naloxone neither antagonizes the respiratory depressant effects of barbiturates and other hypnotics nor aggravates their depressant effects on respiration. Similar to nalorphine, naloxone precipitates an abstinence syndrome when administered to patients addicted to opiate-like drugs. 

In the elderly there is a consistent increase in the maximum plasma concentration and the ti/2 of zolpidem. This is related to a reduced volume of distribution associated with a decrease in clearance [36], As with other hypnotics that are extensively degraded in the liver and show high protein binding, the pharmacokinetics of zolpidem is altered in patients with liver disease. Accordingly, in patients with hepatic insufficiency receiving zolpidem, the Cmax and the ti/2 are consistently increased [36, 37], In patients with renal insufficiency the disposition rate of zolpidem is decreased compared with that of age-matched healthy adults (Tab. 3). 

Trewin VF, Lawrence CJ, Veitch GB (1992) An investigation of the association of benzodiazepines and other hypnotics with the incidence of falls in the elderly. J Clin Pharm Ther 17 129-133... 

Two types of receptor have been identified, termed Bzl and Bz2. These receptors occupy different sub-units of the GABA-A receptor and therefore have different affinities for the benzodiazepine ligands. For example, the potent hypnotic zolpidem binds to the Bzl receptor that is linked to the alpha-1 site on the GABA-A receptor while the hypnotic zopiclone binds to the Bz2 receptor which occupies both the alpha-2 and 3 sites on the GABA receptor. This selectivity for the Bzl receptor may account for the fewer side effects of zolpiden in comparison to other hypnotic benzodiazepines. 

Neuroleptic drugs increase sedative- and hypnotic-induced sleep time and respiratory depression. Lower dosages of barbiturates or other hypnotics should be used, at least initially, in patients receiving neuroleptic drugs (622). 

Much of the literature on the adverse effects of triazolam is based on doses of 0.25 mg and above the reduction in recommended dose to 0.125 mg may improve therapeutic safety, at the cost of compromising hypnotic efficacy in most patients. A low therapeutic index is also suggested by the possibility of amnesia, even after a single dose (6), and triazolam appears to be associated with a greater incidence of behavioral disturbances than other hypnotic benzodiazepine agonists, such as temazepam and zopiclone. 

Zaleplon is a non-benzodiazepine that induces sleep comparable to other hypnotics but with significantly fewer residual effects (1), related at least in part to its short half-life. It is a pyrazolopyrimidine hypnotic that binds selectively to the GABAa1a receptor, previously known as the benzodiazepine type 1 (BDZi) receptor. Whereas such agonist selectivity was hoped to confer advantages in terms of the risk of adverse effects, in practice zaleplon is similar to the older non-selective benzodiazepines in terms of both efficacy and safety (2-4). The so-called Z drugs, including zaleplon, are significantly more expensive than benzodiazepines and are therefore likely to be less cost-effective (5). 

Initial pharmacodynamic data suggested that sleep latency is improved by zaleplon and there is no significant next-day psychomotor impairment or memory impairment (8), and evaluations at zaleplon peak plasma concentrations show much less impairment than with other hypnotics, suggesting an improved benefit-to-harm balance for zaleplon compared with older agents. However, outcome data are mainly from industry-sponsored trials and are often difficult to compare. Differences between... 

Opioid analgesics Tricyclic antidepressants Sedating antihistamines Benzodiazepines and other hypnotics Barbiturates... 

Hamor and Lien have analyzed anticonvulsant activities of sulfamoyl-benzoates. For the test of antistrychnine activity, compounds having the same aromatic substituents are used so that no 2o-(X,Y) term appears in Equation 22. They have suggested that the similarity of equations in terms of steric, hydrophobic, and electronic properties of substituents indicates a common anticonvulsant mechanism for the two biological effects of this set of compounds. They have also suggested that the mechanism of action of these drugs was quite different from those of barbiturates and other hypnotics where quite different structure-activity correlations of physicochemical significance have been obtained. 

The clinical features of overdose with etiichlorvynol resemble those due to poisoning with other hypnotics, but coma is often prolonged and accompanied by severe respiratory depression. Ethchlorvynol has a pungent odour which is often detected in the stomach contents. A qualitative test for ethchlorvynol in stomach contents is given on p. 6. A gas chromatographic mediod for the quantification of ethchlorvynol in plasma is given on p. 17. 

There has been a literature review of the abuse potential of zolpidem (22). There were 15 published cases of abuse or dependence. In six patients the abuse was secondary to other forms of abuse or dependence. The authors concluded that the abuse potential of zolpidem is much less than with other hypnotics and that it is also safer than conventional hypnotics. Patients with a history of other substance abuse may be considered as being at risk of later abuse of zolpidem. 

It is eliminated by ester hydrolysis in plasma and liver (59). Etomidate is a potent intravenous (i.v.) hypnotic agent with a very rapid onset of action. However, its acid metabolite is inactive, and the duration of hypnosis after etomidate administration can be very short (<5 min) (60). Therefore, the therapeutic index of etomidate (18.0-32.0)is considerably larger than that of other hypnotic agents. 

These are active orally and. although most are metabolized by oxidation in Ihe liver, they do nm induce hepatic enzyme systems. Hiey are cciiiral depressants but. in contrast to other hypnotics and anxiolytics, their maximum effect when given orally docs not noimally cause fatal, or even... 

A TLC system used to identify methyprylon from other hypnotics was published by Frahm et al. (20). This system utilized a Kieselgel G plate and a developing solvent of 2-propanolrchloroform 25% ammonium hydroxide (9 9 2). The Rf values were very sensitive to the amount of solvent saturation in the tank and therefore a reference standard was always run along with the sample for identification purposes. 

Do barbiturates have a mode of action different from other hypnotics Although they become adsorbed on the GABA receptor (Section 12.7), their... 

Some Other Hypnotic Drugs in the Blood Plasma as an Aid to the Diagnosis of Acute Poisoning J. Chromatogr. 131 131-146 (1977) CA 86 100681s... 

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