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PubMed1996

Sedative-hypnotic drugs and the risk of hip fracture.

A retrospective cohort study was conducted in individuals 65 years of age and older using Medicaid-reimbursed claims to assess the risk of hip fracture in users of two sedative-hypnotic drugs, triazolam and temazepam. Using the triazolam cohort as the referent group, the rate ratio was 0.92 (95% confidence interval, 0.72 to 1.17) for hip fracture with temazepam. Stratifying by age, sex, race, residence, time enrolled in Medicaid, prescription number, combinations of these, and several other potential confounding variables did not materially change the results. Compared with the short-acting benzodiazepine hypnotic temazepam, use of triazolam, an ultra-short-acting benzodiazepine hypnotic, did not decrease the risk of hip fracture. This study did not determine that either drug, compared with no use in an insomniac control group, increases the risk of hip fracture. However, because sedative-hypnotic drugs have been found in other studies to increase the risk of falling and hip fracture, they should be used with caution, especially in the elderly.

Accidental Falls↗

PubMed1993

A review of the utilization of sedative-hypnotic drugs in a general hospital.

A retrospective review of 493 patients treated during a single month in a general hospital in mid-Michigan revealed that a majority (84.2%) of them received prescriptions for sedative-hypnotic drugs. These were p.r.n. in 66% of cases and routine prescriptions in the remainder. Prescriptions were equally distributed across the specialties: internal medicine 15%, surgery 23%, family practice 19%, psychiatry 22%, and OB/GYN 20%. Flurazepam was the most frequently prescribed drug (48.4%), followed by triazolam (24.6%) and temazepam (12.2%). Actual utilization rates were highest among psychiatric patients (85%) and lowest in obstetrics (33%). The therapeutic rationale for prescribing sedative hypnotic agents to hospitalized patients is discussed.

Drug Prescriptions↗

PubMed1983

Relationship of sedative-hypnotic response to self-injurious behavior and stereotypy by mentally retarded clients.

Groups of clients exhibiting both self-injurious behavior (SIB) and stereotypy, stereotypy alone, SIB alone, or neither of these types of behavior were rated in terms of response to sedative-hypnotic medication. Sixty-eight percent of the clients with both SIB and stereotypy maintained wakefulness and were either resistive, combative, restless, uncooperative, or abusive after treatment with sedative-hypnotics. Thirty-nine percent of the clients with only SIB and 35 percent of the clients with only stereotypy evidenced such "paradoxical" responses to these medications. None of the matched control clients displayed paradoxical responses. This result suggests that an impaired endogenous opiate system characterized by increased levels of beta-endorphin may mediate and maintain a type of syndrome of SIB that involves the presence of stereotypy, implying the need for a new diagnostic classification and treatment of these aberrant behavioral disorders.

Adolescent↗

PubMed1992

[Syntheses and central depressant activity in mice of uracil derivatives. Studies on development of new sedative-hypnotics. II].

Fifteen kinds of uracil derivatives, which were substituted with functional groups such as benzyl (Bn), methoxymethyl (MOM), n-propyl (Pr) or allyl (A) group at the N1 and/or N3 position of uracil, were synthesized. Sedative-hypnotic activity, pentobarbital (PB)-induced sleep prolongation and acute toxicity as indices of their pharmacological activities were evaluated using mice. Spontaneous activities of mice treated with N1-benzyluracil (N1-BnU, 7), N3-benzyluracil (N3-BnU, 8), N1,N3-dibenzyluracil (DBnU, 9), N1-benzyl-N3-allyluracil (BnAU, 14) and N1-allyl-N3-benzyluracil (ABnU, 15) were measured. Ten kinds of uracil derivatives showed hypnotic activity. ED50's values of ABnU (15) and N1-propyl-N3-benzyluracil (PrBnU, 13) were 155 and 172 mg/kg, i.p., respectively. Those effects were more potent than that of barbital (179 mg/kg, i.p.) Ten kinds of uracil derivatives tested significantly prolonged the PB-induced sleeping time. N3-BnU (8) increased the spontaneous activity of mice at a dose of 80 mg/kg, i.p., while ABnU (15) depressed the spontaneous activity at a dose of 160 mg/kg, i.p. The other compounds did not show any significant effect on the spontaneous activity of mice. LD50's values of ABnU (15), PrBnU (13) and N1-methoxy-methyl-N3-benzyluracil (MOMBnU, 11) were 199, 229 and 363 mg/kg, i.p., respectively. LD50's values of the other derivatives were more than 480 mg/kg, i.p. These results indicate that the benzyl group at the N3 position of uracil is important for exhibiting sedative-hypnotic activity of uracil derivatives, and that ABnU (15) has the most potent central depressant activity among the uracil derivatives tested.

Animals↗

PubMed2005

Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits.

OBJECTIVES: To quantify and compare potential benefits (subjective reports of sleep variables) and risks (adverse events and morning-after psychomotor impairment) of short term treatment with sedative hypnotics in older people with insomnia. DATA SOURCES: Medline, Embase, the Cochrane clinical trials database, PubMed, and PsychLit, 1966 to 2003; bibliographies of published reviews and meta-analyses; manufacturers of newer sedative hypnotics (zaleplon, zolpidem, zopiclone) regarding unpublished studies. SELECTION CRITERIA: Randomised controlled trials of any pharmacological treatment for insomnia for at least five consecutive nights in people aged 60 or over with insomnia and otherwise free of psychiatric or psychological disorders. RESULTS: 24 studies (involving 2417 participants) with extractable data met inclusion and exclusion criteria. Sleep quality improved (effect size 0.14, P < 0.05), total sleep time increased (mean 25.2 minutes, P < 0.001), and the number of night time awakenings decreased (0.63, P < 0.001) with sedative use compared with placebo. Adverse events were more common with sedatives than with placebo: adverse cognitive events were 4.78 times more common (95% confidence interval 1.47 to 15.47, P < 0.01); adverse psychomotor events were 2.61 times more common (1.12 to 6.09, P > 0.05), and reports of daytime fatigue were 3.82 times more common (1.88 to 7.80, P < 0.001) in people using any sedative compared with placebo. CONCLUSIONS: Improvements in sleep with sedative use are statistically significant, but the magnitude of effect is small. The increased risk of adverse events is statistically significant and potentially clinically relevant in older people at risk of falls and cognitive impairment. In people over 60, the benefits of these drugs may not justify the increased risk, particularly if the patient has additional risk factors for cognitive or psychomotor adverse events.

Cognition Disorders↗

PubMed1987

Calcium channels. Interactions with ethanol and other sedative-hypnotic drugs.

Biochemical and electrophysiological studies have shown that ethanol potently inhibits voltage-dependent calcium channels in presynaptic nerve terminals in brain. The ability of ethanol to inhibit calcium channels appears to vary from one brain region to another. Chronic ethanol administration results in adaptation of the calcium channels in certain brain regions such that they become tolerant to the inhibitory actions of ethanol. Other sedative-hypnotic drugs, such as barbiturates and benzodiazepines, also inhibit calcium channels but may differ from ethanol in their brain regional potency. These studies suggest that the pharmacological actions of ethanol and other sedative-hypnotic drugs may be linked with alterations in calcium channel function.

Animals↗

PubMed1960

Pharmacological properties of thalidomide (alpha-phthalimido glutarimide), a new sedative hypnotic drug.

Thalidomide (alpha-phthalimidoglutarimide, "Distaval," "Contergan") is a new sedative hypnotic drug which produces no toxic effects when administered orally to animals in massive doses. This lack of toxicity may be due to limited absorption. The drug has a quietening effect on the central nervous system, reducing the voluntary activity of laboratory animals and promoting sleep. Unlike the barbiturate drugs it does not cause an initial excitation in mice, incoordination or narcosis. It potentiates the actions of other central nervous system depressants, in particular the barbiturates. Its sedative effects are counteracted by central nervous system stimulants. It has no deleterious side effects and does not affect the heart, respiration or autonomic nervous system.

Animals↗

PubMedDate not supplied

A study in mice of bromo and chloro acylurea analogues of the sedative-hypnotic bromureides.

1. A series of 1-(2-chloroacyl)ureas, related to the sedative-hypnotic drugs bromvaletone and carbromal, was synthesized and tested in mice to determine central depressant and acute toxic effects. Four 1-(2-bromoacyl)ureas and two 3-halo compounds were included for comparison. 2. Large variations in potency were seen between the compounds. Much of this can be ascribed to differences in lipophilicity. Among homologous 1-(2-chloroacyl)ureas, those with 6 acyl carbons had maximal potency. Among groups of structural isomers, the most potent were 2-halo, 3-alkyl substituted compounds. 3. The most potent compounds were also those with the largest ratios of hypnotic to lethal activity. 4. The variation in the onset and duration of action of these compounds enables a choice to be made for a compound with a particular set of characteristics.

Animals↗

PubMed1984

Stimulant and depressant properties of sedative-hypnotics in mice selectively bred for differential sensitivity to ethanol.

A genetic analysis of sedative-hypnotic response in selectively bred Long-Sleep (LS) and Short-Sleep (SS) mice showed LS mice to be more depressed by acetaldehyde, ethanol (ETOH), and t-butanol, but less sensitive to pentobarbital. Intermediate inheritance was shown by the two reciprocal F1 hybrids for the alcohols, but dominance to the LS genotype occurred for the aldehyde and the barbiturate. At several subhypnotic doses of ETOH in two experiments, LS mice showed less locomotor stimulation and greater disruption of coordination than the SS mice. The two reciprocal F1 hybrids did not differ from one another and had dose-response curves intermediate to the two parental lines. Study of the effects of t-butanol on locomotor activity revealed a pattern of line differences similar to that for ETOH. The genetic selection for LS and SS mice appears to have differentiated loci that pleiotropically influence a variety of behavioral responses to alcohols.

Analysis of Variance↗

PubMed1983

Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy.

Sedative-hypnotic antiepileptic drugs have potentially toxic effects, but their removal is often thought to be difficult and dangerous. We completely withdrew all barbiturates and benzodiazepines from 78 patients with intractable epilepsy (48 inpatients and 30 outpatients). Initially, 19 patients had plasma levels of sedative drugs above the therapeutic range; 28 were taking more than one of these drugs. Dosages of nonsedative antiepileptic drugs were adjusted to provide optimal seizure control. After 6 months of outpatient follow-up, 69 patients remained on a nonsedative regimen: 35 (51%) showed improvement in both drug toxicity and seizure control, 13 (19%) in toxicity alone, 8 (12%) in seizure control alone; 12 (16%) were unchanged, and 1 was worse. Of 9 patients restarted on sedative antiepileptic drugs by their private physicians, 4 had more toxic symptoms than at discharge, 1 had more frequent seizures, 3 were unchanged, and 1, who had had a temporal lobectomy after drug withdrawal, had less frequent seizures. Sedative drugs are not necessary for optimal seizure control, even in intractable epilepsy, and they may be safely withdrawn.

Adolescent↗

PubMed1983

Effects of barbiturates and other sedative hypnotics in pigeons trained to discriminate phencyclidine from saline.

Pigeons were trained to peck the center key (lighted white) of three response keys to turn off the center keylight and to light one of the side keys with a red keylight and the other side key with a green keylight. Five responses (fixed-ratio component) on either side key relighted the center key. Food was delivered following 10 fixed-ratio components on the red key if 1.5 mg/kg phencyclidine had been given before the session. The position of the red and green keylights on the side keys varied randomly each time they were lighted by a peck on the center key. Subsequently, increasing doses of phencyclidine, barbital, amobarbital, phenobarbital, methaqualone, methyprylon, diazepam, oxazepam, and d-amphetamine were substituted for the training dose of phencyclidine, using a cumulative dosing procedure. At low doses of the sedative hypnotics, birds pecked the keylight color associated with saline. At higher doses, birds pecked both key colors. At the highest doses of pentobarbital and amobarbital, some birds responded almost exclusively On he color associated with phencyclidine. When responding on keys of both colors occurred following administration of phencyclidine or other sedative hypnotics, this responding was controlled by key position rather than by key color.

Animals↗

PubMed1975

Sedative-hypnotic properties of a new benzodiazepine in comparison with flurazepam. Pharmacological and clinical findings.

The sedative-hypnotic effects of a new benzodiazepine, 1-(2-hydroxyethyl)-3-hydroxy-7-chloro-1,3-dihydro-5-(o-fluorophenyl)-2H-1,4-benzodiazepin-2-one (SAS 643), were compared with those of flurazepam in mice and rats as well as in a double-blind clinical trial. It was found that SAS 643 has a potency 2--4 times greater than that of flurazepam while it is about one half less toxic than the latter drug. The results of the clinical trial confirm the greater activity of SAS 643 and indicate that the new benzodiazepine causes a significantly less amount of hangover than flurazepam.

Aged↗

PubMed1985

Pharmacological effects of sedative-hypnotics, narcotic analgesics, and alcohol during sleep.

This article briefly reviews the well known effects of sedative-hypnotics, alcohol and narcotics on sleep. These drugs also have respiratory depressant effects, and the limited information about their effects on sleep-related breathing disturbances is reviewed. They exacerbate obstructive sleep apnea syndrome and have moderate to minimal effects on occasional apnea or hypopnea, but do not induce breathing disturbances de novo.

Adult↗

PubMed1986

Barbiturate and nonbarbiturate sedative hypnotic intoxication in children.

This article reviews the pharmacology, toxicology, and treatment of both barbiturate and nonbarbiturate sedative hypnotic overdose. Although poisoning with these agents has declined over recent years, intoxication with them can still result in a life-threatening situation requiring immediate assessment and treatment.

Anti-Anxiety Agents↗

PubMed1996

Sedative-hypnotic use and increased hospital stay and costs in older people.

OBJECTIVE: To assess the relationship between sedative-hypnotic (S/H) utilization, severity of illness, length of stay, and hospital costs among older patients admitted to a tertiary care university hospital. DESIGN: Retrospective review of computerized hospital and pharmacy data bases. SUBJECTS: A total of 856 older consecutive medical and surgical admissions from November 1993 to March 1994. MEASUREMENTS: Sedative/hypnotic utilization in accord with the Health Care Financing Administration (HCFA) guidelines for S/H use in nursing homes. Jefferson Disease Staging to estimate severity of illness. Hospital records to obtain demographic characteristics, length of stay, and hospital costs. RESULTS: Patients whose S/H use exceeded HCFA guide lines, compared with those within the guidelines and those receiving no drugs, had longer lengths of stay (21.5 days vs 12.3 days vs 6.7 days, P < .001), increased hospital costs ($29,245 vs $15,219 vs $7,516, P < .001). and greater severity of illness (245.8 vs 189.5 vs 148.5, P < .001). S/H use exceeding and within HCFA guidelines were associated with increased length of stay (both P < .0001) and hospital costs (both P < .0001). CONCLUSIONS: Older hospitalized patients receiving S/H have greater severity of illness, longer lengths of stay, and higher hospital costs compared with other patients. S/H use, and, in particular, S/H use exceeding the HCFA guidelines, are associated with increased hospital stay and cost.

Aged↗

PubMed2000

Cortical evoked response audiometry thresholds and neuroleptic, sedative, hypnotic drugs.

Cortical evoked response audiometry is adequate for approximating hearing threshold levels with frequency specificity when the psychoacoustic responses lack reliability and reproducibility (compensation claim). It is well-known that control of wakefulness is essential for the reliability of slow vertex responses (SVR). Therefore, sedative, hypnotic, and neuroleptic drugs are supposed to have possible adverse effects on the detection of SVR. In contrast, brainstem evoked responses (BER) have proved not to be significantly affected by therapeutic doses of these compounds. The purpose of our study was to assess the reliability of SVR-threshold definition in subjects taking neuroleptic, sedative, and hypnotic drugs. Fifteen subjects examined for occupational hearing loss at the Fund for Occupational Diseases in Brussels and regularly taking one or several of these drugs were compared with 27 comparable controls. In each subject the auditory thresholds were defined with both techniques: SVR (1, 2, and 3 kHz) and BER (clicks). A highly significant difference is observed between the two groups: In the group receiving drugs, the SVR threshold for 3 kHz is 12.1 dB (average) higher than the BER threshold, whereas in the group without drugs, the SVR threshold for 3 kHz is 7.77 dB (average) lower than the BER threshold. In the drug group, large interindividual differences are observed. It may be concluded that the use of neuroleptics, sedatives, and hypnotics renders the auditory threshold definition with SVR completely unreliable. In using SVR for medicolegal threshold definition, controlling the 3-kHz threshold with BER always is necessary.

Adult↗

PubMed2004

Voltammetric behavior and quantification of the sedative-hypnotic drug chlordiazepoxide in bulk form, pharmaceutical formulation and human serum at a mercury electrode.

Chlordiazepoxide is a sedative-hypnotic drug widely employed as a transquilizer and anti-depressant. Its electrochemical behavior in Britton-Robinson (B-R) buffers of pH 2-11 at a mercury electrode has been investigated using dc-polarography, cyclic voltammetry and controlled-potential coulometry. Polarograms of the drug in B-R buffers of pH 2-10 exhibited three 2-electron waves, while at pH>10, only a single 4-electron wave was observed. The first, second, and third waves in buffers of pH 10) may be due to the reduction of both the N-oxide and C=N centers in a one step. The shift of the E(1/2,) values to more negative potentials upon the increase of pH indicated the involvement of protons in the electrode reaction and that the proton-transfer reaction precedes the electrode process proper. The estimated data indicated that, one proton and two electrons are participated in the rate-determining step of each of the reduced centers. The general sequence of chlordiazepoxide reduction processes via each of its reactant centers may be expressed as: H(+), e, e, H(+)((fast)).Based on the interfacial adsorptive character of the drug onto the mercury electrode, a validated direct square-wave adsorptive cathodic stripping (SWAdCS) voltammetric procedure has been described for the trace determination of the drug in bulk form, tablets and human serum. The procedure did not require sample pretreatment or time-consuming extraction or evaporation steps prior to the assay of the drug. The optimized operational conditions of the proposed procedure have been found to be: accumulation potential E(acc.)=-0.9 V, accumulation time t(acc.)=30s, pulse-amplitude=50 mV, scan increment=10 mV and frequency=120 Hz. The proposed procedure is much more simple, fast, sensitive, costly low and achieved much more lower limits of detection (LOD) (4.4 x 10(-10)M and 6.6 x 10(-10)M) and limits of quantitation (LOQ) (1.5 x 10(-9)M and 2.2 x 10(-9)M), respectively in pharmaceutical formulation and spiked human serum, compared to previously reported methods.

Chemistry, Pharmaceutical↗

PubMed1982

Sedative-hypnotics and human performance.

In 52 studies, performance data were obtained the next day following bedtime ingestion of a sedative-hypnotic or a placebo. Only eight of these studies used insomniac patients. Most studies used young adult males. Benzodiazepine hypnotics were most frequently administered and psychomotor performance was most often measured. Little consistent data are available on cognitive functioning and more complex behavior. Drug-related improvement in performance was not found, and, in comparing active drug to placebo, it is clear that all hypnotics, at some doses, produce decrements in performance the next day. Higher doses consistently showed a decrement, and this decrement was usually persistent over the entire day. Although long-acting drugs generally showed more performance decrement, half-life data were not consistent.

Adolescent↗