A comparison between chlormethiazole and nitrazepam as hypnotics in psycho-geriatric patients

Harenko, A

doi:10.1185/03007997409111879

Cited by 17 publications

(26 citation statements)

References 10 publications

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“…At low doses, such reactions were rare regardless of age. The hazards of nitrazepam in the elderly, particularly at high doses, have been observed by others (Evans & Jarvis, 1972;Harenko, 1975;Castleden et aL, 1977). There appears to be little reason to initiate nitrazepam therapy with 10 mg doses in most patients, and certainly not in the elderly.…”

Section: Patient Characteristicsmentioning

confidence: 76%

“…Nitrazepam, a 1,4-benzodiazepine derivative, is extensively used as a hypnotic agent throughout the eastern hemisphere. The sleep-inducing efficacy and relative safety of nitrazepam are well established (Greenblatt & Shader, 1974), but recent reports suggest that the drug presents a hazard to certain elderly individuals (Evans & Jarvis, 1972;Harenko, 1975;Castleden, George & Mercer, 1977). Previous studies from the Boston Collaborative Drug Surveillance Program (BCDSP) indicate an increased frequency of adverse reactions to three other benzodiazepine derivatives-chlordiazepoxide, diazepam and flurazepam-in elderly patients (Boston Collaborative Drug Surveillance Program, 1973;Greenblatt, Allen & Shader, 1977).…”

Section: Introduction Methodsmentioning

confidence: 99%

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Toxicity of nitrazepam in the elderly: a report from the Boston Collaborative Drug Surveillance Program.

Dj¹,

Allen²

1978

Brit J Clinical Pharma

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1 To assess the potential hazards of nitrazepam therapy of insomnia in the elderly, adverse reactions to nitrazepam were studied in 2111 hospitalized medical patients who received the drug. 2 Manifestations of unwanted central nervous system (CNS) depression (such as drowsiness or 'hangover') were reported in 49 nitrazepam recipients (2.3%), and signs of unwanted CNS stimulation (such as nightmares, insomnia, agitation, etc.) in 15 (0.7%). None of the adverse reactions were considered serious. 3 Physician‐rated clinical efficacy of nitrazepam was not related to dose, but the frequency of both types of adverse reactions increased significantly at higher daily doses. CNS depression also was significantly more frequent in the elderly, being reported in 11% of those aged 80 years or older, whereas the frequency of CNS stimulation was not correlated with age. 4 The effect of age on the reported rate of unwanted CNS depression was most striking at high doses. Among patients aged 80 years or over whose daily dose averaged 10 mg or more, 55% experienced unwanted CNS depression attributed to nitrazepam. 5 Low doses of nitrazepam are safe for elderly individuals, but the elderly are readily susceptible to excessive CNS depression at high doses. The findings suggest that there is little reason to exceed 5mg doses of nitrazepam for most patients, particularly those who are elderly.

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Section: Patient Characteristicsmentioning

confidence: 76%

Section: Introduction Methodsmentioning

confidence: 99%

Toxicity of nitrazepam in the elderly: a report from the Boston Collaborative Drug Surveillance Program.

Dj¹,

Allen²

1978

Brit J Clinical Pharma

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“…Chlormethiazole appears to be particularly effective in the treatment of status epilepticus in patients failing to respond to benzodiazepines and barbiturates (10)(11)(12)(13) and also in the management of pre-eclampsia and eclampsia (14)(15)(16)(17). In recent years, chlormethiazole has been used as a hypnotic in the elderly (18)(19)(20)(21)(22) particularly in the management of psychogeriatric patients (23)(24)(25)(26)(27)(28).…”

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confidence: 99%

Chlormethiazole‐mode of action

Ögren

1986

Acta Psychiatr Scand

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Studies in mice demonstrated that the anticonvulsant profile of chlormethiazole differs from that of diazepam and the barbiturates. Chlormethiazole protects animals from convulsions induced by a wide variety of chemoconvulsants known to block the action of the inhibitory neurotransmitter y-aminobutyric acid (GABA), such as bicuculline, picrotoxin, isoniazid and pentetrazol, thus confirming and extending earlier studies on its broad anticonvulsant characteristics. Chlormethiazole is particularly potent against isoniazid-induced convulsions, which are probably induced by reductions of GABA levels in the brain.Chlormethiazole was found to have a weak action on benzodiazepine receptor binding, GABA receptor binding and kainic acid receptor binding. Chlormethiazole inhibited picrotoxin binding at very high concentrations, but lowered the functional effects of picrotoxin at much lower concentrations than those affecting picrotoxin binding. Moreover, chlormethiazole failed to change GABA or glutamate levels in the brain and did not affect glutamic acid decarboxylase (GAD) activities in the rat brain. Muscimol (a GABAA agonist) enhanced the anticonvulsant activity of chlormethiazole against picrotoxin but not against bicuculline-induced convulsions. Muscimol enhanced the anticonvulsant potency of diazepam against both chemoconvulsants. These data suggest that the anticonvulsant activity of chlormethiazole is not mediated directly through changes in GABA or glutamate levels or by a direct (agonist) action at the GABA or benzodiazepine receptor complex. These findings suggest that chlormethiazole may enhance GABA transmission beyond the GABA receptors, hypothetically at the level of the GABA receptor coupled ionophore (e.g. the chloride ion channel).Applied micro-iontophoretically, chlormethiazole was found to potentiate the inhibitory responses to GABA, muscimol and glycine, but not to acetylcholine. The potentiation of glycine-mediated inhibition is unique for chlormethiazole and does not occur with any other known anticonvulsant (barbiturates, benzodiazepine, phenytoin or sodium valproate). Studies in primary cultures, derived from spinal cord neurones, showed that chlormethiazole produces hyperpolarization together with an increase in the threshold for action potential generation. Further in vitro studies indicated that chlormethiazole acts on some types of Ca2+-dependent chloride ion channels.In vivo studies indicated that the hypnotic effect of chlormethiazole

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“…It is effective in status epilepticus in patients failing to respond to benzodiazepines or barbiturates (Harvey, Higenbottam & Loh, 1975). More recently it has been used as a hypnotic (Briggs, Castleden & Kraft, 1980) particularly in psycho-geriatric patients (Harenko, 1975).…”

Section: Introductionmentioning

confidence: 99%

The effects of chlormethiazole on single unit activity in rat brain; interactions with inhibitory and excitatory neurotransmitters

Gent

Wacey

1983

British J Pharmacology

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A comparison between chlormethiazole and nitrazepam as hypnotics in psycho-geriatric patients

Cited by 17 publications

References 10 publications

Toxicity of nitrazepam in the elderly: a report from the Boston Collaborative Drug Surveillance Program.

Toxicity of nitrazepam in the elderly: a report from the Boston Collaborative Drug Surveillance Program.

Chlormethiazole‐mode of action

The effects of chlormethiazole on single unit activity in rat brain; interactions with inhibitory and excitatory neurotransmitters

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