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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years the effectiveness of hypnotic drugs has had to be assessed in terms of a greatly increased knowledge of the physiology and pathology of sleep. The normal pattern of sleep and wakefulness involves a cyclic alternation between three rather than two basically dissimilar states of the brain and body - alert wakefulness, rapid-eye-movement (REM) sleep and non-rapid-eye-movement (NREM) sleep. The pattern of this alternation in individual people results from the interaction of many influences - biological (including genetic, early developmental and later degenerative influences), psychological, social and environmental factors, various physical and psychiatric disorders, and most drugs which affect the central nervous system. The quality of sleep is not related in any simple or constant manner either to its duration or to the proprotions of time spent in each stage of sleep. Among the disorders of sleep, insomnia is a far more common problem of medical management than are enuresis, narcolepsy, somnambulism or nightmares. With a few exceptions, most hypnotic drugs now in widespread use cease to be effective in treating insomnia after the first few nights. However, the ineffective treatment is often continued because insomnia will be even worse during the initial period of drug withdrawal. These factors and the toxicity of hypnotic drugs when taken in overdose make the long-term treatment of insomnia more difficult than was previously supposed. Barbiturates should no longer be prescribed. Some of the non-barbiturates, such as glutethimide and methaqualone, have no advantage over the barbiturates. The benzodiazepine hypnotics, nitrazepam and flurazepam, are less toxic in overdose and are relatively effective in treating insomnia. Chloral hydrate and its derivates are useful alternative drugs for short-term use. Measures to improve sleep without drugs deserve greater emphasis than they have had in the past.
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PMID:Sleep and hypnotic drugs. 23 26

Synthesised by Justin Liebig in 1832 chloral hydrate is one of the oldest synthetic agents. Since 1869 it has been in use for hypnotic or sedative purposes. Chloral hydrate was used a lot from the end of the 19th century to the middle of the 20th century. Since then chloral hydrate has been less frequently in use as a hypnotic. In the 1990's, the principal use of chloral hydrate in pediatrics was the sedation of children for minor surgery during dental or diagnostic procedures. In general practice, it is an analgesia found in topical preparations. It was known as safe and easy to use. Now it is shown to be potentially dangerous (risk of death in case of intoxication) and there is doubt about genotoxicity and carcinogenecity. The pharmacological property was known in 1948 when Butler discovered the principal active metabolite, trichloroethanol. The gastro-intestinal tract rapidly absorbs chloral hydrate after oral or rectal use. The sedative and hypnotic effects appear in 20 to 60 minutes. The main metabolites [trichloroethanol (TCE) and trichloroacetic acid (TCA)] are formed by hepatocytes and erythrocytes. The half-life of chloral hydrate is short (a few minutes), the half lives of the metabolics are longer, 8 to 12 hours for TCE and 67 hours for TCA. The affinity for lipids is high. It is eliminated principally by the kidneys. Its mechanism of action is unknown. It is a depressor of the SNC, and the sedation is attributed to chloral hydrate and the hypnotic effect to TCE. The interactions appear with: alcohol, anticoagulants, amitriptyline and furosemide. The use of flumazenil (a gaba antagonist), in case of intoxication, indicates a possible action of GABA. The posology is usually between 0.5 to 2 g per day. Chloral hydrate is taken during meals to prevent gastric irritation. The main side effects are digestive, cardiologic (risk of rhythm disorder), dermatologic, neuropsychiatric (withdrawn, delusions, hallucination, dependence) and ophthalmologic. Death occurs after absorption of doses of around 10 g of hydrate chloral, some cases were reported with 5 g. The use of hydrate chloral is contra-indicated in cases of gastric ulcers, hepatic insufficiency, porphyry, respiratory insufficiency, association with anticoagulants and hyper sensibility. Nowadays should we be using chloral hydrate in cases of insomnia in adult and older people? A recent preclinical working group of the French Agency for evaluation of medicinal products reassessed the benefit/risk ratio of chloral hydrate. Many references are found about genotoxicity and carcinogenicity in recent literature. In France, since the end of 2000, chloral hydrate has been withdrawn from many medications for external use in dermatology and in stomatology. Chloral hydrate can be used as a pediatric sedative only once in a lifetime. The psychiatric indication for insomnia is no longer justified and especially in older people.
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PMID:[Chloral hydrate: a hypnotic best forgotten?]. 1209 79