Chloral hydrate dependence

Chloral hydrate dependence can occur (7), the most famous case being that of Anna O. (Bertha Pappenheim), who was treated by Breuer from 1880 to 1882, and whose pathology was discussed by him and Freud in 1895 (8). 

Stone CB, Okun R. Chloral hydrate dependence report of a case. Chn Toxicol 1978 12(3) 377-80. 

Derivatives. The precise identification of a compound normally depends upon the preparation of a derivative and the determination of physical constants such as m.p. in the case of a solid. Many simple compounds can, however, be identified with a fair degree of certainty by intelligently-selected qualitative tests alone, e.g., formates, oxalates, succinates, lactates, tartrates, chloral hydrate. 

Schedule IV - This class represents medications considered to be of low abuse potential with the possibility of limited dependence especially when compared to the previous schedules. Examples are phenobarbital, chloral hydrate, the benzodiazepine tranquilizers, propoxyphene and meprobamate (all are sedatives). 

Drugs in this category have an accepted medical use and a relatively low potential for abuse compared to Schedule 3. Use may lead to limited physical dependence or psychological dependence. Many drugs in this category are hypnotic (sleep-inducing) or anesthetic in effect. Phenobarbital, barbital, and chloral hydrate are examples. 

Elixir is an example 23% alcohol with 40 mg of morphine in every bottle. Also, Mrs. Winslow s Soothing Syrup, with 0.05 g of morphine per bottle. Even patent medicines to cure morphine dependence were sold inevitably they contained alcohol or opium. Thomas Edison patented and marketed his own nostrum, Poly-Form. It contained morphine, chloroform, ether, chloral hydrate, alcohol, and spices. 

The drugs in Schedule IV have a relatively low abuse potential and risk for psychological or physical dependence relative to those listed in Schedule in and include such drugs as barbital, phenobarbital, methylphe-nobarbital, chloral betaine (Beta Chlor), chloral hydrate, ethchlorvynol (Placidyl), ethinamate (Valmid), meprobamate (Equanil, Miltown), paraldehyde, methohexital, fenfluramine, diethyipropion, phentermine, chlor-diazepoxide (Librium), diazepam (Valium), oxazepam (Serax), clorazepate (Tranxene), flurazepam (Dalmane), clonazepam (Clonopin), prazepam (Verstran), lorazepam (Ativan), mebutamate, and dextropropoxyphene (Dar-von). 

Insomnia is a common complaint in the elderly. As people age they require less sleep, and a variety of physical ailments to which the elderly are subject can cause a change in the sleep pattern (e.g. cerebral atherosclerosis, heart disease, decreased pulmonary function), as can depression. Providing sedative hypnotics are warranted, the judicious use of short half-life benzodiazepines such as temazepam, triazolam, oxazepam and alprazolam for a period not exceeding 1-2 months may be appropriate. Because of their side effects, there would appear to be little merit in using chloral hydrate or related drugs in the treatment of insomnia in the elderly. It should be noted that even benzodiazepines which have a relatively short half-life are likely to cause excessive day-time sedation. The side effects and dependence potential of the anxiolytics and sedative hypnotics have been covered elsewhere in this volume (Chapter 9). 

Barbiturate overdose may be treated with gastric lavage and oral administration of activated charcoal. Supportive therapy of cardiovascular, respiratory, and renal function also should be provided. Coadministration of alcohol and barbiturates may increase the sedative effect of chloral hydrate. Long-term use of barbiturates leads to dependence. Sudden discontinuation of an antipsychotic drug may cause withdrawal symptoms such as nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, insomnia, restlessness, and vertigo.151... 

The induced dipole moment depends on the electric field strength and the structure of the molecule. Charge-induced dipole interactions occur between a charged ion and polarized molecules. A molecule possessing conjugated double bonds is readily polarized. Examples of solutions due to the dipole-induced dipole interaction are benzene in methanol, chloral hydrate in CC14, and phenol in mineral oil. 

Nonbarbiturate sedative-hypnotics have a similar mechanism of action as barbiturates and have high potential for tolerance, abuse, dependence, overdose, and withdrawal reactions. Chloral hydrate is still commonly used today due to its efficacy as a short-term sedative hypnotic and low cost. Chloral hydrate should not be used in patients with severe renal, hepatic, or cardiac disease. 

Prolonged administration of chloral hydrate may lead to the development of gastritis, skin eruptions, and renal damage. Chronic use of high doses may produce psychologic and physical dependence. Abrupt discontinuation may lead to delirium and seizures. 

HYPNOTICS are agents that induce sleep. They are used mainly to treat short-term insomnia, for instance in shiftwork, to cope with Jet-lag or in sleep disturbances due to emotional problems or in serious illness. The best-known and most-used hypnotics in current use are the benzodiazepines - and this class of drug is also used, at a lower dose, as ANXIOLYTICS. Examples from the class that are of relatively long-lasting action and may cause drowsiness the next day include diazepam, flunitrazepam, flurazepam and nitrazepam. Examples with a shorter duration include loprazolam, lormetazepam and temazepam. All can cause drug dependence on continued usage. Examples of hypnotics that are now much less used include chloral hydrate, chlormethiazole and triclofos. The barbiturates (e.g. amylobarbitone) are now very little used, as they are prone to cause serious dependence and are dangerous in overdose. 

The treatment of anxiety throughout human history has involved a variety of natural agents which were administered to relieve tension and induce a state of altered consciousness, with ethanol in its various forms the most widely used [4]. Within the last century, general CNS depressants such as barbiturates, bromide salts, and ethanol surrogates such as chloral hydrate and paraldehyde have been employed to treat anxiety. Because of side-effects of the other drugs, barbiturates were used predominantly in the first half of this century as anxiolytics, but their clinical utility was limited by tolerance and dependence liability. Propanediolcarbamates such as meprobamate were also used to treat anxiety but displayed many of the barbiturate side-effects. 

The N.M.R. spectrum obtained depends on the position of the chloral —chloral hydrate equilibrium. Chloral gives a simple spectrum (CDClj), the aldehyde proton absorbing at 69.1. Chloral hydrate, however, consistently gives a peak at 9.1, plus other peaks whose positions are more variable, for hydroxyl absorptions are greatly influenced by temperature and concentration (see fig.3) ... 

The toxieity of triehloroethylene is dependent upon metabolism and induction of cytochrome P450. Triehloroethylene is metabolized through chloral hydrate to compounds including trichloroacetic acid and dichloroacetic acid which alter intercellular communication, induce peroxisome proliferation and may promote tumor production. Significant variability in trichloroethylene metabolism in 23 human haptic microsomal samples was reported by Lipscomb et al. It was also demonstrated that the trichloroethylene metabolism is dependent on enzymatic activities of the cytochrome system, and they conclude that their data indicates that humans are not uniform in their capacity for CPY dependent metabolism of trichloroethylene and increased activity may increase susceptibility to trichloroethylene induced toxicity in humans. These observations are compatible with the variability reaction which is depending on nutritional factors, enzyme induction factors, hormonal factors and interaction with other environmental chemicals, prescription medications and general health conditions, and explains the variable reports as far as trichloroethylene and level of liver toxicity in the various individuals studied. 

The position of equilibrium depends on the nature of the substituent R. In some aldehydes such as chloral, CCI3CHO or formaldehyde HCHO, the equilibrium is shifted towards the diol. In its diol form chloral is known as chloral hydrate and serves as a disinfectant. The trade name of formaldehyde is formol which is actually the water solution of formaldehyde. 

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