Chloral hydrate toxicity

Chloral hydrate toxicity can cause a number of dysrhythmias, including supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, and torsade de... 

The oldest anti-anxiety agent is undoubtedly alcohol and it is certain that this drug is still routinely self-administered for this purpose. Towards the end of the eighteenth century, bromide salts were used to relieve conditions akin to anxiety despite the risk of a characteristic toxic delirium, known as bromism . Alternative treatments, such as paraldehyde and chloral hydrate, were also widely used but these too had adverse effects the former can cause psychosis but the latter is still used as a sedative and anaesthetic agent. 

These drugs include alcohols (ethchlorvynol, chloral hydrate), piperidinediones (glutethimide, methyprylon), and carbamates (meprobamate). They are rarely used in therapy, though the low cost of chloral hydrate makes it attractive for institutional use. Little is known about their molecular mechanisms of action. Most of these drugs are biotransformed to more water-soluble compounds by hepatic enzymes. Trichloroethanol is the pharmacologically active metabolite of chloral hydrate and has a half-life of 6-10 hours. However, its toxic metabolite, trichloroacetic acid, is cleared very slowly and can accumulate with the nightly administration of chloral hydrate. 

Historically the first sedative hypnotics to be introduced were the bromides in the mid 19th century, shortly followed by chloral hydrate, paraldehyde and urethane. It was not until the early years of this century that the first barbiturate, sodium barbitone, was developed and this was shortly followed by over 50 analogues, all with essentially similar pharmacological properties. The major breakthrough in the development of selective, relatively non-toxic sedative hypnotics followed the introduction of chlordiazepoxide in 1961. Most of the benzodiazepines in current use have been selected for their high anxiolytic potency relative to their central depressant effects. Because of their considerable safety, the benzodiazepines have now largely replaced the barbiturates and the alcohols, such as chloral hydrate and trichloroethanol, as the drugs of choice in the treatment of insomnia. 

The IUPAC rules for naming aldehydes append the suffix -al to the parent name. The aldehyde carbon is always the first carbon in the chain, so a locant is not necessary. The simplest aldehyde, methanal, is commonly known as formaldehyde, a highly toxic gas used to preserve biological specimens. Ethanal is the next aldehyde, although most organic chemists call it acetaldehyde. 2,2,2-Tri-chloroethanal, more commonly known as chloral, reacts with water to form the sedative chloral hydrate. Phenylmethanal, more commonly known as benzalde-hyde, is used as artificial cherry or almond flavoring. Nomenclature examples of aldehydes are shown in Figure 11.34. 

Zahedi A, Grant MH, Wong DT. Successful treatment of chloral hydrate cardiac toxicity with propranolol. Am J Emerg Med 1999 17(5) 490-1. 

In Western medicine, picrotoxanes have played but a marginal role therapeutically. Picrotoxin was described as analeptic. Porter recorded that picrotoxin was found to be an antidote against chloral hydrate and in consequence it was used also as an antidote against barbiturate intoxication (2). It was this activity that made biomedical researchers aware of its potential as research tool in neurochemistry. Due to its high toxicity, even its use as antidote is restricted, however. Picrotoxin is employed to treat vertigo and nausea in homeopathic preparations (25i). 

A few (hugs have distinctive odours md this can provide a clue to the compoimd or at least to the type of preparation. A yeast-like or meaty smell may indicate a harmless vitamin preparation, an odour of peppermint may indicate a non-toxic indigestion remedy. Antibiotics, especially of the penicillin group, sometimes have a rather unpleasant sulphide-type smell. Other drugs with characteristic odours are chlormethiazole, phenelzine, ethchlorvynol, chloral hydrate, and methylpentynol. 

SAFETY PROFILE Poison by ingestion. A narcotic. A skin and eye irritant. Mutation data reported. See also CHLORAL HYDRATE, which acts similarly. Dangerous can react with oxidi2ing materials. Combustible when exposed to heat or flame. When heated to decomposition it emits toxic fumes of CP. See also PHOSGENE. 

As in humans, chloral hydrate is used in veterinary medicine as a sedative and hypnotic. Similar therapeutic and toxic effects are seen in humans and in animals. 

Chloral hydrate, first employed as a sedative by Liebreich in 1869, immediately proved effective. It remains one of the least toxic and most useful seda-... 

Chloral hydrate (Noctec and Somnos) lacks analgesic effects. It also has no effect on respiration or circulation when given in therapeutic doses. In toxic doses (10 mg), it causes hypotension and respiratory depression. Chloral hydrate is reduced to trichlorethanol. 

Decomposes when heated above melting point, 536°F/280°C, producing toxic fumes of arsenic, lead. Lead arsenates may be subject to redox reactions. Both arsenic and lead are known human carcinogens. PLUMBOUS ACETATE (6080-56-4) Pb(CjH302)2 3H,0 Contact with acids forms acetic acid. Incompatible with oxidizers, bases, acetic acid alkalis, alkylene oxides, ammonia, amines, bromates, carbonates, citrates, chlorides, chloral hydrate cresols, epichlorohydrin, hydrozoic acid, isocyanates, methyl isocyanoacetate, phenols, phosphates, salicylic acid sodium salicylate, sodium peroxyborate, potassium bromate resorcinol, salicylic acid, strong oxidizers, sulfates, sulfites, tannin, tartrates, tinctures trinitrobenzoic acid, urea nitrate. On small fires, use dry chemical, Halon, or CO2 extinguishers. 

Chloral hydrate is metabolized into two major metabolites—one which is pharmacologically active and relatively non-toxic (trichloroethanol) and the other which is toxic (trichloroacetic acid). Trichloroethanol is cleared fairly rapidly, with a half-life of less than ten hours. Trichloroacetic acid is cleared much more slowly, and will accumulate with nightly administration. 

---