Chloral hydrate is one of the oldest sedatives used for dental sedation. It was first synthesized in 1832 by Justus von Liebig and was the first synthetic central nervous system (CNS) depressant. It was used to treat delirium tremens, insomnia, and anxiety, although it is considered an unapproved drug by the US Food and Drug Administration. Initially considered to be a safer alternative to opium, it was noted to produce rapid unconsciousness when combined with ethanol. Physical dependence can occur with chronic use.
Chloral hydrate is classified as a sedative-hypnotic and is known to induce sleep in children. It has been very popular in pediatric dentistry since the mid-1950s. Chloral hydrate is rapidly absorbed following oral administration and is converted through its first pass in the liver to trichloroethanol，its active form. Trichloroethanol is conjugated in the liver and excreted in the urine. Like other agents that are metabolized in the liver, chloral hydrate may interact with other drugs, herbs, or foods resulting in clinically significant alterations of the agents (e.g.,warfarin).
Chloral is a combustible, oily liquid with a
pungent irritating odor.
Chloral hydrate is used as an intermediate in the production of insecticides, herbicides and hypnotic drugs. It has also been widely used as a sedative or hypnotic drug in humans at oral doses of up to about 750-1000 mg/day. Chloral hydrate is used as a sedative hypnotic, more commonly in pediatrics. With the advent of newer sedative hypnotics, its use has significantly decreased. It is also a drug of abuse, particularly in combination with ethanol to produce an amnestic effect in an individual who ingests it unknowingly.
Trichloroacetaldehyde Hydrate is a useful chemical reagent used as a sedative/hypnotic agent for the short-term treatment of insomnia. First developed in 1832, chloral hydrate is the oldest sleep medication still in use today. This medication is also used to calm you just before surgery or other procedures. It works by affecting certain parts of the brain to cause calmness.
Studies have shown that when used in pediatric sedation side effects such as hallucination, excessive sleep and seizures were observed. Drowsiness and trouble waking up in the morning, nausea, vomiting, stomach pain, diarrhea, and headache may occur. Stomach problems can be reduced by taking chloral hydrate with a full glass of water. It is sometimes administered to patients being treated with cyclophosphamide and it is known to inhibit some aldehyde dehydrogenases.
Besides, Chloral hydrate is a starting point for the synthesis of other organic compounds. It is the starting material for the production of chloral, which is produced by the distillation of a mixture of chloral hydrate and sulfuric acid, which serves as the desiccant.
ChEBI: Chloral hydrate is an organochlorine compound that is the hydrate of trichloroacetaldehyde. It has a role as a sedative, a general anaesthetic, a mouse metabolite and a xenobiotic. It is an organochlorine compound, an aldehyde hydrate and an ethanediol.
Chloral hydrate (Noctec, Somnos) was developed in
the late 1800s and is still used as a sedative–hypnotic
agent. It is a hydrated aldehyde with a disagreeable
smell and taste that is rapidly reduced in vivo to
trichloroethanol, which is considered to be the active
metabolite. It produces a high incidence of gastric irritation
and allergic responses, occasionally causes cardiac
arrhythmias, and is unreliable in patients with liver
damage.
Chloral hydrate, trichloroacetaldehydemonohydrate, CCl3CH(OH)2 (Noctec), is analdehyde hydrate stable enough to be isolated. The relativestability of this gem-diol is largely a result of an unfavorabledipole–dipole repulsion between the trichloromethyl carbonand the carbonyl carbon present in the parent carbonylcompound.
Chloral hydrate is unstable in alkaline solutions, undergoingthe last step of the haloform reaction to yield chloroformand formate ion. In hydroalcoholic solutions, it formsthe hemiacetal with ethanol. Whether or not this compoundis the basis for the notorious and potentially lethal effect of the combination of ethanol and chloral hydrate (the “MickeyFinn”) is controversial. Synergism between two differentCNS depressants also could be involved. Additionally,ethanol, by increasing the concentration of nicotinamideadenine dinucleotide (NADH), enhances the reduction ofchloral to the more active metabolite trichloroethanol, andchloral can inhibit the metabolism of alcohol because it inhibitsalcohol dehydrogenase. Chloral hydrate is a weak acidbecause its CCl3 group is very strong electron withdrawing.A 10% aqueous solution of chloral hydrate has pH 3.5 to4.4, which makes it irritating to mucous membranes in thestomach. As a result, GI upset commonly occurs for thedrug if undiluted or taken on an empty stomach. Chloral hydrateas a capsule, syrup, or suppository is currently available.
Chloral hydrate is incompatible with alkalis, alkaline earth metals, alkali carbonates and soluble barbiturates. Chloral hydrate is decomposed by sodium hydroxide. Chloral hydrate reduces ammoniacal silver nitrate. Chloral hydrate liquefies when triturated with an equal quantity of menthol, camphor or thymol. . Reaction of Chloral hydrate with hydroxylamine produces toxic hydrogen cyanide gas, Org. Synth., 1941, Vol. 1, 377.
Overdose toxic, hypnotic drug, dangerous
to eyes. Probable carcinogen.
Flash point data for Chloral hydrate are not available; however, Chloral hydrate is probably combustible.
Flammability and Explosibility
Non flammable
reagent type: cross-linking reagent
Chloral hydrate is a sedative/hypnotic.
Although it is suggested that chloral hydrate per semay act as a hypnotic,chloral hydrate is very quickly convertedto trichloroethanol, which is generally assumed toaccount for almost all of the hypnotic effect. Thetrichloroethanol is metabolized by oxidation to chloral andthen to the inactive metabolite, trichloracetic acid, which is also extensively metabolized to acylglucuronidesvia conjugation with glucuronic acid. It appears tohave potent barbiturate-like binding to GABAAreceptors.Although an old drug, it still finds use as a sedative in nonoperatingroom procedures for the pediatric patient.
A human poison by
ingestion and possibly other routes. Poison
experimentally by ingestion, intravenous,
and rectal routes. Moderately toxic by
subcutaneous, parenteral, and intraperitoneal
routes, Experimental reproductive effects.
Human systemic effects by ingestion:
general anesthetic, cardiac arrhythmias,
blood pressure depression, eye effects,
coma, pulse rate increase, arrhythmias.
Human mutation data reported.
Questionable carcinogen with experimental
carcinogenic and tumorigenic data by skin
contact. A sedative, anesthetic, and narcotic.
Combustible when exposed to heat or
flame. When heated to decomposition it
emits toxic fumes of Cl-.
Chloral hydrate, 2,2,2-trichloro-1,1-ethandiol (4.3.1), is synthesized
either by chlorination of ethanol or chlorination of acetaldehyde and the subsequent addition of water molecules to the resulting trichloroacetic aldehyde [31].
Chloral is used as an intermediate
in the manufacture of such pesticides as DDT, methoxychlor, DDVP, naled, trichlorfon, and TCA. Chloral is
also used in the production of chloral hydrate; used as
a therapeutic agent with hypnotic, sedative, and narcotic
effects; used in a time prior to the introduction of
barbiturates
Potentially hazardous interactions with other drugs
Anticoagulants: may transiently enhance effect of
coumarins.
Antipsychotics: enhanced sedative effects.
Antivirals: concentration possibly increased by
ritonavir.
Chloral hydrate has not been adequately tested for teratogenicity,
reproductive effects, or chronic toxicity. Similarly, no
histological evaluations have been conducted.
Chloral hydrate is a CNS depressant, but its mechanism of
action is not well known. Coingestion with ethanol produces
enhanced effects by several mechanisms. First, ethanol
competes for alcohol and aldehyde dehydrogenase, which then
prolongs the half-life of ethanol. The metabolism of ethanol
generates the reduced form of NADH, which is a cofactor for
the metabolism of chloral hydrate to its active metabolite
trichloroethanol. Finally, ethanol inhibits the conjugation of
trichloroethanol to its inactive form urochloralic acid. This
results in enhanced CNS depression.
Chloral hydrate is rapidly metabolised to trichloroethanol
(the active metabolite) and trichloroacetic acid in the
erythrocytes, liver, and other tissues. It is excreted partly
in the urine as trichloroethanol and its glucuronide
(urochloralic acid) and as trichloroacetic acid. Some is
also excreted in the bile.
UN2811 Toxic solids, organic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials, Technical
Name Required.
Chloral hydrate has been detected at 5 mg l-1 in the US drinking
water supply. Although chloral hydrate does not exist naturally,
it can be produced as a by-product of chlorination of water at
water treatment facilities, specifically in exposed water with
high amounts of humic and fulvic substances.
Chloral hydrate reacts with strong bases
forming chloroform. Contact with acids, or exposure to
light may cause polymerization. Reacts with water, forming
chloral hydrate. Reacts with oxidizers, with a risk of fire or
explosions.
Incineration after mixing with
another combustible fuel; care must be taken to assure complete combustion to prevent phosgene formation; an acid
scrubber is necessary to remove the halo acids produced.
Herbicide; Veterinary substance
