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Paraldehyde

Drug Nomenclature

Synonyms: Paracetaldehyde; Paraldehído; Paraldehid; Paraldehidas; Paraldehyd; Paraldehydi; Paraldehydum
Chemical name: The trimer of acetaldehyde; 2,4,6-Trimethyl-1,3,5-trioxane
Molecular formula: (C2H4O)3 =132.2
CAS: 123-63-7
ATC code: N05CC05

Pharmacopoeias. In Europe and US.

European Pharmacopoeia, 6th ed. (Paraldehyde). A colourless or slightly yellow, transparent liquid. It solidifies on cooling to form a crystalline mass. It may contain a suitable amount of an antoxidant. Relative density 0.991 to 0.996. F.p. is 10° to 13° not more than 10% distils below 123° and not less than 95% below 126°. Soluble in water but less soluble in boiling water miscible with alcohol and with volatile oils. Store in small well-filled airtight containers. Protect from light.

The United States Pharmacopeia 31, 2008 (Paraldehyde). A colourless transparent liquid with a strong characteristic, but not unpleasant or pungent, odour. It is subject to oxidation to form acetic acid. It may contain a suitable stabiliser. Specific gravity is about 0.99. It has a congealing temperature of not lower than 11° and distils completely between 120° and 126°. Soluble 1 in 10 of water v/v, but only 1 in 17 of boiling water v/v miscible with alcohol, with chloroform, with ether, and with volatile oils. Store in well-filled airtight containers of not more than 30 mL at a temperature not exceeding 25°. Protect from light. It must not be used more than 24 hours after opening the container.

Incompatibility. Paraldehyde exerts a solvent action upon rubber, polystyrene, and styrene-acrylonitrile copolymer and should not be given in plastic syringes made with these materials. An evaluation of the compatibility of paraldehyde with plastic syringes and needle hubs concluded that, if possible, all-glass syringes should be used with paraldehyde. Needles with plastic hubs could be used. Polypropylene syringes with rubber-tipped plastic plungers (Plastipak), or glass syringes with natural rubber-tipped plastic plungers (Glaspak) were acceptable only for the immediate administration or measurement of paraldehyde doses.

Stability. Paraldehyde decomposes on storage, particularly after the container has been opened. Partly decomposed paraldehyde is dangerous if given. It must not be used if it has a brownish colour or a sharp penetrating odour of acetic acid.

Paraldehyde

Dependence and Withdrawal

Prolonged use of paraldehyde may lead to dependence, especially in alcoholics. Features of dependence and withdrawal are similar to those of barbiturates (see Amobarbital).

Adverse Effects and Treatment

Paraldehyde decomposes on storage and deaths from corrosive poisoning have followed the use of such material. Paraldehyde has an unpleasant taste and imparts a smell to the breath it may cause skin rashes.

Oral or rectal use of paraldehyde may cause gastric or rectal irritation. Intramuscular injection is painful and associated with tissue necrosis, sterile abscesses, and nerve damage. Intravenous use is extremely hazardous since it may cause pulmonary oedema and haemorrhage, hypotension and cardiac dilatation, and circulatory collapse thrombophlebitis is also associated with intravenous use.

Overdosage results in rapid laboured breathing owing to damage to the lungs and to acidosis. Nausea and vomiting may follow an overdose by mouth. Respiratory depression and coma as well as hepatic and renal damage may occur. Treatment is as for barbiturate overdose (see Amobarbital).

Precautions

Paraldehyde should not be given to patients with gastric disorders and it should be used with caution, if at all, in patients with bronchopulmonary disease or hepatic impairment. It should not be given rectally in the presence of colitis. Old paraldehyde must never be used.

Paraldehyde must be well diluted before oral or rectal use if it is deemed essential to give paraldehyde intravenously it must be well diluted and given very slowly with extreme caution (see also Adverse Effects, above and Uses, below). Intramuscular injections may be given undiluted but care should be taken to avoid nerve damage. Plastic syringes should be avoided (see Incompatibility, above).

Interactions

The sedative effects of paraldehyde are enhanced by CNS depressants such as alcohol, barbiturates, and other sedatives. A few case reports suggest that disulfiram may enhance the toxicity of paraldehyde use together is not recommended.

Pharmacokinetics

Paraldehyde is generally absorbed readily, although absorption is reported to be slower after rectal than after oral or intramuscular doses. It is widely distributed and has a reported half-life of 4 to 10 hours. About 80% of a dose is metabolised in the liver probably to acetaldehyde, which is oxidised by aldehyde dehydrogenase to acetic acid. Unmetabolised drug is largely excreted unchanged through the lungs only small amounts appear in the urine. It crosses the placental barrier and is distributed into breast milk.

Uses and Administration

Paraldehyde is a hypnotic and sedative with antiepileptic effects. However, because of the hazards associated with its use, its tendency to react with plastic, and the risks associated with its deterioration, it has largely been superseded by other drugs. It is still occasionally used to control status epilepticus resistant to conventional treatment. Given rectally or intramuscularly it causes little respiratory depression and is therefore useful where facilities for resuscitation are poor.

At low temperature it solidifies to form a crystalline mass. If it solidifies, the whole should be liquefied before use. A usual dose for adults is 10 to 20 mL given rectally as a 10% solution in sodium chloride 0.9% solution or diluted with 1 or 2 parts of oil. Doses of 5 to 10 mL are also occasionally given intramuscularly up to a maximum of 20 mL daily with not more than 5 mL being given at any one site. In the UK it is licensed for intramuscular use in children however, the BNFC advocates use of the rectal route instead, diluted as above. Recommended single daily doses by either route are:

• up to 3 months, 0.5 mL (the BNFC suggests a single rectal dose of 0.4 mL/kg (maximum of 0.5 mL) in those under 1 month)

• 3 to 6 months, 1 mL

• 6 to 12 months, 1.5 mL

• 1 to 2 years, 2 mL

• 3 to 5 years, 3 to 4 mL

• 6 to 12 years, 5 to 6 mL

Paraldehyde has been given by slow intravenous infusion in specialist centres with intensive care facilities but this route is not usually recommended it must be diluted in sodium chloride 0.9% before use.

Paraldehyde has been given orally it should always be well diluted to avoid gastric irritation.

Preparations

British Pharmacopoeia 2008: Paraldehyde Injection.

Proprietary Preparations

USA: Paral.

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