Paraldehyde is a hypnotic that has been used primarily for the treatment of substance withdrawal seizures and status epilepticus. Today, the sole indication for paraldehyde is in the treatment of acute seizures or status epilepticus. The literature concerning efficacy comprises case reports and small case series, and there are no modern assessments or controlled studies. Paraldehyde probably has similar efficacy in acute seizures as benzodiazepines, barbiturates or phenytoin. It is apparent that paraldehyde is highly effective in stopping seizures. The mechanisms underlying its anticonvulsant action are unclear. Paraldehyde has a small but useful place in contemporary therapy in early status epilepticus as an alternative or sequel to BDZ. Advantages are little sedation or cardiorespiratory risk, and therefore it can be given rectally in situations where there are no facilities for resuscitation (e.g. at home or in residential institutions).

The main toxicity risks result from the use of inappropriately diluted or decomposed paraldehyde. Paraldehyde has a short shelf life, and should not be exposed to light.

Paraldehyde is a medicine that helps to control seizures. Paraldehyde is given rectally.

What Paraldehyde Injection is used for:
Paraldehyde Injection is used to treat convulsions, seizures and fits. It is also used as a sedative or to induce sleep. It is only recommended for use when other treatments do not work or are not appropriate for the condition to be treated. Paraldehyde Injection must only be given by a doctor, nurse or other trained person. Paraldehyde Injection is given by injection into a muscle usually the buttocks. No more than 5 mL should be injected into the same spot. This medicine belongs to a group of medicines called sedatives and hypnotics.

Paraldehyde is an anti-epileptic medicine:
Belonging to a group of medicines called barbiturates. It is used to control repeated fitting in children and works by stabilising the electrical nerve activity in the brain. Paraldehyde is mixed with olive oil for use as an enema.

When abnormally rapid and repetitive electrical signals are released in the brain, it becomes over-stimulated and normal function is disturbed. This results in fits or seizures. Paraldehyde is thought to act mainly by preventing chemicals from passing through openings on the nerve cells, which stops electrical signals building up in the nerves. In addition, paraldehyde acts to increase the effects of a natural 'nerve-calming' agent called GABA and to decrease the effect of other chemicals such as glutamate that excite nerve activity. The overall result is stabilised electrical nerve activity in the brain, which helps to stop a fit. Paraldehyde also has a sedative action and the child will usually sleep after they have been given the medicine.

It is not licensed in the UK, so has to be made as a 'special' or imported from abroad by a licensed pharmaceutical importer.

Paraldehyde is the cyclic trimer of acetaldehyde molecules. It was introduced into clinical practice in the UK by the Italian physician Vincenzo Cervello in 1882. It is a central nervous system depressant and was soon found to be an effective anticonvulsant, hypnotic and sedative. It was included in some cough medicines as an expectorant (though there is no known mechanism for this function beyond the placebo effect). Paraldehyde also has been used in the treatment of alcoholism and in the treatment of nervous and mental conditions to calm or relax patients who are nervous or tense and to produce sleep. However, this medicine has generally been replaced by safer and more effective medicines for the treatment of alcoholism and in the treatment of nervous and mental conditions.

Paraldehyde:
https://drugs.ncats.io/drug/S6M3YBG8QA

Clinical pharmacology:
Paraldehyde is a hypnotic and sedative with anticonvulsant effects. Its possible action is to depress parts of the CNS including the ascending reticular activating system to cause an imbalance between inhibitory and facilitatory mechanisms. The drug is used to control seizures in infants, including those refractory to phenobarbitone and phenytoin, and is as effective as phenobarbitone in the emergency treatment of convulsions in children. Adult metabolism of paraldehyde involves 80% conversion to acetaldehyde, which is oxidised by aldehyde dehydrogenase to acetic acid. Unmetabolised drug is largely excreted unchanged through the lungs with a smaller amount excreted in the urine. The drug diffuses into the CSF and has a rapid onset of action. At therapeutic doses, paraldehyde has little effect on respiration and blood pressure.

Pediatric:
Although there is no specific information comparing use of paraldehyde in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric:
Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people.

There is no specific information comparing use of paraldehyde in the elderly with use in other age groups.

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse (or history of)
• Drug abuse or dependence (or history of) - Dependence on paraldehyde may develop

• Colitis - Paraldehyde used rectally may make the condition worse

• Emphysema, asthma, bronchitis, or other chronic lung disease
• Liver disease - Higher blood levels of paraldehyde may occur, increasing the chance of side effects

• Gastroenteritis (stomach flu)
• Stomach ulcer - Paraldehyde taken by mouth may make the condition worse

Paraldehyde (Oral Route, Injection Route, Rectal Route):
https://www.mayoclinic.org/drugs-supplements/paraldehyde-oral-route-injection-route-rectal-route/description/drg-20065329

Interactions:
Interactions with medicines:
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking paraldehyde, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using paraldehyde with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Disulfiram

Using paraldehyde with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Fospropofol
• Propofol

Using paraldehyde with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ginkgo

Paraldehyde Interactions:
https://www.drugs.com/cons/paraldehyde-oral-injection-rectal.html

Medicines for Children:

When should I give paraldehyde?
You should give rectal paraldehyde if your child's seizure lasts more than 5 minutes. Follow these steps.

(If you have been given paraldehyde to use in case buccal midazolam doesn't help, follow your doctor's advice for when to give it.)

Do not give your child another dose of paraldehyde, unless you have been told to do so by your doctor.

Paraldehyde, also known as paral or paraacetaldehyde, belongs to the class of organic compounds known as trioxanes. Production in the US has been discontinued, but it was previously marketed as Paral. Paraldehyde is a drug. Paraldehyde is an extremely weak basic (essentially neutral) compound (based on its pKa). Paraldehyde is a sweet and aromatic tasting compound. Intramuscular injection can be very painful and lead to sterile abscesses, nerve damage, and tissue necrosis.

Metabocard for Paraldehyde:
https://hmdb.ca/metabolites/HMDB0032456

Paraldehyde was first observed in 1835 by a German chemist. Its empirical formula was determined in 1838. Paraldehyde was first synthesized in 1848. Paraldehyde was introduced into clinical practice in the UK in 1882. It is a central nervous system depressant and was soon found to be an effective anticonvulsant, hypnotic and sedative.

It was commonly used to induce sleep in sufferers from delirium tremens but has been replaced by other drugs in this regard. It is one of the safest hypnotics and was regularly given at bedtime in psychiatric hospitals and geriatric wards up to the 1970s. Up to 30% of the dose is excreted via the lungs (the rest via the liver). This contributes to a strong unpleasant odor on the breath. Today, paraldehyde is sometimes used to treat status epilepticus. Unlike diazepam and other benzodiazepines, it does not suppress breathing at therapeutic doses and so is safer when no resuscitation facilities exist or when the patient's breathing is already compromised. This makes it a useful emergency medication for parents and other caretakers of children with epilepsy. Since the dose margin between the anticonvulsant and hypnotic effect is small, paraldehyde treatment usually results in sleep.

A colourless liquid, it is sparingly soluble in water and highly soluble in ethanol. Paraldehyde slowly oxidizes in air, turning brown and producing an odour of acetic acid.