Phenobarbital

phenobarbitoneLuminalHaplosphenobarbitolBarbitabarbiturateFenemalfenobarbitalPhenobarbphenobarbital sodium
Phenobarbital, also known as phenobarbitone or phenobarb, is a medication recommended by the World Health Organization for the treatment of certain types of epilepsy in developing countries.wikipedia
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Barbiturate

barbituratesbarbiturate withdrawalsleeping pill
Phenobarbital is a barbiturate that works by increasing the activity of the inhibitory neurotransmitter GABA.
Barbiturates such as phenobarbital were long used as anxiolytics and hypnotics.

Status epilepticus

super-refractory status epilepticusnonconvulsive status epilepticusprolonged seizures
The injectable form may be used to treat status epilepticus. The first-line drugs for treatment of status epilepticus are benzodiazepines, such as lorazepam or diazepam.
A number of other medications may be used if these are not effective such as valproic acid, phenobarbital, propofol, or ketamine.

WHO Model List of Essential Medicines

World Health Organization's List of Essential MedicinesList of Essential MedicinesModel List of Essential Medicines
It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.

Anticonvulsant

anticonvulsantsantiepilepticantiepileptic drugs
Phenobarbital was discovered in 1912 and is the oldest still commonly used anti-seizure medication.
According to guidelines by the American Academy of Neurology and American Epilepsy Society, mainly based on a major article review in 2004, patients with newly diagnosed epilepsy who require treatment can be initiated on standard anticonvulsants such as carbamazepine, phenytoin, valproic acid/valproate semisodium, phenobarbital, or on the newer anticonvulsants gabapentin, lamotrigine, oxcarbazepine or topiramate.

Lorazepam

Ativanbenzodiazepine lorazepamdrug of the same name
The first-line drugs for treatment of status epilepticus are benzodiazepines, such as lorazepam or diazepam.
However, phenobarbital has a superior success rate compared to lorazepam and other drugs, at least in the elderly.

Gilbert's syndrome

Gilbert syndromeGilbert diseaseGilbert's disease
Phenobarbital is occasionally prescribed in low doses to aid in the conjugation of bilirubin in people with Crigler–Najjar syndrome, type II, or in patients with Gilbert's syndrome.
If jaundice is significant phenobarbital may be used.

Benzodiazepine withdrawal syndrome

benzodiazepine withdrawalwithdrawal syndromebenzodiazepine
Phenobarbital is sometimes used for alcohol detoxification and benzodiazepine detoxification for its sedative and anti-convulsant properties.

Epilepsy

epilepticseizure disorderepilepsies
Phenobarbital, also known as phenobarbitone or phenobarb, is a medication recommended by the World Health Organization for the treatment of certain types of epilepsy in developing countries.
The least expensive anticonvulsant is phenobarbital at around US$5 a year.

Crigler–Najjar syndrome

Crigler–Najjar syndrome, type ICrigler–Najjar syndrome, type IICrigler-Najjar
Phenobarbital is occasionally prescribed in low doses to aid in the conjugation of bilirubin in people with Crigler–Najjar syndrome, type II, or in patients with Gilbert's syndrome.
Hence, there is no response to treatment with phenobarbital, which causes CYP450 enzyme induction.

Carbamazepine

TegretolEpitolAtretol
Phenobarbital may provide a clinical advantage over carbamazepine for treating partial onset seizures.
Lower levels of carbamazepine are seen when administrated with phenobarbital, phenytoin, or primidone, which can result in breakthrough seizure activity.

Paradoxical reaction

paradoxical effectparadoxical effectsparadoxical
In elderly patients, it may cause excitement and confusion, while in children, it may result in paradoxical hyperactivity.
Phenobarbital can cause hyperactivity in children.

Diazepam

ValiumDizacCANA
The first-line drugs for treatment of status epilepticus are benzodiazepines, such as lorazepam or diazepam.

CYP2B6

2B6CYP2B6 inhibitors
Cytochrome P450 2B6 (CYP2B6) is specifically induced by phenobarbital via the CAR/RXR nuclear receptor heterodimer.
This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital.

Neonatal withdrawal

neonatal abstinence syndromeneonatal withdrawal syndromewithdrawal symptoms in the newborn
Phenobarbital is used as a secondary agent to treat newborns with neonatal abstinence syndrome, a condition of withdrawal symptoms from exposure to opioid drugs in utero.
Phenobarbital is sometimes used as an alternative but is less effective in suppressing seizures; however, phenobarbital is superior to diazepam for neonatal opiate withdrawal symptoms.

Chlordiazepoxide

LibriumLimbitrolA-Poxide
The benzodiazepines chlordiazepoxide (Librium) and oxazepam (Serax) have largely replaced phenobarbital for detoxification.
Chlordiazepoxide is similar to phenobarbital in its anticonvulsant properties.

Bayer

Bayer AGBayer CropScienceBayer HealthCare
The first barbiturate drug, barbital, was synthesized in 1902 by German chemists Emil Fischer and Joseph von Mering and was first marketed as Veronal by Friedr. Bayer et comp.
Bayer also introduced phenobarbital; prontosil, the first widely used antibiotic and the subject of the 1939 Nobel Prize in Medicine; the antibiotic Cipro (ciprofloxacin); and Yaz (drospirenone) birth control pills.

Phenytoin

Dilantindiphenylhydantoindephenylhydantoin
It is no less effective at seizure control than phenytoin, however phenobarbital is not as well tolerated.
In 1938, outside scientists including H. Houston Merritt and Tracy Putnam discovered phenytoin's usefulness for controlling seizures, without the sedative effects associated with phenobarbital.

Clonazepam

KlonopinRivotril
Among anti-convulsant drugs, behavioural disturbances occur most frequently with clonazepam and phenobarbital.
Of anticonvulsant drugs, behavioural disturbances occur most frequently with clonazepam and phenobarbital.

Absence seizure

absence seizuresabsence epilepsypetit mal
Phenobarbital is used in the treatment of all types of seizures, except absence seizures.
Similarly, oxcarbazepine, phenytoin, phenobarbital, gabapentin, and pregabalin should not be used in the treatment of absence seizures because these medications may worsen absence seizures.

Barbiturate dependence

barbiturate abusecan be used recreationally
Like other barbiturates, phenobarbital can be used recreationally, but this is reported to be relatively infrequent.
The management of a physical dependence on barbiturates is stabilisation on the long-acting barbiturate phenobarbital followed by a gradual titration down of dose.

Epilepsy in animals

epilepsycanine epilepsyepilepsy in dogs
Phenobarbital is one of the initial drugs of choice to treat epilepsy in dogs, and is the initial drug of choice to treat epilepsy in cats.
Oral phenobarbital, in particular, levetiracetam and imepitoin are considered to be the most effective antiepileptic drugs and usually used as ‘first line’ treatment.

Potassium bromide

KBrbromidebromide of potassium
Most of these patients were using the only effective drug then available, bromide, which had terrible side effects and limited efficacy.
There was not a better epilepsy drug until phenobarbital in 1912.

Abbie Hoffman

AbbieAmerica HoffmanAbbie Hoffman incident
Activist Abbie Hoffman also committed suicide by consuming phenobarbital, combined with alcohol, on April 12, 1989; the residue of around 150 pills was found in his body at autopsy.
He committed suicide by a phenobarbital overdose in 1989.

Diethyl phenylmalonate

Upon heating this intermediate easily loses carbon monoxide, yielding diethyl phenylmalonate.
Diethyl phenylmalonate is an aromatic malonic ester used in the synthesis of moderate to long lasting barbiturates such as phenobarbital.

Constitutive androstane receptor

CARNR1I3
Cytochrome P450 2B6 (CYP2B6) is specifically induced by phenobarbital via the CAR/RXR nuclear receptor heterodimer.
CAR can be activated in two ways: by direct binding of a ligand (e.g. TCPOBOP) or indirect regulation by phenobarbital (PB), a common seizure medication, facilitating the dephosphorylation of CAR through protein phosphatase 2 (PP2A) (Fig.