Products
Phenobarbital is commercially available in tablet form and as a solution for injection (aphenylbarbit, phenobarbital Bichsel). It was approved in many countries in 1944. Luminal has been off the market in many countries since late August 2011. Barbexaclone (maliasin), a fixed combination of phenobarbital and L-propylhexedrine, is also no longer available.
Structure and properties
Phenobarbital (C12H12N2O3, Mr = 232.2 g/mol) is a white crystalline powder that is very sparingly soluble in water. In contrast, the sodium salt phenobarbital sodium, which is present in injection solutions, is readily soluble. Like other barbiturates, phenobarbital is a derivative of barbituric acid. Phenyl-ethyl barbituric acid was synthesized by the noted chemist Emil Fischer in the early 20th century, displacing previously used antiepileptic bromine salts such as potassium bromide.
Effects
Phenobarbital (ATC N03AA02) has anticonvulsant, sedative, sedative to sleep-inducing, and narcotic properties. In contrast, no pain relief is detectable. The central depressant effects are due to allosteric interaction with GABA receptors, resulting in increased chloride transport and hyperpolarization of the cell membrane. Phenobarbital has a long half-life, ranging from 2 to 6 days in adults.
Indications
Phenobarbital is approved for the treatment of epilepsy, for agitation, febrile convulsions, and as an adjuvant in withdrawal treatment-but no longer as a sedative or sleep aid. As a second-line agent, it can be used parenterally to treat status epilepticus. Other potential uses are mentioned in the literature. Off-label use:
- For physician-assisted euthanasia.
Abuse
Phenobarbital can be abused as a sedative due to its sedative effects and has a high potential for dependence. Overdose causes coma and life-threatening respiratory arrest, among other effects, and can cause death. For this reason, it has been widely used in suicides in the past.
Dosage
According to the drug label. Dose must be adjusted on an individual basis. Discontinuation is gradual. Strong sun exposure should be avoided during treatment because the active substance can make the skin sensitive to sun.
Contraindications
- Hypersensitivity
- Acute intoxication with centrally acting drugs, such as sleeping pills and sedatives
- Hepatic porphyria
- Severe renal and hepatic dysfunction
- Cardiac muscle damage
Full precautions can be found in the drug label.
Interactions
Phenobarbital is a potent inducer of hepatic enzymes, including CYP3A4 and CYP2B6, which play a central role in the metabolism of many drugs. It thus has the potential to attenuate the effects of many drugs. Conversely, the effects and side effects of prodrugs may be enhanced because more active drug is formed. Phenobarbital additionally induces enzymes involved in phase II metabolism, for example UDP-glucuronosyltransferases. This can also be exploited therapeutically, see under Meulengracht’s disease. Furthermore, the sedative effects of central depressant agents and alcohol are enhanced. Other interactions are possible with methotrexate and valproic acid.
Adverse effects
The most common potential adverse effects are due to the central depressant properties of the drug. These include, for example, drowsiness, drowsiness, weakness, dizziness, and headache. Occasionally, and especially in children and the elderly, paradoxical agitation is observed. Muscle and joint pain is also common. Rarer possible side effects include cardiac arrhythmias, respiratory depression, blood count disturbances, anemia, digestive disorders, liver dysfunction, hypersensitivity reactions, osteomalacia, and hypocalcemia.
