Phenobarbital is a drug that belongs to the barbiturate group. It is used in epilepsy treatment and in anesthesia preparation.
What is phenobarbital?
Phenobarbital is a drug that belongs to the barbiturate group. It is used in epilepsy treatment and in anesthesia preparation. Phenobarbital is a barbiturate. Barbiturates are drugs that have hypnotic, narcotic or sedative effects. The name barbiturates is derived from barbituric acid, one of the active ingredients of barbiturates. Barbiturates act biochemically via the so-called GABA receptor. A distinction can be made between short-acting, medium-acting and long-acting barbiturates. Phenobarbital belongs to the long-acting barbiturates. Well into the 1960s and 1970s, phenobarbital was still prescribed as a sleeping pill. Due to its considerable side effects and high dependence potential, phenobarbital may no longer be prescribed as a sleeping pill since 1992. Today, the drug is used to treat epilepsies. The sedative and anticonvulsant drug is also used in the preparation of anesthesia. The drug is synthesized via a condensation reaction between urea and ethyl-phenyl-malonic acid diethyl ester.
Pharmacological action
Phenobarbital is almost completely absorbed by the body after oral and after intramuscular administration. Maximum concentrations in the blood are found after 6 to 19 hours when administered orally. With intramuscular administration, the highest concentrations are found in the blood after only 3 to 5 hours. Phenobarbital acts as a sleep and sedative agent. The drug is also used against seizures. The effect is strongly dependent on the dosage. Like most other barbiturates, phenobarbital develops its effect at the GABA receptor. GABA receptors are proteins in nerve cells that can bind the neurotransmitter gamma-aminobutyric acid. This transmitter is also known as GABA. GABA is the main inhibitory neurotransmitter in the human central nervous system (CNS). Like benzodiazepines, barbiturates such as phenobarbital enhance the action of GABA at the receptor. They also cause the channel to remain open longer after GABA has attached. At the same time, phenobarbital blocks AMPA receptors. AMPA receptors are a subgroup of glutamate receptors. Glutamate is also an important neurotransmitter. It has an excitatory effect. The combination of GABA inhibition and blockade of the excitatory action of glutamate is responsible for the sedative and depressant effects of phenobarbitone. For the drug to have an anticonvulsant effect in the body, a plasma concentration of 15-25 μg/ml is required.
Medical application and use
The main indication for phenobarbital is epilepsy. The drug is used to treat grand mal, impulsive petit mal, and also status epilepticus. Here, however, it is used as an injection solution. Status epilepticus is an unusually long-lasting epileptic seizure. Most often, it is a series of seizures that merge into one another. Status epilepticus is life-threatening and can lead to severe damage. Phenobarbital is also used as an injection solution in the preparation for anesthesia. For a long time, the drug was in circulation as a sleeping pill. Since 1992, phenobarbital-containing drugs have not been approved as sleep-inducing agents.
Risks and side effects
Phenobarbital should not be taken if you are hypersensitive to phenobarbital or to other barbiturates. The use of phenobarbital is also contraindicated in acute alcohol, sleeping pill, and painkiller poisoning. The same applies to poisoning by stimulant drugs or by depressant psychotropic drugs. Phenobarbital can cause severe side effects, so it should only be used after a very careful risk-benefit assessment. Close monitoring must be maintained throughout treatment with phenobarbital. Headache, dizziness, and nausea are common while taking the drug. Patients may be confused and show prolonged reaction time. Paradoxical states of agitation are also observed. A possible serious consequence of phenobarbital is acute hepatic porphyria.Porphyria is a metabolic disease associated with impaired breakdown of the blood pigment heme. It is characterized by an episodic course with severe abdominal pain and light intolerance reactions. Patients suffer from colicky abdominal pain, vomiting, nausea, red coloration of the urine, seizures and psychiatric symptoms such as psychosis. Severe liver and kidney dysfunction can also develop during treatment with phenobarbital. Severe heart muscle damage is also a possible consequence of use. People who have a history of affective disorders, or people whose relatives suffer from affective disorders, have a higher risk of developing psychiatric side effects. If phenobarbital is co-administered with other centrally acting drugs, the effects and side effects of these drugs may increase. In addition to alcohol, these medications include painkillers, sleeping pills, allergy medications, and psychotropic drugs. Phenobarbital also causes increased formation of drug-degrading enzymes, so that the breakdown of some drugs in the liver is accelerated. The loss of effect affects drugs such as thyroid hormones, doxycycline, griseofulvin, oral contraceptives, lamotrigine, corticosteroids, or oral drugs that inhibit blood clotting. Children whose mothers were treated with phenobarbital during pregnancy show increased malformations. The drug reaches the child via the placenta and causes damage there. Therefore, phenobarbital may only be prescribed and taken during pregnancy after a careful risk-benefit assessment. Folic acid deficiency can occur during treatment with phenobarbital. This in turn also favors malformations of the unborn child. If the mother has to take phenobarbital during pregnancy, close monitoring of the unborn child’s development with α-fetoprotein determination and ultrasound is recommended. Phenobarbital has a high potential for dependence. Withdrawal symptoms have even been described in newborns whose mothers were treated with phenobarbiol.
