Barbiturates are considered the first anxiolytics to appear on the market. They are derived from barbituric acid, and have mainly sedative and hypnotic properties, but also anticonvulsants. One of them is phenobarbital, especially used in epilepsy
This barbiturate has been one of the most used in medicine and psychiatry, and, although it was originally used as an anxiolytic, it is currently indicated to treat cases of epilepsy, seizures and severe insomnia. In this article we will learn about its general characteristics, mechanism of action, indications and adverse effects.
Phenobarbital is a drug belonging to the first group of anxiolytics that were discovered It is a barbiturate with hypnotic properties (induce drowsiness and sleep), sedative and anticonvulsant or antiepileptic properties (used to treat seizures and epilepsy). It can present two commercial names: Gardenal and Luminal.
More specifically, phenobarbital is a long-acting barbiturate This means that it is released and distributed progressively in the body, slowly. On the other hand, the onset of action of phenobarbital is slow.
Its action consists of inhibit seizures caused by epileptic seizures, electroshock or pentylenetetrazole (Central Nervous System stimulant drug). At a chemical level, phenobarbital is a metabolite of mephobarbital (also a barbiturate) and pidone (an anticonvulsant).
1. Mechanism of action
The mechanism of action of phenobarbital focuses on GABA; let’s remember that GABA is the main depressive and inhibitory neurotransmitter in the brain Thus, phenobarbital is based on facilitating the inhibition of synaptic transmission mediated by GABA; that is, it enhances the inhibitory action of GABA.
Specifically, what it does is open the Chlorine (Cl-) channels of the GABA A receptor; Barbiturates have the property of increasing the probabilities of these channels opening, as well as the time they remain open. This mechanism is the same as that used by pidone, another anticonvulsant drug.
On the other hand, it is unknown exactly how phenobarbital acts, but it is known that it also exerts some type of action on K+ (potassium) channels.
Phenobarbital, along with other drugs such as valproic acid (antiepileptic and mood stabilizer), benzodiazepines (anxiolytics), carbamazepine (anticonvulsant and mood stabilizer) and rimidone (anticonvulsant), has the ability to block trains of recurrent high-frequency action potentials (APs) which are generated in the neuron that suffers from epilepsy.
Action on glutamate
Another action that phenobarbital exerts is reduce the excitement produced by glutamate (main brain-stimulating amino acid).
However, this action is not related to the reduction of seizures, since this effect is produced by drugs that block NMDA receptors (glutamate receptors), and what phenobarbital does is act on non-NMDA receptors, joining them.
Thus, it may be that non-NMDA receptors (excitatory amino acid receptors), or even AMPA (glutamate receptors), are related to epileptic disorders (epilepsy).
2. Absorption
The absorption of a drug indicates when it has entered the bloodstream In the case of phenobarbital, this is produced quickly and completely.
3. Other properties
Phenobarbital is a highly effective, safe and economical drug. It can be used on both children and adults; However, in the pediatric population, care must be taken because frequently causes alterations in cognitive functions behavioral problems and central nervous system (CNS) arousal (called “paradoxical arousal”).
Regarding its intake and dosage, a single dose per day is generally prescribed; this is due to the long half-life of phenobarbital. Let us remember that the half-life of a drug is the time it takes for the body to eliminate 50% of it. The long half-life of phenobarbital means its effects last longer.
Phenobarbital has three main indications: epilepsy, seizures (and their prevention) and severe insomnia disorder.
1. Eplepsy
Phenobarbital is used in cases of epilepsy, specifically to relieve generalized seizures and status epilepticus The seizures that it especially relieves are of the generalized tonic-clonic type (affecting the entire brain); These lead to symptoms such as body rigidity, recurring pulling in the arms and/or legs, and loss of consciousness.
For other types of seizures, phenobarbital is also effective but not as effective. These are partial, myoclonic and akinetic seizures. Specifically, partial or focal seizures appear when the electrical activity of the brain is limited to a specific area of the brain; Myoclonic ones are characterized by a sudden and very rapid jerk of the extremities, and akinetic ones are characterized by the loss of muscle tone and a possible fall.
2. Seizures
Seizures, typical in epilepsy, are repeated, trembling contractions and distensions in one or more muscles of the body. They appear abruptly and violently, as a result of a sudden increase in the electrical activity of the brain this activity also being abnormal.
Phenobarbital is indicated to prevent these seizures (prophylaxis) and to relieve them (treatment).
3. Severe insomnia
In cases of severe insomnia disorder, phenobarbital is also used. Insomnia is a sleep disorder that involves difficulties starting sleep (onset insomnia), maintaining it for a minimum of time (maintenance insomnia) or sleeping until the end of the night (the person wakes up early) (terminal insomnia). ).
In these cases, this barbiturate used as short-term treatment (In fact, it is not recommended to use it as a long-term treatment, since it may lose its effectiveness after 2 or 3 weeks of starting it).
An interesting fact to know is that in the pediatric population with epileptic disorders and/or seizures, phenobarbital currently has been replaced by other anticonvulsant drugs such as carbamazepine or phenytoin as first choice drugs.
On the other hand, although it is considered an effective drug for epilepsy, Its use is not recommended for anxiety disorders since its effect is too powerful (in fact, barbiturates have been widely used to commit suicidal acts).
Regarding clinical research with phenobarbital, there are really few rigorous studies that have studied (and/or demonstrated) its efficacy or toxicity.
Side effects
Phenobarbital, like other barbiturates, can produce a number of important adverse effects especially those related to behavioral excitement and hyperactivity (especially in young children).
On the other hand, it can also alter cognitive functions (especially those related to intelligence), especially if the drug is taken for a long time (even at low doses).
Other adverse effects of phenobarbital include gastrointestinal upset, megaloblastic anemia (not enough cells in the bone marrow), and jaundice (increased bilirubin in the blood).
Regarding prenatal exposure to phenobarbital in neonates, it has been seen how the drug can cause certain reproductive dysfunctions, such as irregular menstrual cycles in women, decreased fertility and a delay in the onset of puberty.
