Phenobarbital: uses and side effects of this drug.

An anxiolytic drug of the barbiturate group used in cases of epilepsy.

Barbiturates are considered to be the first anxiolytics to appear on the market. They are derived from barbituric acid, and have sedative and hypnotic properties, mainly, but also anticonvulsant. One of them is phenobarbital, especially used in epilepsy..

This barbiturate has been one of the most widely used in medicine and psychiatry, and, although it was originally used as an anxiolytic, it is currently indicated to treat cases of epilepsy, convulsions and severe insomnia. In this article we will learn about its general characteristics, mechanism of action, indications and adverse effects.

Phenobarbital: general characteristics

Phenobarbital is a drug belonging to the first group of anxiolytics to be discovered.. It is a barbiturate with hypnotic (inducing drowsiness and sleep), sedative and Anticonvulsant or antiepileptic (used to treat seizures and epilepsy) properties. It may have two trade names: Gardenal and Luminal.

More specifically, phenobarbital is a long-acting barbiturate, a a long-acting barbiturate. This means that it is released and distributed progressively and slowly in the body. On the other hand, the onset of action of phenobarbital is slow.

Its action consists of to inhibit seizures produced by epileptic seizures, electroshock or pentylenetetrazol (Central Nervous System stimulant drug). On a chemical level, phenobarbital is a metabolite of mephobarbital (also a barbiturate) and primidone (anticonvulsant).

Mechanism of action

The mechanism of action of phenobarbital is centered on GABA; let's remember that GABA is the main depressant and inhibitory neurotransmitter in the brain.. Thus, phenobarbital is based on facilitating GABA-mediated inhibition of synaptic transmission, i.e., it enhances the inhibitory action of GABA.

Specifically, what it does is to open the chloride (Cl-) channels of the GABA A receptor; barbiturates have the property of increasing the probability of opening these channels, as well as the time they remain open. This mechanism is the same used by primidone, another anticonvulsant drug.

On the other hand, it is not known exactly how phenobarbital acts, but it is known that it also exerts some kind of action on K+ (potassium) channels.

Phenobarbital, along with other drugs such as valproic acid (antiepileptic and mood stabilizer), benzodiazepines (anxiolytic), carbamazepine (anticonvulsant and mood stabilizer) and primidone (anticonvulsant), has the ability to block trains of recurrent high-frequency action potentials (APs), which are generated in the neuron.generated in the epileptic neuron.

Action on glutamate

Another action exerted by phenobarbital is to to reduce the excitation produced by glutamate (main stimulating amino acid of the brain).

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 phenobarbital acts on non-NMDA receptors, binding to 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 the drug has entered the bloodstream.. In the case of phenobarbital, this occurs rapidly and completely.

3. Other properties

Phenobarbital is a highly effective, safe and inexpensive drug. It can be used in both children and adults; however, in the pediatric population, caution should be exercised because it it frequently causes alterations in cognitive functions, behavioral problems, and excitation of the brain.It can be used in both children and adults; however, caution should be exercised in the pediatric population because it frequently causes alterations in cognitive functions, behavioral problems and excitation of the Central Nervous System (CNS) (called "paradoxical excitation").

As for its intake and dosage, it is generally prescribed once a day; this is due to the long half-life of phenobarbital. Recall that the half-life of a drug is the time it takes for the body to eliminate 50% of the drug. The long half-life of phenobarbital means that its effects last longer.

Indications

Phenobarbital has three main indications: epilepsy, seizures (and their prevention) and severe insomnia disorder.

1. Eplepsia

Phenobarbital is used in cases of epilepsy, specifically to relieve generalized seizures and status epilepticus.. The seizures it especially relieves are of the generalized tonic-clonic type (involving the whole brain); these involve symptoms such as stiffness of the body, jerking of the arms and/or legs that recur, and loss of consciousness.

For another type of seizures, phenobarbital is also effective but not as effective. These are partial, myoclonic and akinetic seizures. Specifically, partial or focal seizures occur when the electrical activity of the brain is limited to a specific area of the brain; myoclonic seizures are characterized by an abrupt and very rapid jerking of the limbs, and akinetic seizures are characterized by 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 consequence of a sudden increase of the electrical activity of the brain.This activity being, in addition, abnormal.

Phenobarbital is indicated to prevent these convulsions (prophylaxis) and to alleviate them (treatment).

3. Severe insomnia

Phenobarbital is also used in cases of severe insomnia disorder. Insomnia is a sleep disorder that involves difficulties in initiating sleep (onset insomnia), maintaining sleep for a minimum amount of time (maintenance insomnia) or sleeping until the end of the night (early awakening) (terminal insomnia).

In these cases, this barbiturate is used as a short-term treatment (in fact, it is not advisable to use it as a long-term treatment, as it can lose its effectiveness 2 or 3 weeks after the beginning of the treatment).

Efficacy

An interesting fact to know is that in the pediatric population with epileptic disorders and/or convulsive seizures, phenobarbital has been replaced by other anticonvulsant drugs such as carbamazepine or phenytoin as drugs of first choice.as drugs of first choice.

On the other hand, although it is considered an effective drug for epilepsy, its use for anxiety disorders is discouraged.The effect is too potent (in fact, barbiturates have been widely used to commit suicidal acts).

As for clinical research with phenobarbital, few rigorous studies have actually studied (and/or demonstrated) the efficacy or toxicity of phenobarbital.

Side effects

Phenobarbital, like other barbiturates, can produce a number of important adverse effectsespecially those related to behavioral excitation 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 (failure of cells in the bone marrow) and jaundice (increased bilirubin in the blood).

With regard to prenatal exposure to phenobarbital in neonates, it has been shown that the drug can cause certain reproductive dysfunctions, such as irregular menstrual cycles in females, decreased fertility and a delay in the onset of puberty.