Barbiturates are considered the first anti-anxiety drugs 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 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 know 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 properties (induces sleepiness and drowsiness), sedatives and anticonvulsants or antiepileptics (used to treat seizures and epilepsy). It may have two trade names: Gardenal and Luminal.
More specifically, phenobarbital is a long-acting barbiturate . This means that it is progressively released and distributed in the body, slowly. On the other hand, the onset of action of phenobarbital is slow.
Its action consists of inhibiting the crises produced by epileptic attacks, electroshock or pentylenetrazol (Central Nervous System stimulating drug). On a chemical level, phenobarbital is a metabolite of mephobarbital (also barbiturate) and primidone (anticonvulsant).
Mechanism of action
The mechanism of action of phenobarbital is focused on GABA; let us remember that GABA is the main neurotransmitter depressant and inhibitor of 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, it opens the chlorine (Cl-) channels of the GABA A receptor; the barbiturates have the property of increasing the probabilities of opening these channels, as well as the time they remain open. This mechanism is the same as that used by primidone, another anticonvulsant drug.
On the other hand, it is not known how phenobarbital acts exactly, 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 (anti-anxiety), carbamazepine (anticonvulsant and mood stabilizer) and primidone (anticonvulsant), have the ability to block the trains of recurrent high frequency action potentials (PA) , which are generated in the neuron suffering from epilepsy.
Action on glutamate
Another action of phenobarbital is to reduce the excitation produced by glutamate (the 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 phenobarbital what it does is act on non-MMDA receptors, binding to them.
Thus, it may be that non-MDA (excitatory amino acid) receptors, or even AMPA (glutamate receptors), are related to epileptic disorders (epilepsy).
The absorption of a drug indicates when it has entered the bloodstream . In the case of phenobarbital, this occurs rapidly and completely.
3. Other properties
Phenobarbital is a highly effective, safe and economical drug. It can be used in both children and adults; however, in the pediatric population care must be taken because 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, generally only one dose per day is prescribed; this is due to the long half-life of phenobarbital. 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 that its effects last longer.
Phenobarbital has three main indications: epilepsy, seizures (and their prevention) and severe insomnia disorder.
Phenobarbital is used in cases of epilepsy, specifically to relieve generalized seizures and epileptic states . The seizures that it relieves are especially of the generalised tonic-clonic type (affecting the whole brain); these involve symptoms such as stiffness of the body, repeated tugging on the arms and/or legs, and loss of consciousness.
For other types of seizures, phenobarbital is also effective but not as much. These are partial, myoclonic, and akinetic seizures. Specifically, partial or focal seizures occur when the electrical activity of the brain is limited to a particular area of the brain; myoclonic seizures are characterized by a very rapid and sudden jerking of the extremities, and akinetic seizures are characterized by loss of muscle tone and possible falling.
Seizures, typical in epilepsy, are repeated shaky contractions and distensions in one or more muscles of the body. They appear suddenly and violently as a consequence of a sudden increase in the electrical activity of the brain , which is also 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 leads to difficulties in initiating sleep (baseline insomnia), in keeping sleep to a minimum (maintenance insomnia), or in sleeping through the night (early awakening) (terminal insomnia).
In these cases, this barbiturate is used as a short term treatment (in fact, it is not recommended to use it as a long term treatment, as it can lose its effectiveness, after 2 or 3 weeks of starting it).
An interesting fact is that in the paediatric population with epileptic disorders and/or seizures, phenobarbital has now 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 for anxiety disorders is discouraged, as its effect is too strong (in fact, barbiturates have been widely used to commit suicidal acts).
As for clinical research with phenobarbital, there are really few rigorous studies that have studied (and/or demonstrated) its efficacy or toxicity.
Phenobarbital, like other barbiturates, can produce a number of important adverse effects , especially those related to behavioral arousal 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 distress, megaloblastic anemia (bone marrow cell failure), 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 manifestation of puberty.
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- Vademecum. (2016). Phenobarbital.
- Valsecia, M. and Malgor, L. (2012). Anticonvulsant or antiepileptic drugs. Medical Pharmacology, Chapter 4, 5: 37-58.