Generality
Phenobarbital is a sedative and anticonvulsant drug belonging to the class of barbiturates.
Phenobarbital - Chemical Structure
It is probably best known under the trade names Gardenale® or Luminale®, but equivalent medicines are also available.
Indications
For what it uses
The use of phenobarbital - orally or intramuscularly - is indicated in the following cases:
- As a general sedative, especially in epilepsy and in conditions requiring long-lasting sedation;
- In the treatment of tonic-clonic seizures of the great evil;
- In the treatment of focal cortical convulsions;
- In the detoxification of chronic barbiturismo.
Intravenous phenobarbital, on the other hand, is used as a second-line treatment of the status epilepticus, in cases where oral administration is not possible and in patients who have not responded adequately to benzodiazepine or phenytoin therapy.
Warnings
Phenobarbital can be addictive.
A lot of caution should be used when administering the drug in patients with hepatic and / or renal insufficiency, in elderly patients or in patients with alcoholism.
Abrupt discontinuation of phenobarbital therapy in patients with epilepsy may cause a status epilepticus.
Since cases of suicidal ideation and behavior have been reported during treatment with phenobarbital, patients should be monitored to be able to promptly identify the onset of such symptoms.
Phenobarbital can cause serious skin reactions that can even have fatal outcomes. Therefore, caution should be used and - if skin symptoms appear - it is necessary to immediately inform the doctor.
Phenobarbital is able to alter the ability to drive and use machines, therefore these activities must be avoided.
Interactions
Phenobarbital can decrease the contraceptive power of progestins and estroprogestinics .
Alcohol potentiates the sedative effect of phenobarbital, so this association must be avoided.
The efficacy of phenobarbital may be decreased by concomitant intake of St. John's wort preparations ( St. John's wort).
Phenobarbital can reduce plasma concentration and - consequently - the therapeutic efficacy of cyclosporine (a drug with an immunosuppressive action used to prevent rejection in transplants).
Phenobarbital may decrease the therapeutic efficacy of glucocorticoids, mineralocorticoids, digitoxin and oral anticoagulants .
Phenobarbital can decrease the plasma concentration of doxycycline (an antibiotic), quinidine, hydroquinidine, disopyramide (antiarrhythmic drugs), theophylline and β-blockers (such as, for example, alprenolol, metoprolol and propranolol ).
Concomitant administration of phenobarbital and folic acid may cause a reduction in the plasma concentration of phenobarbital itself.
Phenobarbital plasma concentration may be increased by concomitant administration of valproic acid or progabid (drugs used in the treatment of epilepsy).
The depressant effect on the central nervous system induced by phenobarbital can be increased by the concomitant administration of drugs, such as:
- Antidepressants (except selective MAOIs-A);
- H1 histamine receptor antagonists;
- Benzodiazepines;
- Clonidine;
- Hypnotic sedative drugs;
- Morphine derivatives.
Side effects
Phenobarbital can induce various types of side effects, although not all patients experience them. This depends on the different sensitivity that each individual has towards the drug.
Below are the main side effects that may occur during treatment with phenobarbital.
Skin and subcutaneous tissue disorders
Treatment with phenobarbital can cause hives, angioedema, morbilliform eruptions, pemphigus vulgaris and very serious skin reactions that can also have fatal outcomes, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
Gastrointestinal disorders
Phenobarbital therapy can cause nausea and vomiting.
Hepatobiliary disorders
Phenobarbital treatment can cause toxic hepatitis.
Lung and respiratory tract disorders
Phenobarbital therapy can cause apnea, respiratory depression, laryngospasm and cough.
Cardiovascular disorders
Phenobarbital treatment can cause hypotension, shock, vasculitis and thrombophlebitis.
Metabolism and nutrition disorders
During phenobarbital therapy, changes in lipid levels, hypocelcemia (decreased blood calcium concentration) and acute intermittent porphyria may occur.
Blood and lymphatic system disorders
Treatment with phenobarbital can create disorders in the system responsible for the synthesis of blood cells. These disorders can lead to thrombocytopenia (reduction in the number of platelets in the bloodstream) with consequent coagulation disorders, leukopenia (decrease in the number of white blood cells in the blood) and anemia (decrease in the amount of hemoglobin in the blood).
Nervous system disorders
Phenobarbital therapy may cause:
- Drowsiness;
- Lethargy;
- Confusion, especially in elderly patients;
- Headache;
- Dizziness;
- Excitement;
- agitation;
- Hyperactivity, especially in pediatric patients;
- Delusions;
- Ataxia;
- Dysarthria;
- Depression;
- Cognitive disorders and deficits.
Musculoskeletal and connective tissue disorders
Phenobarbital treatment can cause:
- Dupuytren's disease;
- La Peyronie's disease;
- Decreased bone mineral density;
- Osteopenia;
- Osteoporosis;
- Shoulder pain.
Renal and urinary tract disorders
Phenobarbital therapy can cause nephropathy, interstitial nephritis and oliguria.
Other side effects
Other adverse effects that may occur during phenobarbital therapy are:
- Hypersensitivity syndrome to anticonvulsants;
- Miosis (pupil constriction);
- Mydriasis (dilation of the pupil);
- nystagmus;
- Optic neuropathy;
- Genetic mutations.
Overdose
The symptoms that may appear immediately after taking an overdose of phenobarbital are:
- Headache;
- Nausea;
- He retched;
- lightheadedness;
- Confusion;
- Comatose state accompanied by irregular bradipnea, trecheobronchial obstruction and arterial hypotension.
In case of intoxication it is necessary to immediately perform a gastric lavage, as long as the patient's condition allows it.
The elimination of already absorbed phenobarbital can be carried out by forced diuresis or urine alkalinization.
In severe cases, hemodialysis may be useful.
In addition, antibiotic drugs can be administered to avoid the onset of any pulmonary complications.
In any case, if you suspect you have taken an overdose of medication, you must contact a doctor immediately and contact the nearest hospital.
Action mechanism
Phenobarbital increases the signal of γ-aminobutyric acid (or GABA).
GABA is the main inhibitory neurotransmitter of the brain and performs its functions by binding to its receptors: GABA-A, GABA-B and GABA-C.
More precisely, phenobarbital binds to a particular binding site present on the GABA-A receptor, the site for picrotoxin.
By binding to the receptor, phenobarbital activates it and promotes the initiation of a cascade of inhibitory signals, with a consequent increase in GABAergic inhibitory transmission.
Mode of Use - Posology
Phenobarbital is available for oral administration (in tablet form) and for intramuscular and intravenous administration.
Oral administration
When administered orally as an anticonvulsant, the dose of phenobarbital usually used in adults is 100-300 mg a day.
When used as a sedative, the usual dose of medication is 50-100 mg a day.
The usual dose of phenobarbital used in children is 20-100 mg and varies according to age and body weight.
Intramuscular administration
The dose of phenobarbital usually administered, in adults and adolescents (15 to 18 years), is 200-400 mg a day.
In children aged 1 to 12 and in adolescents up to 15 years, the usual dose is 10 mg per year of age.
In patients with renal and / or hepatic impairment and in elderly patients, a reduction in the dose of phenobarbital usually administered may be necessary.
Intravenous administration
Intravenous administration of phenobarbital should only be performed in emergency situations for the treatment of an acute convulsive state and only in patients who do not respond to benzodiazepine or phenytoin therapy.
In these cases, the dose of phenobarbital usually administered, in adults and children, is 10 mg / kg of body weight per day.
Pregnancy and breastfeeding
Phenobarbital can cause harm to the fetus, therefore the drug should not be used during pregnancy, unless the doctor considers it absolutely essential.
Phenobarbital is excreted in breast milk, therefore breast-feeding mothers should not take the drug.
Contraindications
The use of phenobarbital is contraindicated in the following cases:
- Known phenobarbital hypersensitivity;
- In patients with porphyria;
- In patients with severe hepatic and / or renal insufficiency;
- In patients with respiratory diseases;
- In patients with severe heart disease;
- In patients with acute alcohol intoxication, analgesic drugs or hypnotic sedatives;
- In pregnancy and during lactation.
Furthermore - when given intravenously - phenobarbital is contraindicated in patients who have recently taken other drugs containing phenobarbital or primidone (an anti-epileptic drug).
