Phenobarbital - instructions for use, dose, side effects, contraindications

An antiepileptic agent interacts with the barbiturate GABA site_A- benzodiazepine-barbiturate receptor complex and increases the sensitivity of GABA-receptors to the mediator gamma-aminobutyric acid (GABA),as a result, the duration of the neuronal canal opening time for incoming chlorine ion currents increases and the intake of chloride ions into the cell increases. An increase in the content of chloride ions inside the neuron entails hyperpolarization of the cell membrane and lowers its excitability. As a result, the inhibitory effect of GABA and the inhibition of interneuronal transmission in different parts of the central nervous system are increased. It was shown that at therapeutic concentrations phenobarbital enhances GABAergic transmission, inhibits glutamatergic neurotransmission, especially mediated by glutamate alpha-amino-5-methylisoxazole-4-propionate (AMPA) -receptors. In high concentrations affects the current of sodium ions and blocks the current of calcium ions through the cell membranes (channels of L and N types).

Anticonvulsant action is caused by activation of the GABAergic system, influence on the potential-dependent sodium channels, and also by suppression of the activity of glutamate, etc. Phenobarbital reduces the excitability of neurons in the epileptogenic focus and prevents the appearance and propagation of impulses. It blocks high-frequency repeated discharges of neurons (due to the effect on the ion currentsodium). Barbiturates also increase the threshold of electrical stimulation of the motor cortex of the cerebral cortex. Barbiturate long-acting.

Has a hypnotic, spasmolytic and miorelaksiruyuschee effect. In small doses has a sedative effect. The sedative-hypnotic effect is due mainly to the inhibition of the activity of the cells of the ascending activating reticular formation of the brain stem, thalamus nuclei, inhibition of the interaction of these structures with the cortex of the brain.

Causes a dose-dependent respiratory depression. Has a direct inhibitory effect on the respiratory center (reduces sensitivity to carbon dioxide), lowers the tone of the smooth muscles of the gastrointestinal tract. In hypnotic doses to a small extent reduces the intensity of metabolism in humans. Slightly decreases body temperature due to a decrease in activity and inhibition of the central mechanisms of thermoregulation.

In conventional hypnotic doses, it has no significant effect on the cardiovascular system. In high doses lowers blood pressure (except, central action - depression of the vasomotor center, the effect is mediated by the effect on the heart, ganglia, and also is associated with direct myotropic vasodilating action).It has no direct damaging effect on the kidneys, but with acute poisoning, it is possible to develop oliguria or anuria, largely as a result of marked arterial hypotension.

The antihyperbilirubinemic effect is presumably due to the induction of UDP-glucuronyltransferase, which regulates the conjugation of bilirubin, which leads to a decrease in the concentration of free bilirubin in the serum.

Like other barbiturates, it promotes the induction of microsomal liver enzymes, thereby enhancing or altering the metabolism of other drugs.

Interacting with membranes and changing their physicochemical properties, reduces the excitability of neurons in the epileptogenic focus and the spread of nerve impulses. It shows antagonism against a number of excitatory mediators (glutamate, etc.). It suppresses the sensory areas of the cerebral cortex, reduces motor activity, depresses the cerebral functions and leads to dizziness, sedation, drowsiness. The sleep caused by barbiturates differs in structure from physiological, the phase of rapid (paradoxical) sleep is shortened and stages 3 and 4 of slow sleep decrease.Sleeping effect develops within 0.5-1 hour (less often - later), lasts 6-8 hours (up to 12 hours) and decreases after 2 weeks of admission.

A sharp discontinuation may lead to the development of the "withdrawal" syndrome (headaches, nightmares, drowsiness and / or insomnia).

Pharmacokinetics:

When ingestion is absorbed completely, slowly. The time of maximum plasma concentration is 1-2 hours, the connection with plasma proteins is 50%, in newborns 30-40%.

Metabolized in the liver, induces microsomal liver enzymes CYP_3A4, FROMYR_3A5 and CYR_3A7 (the rate of enzymatic reactions increases 10-12 times).

Cumulates. The elimination half-life is 3-4 days. It is excreted by the kidneys in the form of inactive metabolites, 25-50% - unchanged.

It penetrates well through the placenta.

Indications:

Epilepsy (all types of seizures except for absences), seizures of non-epileptic genesis, chorea, spastic paralysis, sleep disturbances, psychomotor agitation, anxiety, fear.

Contraindications:

Hypersensitivity, severe liver and / or kidney disease, acute intermittent or mixed porphyria (including anamnesis), respiratory diseases accompanied by shortness of breath or airway obstruction, myasthenia gravis, alcoholism,drug or drug dependence, sugar / isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption, hepatic and / or renal insufficiency, children under 18 years of age (for this dosage form).

Carefully:

Depression and / or suicidal tendencies, anemia, chronic obstructive pulmonary disease, bronchospasm (including in anamnesis), asthmatic status, dyspnea, diabetes mellitus, drug dependence, hyperkinesia, thyrotoxicosis, adrenal hypofunction (including borderline conditions), acute and / or chronic pain syndrome, impaired liver and / or kidney function; weakened patients.

Pregnancy and lactation:

Contraindicated in the first trimester of pregnancy (teratogenic effect is possible). Application during pregnancy is possible only on strict indications, if other means are not possible.

The results of retrospective controlled studies have shown that taking barbiturates by pregnant women. is the cause of an increase in the frequency of abnormalities of the fetus.

In newborns, whose mothers were taking phenobarbital in the third trimester, pregnancy, the development of physical dependence and the "withdrawal" syndrome is possible (there are reports of the development of an acute "withdrawal" syndrome manifested in epileptic seizures and excessive excitability immediately after birth or within 14 days in newborns exposed to prolonged intrauterine exposure to barbiturates) .

There is evidence that the use of phenobarbital as an anticonvulsant during pregnancy leads to a violation of blood clotting (associated with vitamin K deficiency) in newborns, which can cause bleeding in the neonatal period (usually the first day after childbirth).

Use during labor can cause respiratory depression in a newborn, especially premature (in connection with the underdevelopment of liver function).

For the duration of treatment, breastfeeding should stop (penetrates into breast milk and may cause CNS depression in infants).

Phenobarbital, being an inducer of microsomal oxidation enzymes in the liver, increases its detoxification function, reduces the concentration of bilirubin in the serum. This property makes it expedient to use phenobarbital in hemolytic disease of newborns.

Dosing and Administration:

Inside.The dosage regimen is set strictly individually depending on the indications, the course of the disease, tolerability, age, etc. Treatment should be started with the lowest effective dose corresponding to a particular form of pathology.

In patients with impaired liver and / or kidney function, elderly and weakened patients, treatment should begin with smaller doses.

Epilepsy (all types of seizures except for absences), seizures of non-epileptic genesis, spastic paralysis, chorea - 50-100 mg 2 times a day.

Psychomotor agitation, anxiety, fear - 30-50 mg 2-3 times a day.

Sleep Disorders - 100-200 mg per 0.5-1 hour before bedtime.

The maximum single dose is 200 mg, the maximum daily dose is 500 mg.

Side effects:

From the nervous system and sensory organs: dizziness, weakness, syncope, impaired coordination of movements, agitation, inhibition, irritability, anxiety, headache, hand tremors, drowsiness, lethargy, respiratory center depression, paradoxical reaction (especially in children, elderly and weakened patients - unusual arousal), hallucinations, depression, nightmarish dreams, hyperkinesia (in children), violation of the thinking process, sleep disturbances, the effect of aftereffect (asthenia, feeling of frustration, lethargy, decreased psychomotor reactions and concentration of attention).

From the side of the musculoskeletal system: with prolonged use - violation of osteogenesis, rickets.

From the digestive system: nausea, vomiting, constipation, with prolonged use - a violation of liver function.

From the hematopoiesis: agranulocytosis, megaloblastic anemia, thrombocytopenia.

From the cardiovascular system: lowering of blood pressure, collapse.

Allergic reactions: skin rash, urticaria, puffiness of the eyelids, face and lips, shortness of breath, exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome, toxic epidermal necrolysis), possible fatal outcome.

Other: impaired vision; with long-term use - drug dependence (mental and physical), liver damage (icteric sclera or skin); withdrawal syndrome: minor symptoms (within 8-12 hours after stopping the use of the drug) - anxiety, motor anxiety, muscle twitching, hand trembling, weakness, dizziness, blurred vision, nausea, vomiting, impaired sleep,"nightmarish" dreams, orthostatic hypotension; the main symptoms (within 16 hours and lasts up to 5 days) - convulsions, hallucinations; deficiency of folate; hypocalcemia; osteomalacia; violation of libido; impotence.

Overdose:

Symptoms:

- for acute toxicity (reception 1 g) - nystagmus, ataxia, severe weakness, severe drowsiness, blurred speech, agitation, dizziness, headache, confusion, delay and difficulty in breathing, shortness of breath, decrease or loss of reflexes, increase or decrease in body temperature, oliguria, cyanosis, hemorrhage in the pressure field , confusion, decreased blood pressure, bradycardia or tachy arrhythmia, heart failure development phenomena, pupillary (alternating paralytic extension), reduction of the electrical activity of brain edema l soft, coma, and later - pneumonia; when taking 2-10 g - death;

- for chronic toxicity: irritability, weakening the ability to critically assess their own actions, sleep disorders, confusion.

Treatment: carrying out detoxication therapy, symptomatic treatment, there is no specific antidote, maintenance of vital body functions.

Interaction:

Interaction with other drugs is due, mainly, to the ability of phenobarbital to inhibit cytochrome P450 (mainly isoenzyme CYP3A4).

Reduces antibacterial activity of antibiotics and sulfonamides, antifungal action of griseofulvin (reduces absorption).

Reduces the effectiveness of indirect anticoagulants, glucocorticosteroids, doxycycline, estrogens and other drugs metabolized by microsomal enzymes of the liver.

Sleeping effect is reduced with simultaneous administration of atropine, belladonna extract, dextrose, thiamine, nicotinic acid, analeptics and psychostimulating drugs.

When combined with reserpine, anticonvulsant action decreases, under the influence of amitriptyline, nialamide, diazepam, chlordiazepoxide - is amplified.

Acetazolamide, alkalinizing urine, reduces the reabsorption of phenobarbital in the kidneys and weakens its effect.

Special instructions:

Use with caution in patients who abuse drugs or with history of drug dependence, renal dysfunction, respiratory diseases,accompanied by shortness of breath or airway obstruction, especially with asthmatic status.

The risk of drug dependence increases with the use of large doses and with an increase in the duration of admission in connection with the possibility of its cumulation in the body and the development of addiction. The constant use of barbiturates in doses 3-4 times higher than therapeutic, leads to the development of physical dependence.

Being an inducer of microsomal enzymes of the liver, it increases its detoxification function, reduces the concentration of bilirubin in the blood serum.

Caution should be exercised in weakened patients (high risk of paradoxical arousal, depression and confusion even in normal doses), in patients with acute and / or chronic pain syndrome (paradoxical agitation may occur or important symptoms may masquerade).

With prolonged use, liver damage is possible.

Patients who are hypersensitive to one of the barbiturates may have an increased sensitivity to other barbiturates.

Do not use phenobarbital simultaneously with griseofulvin.With simultaneous application it is necessary to monitor the concentrations of hydantoin derivatives in the blood plasma.

During the treatment period, do not drink alcohol.

Prolonged use often leads to a decrease in mnestic-intellectual functions and depression, and even suicidal thoughts and behavior in patients with epilepsy.

When using phenobarbital for the treatment of epilepsy, monitoring of its concentration in the blood is recommended. With long-term treatment it is necessary to periodically determine the concentration of folate in the blood, control the picture of peripheral blood, functions of the liver and kidneys.

To avoid the development of the "withdrawal" syndrome, discontinuation of treatment should be gradual.

During treatment it is necessary to monitor the function of the liver, kidneys, a general blood test.

Effect on the ability to drive transp. cf. and fur:

Do not use during work drivers of vehicles and people whose activities require a quick mental and physical reaction, and is also associated with increased concentration of attention.

Form release / dosage:

Tablets, 100 mg.

Packaging:

6 or 10 tablets per contour cell package.

1 or 2 contour squares, together with instructions for use, are placed in a pack of cardboard.

Storage conditions:

List III of the List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation. Store in specially equipped premises if there is a license for the specified type of activity. In a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-000850

Date of registration:03.08.2011

The owner of the registration certificate:TATHIMFARMPREPARATY, JSC TATHIMFARMPREPARATY, JSC Russia

Manufacturer: & nbsp

TATHIMFARMPREPARATY, JSC Russia

Representation: & nbspTATHIMFARM PREPARATIONS OJSC TATHIMFARM PREPARATIONS OJSC Russia

Information update date: & nbsp19.09.2015

Illustrated instructions

Instructions

Phenobarbital (Phenobarbitalum)