Phenobarbital

Phenobarbital is included in the category of hypnotics and anticonvulsants.

[1], [2], [3], [4], [5], [6], [7], [8]

Indications Phenobarbital

It is used for the treatment of tetanus, epilepsy, HDN, as well as the need for immediate elimination of acute seizures and for therapy with hyperbilirubinemia (sometimes used to prevent it).

Along with this, the medication can be prescribed as a sedative (for example, as part of a comprehensive treatment) in order to ease the sense of fear, anxiety and tension.

[9]

Release form

The release of the drug is realized in the form of a 0.2% solution or tablets, and in addition it can be produced as a lyophilizate.

[10], [11], [12], [13]

Pharmacodynamics

Phenobarbital is a barbiturate with a long type of exposure. The medication has a sedative, anticonvulsant and hypnotic effect.

In addition, it enhances the sensitivity of GABA endings to the mediator, prolongs the period of opening the nerve channels through which the currents of chloride ions pass, and helps them move inside the cells. As a result, the hyperpolarization of the cell walls begins, which leads to a weakening of their activity. Further, there is an increase in the slowing effect of GABA and inhibition of interneuronal transport within the NS.

When used in medicinal portions, the drug increases GABAergic transport and interferes with the processes of glutamatergic neurotransmission. At high concentrations, the medicated element prevents the flow of calcium ions through the cell walls.

Phenobarbital has an overwhelming effect on HC. It weakens the excitability of the motor centers of the cerebral subcortex and crust, reduces motor activity and promotes the development of sedative effect with the subsequent falling asleep of the patient.

The drug can be used to stop a variety of etiologies of seizures. An anticonvulsant influence develops as a result of oppression of the activity of glutamate, activation of the functions of the GABAergic system, and in addition to this effect of drugs in relation to the potential-dependent Na channels. Also, the level of excitability of neurons located on the epileptogenic site decreases and the development and movement of impulses is blocked. The drug slows down the high frequency of repeated neuronal discharges.

Used in small portions of Phenobarbital has a soothing effect. In this case, its large dosages can cause suppression of the activity of the centers of the medulla oblongata. At the same time, it suppresses the work of the respiratory center and reduces its sensitivity to CO2, while also reducing the volume of respiration.

[14], [15], [16], [17], [18], [19], [20],

Pharmacokinetics

The substance absorbed orally is completely absorbed inside the small intestine. Peak values are noted after 60-120 minutes. The level of bioavailability is 80%. Approximately half of a single dosage of drugs is synthesized with an intraplasma protein (20-45%).

The medicinal element in uniform amounts is distributed inside the tissues with organs; a small part of it is also noted inside the brain tissue. The plasma half-life of the component is 2-4 days (adult person). The substance penetrates the placenta and is capable of being distributed within all the tissues of the fetus; excreted with breast milk.

Excretion of the drug from the body proceeds slowly. Splitting occurs with the help of microsomal hepatic enzymes. During these processes, inactive metabolic products are formed. Derivation in the form of glucuronide occurs through the kidneys. Approximately 25-50% of the LS is excreted unchanged.

In case of problems with renal activity, there is a significant prolongation of the action of the drug.

[21], [22], [23], [24], [25], [26], [27]

Dosing and administration

For young children (up to 7 years old), use 0.2% solution for 30-40 minutes before bedtime. It is also possible to use the scheme with drug administration twice a day (before bedtime and overnight). Use Phenobarbital is allowed without binding to meals.

1 teaspoon contains about 10 mg of medicinal substance; 1 dessert - about 20 mg; 1 dining room - about 30 mg.

Dimensions of maximum permissible single portions:

• infants up to 6 months of age - 0,005 g of the drug;
• children aged 0.5-1 year - receiving 0.01 g of drugs;
• children 2 years of age - use of 0.02 g of medicament;
• children of the age category of 3-4 years - use of 0.03 g of medication;
• children from the group of 5-6 years - receiving 0.04 g of Phenobarbital;
• children age 7-9 years - 0.05 g of substance;
• children age 10-14 years - the use of 0.075 g of drugs.

To provide spasmolytic and sedative effects, it is required to take the drug 2-3 times per day.

The sizes of single portions for an adult are selected individually by the treating doctor. The medication is taken 1-3 times a day, and the dose is usually in the range of 10-200 mg. You need to take tablets inside.

If the drug is taken as a sleeping pill, you should use it before bedtime at a rate of 100-200 mg. If an anticonvulsant effect is required, 50-100 mg (twice) are taken per day. To provide sedative effect, it is required to take a dosage of 30-50 mg LS 2-3 times a day. To cause spasmolytic effects, you need 10-50 mg of medication per day (2-3 times).

For iv injection of a single dose of LS (adult), 0.1-0.14 g of substance is required, and for an im injection of 0.01-02 g. Children are required to be injected intravenously at 1-20 mg / kg, and intramuscularly - 1-10 mg / kg of the drug. Multiplicity of procedures is selected by the treating doctor, for each of the patients separately. With IV injection, it takes at least 30 minutes for the medicine to act.

The size of the maximum permissible single dose for an adult is 0.2 g. For a day, a maximum of 0.5 g of the drug can be administered in total.

Approximately after the expiration of 14 days of use, the drug usually begins to become addictive. Psychic or physical dependence on a drug may develop. There is also a withdrawal syndrome.

[33], [34], [35], [36]

Use Phenobarbital during pregnancy

Can not be appointed on the 1st trimester.

With the use of a pregnant medication in the 3rd trimester, a newborn can experience physical dependence on it, as well as withdrawal syndrome (perhaps even in an acute form), whose symptoms are epileptic seizures and increased excitability, immediately after birth or during the first few weeks life.

In the case of taking drugs during childbirth, sometimes the respiratory function of the baby begins to be suppressed, especially if it was born prematurely.

When using a medication as an anticonvulsant in pregnancy, the baby may have bleeding in the early days of his life.

Contraindications

The main contraindications:

• porphyria, which has a mixed, acute or intermittent form (also in the presence of this disease in the anamnesis);
• myasthenia gravis;
• disorders affecting the functioning of the kidneys or liver, and having a severe form;
• drug or alcohol dependence;
• the presence of intolerance with respect to the drug;
• lactation.

[28], [29], [30], [31]

Side effects Phenobarbital

Development of negative signs is usually noted with prolonged use of the drug. Among these, often allergy symptoms, suppression of the central nervous system and a significant decrease in blood pressure.

In addition, thrombocytopenia, agranulocytosis, a calcium metabolism disorder, headaches and vascular collapse may occur.

Among the possible reactions are also nausea, osteomalacia, constipation, bradycardia, megaloblastic form of anemia and vomiting.

Also recorded is hypocalcemia, a lack of folate, a disorder of libido and impotence.

[32]

Overdose

When the drug is intoxicated, signs of a disorder may not manifest itself during the next few hours. An adult can have severe poisoning if he takes orally 1000 mg LS. If you take it in a dose of 2-10 g, this will lead to the death of the patient.

When acute intoxication develops a sense of excitement or strong confusion of consciousness, and in addition, ataxia, oliguria, cyanosis. In addition, there are headaches, blood pressure decreases, strange eye movements, hypothermia, a feeling of severe drowsiness and weakness, dizziness and blurred speech. Also develops tachycardia, coma and periodic breathing. Along with this, suppression of respiratory function, constriction of the pupils and nystagmus, hemorrhage (on the areas of pressure) may occur, the pulse may be weakened, and the reflex reactions may decrease or disappear altogether.

In severe forms of poisoning, apnea, pulmonary edema, vascular collapse (with a decrease in the tone of vessels of the peripheral type), stopping of cardiac and respiratory activity and death are noted.

With the use of drugs in a dose that threatens life, depression of electrical brain activity may occur, but it should not be considered a clinical death, because this effect is completely reversible (provided there is no damage caused by hypoxia).

With a chronic overdose of medication, insomnia, a feeling of apathy, dizziness, constant irritability, deterioration of mental activity and a sense of confusion are noted. In addition, there is drowsiness, a feeling of general weakness, speech confusion and problems with maintaining balance. However, convulsions with hallucinations, severe agitation and upset of renal activity or gastrointestinal function with CVS may occur.

Intoxication can provoke heart failure in stagnant form, pneumonia, renal failure, and arrhythmia.

When acute poisoning is required to accelerate the process of excretion of the active component of drugs and support the work of life-important systems of the body.

To weaken the absorption of the drug, you can induce vomiting, and then give the affected activated carbon. In addition, procedures are performed to prevent aspiration of vomit. If it is impossible to induce vomiting, a gastric lavage is performed.

To increase the rate of excretion of Phenobarbital, the use of alkaline solutions and laxative salt types is prescribed, as well as conducting forced diuresis.

Together with this, it is necessary to control the work of important for the organism systems and maintain the water balance.

Possible support procedures include:

• maintenance of stable values of blood pressure;
• ensuring free air penetration into respiratory ducts;
• if necessary - anti-shock measures;
• reception of antibiotics (if there is a suspicion of pneumonia);
• oxygen supply and use of ventilation;
• use of vasoconstrictors (if there is a decrease in blood pressure);
• prevention of aspiration, congestive pneumonia, pressure sores and other complications.

It is recommended to abandon the use of analeptics, as well as to prevent overloading of the body with sodium or liquid.

At a severe degree of poisoning, anuria or a shock state, hemodialysis or peritoneal dialysis sessions are performed. At the same time, it is necessary to monitor blood levels of drugs.

When treating poisoning in a chronic form, it is necessary to gradually reduce the dosage until it is completely eliminated. Symptomatic procedures are also performed. Sometimes you may need a psychotherapy session.

[37], [38], [39], [40]

Interactions with other drugs

When combined with drugs that suppress the work of HC, and in addition with drugs containing ethyl alcohol, and actually ethanol itself, it is possible to increase the inhibitory effect on the CNS.

Weakening of the hypnotic effect of the drug is noted when taken with caffeine.

Combination with MAOI and methylphenidate leads to an increase in the plasma parameters of phenobarbital, so its toxicity and inhibitory effect on HC are also enhanced.

Reduction in the effectiveness and duration of exposure to such drugs is noted when used with phenobarbital: chloramphenicol, carbamazepine with GCS, and in addition dacarbazine with anticonvulsants from the category succinimides, metronidazole with doxycycline and corticotropin. This list also includes anticoagulants (coumarin derivatives with indanedione), cyclosporine with chlorpromazine, quinidine, calciferol with tricyclics, digitalis glycosides, phenylbutazone, oral contraceptives containing estrogen, and in addition xanthines and phenoprofen.

When combined with the substance acetazolamide, rickets or osteomalacia may develop.

The use of valproic acid causes an increase in the values of drugs inside the plasma, which can provoke a strong sedative effect and a state of lethargy. The plasma index of valproic acid decreases slightly.

Combination with nimodipine, verapamil, and in addition felodipine reduces the values of these agents inside the plasma.

Simultaneous use with enflurane, halothane, and also ftorotan or methoxyflurane can lead to potentiation of the metabolism of the agents used for anesthesia. As a result, the risk of toxic effects on the liver (and kidneys if methoxyflurane is used) increases.

Combination with griseofulvin reduces the degree of intestinal absorption.

Application together with large portions of maprotiline leads to a decrease in the convulsive threshold and anticonvulsant effects of barbiturates.

Combination with the drug causes a decrease in the effectiveness of paracetamol. Hepatotoxicity may occur.

Admission per day 0.2 g of pyridoxine reduces the plasma index of phenobarbital. Simultaneous use with felbamate or primidonom on the contrary increases.

With a deficiency of folic acid, administration of drugs with its content causes a weakening of the effect of the drug.

Combination with other sedative drugs can cause intense suppression of respiratory processes.

[41], [42], [43], [44], [45]

Storage conditions

Phenobarbital is required to be kept out of the reach of children, under normal conditions for any medication.

[46], [47], [48], [49], [50]

Shelf life

Phenobarbital is allowed to be used within 5 years from the date of its release.

[51], [52], [53]

Application for children

Prescribe the drug to newborns is allowed exclusively for the treatment of HDN. Phenobarbital increases the detoxification activity of the liver and reduces serum bilirubin.

[54], [55], [56], [57],

Reviews

Phenobarbital is often used in a variety of poisoning, because it increases the detoxification of liver activity. However, many reviews indicate that the drug has a good sedative effect (often in combination with other drugs) and works well in the treatment of neurovegetative disorders.

Of the shortcomings of drugs, it is noted that it causes some negative manifestations. Children or weakened adults often develop strong arousal. Along with this, there is information about the appearance of asthenia, vomiting, dizziness, constipation, a feeling of general weakness and nausea. Occasionally they talk about ataxia, depressive state, allergies, fainting, hallucinations and hemolytic disorders. Some people who took the medicine for a long period, noted the appearance of rickets.