Phenobarbital

Phenobarbital belongs to the category of sleeping pills and anticonvulsants.

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Indications Phenobarbital

It is used to treat tetanus, epilepsy, HDN, and also when there is a need for immediate elimination of acute convulsive seizures and for the treatment of hyperbilirubinemia (sometimes used to prevent it).

In addition, the medication may be prescribed as a sedative (for example, as part of a combination treatment) to relieve feelings of fear, anxiety and tension.

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Release form

The medicinal product is produced in the form of a 0.2% solution or tablets, and in addition, it can be produced in the form of a lyophilisate.

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Pharmacodynamics

Phenobarbital is a long-acting barbiturate. The drug has a sedative, anticonvulsant, and hypnotic effect.

In addition, it increases the sensitivity of GABA endings to the mediator, prolongs the period of opening of nerve channels through which chloride ion currents pass, and helps them move inside the cells. As a result, hyperpolarization of cell walls begins, which leads to a weakening of their activity. Then, the slowing effect of GABA increases and interneuronal transport inside the NS is inhibited.

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

Phenobarbital has a suppressive effect on the nervous system. It weakens the excitability of the motor centers of the cerebral subcortex and cortex, reduces motor activity and promotes the development of a sedative effect with subsequent patient sleep.

The drug can be used to stop seizures of various etiologies. The anticonvulsant effect develops as a result of inhibition of glutamate activity, activation of the GABAergic system functions, and in addition to this, the effect of the drug on potential-dependent Na channels. It also reduces the excitability of neurons located in the epileptogenic area and blocks the development and movement of impulses. The drug slows down high-frequency repeated neuronal discharges.

Phenobarbital, when used in small doses, has a calming effect. However, large doses of it can cause suppression of the activity of the medulla oblongata centers. At the same time, it suppresses the work of the respiratory center and reduces its sensitivity to CO2, simultaneously reducing the volume of breathing.

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Pharmacokinetics

The substance taken orally is completely absorbed in the small intestine. Peak values are noted after 60-120 minutes. The bioavailability level is 80%. Approximately half of a single dose of the drug is synthesized with intraplasmic protein (20-45%).

The medicinal element is distributed in equal quantities within tissues with organs; a small part of it is also noted within brain tissues. The plasma half-life of the component is 2-4 days (adult). The substance penetrates the placenta and is able to distribute within all tissues of the fetus; it is excreted with mother's milk.

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

In case of problems with kidney function, a significant prolongation of the drug's action is observed.

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Dosing and administration

For small children (up to 7 years old), a 0.2% solution is prescribed 30-40 minutes before bedtime. It is also possible to use a regimen with taking the drug twice a day (before a daytime nap and at night). Phenobarbital can be used without reference to meals.

1 teaspoon contains about 10 mg of the medicinal substance; 1 dessert spoon – about 20 mg; 1 tablespoon – approximately 30 mg.

Maximum single serving sizes:

• infants up to 6 months of age – 0.005 g of the drug;
• children aged 0.5-1 year – intake of 0.01 g of the drug;
• children 2 years of age – use of 0.02 g of medication;
• children aged 3-4 years – use of 0.03 g of the drug;
• children from the 5-6 year old group – taking 0.04 g Phenobarbital;
• children aged 7-9 years – 0.05 g of substance;
• Children aged 10-14 years – consumption of 0.075 g of the drug.

To provide an antispasmodic and sedative effect, the drug must be taken 2-3 times a day.

The sizes of single portions for an adult are selected by the attending physician individually. The medicine is taken 1-3 times a day, and the portion is usually within 10-200 mg. The tablets should be taken orally.

If the medication is taken as a sleeping pill, it should be taken before bedtime in the amount of 100-200 mg. If an anticonvulsant effect is required, 50-100 mg should be taken per day (twice). To provide a sedative effect, it is necessary to take 30-50 mg of the drug 2-3 times a day. To cause an antispasmodic effect, it is necessary to take 10-50 mg of the drug per day (2-3 times).

For intravenous administration of a single dose of the drug (for an adult), 0.1-0.14 g of the substance is required, and for an intramuscular injection - 0.01-02 g. Children need to be administered 1-20 mg / kg intravenously, and 1-10 mg / kg of the drug intramuscularly. The frequency of procedures is selected by the attending physician, for each patient individually. With intravenous injection, at least 30 minutes are required for the drug to begin to act.

The maximum permissible single dose for an adult is 0.2 g. A maximum of 0.5 g of the drug can be administered per day.

After about 14 days of use, the drug usually begins to cause addiction. Mental or physical dependence on the drug may develop. Withdrawal syndrome is also noted.

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Use Phenobarbital during pregnancy

Should not be prescribed in the 1st trimester.

If a pregnant woman takes the drug in the 3rd trimester, the newborn may develop physical dependence on it, as well as withdrawal syndrome (possibly even in an acute form), the symptoms of which are epileptic seizures and increased excitability, observed immediately after birth or during the first few weeks of life.

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

When using the medication as an anticonvulsant during pregnancy, the baby may experience bleeding in the first days of life.

Contraindications

Main contraindications:

• porphyria, which has a mixed, acute or intermittent form (also if there is a history of this disease);
• myasthenia;
• disorders affecting the functioning of the kidneys or liver and having a severe form;
• drug or alcohol addiction;
• the presence of intolerance to the drug;
• breastfeeding.

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Side effects Phenobarbital

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

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

Possible reactions also include nausea, osteomalacia, constipation, bradycardia, megaloblastic anemia, and vomiting.

Hypocalcemia, folate deficiency, libido disorder and impotence have also been reported.

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Overdose

In case of drug intoxication, symptoms of the disorder may not appear for several hours. An adult can suffer severe poisoning if he takes 1000 mg of the drug orally. If he takes it in a dose of 2-10 g, it will lead to the death of the patient.

Acute intoxication causes a feeling of excitement or severe confusion, as well as ataxia, oliguria, and cyanosis. In addition, headaches occur, blood pressure drops, strange eye movements, hypothermia, a feeling of severe drowsiness and weakness, dizziness, and slurred speech are noted. Tachycardia, coma, and periodic breathing also develop. Along with this, respiratory function suppression, pupil constriction, and nystagmus, hemorrhages (at pressure sites), weakening of the pulse, and a decrease or complete disappearance of reflex reactions may occur.

In severe cases of poisoning, apnea, pulmonary edema, vascular collapse (in which the tone of peripheral vessels decreases), cardiac and respiratory arrest, and death are observed.

When taking drugs in a dose that is life-threatening, suppression of electrical brain activity may occur, but it should not be considered clinical death, because this effect is completely reversible (provided there is no damage caused by hypoxia).

Chronic overdose of the drug causes insomnia, a feeling of apathy, dizziness, constant irritability, deterioration of mental activity and a feeling of confusion. In addition, drowsiness, a feeling of general weakness, speech confusion and problems with maintaining balance occur. At the same time, convulsions with hallucinations, severe agitation and renal dysfunction or gastrointestinal tract dysfunction with cardiovascular system may occur.

Intoxication can provoke congestive heart failure, pneumonia, renal failure and arrhythmia.

In case of acute poisoning, it is necessary to accelerate the process of excretion of the active component of the drug and support the functioning of vital body systems.

To reduce the absorption of the drug, vomiting can be induced and then activated carbon can be given to the victim. In addition, procedures are carried out to prevent aspiration of vomit. If vomiting cannot be induced, gastric lavage is performed.

To increase the rate of excretion of Phenobarbital, the use of alkaline solutions and saline laxatives is prescribed, as well as forced diuresis.

At the same time, it is necessary to monitor the functioning of systems important to the body and maintain water balance.

Possible supportive procedures include:

• maintaining stable blood pressure values;
• ensuring free passage of air into the respiratory tract;
• if necessary – anti-shock measures;
• taking antibiotics (if pneumonia is suspected);
• oxygen supply and use of artificial ventilation;
• use of vasoconstrictors (if a decrease in blood pressure is observed);
• prevention of the development of aspiration, congestive pneumonia, bedsores and other complications.

It is recommended to avoid using analeptics, and also to avoid overloading the body with sodium or liquid.

In severe cases of poisoning, anuria or shock, hemodialysis or peritoneal dialysis sessions are performed. At the same time, it is necessary to monitor blood levels of the drug.

In the treatment of chronic poisoning, it is necessary to gradually reduce the drug dosage until it is completely discontinued. Symptomatic procedures are also performed. Sometimes psychotherapy sessions may be necessary.

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Interactions with other drugs

When combined with drugs that suppress the nervous system, and also with drugs containing ethyl alcohol, and ethanol itself, it is possible to increase the suppressive effect on the central nervous system.

A weakening of the hypnotic effect of the drug is observed when taken together with caffeine.

Combination with MAOIs and methylphenidate leads to an increase in plasma levels of phenobarbital, so its toxicity and suppressive effect on the nervous system are also enhanced.

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

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

The use of valproic acid causes an increase in the values of the drug 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 also felodipine reduces the values of these drugs in plasma.

Concomitant use with enflurane, halothane, and fluorothane or methoxyflurane may result in increased metabolism of the anesthetic agents, increasing the risk of liver toxicity (and kidney toxicity if methoxyflurane is used).

Combination with the substance griseofulvin reduces the degree of its intestinal absorption.

Use together with large doses of maprotiline leads to a decrease in the seizure threshold and the anticonvulsant effect of barbiturates.

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

Taking 0.2 g of pyridoxine per day reduces the plasma level of phenobarbital. Simultaneous use with felbamate or primidone, on the contrary, increases it.

In case of folic acid deficiency, the administration of drugs containing it causes a weakening of the effect of the drug.

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

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Storage conditions

Phenobarbital should be kept out of reach of children, under the usual conditions for any medication.

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Shelf life

Phenobarbital is permitted for use within 5 years from the date of its release.

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Application for children

Prescribing the drug to newborns is permitted only for the treatment of HDN. Phenobarbital enhances the detoxifying activity of the liver and reduces serum bilirubin levels.

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Reviews

Phenobarbital is often used for various poisonings, because it enhances liver detoxification activity. At the same time, 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.

The disadvantages of the drug include the fact that it causes some negative effects. Children or weakened adults often develop severe agitation. Along with this, there is information about the appearance of asthenia, vomiting, dizziness, constipation, a feeling of general weakness and nausea. Occasionally, ataxia, depression, allergies, fainting, hallucinations and hemolytic disorders are reported. Some people who took the drug for a long period noted the appearance of rickets.