Phenobarbital

When ATH:
N03AA02

Characteristic.

Barbituric acid derivatives. The white crystalline powder slabogorkogo taste, without smell. Very slightly soluble in cold water, hard - in boiling water (1:40) and chloroform, soluble in alcohol, ether, alkaline solutions.

Pharmacological action.
Anticonvulsant, snotvornoe, sedation.

Application.

Epilepsy, xoreja, spastic paralysis, peripheral arterial spasm, eclampsia, excitation, insomnia, hemolytic disease of newborn.

Contraindications.

Hypersensitivity (incl. other barbiturates), manifesting or latent porphyria history (symptoms may increase due to enzyme induction, responsible for the synthesis of porphyrin), respiratory diseases, accompanied by shortness of breath, or airway obstruction, liver and / or kidney failure, myasthenia, alcoholism, or drug addiction, incl. history, pregnancy (especially I trimester), lactation.

Restrictions apply.

Depression and / or suicidal, asthma history, liver dysfunction and / or kidney, hyperkinesia, hyperthyroidism (may increase symptoms, tk. barbiturates displace thyroxine, bound to plasma proteins), hypoadrenalism (possible weakening of the systemic effects of exogenous and endogenous hydrocortisone under the influence of barbiturates), acute or persistent pain (may experience paradoxical excitement or may mask important symptoms), pregnancy (II and III trimester), childhood.

Pregnancy and breast-feeding.

It contraindicated in I trimester of pregnancy (possible teratogenic effects). Application during pregnancy is possible only under strict conditions, if you can not use other means.

The results of the retrospective controlled studies have shown, that taking barbiturates pregnant women is the cause of increased frequency of fetal abnormalities.

Newborns, mothers took phenobarbital in the III trimester of pregnancy, may develop physical dependence and withdrawal syndrome (have reported the development of acute withdrawal syndrome, manifested in epileptic seizures and excessive excitability immediately after birth or within 14 neonatal days, long exposed in utero barbiturates).

There is evidence, that the use of phenobarbital as an anticonvulsant during pregnancy leads to disruption of blood clotting (due to a deficiency of vitamin K) in newborn, which can cause bleeding in the neonatal period (generally the first day after birth).

The use during labor may cause respiratory depression in the neonate, especially premature (in connection with liver function nedorazvitiem).

At the time of treatment should stop breastfeeding (It passes into breast milk and may cause depression of the central nervous system in infants).

Side effects.

From the nervous system and sensory organs: drowsiness, lethargy, depression of the respiratory center, dizziness, headache, nervousness, alarm, hallucinations, ataxia, nightmares, giperkineziya (children), violation of the thinking process, paradoxical reaction (unusual excitement, insomnia) - Particularly in children, the elderly and debilitated patients, aftereffect (asthenia, a feeling of weakness, half-heartedly, reduction of psychomotor reactions and concentration).

Cardio-vascular system and blood (hematopoiesis, hemostasis): agranulocytosis, thrombocytopenia, hypotension, and megaloblastic anemia (prolonged use), bradycardia, vascular collapse.

From the digestive tract: nausea, vomiting, constipation.

Allergic reactions: skin rash or hives, Local swelling (especially age, cheeks or lips), exfoliative dermatitis (Syndrome Stevens - Johnson, toxic epidermal necrolysis); possible death.

Other: long-term use - liver damage (yellow skin or sclera), folate deficiency, hypocalcemia, osteomalacia, violation of libido, impotence.

Addictive (It revealed approximately 2 weeks of treatment), drug dependence (mental and physical), withdrawal and "return" (cm. Precautions).

Cooperation.

It enhances metabolism of drugs, biotransformed in the liver (by activation of microsomal oxidation enzymes) and reduces the effect of: anticoagulants, incl. varfarina, atsenokumarola, phenindione, etc.. (lowers blood anticoagulants, while the appointment is required periodic monitoring of prothrombin time to correct doses of anticoagulant), corticosteroids, Digitalis preparations, chloramphenicol, metronidazola, doxycycline (reduces T_1/2 doxycycline, This effect may persist for 2 weeks after discontinuation of a barbiturate), tricyclic antidepressants, estrogen, salitsilatov, paracetamol, etc.. Phenobarbital reduces the absorption of griseofulvin and its level in blood.

The effect of barbiturates on the metabolism of anticonvulsants - hydantoin derivatives (incl. phenytoin) unpredictable (possible decrease or increase the concentration of phenytoin in the blood, requires monitoring of plasma concentrations). Valproic Acid, sodium valproate increase in blood levels of phenobarbital. Phenobarbital reduces plasma concentration of carbamazepine, clonazepam.

While the use of other means, CNS depressants (incl. sedativnыe, hypnotics, Some antihistamines, anxiolytics), and alcohol is possible additive inhibitory effect. MAO inhibitors prolong the effect of phenobarbital (probably, due to inhibition of its metabolism).

Overdose.

Symptoms of toxic poisoning may not appear for several hours after taking phenobarbital. Toxic dose varies considerably. Ingestion 1 Mr. cause serious poisoning in adults, Reception 2-10 d usually causes death. Therapeutic levels of phenobarbital in human blood is 5-40 mcg / ml, lethal - 100-200 mg / ml. Barbiturate intoxication should be differentiated from alcohol intoxication, intoxication bromides, with a variety of neurological disorders.

The symptoms of acute intoxication: nistagmo, unusual eye movements, ataxia, expressed weakness and drowsiness, severe confusion, slurred speech, excitation, dizziness, headache, respiratory depression, Cheyne - Stokes, weakening or absence of reflexes, pupillary constriction (In severe poisoning paralytic alternating extension), oligurija, tachycardia, gipotenziya, gipotermiя, cyanosis, low pulse, cold and clammy skin, gemorragii (pressing the points), coma.

In severe poisoning may develop pulmonary edema, vascular collapse with a reduction in peripheral vascular tone, apnea, respiratory arrest and heart; possible death.

If a life-threatening overdose may suppress the electrical activity of the brain (EEG can be "flat"), which should not be regarded as clinical death, tk. This effect is completely reversible, if not developed damage, associated with hypoxia.

Overdose can cause the development of complications such as pneumonia, arrhythmia, congestive heart failure, renal failure.

Treatment of acute overdose: accelerate removal of phenobarbital and maintenance of vital functions.

To reduce the absorption (If phenobarbital is not completely sucked from the gastrointestinal tract) - Induction of vomiting (If the patient is conscious and has not lost the gag reflex) followed by the appointment of activated carbon, It is necessary to take measures to prevent aspiration of vomit. If the induction of vomiting is contraindicated, necessary to carry out gastric lavage.

To speed up the elimination of the drug has grown deep appoint saline laxatives, carry out forced diuresis (with preserved renal function), alkaline solutions used (for urine alkalinization).

Carry out monitoring of vital signs and water balance.

Supportive measures: necessary to ensure the airway, It is possible to use mechanical ventilation and the use of oxygen; appointment analeptikov not recommended (In severe poisoning may worsen); maintenance of normal blood pressure (with hypotension - use of vasoconstrictors) and body temperature; if required - or other fluid therapy. anti-shock measures; should take measures to prevent hypostatic pneumonia (incl. conduct physical therapy in the chest area), bedsores, aspirations, etc.. complications; with suspected pneumonia - antibiotics; It advised to avoid fluid overload, or sodium, especially in violation of the cardiovascular system.

In severe poisoning, development of anuria or shock, may conduct peritoneal dialysis or hemodialysis (during and after dialysis concentrations of phenobarbital necessary monitoring blood).

Symptoms of chronic toxicity: constant irritability, the weakening of the ability to critically assess, sleep disturbance, drowsiness, apathy, weakness, disequilibrium, muddled speech, dizziness, expressed confusion. There are hallucinations, excitation, convulsions, dysfunction of the gastrointestinal tract, cardiovascular and renal.

Treatment of chronic toxicity: gradual dose reduction (to avoid the development of withdrawal symptoms) until complete withdrawal of the drug, simptomaticheskoe treatment and psychotherapy.

Dosing and Administration.

Inside. The mode set strictly individually depending on indications, the disease, Portability, age, etc.. Treatment should start with the lowest effective dose, corresponding specific form of pathology. In patients with impaired liver and / or kidney, the elderly and debilitated patients treatment should be started with lower doses.

As relief - for adults 0.1-0.2 g for 0.5-1 hours before bedtime; as a sedative and antispasmodic - 0,01-0,03-0,05 g 2-3 times a day (usually in combination with antispasmodics, vasodilators et al.); epilepsy: adults - 0.05-0.1 g 2 times per day with gradual increase in the dose until the clinical effect.

The maximum single dose for adults - 0,2 g , maximum daily - 0,5 g.

The dose for children picked individually depending on age, body weight of the child.

Precautions.

When dermatological complications phenobarbital should be abolished. Hypersensitivity reactions are more common with a history of asthma, krapivnicы, angioedema etc..

It will be appreciated, that the elderly and debilitated patients at normal doses may be expressed excitement, depression or confusion. Children barbiturates can cause unusual excitement, irritability, hyperactivity.

With care prescribe for depression (possible deterioration, especially in elderly patients).

The risk of dependence increases when using large doses and with increasing duration of administration, as well as in patients with drug and alcohol addiction in history. The constant use of barbiturates in doses, 3-4 times higher than therapeutic, It leads to the development of physical dependence in 75% patients.

Abolition should be gradual, by reducing the doses for a long time, to reduce the risk of withdrawal symptoms and the "return". A withdrawal syndrome can occur within 8-12 hours after the last dose, and is usually manifested in the following sequence (Small signs): alarm, vellication, hand shake, progressive weakness, dizziness, visual impairment, nausea, vomiting, sleep disturbance, orthostatic hypotension (dizziness, insensibility). In severe cases, symptoms may be more significant (convulsions, delirium), arising during 16 hours and lasts up 5 days after the abrupt withdrawal. Intensity of withdrawal decreases gradually over about 15 days. The risk of delirium and convulsions or even death higher with abrupt cancellation after prolonged use in people with drug dependence. Sudden discontinuation of epilepsy can cause seizures or status epilepticus.

When applied for the treatment of epilepsy phenobarbital recommended monitoring its level in blood. Prolonged treatment is necessary periodic determination of the concentration of folate in the blood, control of peripheral blood picture, liver and kidney function.

If necessary, the use of barbiturates during childbirth is recommended to take birth in a readiness resuscitation equipment.

In the period of treatment is unacceptable consumption of alcoholic beverages.

Should not be used during the drivers of vehicles and people, whose work requires quick mental and physical reactions, and is associated with high concentration of attention.

Cautions.

Currently phenobarbital as a hypnotic practically used.