PHENOBARBITAL (Phenobarbita-lum; synonym: luminal, Gardenal, Luminal, Ph eno bar hi tone, etc.; GFH, joint venture. B) — somnolent and irotivoepi-leptichesky means. 5-Eti l-5-fe-
nilbarbiturovy to - that; C] 2H]2N2 (); >:
White crystal powder of poorly bitter taste, inodorous. We will dissolve in a cold water very little, it is weak — in boiling (1:40) and chloroform, we will easily dissolve in 95% alcohol and solutions of alkalis, it is ether-soluble; pier. weight (weight) 232,24; * °pl 1^4 — 178 °. Is weak to - that with a dissociation constant (rka) 7,2.
T. almost it is completely soaked up in went. - kish. a path both at intake, and at introduction through a rectum. Absorption proceeds rather slowly, and the maximum concentration of drug in plasma is reached on average in 6 — 12 hour. Contacts blood proteins apprx. 60% of the soaked-up drug. Level F. in cerebrospinal liquid makes up to 50% of concentration of drug in plasma. The seeming volume of distribution of phenobarbital (Vd) —
0,5 — 1 l/kg. Phenobarbital is rather evenly distributed in body tissues. In an organism the most part of drug is exposed to biotransformation microsomal enzymes of a liver with formation of a number of metabolites, including the para-oxyphenobarbital which is not possessing expressed pharmakol. activity. In not changed view from an organism it is allocated apprx. 25% of drug. T. gets through a placental barrier. Acceleration of removal of drug through kidneys is promoted by alkali reaction of urine. Time of semi-removal F. makes 70 — 100 hours, clearance — 0,093 ± ± 0,044 ml/min.
It is similar to others barbituratakhm F. exerts the oppressing impact on c. N of page that is shown depending on a dose by development of the calming or somnolent effect. Unlike other derivatives barbituric to - you phenobarbital possesses the expressed antiepileptic action, a cut, apparently, is not in direct dependence on its cumulative oppressing effect concerning c. N of page. Antiepileptic action F. it is caused by decrease in excitability of neurons of the epileptogenic center, and also oppression of distribution of convulsive categories in structures of a brain.
T. causes induction of microsomal enzymes of a liver. In this regard at repeated introduction F. speed of his metabolism increases that is one of the reasons of decrease in sensitivity of an organism to drug. Besides, at the same time the speed of an inactivation of other pharmaceuticals appointed along with F can increase., napr, anticoagulants of indirect action (see Anticoagulants), (folic acid (see), butad an ion (see), dipheninum (see) etc., and also nek-ry endogenous biologically active compounds — steroid hormones (see), bilirubin (see) etc.
F. apply as antiepileptic, somnolent and a calmative.
As antiepileptic means F. it is most effective for the prevention of big attacks of epilepsy. For most of patients with epilepsy average therapeutic concentration F. in plasma make 10 mkg/ml. In the first days regular reception F. can be followed by slackness and drowsiness. Usually these phenomena disappear without dose decline of drug probably owing to development of tolerance. Average efficiency concentrations F. in plasma at epilepsy are reached at purpose of drug in daily doses: to children up to 5 years — 4,5 mg/kg, 5 — 14 years — 3 mg/kg, to persons aged from 15 up to 40 years — 2,5 mg/kg, are more senior than 40 years —
2 mg/kg. Stable concentration F. in plasma and fabrics it is reached in 2 — 3 weeks from an initiation of treatment. At increase in concentration F. in plasma to 30 — 50 mkg/ml a considerable part of patients has a slackness. If concentration F. exceeds 65 — 70 mkg/ml, coma can develop.
As calmative F. apply 0,01 — 0,05 g 2 — 3 times a day. At spasms of unstriated muscles went. - kish. a path, connected with vegetative frustration, T. usually apply in combination with drugs of a belladonna, a papaverine and other antispasmodics (see).
As hypnagogue F. appoint inside the adult but 0,1 — 0,2 g to reception, to children depending on age — 0,005 — 0,075 g. The dream comes in 1 — 1V2 hour.
Like other hypnagogues from group of derivatives barbituric to - you phenobarbital exert the expressed impact on phase structure of a dream (see) and suppresses a phase of a REM sleep. At cancellation F. the phenomenon of return which is expressed increase in duration of a REM sleep that is followed by dreams of frightening character, frequent awakenings is observed.
T. it is effective at a hyperbilirubinemia at newborns that is caused by acceleration of metabolism of bilirubin under the influence of drug (see. Hemolitic disease noyeo-rozhdenn ykh).
At prolonged use F. in connection with its slow removal from an organism material cumulation (see) drug is possible, edges it is shown by apathy, drowsiness, weakness, an ataxy, dizziness. Perhaps also development of medicinal dependence (see).
At nek-ry persons, especially at children, drug causes a paradoxical effect (the phenomena of excitement of c. N of page). At patients of advanced age after reception F. confusion of consciousness is occasionally observed. Sometimes at patients, it is long using drug, can arise a nek-swarm decrease in intelligence. and also deficit of folates with the subsequent development of macrocytic anemia (see). There are data that F. can cause Hypaque of l a tsiye-miya (see the Tetany) and osteomalacy (see) that, apparently, is caused by acceleration of metabolism of cholecalciferol due to induction of microsomal enzymes of a liver. The allergic reactions which more often are shown skin defeats are possible (a punctulate erythema, etc.). Are occasionally observed exfoliative dermatitis (see), an agranulocytosis (see), aplastic anemia (see. Hypoplastic anemia), jaundice (see).
The highest doses for adults inside: one-time 0,2 g, daily
Form of release: powder, tablets on 0,05 and 6,1 g. Storage: in well corked container, in the place protected from light.
T. is a part of the combined tablets containing also analgetic, spasmolytic and other means, napr, the tablets «Dipasalinum», «Sedalginum», «Temina of L», etc.
See also Barbiturates, Antiepileptic means, Sedatives, Hypnagogues.
Bibliography: E d and M. Zh. and That y-
r e r X. Anticonvulsant therapy, the lane with English, M., 1983; The pharmacological basis of therapeutics, ed.
by A. G. Gilman a. o., N. Y. a. o., 1980.
V. V. Churyukanov.