arbiturates tạo thành thể loại lâu đời nhất của các thuốc chống co giật tiếp tục được sử dụng rộng rãi trong việc quản lý chứng động kinh và các rối loạn khác. Tính hữu dụng của họ xuất phát từ một sự kết hợp hiệu quả, an toàn, và chi phí thấp. Những đức tính này tài khoản cho một thực tế rằng loại thuốc an thần | 48 J Barbiturates and Primidone Robert S. Rust B arbiturates constitute the oldest category of anticonvulsant medications that continue to be widely used in the management of epilepsy and other disorders. Their usefulness derives from a combination of efficacy safety and low cost. These virtues account for the fact that barbiturates likely remain among the most widely employed anticonvulsants in the world. Although phenobarbital PB is the major focus of this chapter other drugs are reviewed particularly mephobarbital pentobarbital and primidone. Mephobarbital MPB is a useful alternative to PB more widely employed in some other countries such as Australia than in the United States. Like primidone it undergoes biotransformation to PB. Among the more sedative barbiturates pentobarbital has been useful in the management of severe and persistent seizures that do not respond to more routine anticonvulsant therapy. Primidone PRM is not actually a barbiturate although it is subject to biotransformation into PB and probably exerts most of its anticonvulsant effects in that form. Because the major antiepileptic effects and side effects can be ascribed to the PB metabolite and because of pharmacokinetic and pharmacodynamic similarities it is quite appropriate to consider PRM in this chapter. PHENOBARBITAL Phenobarbital is 5-ethyl-5-phenyl substituted barbituric acid with a molecular weight of . It is a weakly acidic substance with a pKa that is usually reported as 1-4 . The free acid has low aqueous and relatively low lipid solubility however the sodium salt which is used for intravenous IV and intramuscular IM preparations is freely soluble in slightly alkaline aqueous solutions. Mechanisms of Action Phenobarbital exhibits a wide spectrum of anticonvulsant activity conferring protection to animals subjected either to electroshock or to chemically induced pentylenetetrazol or bicuculline experimental seizures 5 6 . This spectrum is shared by most barbiturates and is
