Symposium on Pediatric Neurology
Management of Seizure Disorders with Anticonvulsant Drugs: Current Concepts Peter H. Berman, MD.*
The successful treatment of seizures with anticonvulsant drugs began in 1857 when, during the discussion of a paper read before the Royal Medical and Chirurgical Society of London by Sieverking, Locock remarked that potassium bromide had been successful in controlling seizures in a small number of his patients. 72 Fifty-five years later, Hauptman presented an anecdotal account of his experience with phenobarbital as an anticonvulsant drug. 59 No significant investigation preceded the introduction of either of these drugs into clinical practice. The introduction of diphenylhydantoin in 1938, however, occurred only after extensive preclinical testing had established its efficacy in suppressing seizures in experimental animals. 82 ,83 Subsequently all anticonvulsant drugs have been subjected to extensive experimental investigation to assess their effectiveness and safety prior to their introduction into clinical practice. The clinical management of seizures with anticonvulsant drugs, however, has remained quite empiric. Recommended "standard" doses are based predominantly on rough estimates which attempt to bridge the gap between clinical effectiveness and toxicity. Such "standard" doses fail to recognize the wide variation in drug metabolism among patients. Therapeutic failure can result when the "standard" dose proves ineffective in a particular patient who metabolizes a drug more rapidly. Conversely toxic symptoms can result from the "standard dose" of a potentially beneficial drug because of excessively slow detoxification and excretion. Recent technologic advances have led to the availability of laboratory procedures which allow for the rapid, reliable, and specific measurement of the concentration of most anticonvulsant drugs and their metabolites in small samples of tissues and body fluids,38, 79, 99 With these methods it has become more practical to study drug metabolism and pharmacokinetics. s2 , 68, 69, 80 The information gained from studies utilizing these techniques is beginning to have important implications for the clinical management of patients with seizures. 2,39,65-67,111 "Associate Professor of Neurology and Pediatrics, School of Medicine, University of Pennsylvania; Director, Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Pediatric Clinics of North America- Vol. 23, No.3, August 1976
443
444
PETER
H.
BERMAN
BARBITURATES
-- ~;: N
H
PHENOBARBITAL
p-HYDROXY PHENOBARBITAL
~
Management of Seizure Disorders with Anticonvulsant Drugs: Current Concepts Peter H. Berman, MD.*
The successful treatment of seizures with anticonvulsant drugs began in 1857 when, during the discussion of a paper read before the Royal Medical and Chirurgical Society of London by Sieverking, Locock remarked that potassium bromide had been successful in controlling seizures in a small number of his patients. 72 Fifty-five years later, Hauptman presented an anecdotal account of his experience with phenobarbital as an anticonvulsant drug. 59 No significant investigation preceded the introduction of either of these drugs into clinical practice. The introduction of diphenylhydantoin in 1938, however, occurred only after extensive preclinical testing had established its efficacy in suppressing seizures in experimental animals. 82 ,83 Subsequently all anticonvulsant drugs have been subjected to extensive experimental investigation to assess their effectiveness and safety prior to their introduction into clinical practice. The clinical management of seizures with anticonvulsant drugs, however, has remained quite empiric. Recommended "standard" doses are based predominantly on rough estimates which attempt to bridge the gap between clinical effectiveness and toxicity. Such "standard" doses fail to recognize the wide variation in drug metabolism among patients. Therapeutic failure can result when the "standard" dose proves ineffective in a particular patient who metabolizes a drug more rapidly. Conversely toxic symptoms can result from the "standard dose" of a potentially beneficial drug because of excessively slow detoxification and excretion. Recent technologic advances have led to the availability of laboratory procedures which allow for the rapid, reliable, and specific measurement of the concentration of most anticonvulsant drugs and their metabolites in small samples of tissues and body fluids,38, 79, 99 With these methods it has become more practical to study drug metabolism and pharmacokinetics. s2 , 68, 69, 80 The information gained from studies utilizing these techniques is beginning to have important implications for the clinical management of patients with seizures. 2,39,65-67,111 "Associate Professor of Neurology and Pediatrics, School of Medicine, University of Pennsylvania; Director, Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Pediatric Clinics of North America- Vol. 23, No.3, August 1976
443
444
PETER
H.
BERMAN
BARBITURATES
-- ~;: N
H
PHENOBARBITAL
p-HYDROXY PHENOBARBITAL
~
