Classic AEDs - Epilepsy Life Links：经典的抗癫痫药物的癫痫生活链接.pptVIP

Classic AEDs John M. Pellock, MDProfessor and ChairmanDivision of Child NeurologyVirginia Commonwealth University Medical College of Virginia HospitalsRichmond, Virginia Older AEDs Phenobarbital (1912) Phenytoin (1938) Ethosuximide (1960) Carbamazepine (1974) Valproic acid (1978) Bromides Benzodiazepines First-Line Therapy Early 20th Century VA Cooperative Study Toxicity of Classic AEDs M de Silva (Lancet 1996) randomized 167 children with partial or tonic-clonic seizures 6 of 10 children assigned to phenobarbital had behavioral or cognitive adverse events Only 15 children had adverse effects requiring withdrawal Phenytoin: 2 with drowsiness; 1 each skin rash, hirsutism and blood dyscrasia Carbamazepine: 1 each drowsiness and blood dyscrasia VPA: 1 each behavioral and tremor Classic Drugs are Equally Effective AED Selection Seizure type and syndrome Neonatal seizures Infantile spasms Generalized epilepsies Partial-onset AED efficacy AED toxicity Need for monitoring Ease of dosing and compliance issues Underlying medical conditions Medication interactions Urgency of initiating therapy Cost Carbamazepine Carbamazepine Dose: 10-35 mg/kg/day (bid-qid) Elimination 85% hepatic Major pathway CYP3A4 Active metabolite 10-11 epoxide, metabolized by epoxide hydrolase (may be increased out of proportion to total level) Autoinduction Clearance can increase by 300% over first 3-5 wks May need 3 to 4x / day dosing in children Carbamazepine: Adverse Effects 10% with transient leukopenia Risk of aplastic anemia and agranulocytosis 5-8x risk in general population Mid-1980s, 31 cases thrombocytopenia 10 cases agranulocytosis 27 cases aplastic anemia 8 cases pancytopenia Rash reported in 17% pts; 10% have been life-threatening Incidence of rash increased with age: 5% at 0-6 yrs, 15.4% at 7 yrs Hepatotoxicity 20 cases of clinical significance reported by mid-1980s Hepatotoxicity reversible, but recurs with re-administration of drug Dose related neurotoxic effects: dizziness, somnol