Drug Carbamazepine Tegretol Carbatrol MOA blocks Na and L type Ca2 channels Stabilizes inactive ion channel state by decreasing conductance Blocks firing of action potential leading to decreased release of excitatory NTs First line for partial and tonic clonic Dosing 600mg PO BID dose adjust based on serum drug levels therapeutic levels 4 12mg L Kinetics Absorption slow erratic Distribution rapid complete Elimination hepatic metabolism Autoinduction begins 3 5 days after start max by 2 4 weeks Also occurs w dose increases Adverse Effects Concentration dependent N V dizziness drowsiness headache nystagmus leukopenia Idiosyncratic agranulocytosis aplastic anemia rash SJS Chronic Hyponatremia osteoporosis Phenytoin Dilantin blocks Na and L type Ca2 channels Stabilizes inactive ion channel state by decreasing conductance Decreases sensitivity and stabilizes surrounding neurons to block propagation blockade lasts longer than CBZ First line for partial and tonic clonic Loading dose Adults usu 1000mg given as 400mg then 300mg then 300mg separated by 2 hrs Maintenance dose 100mg PO TID or 300mg XL PO daily dose adjust based on s sx and serum levels tx range 10 20mcg ml Concentration dependent ataxia nystagmus dizziness headache insomnia Idiosyncratic agranulocytosis SJS lupus Chronic Gingival hyperplasia 50 coarsening of facial features acne behavior changes motor deficits folate deficiency Absorption slow Distribution nonlinear 90 of plasma concentration bound to albumin 10 free fraction protein binding can be maxed out CORRECTED PHT LEVELS Sheiner Tozer Equation Hypoalbuminemia PHT c PHT obs 0 2 Alb 0 1 Renal dysfunction Hypoalb CrCl 20 or ESRD PHT c PHT obs 0 1 Alb 0 1 Elimination hepatic low plasma levels 1st order tx levels zero order small dose change can cause large concentration change Notes Monitoring therapeutic levels 4 12mg L trough peaks may not be representative concentration dependent ADEs at 8 12mg L baseline CBC rash SJS frequency number of seizures BMD fractures osteoporosis Toxicity can occur at tx plasma levels watch out for increased N V nystagmus CNS depression levels 20 ataxia impaired motor function Interactions CBZ decreases levels of Oral contraceptives theophylline warfarin and other AEDs Drugs that decrease CBZ levels Caffeine felbamate parent phenobarbital primidone phenytoin Drugs that increase CBZ levels clarithromycin diltiazem felbamate metabolite valproate verapamil PHT decreases levels of Oral contraceptives digoxin warfarin and other AEDs Drugs that increase PHT levels Amiodarone fluconazole Drugs that decrease PHT levels Antacids CBZ valproic acid Fosphenytoin Cerebryx prodrug of phenytoin same MOA as phenytoin 300 400mg PE equivalent per day max infusion rate 150mg min FOSPHENYTOIN VS PHENYTOIN water soluble prodrug of PHT does not use propylene glycol cardiac depressant IM IV for use in acute seizures less venous irritation more reliable IM absorption MUCH more expensive antiseizure antiepileptogenic blocks Na Ca2 increases GABA levels First line for partial tonic clonic absence seizures less effective vs CBZ for complex partial seizures Valproate Depakote Depakene 500mg BID dose based on serum levels therapeutic 50 150mg dL converting depakote to depakote ER increase daily dose by 8 to 20 Eslicarbazepine Aptiom prodrug converted to active metabolite of OXC same MOA as OXC FDA approved as adjunct in adults with partial seizures 400mg PO daily x 1 wk then 800mg PO daily max 1200mg day CrCl 50 200mg daily x 2 weeks then 400mg daily max 600mg day Absorption 90 100 depakote has delayed absorption but less Ses Distribution 90 95 protein bound saturable sites full at 100mg L Elimination hepatic CYP2C9 inhibitor may be induced by other AEDs monotx advised VPA increases levels of CBZ PHT PB ESM LTG lorazepam Drugs that decrease VPA levels CBZ PHT PB ASA rifampin does not affect oral contraceptives Concentration dependent N V 50 drowsiness dizziness headache blurred vision tremor Idiosyncratic Hepatic failure pancreatitis teratogenic thrombocytopenia rash SJS Chronic Alopecia weight gain folic acid deficiency behavior changes sedation Idiosyncratic SJS TEN Chronic Hyponatremia Pregnancy Category C Oxcarbazepine Trileptal blocks Na channels stabilizes inactive ion channel state by decreasing conductance structurally similar to CBZ better tolerated than CBZ First line for partial seizures 600mg BID CrCl 30 give 300mg daily initially then titrate to effect Concentration dependent Fatigue N V headache dizziness somnolence ataxia diplopia CYP3A4 inducer less than CBZ no autoinduction CYP2C19 inhibitor OXC decreases levels of Oral contraceptives CCBs OXC increases PHT levels Monitoring seizures ADEs Ethosuximide Zarontin blocks T type Ca2 channels major role in absence seizures First line for absence seizures better tolerated than VPA Not effective in other seizure types Adults kids 6yo 500mg PO daily then increase by 250mg q4 7 days Concentration dependent sedation nausea anorexia ataxia hiccups Kids 3 6yo 250mg PO daily then increase by 250mg q4 7 days Idiosyncratic Blood dyscrasias lupus liver failure Absorption complete Distribution not plasma protein bound doesn t distribute to fat Metabolism CYP3A4 substrate no effect on other drugs Elimination 60 removed by dialysis Drugs that decrease ESM levels CBZ PHT PB Drugs that increase ESM levels isoniazid Monitoring therapeutic level 40 100mcg mL Initial pt at steady state kids 6 days adults 12 days Maintenance q4 6 months until stable Chronic Headache behavior changes Concentration dependent ataxia diplopia dizziness somnolence headache N V Idiosyncratic Rash SJS BBW Chronic Weight gain Concentration dependent Dizziness fatigue ataxia somnolence Idiosyncratic None established Chronic Weight gain Lamotrigine Lamictal Gabapentin Neurontin blocks Na channels stabilizes inactive ion channel state by decreasing conductance blocks Ca2 channels decreases release of excitatory neurotransmitters Adjunct tx for partial and tonic clonic seizures as effective as CBZ and PHT but better tolerated can be monotx if converting from CBZ PHT PHB VPA binds to L type Ca2 channels structure similar to GABA increases GABA Adjunct tx for partial seizures Need more data for monotx Also effective in neuropathic pain psych disorders Levetiracetam Keppra unknown MOA chemically unique from other AEDs antiseizure antiepileptogenic Adjunct therapy for partial and tonic clonic seizures IV form available 150mg PO BID increase bi monthly by 50mg