8 Drugs for partial and secondarilygeneralized seizures Phenytoin / fosphenytoinCarbamazepineBarbituratesValproic acidNew and investigational agents
9 Phenytoin Mechanism: Blocks voltage-dependent Na+ channels Understanding pharmacokinetics is crucial to safe and effective use: crucial to safe and effective use:hepatic metabolism with saturation kineticsinduces metabolism of other drugsAcute toxicity: nystagmus, ataxia, diplopiaChronic toxicity: hirsuitism, gums,neuropathy, cerebellar dysfunctionNot water soluble -for IV must be dissolved in propylene glycol
10 Fosphenytoin (Cerebyx) a “prodrug” Fosphenytoin phenytoinfosphenytoin is rapidly metabolized to phenytoinfosphenytoin is water soluble; allows IMadministration, and eliminates toxicity of propyleneglycol vehicle required for phenytoin1200 mg phenytoin = $1.50; fosphenytoin = $119.00
12 Barbiturates Enhances GABA-mediated chloride conductance Two commonly used as anticonvulsants:Phenobarbital:PO, IV, or IMLong half-life (100 hours)hepatic metabolism, strong inducersedatingPrimidonemetabolized to phenobarbital and PEMA
13 Valproic Acid Carboxylic acid Effective in both partial and primary generalized seizuresoral or IV formulationsHepatic metabolism, induces metabolism of other anticonvulsantsToxicity:Common: tremor, weight gain, nauseaRare, but potentially fatal: hepatotoxicity. Most common under 2 years and with multiple anticonvulsants.
14 New and investigational anticonvulsants FelbamateGabapentinLamotrigineTopiramateTiagabinLeviracetamZonisamideAll of these released since 1994None are currently FDA approved for monotherapy
15 Principles for the management of epilepsy Classify, localize and define etiologyNot every seizure needs to be treatedMonotherapy preferredTreat the patient, not the numbers80% of patients can achieve control with 1 agent, 90% with multiple agentsConsider surgical approaches
16 Pregnancy and anticonvulsants All presently available anticonvulsants may have teratogenic effectsUncontrolled seizures also have an adverse effect on the fetusFirst 12 weeks is criticalFewest drugs and lowest doses are bestAvoid valproic acid if possible (neural tube defects)Abrupt discontinuation of any anticonvulsant is not a good idea
17 Management of Status Epilepticus Definition and identificationGoal is control of seizures with 60 minutesABC’s: Airway, Breathing, CirculationIV access, initial labs, history and examThiamin (100mg IV), glucose (50g IV)Lorazepam, 1-2 mg IV Q3-5 min to 10 mg totalFosphenytoin, mg/kg IV or IMPhenobarbital, initial dose 5-10 mg/kg IVRefractory status requires expert consultation
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