Epilepsy Flashcards
Noncompetitive antagonist at AMPA glutamate receptor
Levetiracetam
Dosing:
IR: (tab, oral soln, tab for oral sus)
Initial: 500mg bid; inc every 2 weeks by 500 mg/dose based on response (max dose: 1.5 g bid)
ER: (FDA approved for focal (partial) onset sz
Initial: 1g qd; inc every 2 weeks by 1g/d (max: 3g/d)
Levetiracetam
Generally well tolerated, some weight gain
Levetiracetam
Enhances CNS depressants
Levetiracetam
Levetiracetam renal dose adjustment (50-80 ml/min)
500-1000 mg q12h
Levetiracetam renal dose adjustment (30-50 ml/min)
250-750 mg q12h
Levetiracetam renal dose adjustment ( <30 ml/min)
250-500 mg q12h
Levetiracetam renal dose adjustment (ESRD w/dialysis)
500-1000 mg qd (after dialysis 250-500 mg supp dose)
Active metabolite if CBZ
Oxcarbamazepine (cleaning version)
Dosing:
Starting dose: 5mg/kg/d, w/ weekly increments of 5mg/kg/d
Target dose: 30 (up to 50) mg/kg/d
Daily dose inc by 30% when given to children 2-5 yrs
BID dosing
Oxcarbamazepine
Oxcarbmazepine advantages
-lower drug-drug interaction potential
-Low protein binding
-Low potential for induction of hepatic enzymes
-MHD eliminated by kidenys
Oxcarbmazepine SE
CNS (somnolence, HA, dizziness)
GI (N/V)
Potentially serious: rash (reversible, cross reactivity w/ CBZ
Oxcarbmazepine monitoring
-Sodium (hyponatremia)
-Hepatic (occasionally)
Lamotrigine indications
partial onset, absence, GTC, juvenile myoclonic, lennox-gastaut syndrome
Dosing
Start: 0.5mg/kg/d (div bid) for 2 wks, then 1mg/kg/d for 2 wks, then inc in 1mg/kg/d every 2 weeks
Maintenance: 5-15mg/kg/d (div bid)
Max dose (400 mg/d)
Mod if on VPA +/- other AEDs
Lamotrigine
Lamotrigine advantages
Low teratogenic potential, non sedative, broad spectrum
Lamotrigine disadvantages
slow titration
Lamotrigine rash
hypersensitivity rxn or SJS occurs in 1/1000 children within first 8 weeks, higher incidence with fast titration and adding LTG to VPA
Dosing
-the higher the dose the lower % absorbed
-initial target dose is 30mg/kg/d (few days)
-doses 2-3 x higher often needed to achieve max benefit
Max: 1800 mg/d
TID dosing
Gabapentin
Gabapentin advantages
-no Pk interaction with other drugs
-good for diabetes
-pure renal elimination, no protein binding
-co-morbidities: bipolar, neuropathic pain
Gabapentin SE
-No idiosyncratic, no teratogenic
-somnolence, dizziness, ataxia, weight gain
Gabapentin disadvantages
-TID dosing
-not that potent
-complex absorption pk
Phenytoin dose
200-400 mg/d
-Capacity limited metabolism
-Highly protein bound
-Concentration independent and dependent toxicity
-Insoluble in aqueous soln = unpredictable absorption
Phenytoin
Phenytoin preparations
-Rapid release caps
-Sustained release caps
-Chewable tabs
-Peds sus
(chewable better than peds sus, bc difficult to sus and can overshoot dose)
Phenytoin oral absorption
-Relatively slow (t max at 4-12 hrs)
-Largely variable in rate
-Rate and extent are sensitive to GI factors
Fosphenytoin
-Not capacity limited
-Phosphorylated prodrug for IV/IM use
-Max infusion = 150 mg PE/min
-Monitor BP
Phenytoin AE
-Conc dependent: nystagmus, double vision, blurred vision, incoordination, drowsiness, HA
-Idiosyncratic: aplastic anemia, granulocytopenia, hepatotoxicity, rash, exfoliative derm/SJS, Lupus like rxn
-Chronic: gum hypertrophy, acne, hirsutism, cerebellar damage, osteoporosis, vitamin K depletion
-Gingival hyperplasia induced in phenytoin
VPA dose
-PO for epilepsy 15mg/kg/d initially in div doses, inc in 5-10 mg/kg.d increments at weekly intervals; max = 60mg/kg/d
-Maintenance: 15-40 mg/kg/d in 3 div doses
-Rectal admin has been reported
VPA
-Divalproex can be sub at same daily dose, in some pts can be given bid
-Reduce starting dose in elderly
-Will displace other AEDs from protein binding sites
-Take with food or milk to help with stomach pain
VPA AE
N/V, d, abdominal cramps, liver function tests have elevations, spina bifida in fetus
VPA CI
hepatic dysfunction or disease
CBZ dose
-Adults: 600-2000 mg/d
-Children: 10-40 mg/kg/d
- 3-4 times per day; 2 times per day for sustained release, tegretol XR and Carbatrol
CBZ indications
partial, secondary GS
CBZ
auto induction for 2 cycles, may inc dose twice to account for this
CBZ AE
-d/c if absolute neutrophil count < 1500
-AE minimized at slow titration
-hyponatremia and water intox occur
CBZ interactions
-d/c MAOIs for 14 days before start of CBZ
-Stimulate met of CYP3A4, OCs, oral anticoagulants, corticosteroids, cyclosporine, haloperidol
-CBZ met inc by use of cimetidine, carithromycin, danazol, erythromycin, fluoxetine,
