Epilepsy

Question 1

Noncompetitive antagonist at AMPA glutamate receptor

Answer 1

Levetiracetam

Question 2

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)

Answer 2

Levetiracetam

Question 3

Generally well tolerated, some weight gain

Answer 3

Levetiracetam

Question 4

Enhances CNS depressants

Answer 4

Levetiracetam

Question 5

Levetiracetam renal dose adjustment (50-80 ml/min)

Answer 5

500-1000 mg q12h

Question 6

Levetiracetam renal dose adjustment (30-50 ml/min)

Answer 6

250-750 mg q12h

Question 7

Levetiracetam renal dose adjustment ( <30 ml/min)

Answer 7

250-500 mg q12h

Question 8

Levetiracetam renal dose adjustment (ESRD w/dialysis)

Answer 8

500-1000 mg qd (after dialysis 250-500 mg supp dose)

Question 9

Active metabolite if CBZ

Answer 9

Oxcarbamazepine (cleaning version)

Question 10

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

Answer 10

Oxcarbamazepine

Question 11

Oxcarbmazepine advantages

Answer 11

-lower drug-drug interaction potential
-Low protein binding
-Low potential for induction of hepatic enzymes
-MHD eliminated by kidenys

Question 12

Oxcarbmazepine SE

Answer 12

CNS (somnolence, HA, dizziness)
GI (N/V)
Potentially serious: rash (reversible, cross reactivity w/ CBZ

Question 13

Oxcarbmazepine monitoring

Answer 13

-Sodium (hyponatremia)
-Hepatic (occasionally)

Question 14

Lamotrigine indications

Answer 14

partial onset, absence, GTC, juvenile myoclonic, lennox-gastaut syndrome

Question 15

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

Answer 15

Lamotrigine

Question 16

Lamotrigine advantages

Answer 16

Low teratogenic potential, non sedative, broad spectrum

Question 17

Lamotrigine disadvantages

Answer 17

slow titration

Question 18

Lamotrigine rash

Answer 18

hypersensitivity rxn or SJS occurs in 1/1000 children within first 8 weeks, higher incidence with fast titration and adding LTG to VPA

Question 19

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

Answer 19

Gabapentin

Question 20

Gabapentin advantages

Answer 20

-no Pk interaction with other drugs
-good for diabetes
-pure renal elimination, no protein binding
-co-morbidities: bipolar, neuropathic pain

Question 21

Gabapentin SE

Answer 21

-No idiosyncratic, no teratogenic
-somnolence, dizziness, ataxia, weight gain

Question 22

Gabapentin disadvantages

Answer 22

-TID dosing
-not that potent
-complex absorption pk

Question 23

Phenytoin dose

Answer 23

200-400 mg/d

Question 24

-Capacity limited metabolism
-Highly protein bound
-Concentration independent and dependent toxicity
-Insoluble in aqueous soln = unpredictable absorption

Answer 24

Phenytoin

Question 25

Phenytoin preparations

Answer 25

-Rapid release caps
-Sustained release caps
-Chewable tabs
-Peds sus
(chewable better than peds sus, bc difficult to sus and can overshoot dose)

Question 26

Phenytoin oral absorption

Answer 26

-Relatively slow (t max at 4-12 hrs)
-Largely variable in rate
-Rate and extent are sensitive to GI factors

Question 27

Fosphenytoin

Answer 27

-Not capacity limited
-Phosphorylated prodrug for IV/IM use
-Max infusion = 150 mg PE/min
-Monitor BP

Question 28

Phenytoin AE

Answer 28

-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

Question 29

VPA dose

Answer 29

-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

Question 30

VPA

Answer 30

-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

Question 31

VPA AE

Answer 31

N/V, d, abdominal cramps, liver function tests have elevations, spina bifida in fetus

Question 32

VPA CI

Answer 32

hepatic dysfunction or disease

Question 33

CBZ dose

Answer 33

-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

Question 34

CBZ indications

Answer 34

partial, secondary GS

Question 35

CBZ

Answer 35

auto induction for 2 cycles, may inc dose twice to account for this

Question 36

CBZ AE

Answer 36

-d/c if absolute neutrophil count < 1500
-AE minimized at slow titration
-hyponatremia and water intox occur

Question 37

CBZ interactions

Answer 37

-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,