Pediatric Neurology Quick Talks

Common AEDsMichael Babcock

Summer 2013

Daisy Dilantin (Phenytoin the ugly duckling) (1938)

• Indications: Broad- focal, GTC, neonatal, status (she's a swan this)

• Other uses:

• Dosing: Status- 15-20mg/kg IV

– Daily- 5-10mg/kg/d div BID/TID

– Levels: 10-20mg/l

• ADR: dose-dependent – nystagmus, ataxia, encephalopathy; chronic use- gingival hyperplasia, hirsutism, coarse face (not a pretty woman), tremor, peripheral neuropathy, hepatotoxicity, hematologic effects. *hypotension/arrythmia with IV load.

• Monitor: CBC, LFTs, ekg for IV.

• Pharmaco: high PB, liver met, non-linear, enzyme inducer.

• Preg: Cat. D-bad. (Daisy doesn't have children) +interact with contraception.

Eddie Ethosuximide (Zarontin) (1950s)

• Indications: absence – monotherapy (Eddie just does disco and does it well); can be adjuntive in other generalized.

• Other uses – none

• Dosing– Daily dose – start 5-10mg/kg/d, increase to 20-35 mg/kg/d div BID.

– Levels – 40-100 mcg/ml

• ADRs – GI symptoms (anorexia, abdominal pain, nausea), headache, behavior changes, pyschosis, withdrawal seizures; severe/idiosyncratic – aplastic anemia, SJS, SLE, liver impairment

• Monitor – CBC, LFTs, drug level

• Pharmaco: narrow therapeutic window (disco's cool window was narrow), high oral bioavailable, ~85% PB, hepatic metabolism, half-life 30-60 hrs.

• Preg – cat C, contraception- no interaction

Vinny Valproate (the Depakote Don) (1963)

• Indications: Broad – general, focal (not as good), absence, status (call the Don for status)

• Other uses: bipolar, mood stabilization, migraine-acute and chronic

• Dosing: status: 15-20mg/kg IV

– Daily: 20-30mg/kg/d div BID

– Levels: 50-100 mg/l.

• ADRs: acute liver necrosis/pancreatitis – especially <2yo (1/600), neural tube defects, PCOS, hormonal changes (Don hangs around poker hall, no women and children). Tremor (no longer carries his gun). Calming affect (the Don doesn't lose his temper), thrombocytopenia, weight gain (Don likes pizza), coagulation abnl, encephalopathy-hyperammonemia

• Monitor: LFT, plt, coag at baseline.

• Pharamco: highly PB, hepatic metabolism, lots of interactions with other meds (Don is tough to get along with – especially with Larry Lamictal)

• Preg: cat. D-bad, fetal valproate syndrome.

Professor Larry Lamictal (1991)

• Indications: Broad spectrum, not for status.

• Other uses: bipolar, mood stabalization

• Dosing: start low and go slow, differs for monotherapy, co-therapy with valproate/enzyme inducers – Professor is very meticulous and has many different titration schedules.

• ADRs: lower cognitive effect/less sedating compared to other AEDs – Professor can continue to teach. Bad skin rash- SJS or AED hypersensitivity syndrome – usually within 2 months of starting – imagine Professor in sun with bad sunburn rash. Some hematologic abnormalities and elevated LFTs.

• Monitor – Cr baseline

• Pharmaco: good oral bioavailable, 50% protein bound, liver metabolized.

• Preg: Cat. C. Large changes in plasma levels – breakthrough sz's 1st trimester, toxicity after delivery. Monitor baby LFT's.

Tommy Topamax (1995)

• Indications: Broad – general, focal, spasms

• Other uses: headaches – migraine, psuedotumor

• Dosing: Status – not really, ?for refractory

– Daily- 5-9mg/kg/d div BID, start low, increase slow to try to avoid ADRs

• ADRs: abnormal thinking/word finding difficulties (Can't come up with right words around girls), Weight loss (skinny middle-schooler), parathesias, abdominal pain, kidney stones (always going to nurses station with new complaints), metabolic acidosis, glaucoma (wears glasses)

• Monitor – Cr baseline, bicarb

• Pharmaco: 15-40% PB, excreted unchanged in urine

• Preg: Cat C, no breastfeeding.

Zed Zonegran (Tommy Topamax's Dad)(1989)

• Indications: Broad – general, focal, spasms

• Other uses:

• Dosing: Daily- start 1-2mg/kg/d, titrate every 2 weeks to goal 4-8 mg/kg/d div BID.

• ADRs (like Tommy Topamax): abnormal thinking/word finding difficulties, weight loss, anorexia, kidney stones, oligohydrosis, hyperthermia; also depression, psychosis, treatment emergent status; also SJS, aplastic anemia (sulfonimide)

• Monitor – Cr baseline, bicarb, cbc

• Pharmaco: chemically a sulfonimide; 100% bioavailable, ~50% PB, hepatic metabolism with renal elimination; half-life 60 hrs (can take 2 weeks for steady state)

• Preg: Cat C, high breast milk transfer, no interaction contraception.

Keppra Ken aka Superman (1999)

• Indications: Broad spectrum – generalized, focal, neonatal, status – Superman good against anything.

• Other uses – consider for other uses-low side effects.

• Dosing– Status – load 20mg/kg IV

– Daily dose – 20-60 mg/kg/d div BID

• Dose-dependent ADRs – usual somnolence, dizziness, anorexia.

• Additional ADR – behavior changes, agitation – Don't make Superman angry, caution with psych hx.

– can use vit. B6 to help

• Monitor – Cr baseline

• Pharmaco: good oral availability, PO/IV equivalent. Renal excretion (decreased dose in renal impairment).

• Preg – cat. C. breast milk- high transfer but very low infant levels, contraception – no interaction.

References

C Panayiotopoulos. 2007. A clinical guide to epileptic syndromes and their treatment. 2nd ed. Springer. Ch. 18-Pharmacopia

Simpsons. Fox Network.