Pediatric Neurology Hoops Family Childrens Hospital at Cabell Huntington Hospital Marshall University Department of Neuroscience Ideally Fewest possible seizures Limit side effects ID: 746720
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Slide1
Epilepsy Medications
Mitzi Payne, MD
Pediatric
Neurology
Hoops Family Children’s Hospital at
Cabell
Huntington Hospital
Marshall University Department of NeuroscienceSlide2
Ideally...
Fewest possible seizures
Limit side effects
MonotherapyMinimal dosing schedules (once, twice, three times a day)Limit need for blood tests
2Slide3
In reality...
70% of patients are seizure-free with one medication
With careful monitoring and adjustment
5% to 10% of patients are seizure free with two or more drugs
20% of patients STILL HAVE FREQUENT SEIZURES
3Slide4
Management of seizures
Use the right drug for the correct seizure type
Use one drug and increase the dose until a therapeutic effect is achieved or side effects occur
May need to check blood levelsIf needed, a second drug is added.
4Slide5
Seizure management
If one medication fails, use two medications
Add a third medication IF necessary
Balance frequency of seizures with side effects of medicationsDoseEffect of seizures on daily lifeSide effects patients may experience
5Slide6
Compliance
For a medication to be effective , it must be taken as prescribed!
Non-compliance is a common factor
Patients must be involved in decisions of medications This helps compliance
6Slide7
Why don’t patients take their medications as they should?
Don’t understand why they are taking it
Poor memory
Poor understanding of how to take the medication
SIDE EFFECTS
IMPRACTICAL dose schedules
Poor tasting medications
7Slide8
When should levels be checked?
Frequent seizures, need to adjust meds
Recurrence of seizures, need to adjust meds
Side effects – ensure patient is not toxic and abrupt or inpatient weaning needs to occurAssessment of compliance
Document a “good level” for that patient
Changes to medication regimens, concern for medication interactions (AED’s,
abx
, etc)
8Slide9
However...a number is ONLY a number!
Blood concentrations are guide only
“Doctor / Mom / Patient:
Don’t worry, the level is in the NORMAL RANGE”, says the physician / nurse / receptionist.
9Slide10
A number must be interpreted!
TROUGH levels need to be drawn. PEAK levels are not a good consistent assessment.
“Mom, the level we drew today in the ER was high.
So, even though your son had a seizure at school today, your neurologist has dosed him too high and you need to lower his dose.”
10Slide11
JUST A NUMBER!
Never look at the blood level in isolation
In the
pediatric population (and sometimes adult), the dosage is based on weightDoses will change if multiple seizure medications are used and thus interact with each otherA PERFECT blood level for a particular patient:
Minimal side effects
Low seizure frequency
11Slide12
How do seizures occur ?
A neuron fires, leads to an action potential.
This action potential spreads and involves the brain by excitatory neurotransmitters (glutamate)
Imbalance of excitatory and inhibitory signals – more excitatory than inhibitory
12Slide13
How do the meds stop seizures?
A neuron fires, leads to an action potential.
Stop action potential from
occuringSodium channel blocker or modulatorPotassium channel opener
This action potential spreads and involves the brain by excitatory neurotransmitters (glutamate)
Stop this transmission … or
Encourage inhibitory neurotransmitters (GABA)
GABA uptake inhibitor
GABA
mimics
13Slide14
Sodium channels
Target for many medications
Sodium channels give way to the action potential in excitatory neurons
14
Phenytoin
Carbamazepine
Oxcarbazepine
LamotrigineSlide15
Potassium channels
End neuronal excitability, but bring neuron back to its normal resting potential
Involved in length of action potential
15Slide16
GABA A
and GABA
B
Inhibitory neurotransmittersGABA A post -synaptic; 7 classesDependent upon chloride and bicarbonate ions
GABA
B
pre- and post -synaptic
16Slide17
GABA A
Enhancement
Barbiturates
phenobarbitalBenzodiazepinesClobazam
,
clonazepam
,
diazapam
Tiagabine
Vigabatrin
17Slide18
Glutamate
Main excitatory transmitter
Mainly intracellular
Three receptor types:NMDA
Associated with sodium and calcium ions
Magnesium ions block
Other messengers act at NMDA site
AMPA and
kainate
receptors
metabotropic
18Slide19
Other Mechanisms
Valproic acid
Gabapentin
PiracetamLevetiracetam
19Slide20
Sites of action 1
Valproate, vigabatrin, tiagabine
increase GABA by inhibiting reuptake (2) and preventing breakdown within the cell (3)
Benzodiazepines bind to GABA receptors (4)Phenobarbital opens chloride channels (4)
Topiramate
blocks sodium channels and is a GABA agonist at some sites (4)
20Slide21
21Slide22
Other modes of action
Gabapentin,
has similar structure to GABA
Phenytoin,carbamazepine,oxcarbazepine, lamotrigine, act on sodium channels
Ethosuximide,
reduces calcium currents
Levetiracetam,
has neuroprotective effect
Topiramate, acetazolamide,
are carbonic anhydrase inhibitors
Zonisamide
has
weak carbonic anhydrase activity
22Slide23
Choice of antiepileptic 1
Seizure type
Drug of choice
Alternatives
Simple &
complex partial
Carbamazepine
Phenytoin
Valproate
Lamotrigine
Gabapentin
Levetiracetam
Topiramate
Tiagabine
Oxcarbazepine
Phenobarbital
23Slide24
Choice of antiepileptic 2
Seizure type
Drug of choice
Alternatives
Generalized tonic
clonic
Carbamazepine
Phenytoin
Valproate
Lamotrigine
Topiramate
Phenobarbital
Absence
Ethosuximide
Valproate
Lamotrigine
Clonazepam
Atypical absence
Atonic, myoclonic
Valproate
Clonazepam
24Slide25
Carbamazepine
(
Tegretol, Carbatrol)Dose
Start 10-20 mg/kg/day
Therapeutic plasma concentration
4 to 12 micrograms per ml
Poor
correlation between dose and plasma level in children
Widely distributed in tissues, found in placenta and breast milk (40% plasma level)
t MAX 4 to 8 hours
Indicated for
All forms of seizures
except
absence and
myoclonic
seizures
25Slide26
Carbamazepine 2
Common side effects
Headache, drowsiness, dizziness, ataxia, double vision, Serious effects
Osteomalacea
,
folate
deficency
, peripheral neuropathy, water retention,
hyponatraemia
, rash, blood
dyscrasias-leucopaenia
Comments
Many
drug interactions as enzyme inducer
Can make
myoclonus
worse or appear to cause it
26Slide27
Oxcarbazepine (
Trileptal
)
DoseStart 20-30 mg/kg/day
Therapeutic plasma concentration
Indicated for
Partial seizures with or without secondarily generalised tonic
clonic
seizures
Common side effects
As for
carbamazepine
– less severe
Comments
Fewer drug interactions than
carbamazepine
27Slide28
Clonazepam
Dose
0.5
to 8 mg a dayTherapeutic plasma concentration Indicated for
Refractory absence and
myoclonic
seizures
Sleep
Irritability
28Slide29
Clonazepam
Common side effects
Sedation, ataxia, behaviour problems, hyperactivity
CommentsHalf life 18 to 50 hoursTolerance develops in 30%
29Slide30
Clobazam (
Onfi
)
Dose 10 to 60mg a day
Indicated for
Refractory
seizures
Cluster
seizures
Common side effects
As for
clonazepam
30Slide31
Ethosuximide
(
Zarontin
)Dose Start 10-15 mg/kg/dayTherapeutic plasma concentration
300 -700 micromoles/L
50 -100 micrograms/L
Indicated for
Simple absence
seizures
NOT convulsive seizures
31Slide32
Ethosuximide
(
Zarontin
)Common side effectsGastro intestinal upset, nausea, drowsiness, headache, behavioural changes, hiccups, skin rashesComments
Half life 50 to 60 hours in adults
30 to 40 hours in children
32Slide33
Lamotrigine
(
Lamictal
)Dose Start 5 mg/kg/dayTherapeutic plasma concentration
Not clinically relevant
Indicated for
All forms of seizures
33Slide34
Lamotrigine
(
Lamictal
)Common side effectsDizziness, ataxia, double vision, nausea, somnolence
Rash
(worse in children) less if slow escalation
Comments
Complex interaction with valproate very slow escalation needed
Indicated for partial seizures and secondarily generalised tonic clonic seizures
Half life 25 hours shorter with enzyme inducers
Excreted in breast milk
Reasonably safe in overdose (10x)
34Slide35
Levetiracetam (
Keppra
)
DoseStart 20-30 mg/kg/day
Therapeutic plasma concentration
Not relevant
Indicated for
Partial seizures,
Generalized seizures
Common side effects
Irritability, nausea
, drowsiness
,
rash,
Comments
No drug interactions described
35Slide36
Phenobarbital
Dose
Start 3-4 mg/kg/day
Therapeutic plasma concentration15 to 40 micrograms/mlIndicated for
All forms of seizures except absence seizures
36Slide37
Phenobarbital
Common side effects
Sedation (tolerance develops), headache,
hyperkinesia (old & young) slurred speech, skin reactions, cognitive impairmentComments
Dependency; needs very, very slow withdrawal
Interactions - increases
valproate
effect;
-enzyme inducer, reduces effects of many other drugs
Half life 2 to 7 days
Can cause
folate
deficiency
Concern for developmental delays!
37Slide38
Sodium
valproate
/
valproic acid (Depakote)Dose
Start 15 mg/kg/day
Therapeutic plasma
concentration
50 to 100 micrograms/ml
Indicated
for
All forms of epilepsy
38Slide39
Valproic acid/sodium
valproate
Common side effects
Nausea, gastrointestinal irritation, drowsiness, ataxia, weight gain & also anorexia, alopecia.Rare but serious impaired liver function
thrombocytopenia
Comments
Half life 10 to 20 hours, reduced with polytherapy
GI upset reduced by enteric coating
Interacts with lamotrigine and phenobarbital
39Slide40
Topiramate
(
Topamax, Trokendi)Dose Start 5 mg/kg/day
Therapeutic plasma concentration
Not clinically relevant
Indicated for
Adjunctive treatment for refractory partial seizures
Common side effects
Nausea, abdominal pain, anorexia, cog. impairment, mood disorders (can be aggressive in LD)
40Slide41
Topiramate
Comments
Watch for weight loss and depressive psychosis
Ensure adequate hydration; increased risk of kidney stones. Avoid carbonic anhydrase inhibitors e.g. acetazolamideHalf life 18 to 30 hours reduced where given with enzyme inducing drugs
41Slide42
Diastat
Rectal valium
Syringes: 2.5 mg, 10 mg, 20 mg
Locked to prescribed dose by pharmacistPackage of two syringesSlide43
Diastat
USUALLY prescribed to be given once a seizure has lasted for 4-5 minutes
Exceptions:
Prolonged seizuresDepending on patient, perhaps 2-3 seizures within a certain period of timeSlide44
Diastat unique dosing
Ages 2-5 years: 0.5 mg/kg
Ages 6-11 years: 0.3 mg/kg
Age 12 + years: 0.2 mg/kgSlide45
Lorazepam (Ativan
)
Often used for seizure clusters
Dosing 0.025-0.1 mg/kgMay be given orally – in between seizures