Mitzi Payne, MD Pediatric Neurology Hoops Family Children’s Hospital at Cabell Huntington Hospital...
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- Slide 1
- Mitzi Payne, MD Pediatric Neurology Hoops Family Childrens
Hospital at Cabell Huntington Hospital Marshall University
Department of Neuroscience
- Slide 2
- Fewest possible seizures Limit side effects Monotherapy Minimal
dosing schedules (once, twice, three times a day) Limit need for
blood tests 2
- Slide 3
- 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 3
- Slide 4
- 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 levels If needed, a
second drug is added. 4
- Slide 5
- If one medication fails, use two medications Add a third
medication IF necessary Balance frequency of seizures with side
effects of medications Dose Effect of seizures on daily life Side
effects patients may experience 5
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- 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 6
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- Dont understand why they are taking it Poor memory Poor
understanding of how to take the medication SIDE EFFECTS
IMPRACTICAL dose schedules Poor tasting medications 7
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- 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 occur Assessment of compliance
Document a good level for that patient Changes to medication
regimens, concern for medication interactions (AEDs, abx, etc)
8
- Slide 9
- Blood concentrations are guide only Doctor / Mom / Patient:
Dont worry, the level is in the NORMAL RANGE, says the physician /
nurse / receptionist. 9
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- 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.
10
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- Never look at the blood level in isolation In the pediatric
population (and sometimes adult), the dosage is based on weight
Doses will change if multiple seizure medications are used and thus
interact with each other A PERFECT blood level for a particular
patient: Minimal side effects Low seizure frequency 11
- Slide 12
- 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 12
- Slide 13
- A neuron fires, leads to an action potential. Stop action
potential from occuring Sodium channel blocker or modulator
Potassium 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 13
- Slide 14
- Target for many medications Sodium channels give way to the
action potential in excitatory neurons 14 Phenytoin Carbamazepine
Oxcarbazepine Lamotrigine
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- End neuronal excitability, but bring neuron back to its normal
resting potential Involved in length of action potential 15
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- Inhibitory neurotransmitters GABA A post -synaptic; 7 classes
Dependent upon chloride and bicarbonate ions GABA B pre- and post
-synaptic 16
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- Barbiturates phenobarbital Benzodiazepines Clobazam,
clonazepam, diazapam Tiagabine Vigabatrin 17
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- 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 18
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- Valproic acid Gabapentin Piracetam Levetiracetam 19
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- 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) 20
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- 21
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- 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 22
- Slide 23
- Seizure typeDrug of choiceAlternatives Simple & complex
partial Carbamazepine Phenytoin Valproate Lamotrigine Gabapentin
Levetiracetam Topiramate Tiagabine Oxcarbazepine Phenobarbital
23
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- Seizure typeDrug of choiceAlternatives Generalized tonic clonic
Carbamazepine Phenytoin Valproate Lamotrigine Topiramate
Phenobarbital AbsenceEthosuximide Valproate Lamotrigine Clonazepam
Atypical absence Atonic, myoclonic ValproateClonazepam 24
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- 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 25
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- 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 26
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- Dose Start 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 27
- Slide 28
- Dose 0.5 to 8 mg a day Therapeutic plasma concentration
Indicated for Refractory absence and myoclonic seizures Sleep
Irritability 28
- Slide 29
- Common side effects Sedation, ataxia, behaviour problems,
hyperactivity Comments Half life 18 to 50 hours Tolerance develops
in 30% 29
- Slide 30
- Dose 10 to 60mg a day Indicated for Refractory seizures Cluster
seizures Common side effects As for clonazepam 30
- Slide 31
- Dose Start 10-15 mg/kg/day Therapeutic plasma concentration 300
-700 micromoles/L 50 -100 micrograms/L Indicated for Simple absence
seizures NOT convulsive seizures 31
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- Common side effects Gastro intestinal upset, nausea,
drowsiness, headache, behavioural changes, hiccups, skin rashes
Comments Half life 50 to 60 hours in adults 30 to 40 hours in
children 32
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- Dose Start 5 mg/kg/day Therapeutic plasma concentration Not
clinically relevant Indicated for All forms of seizures 33
- Slide 34
- Common side effects Dizziness, 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)
34
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- Dose Start 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 35
- Slide 36
- Dose Start 3-4 mg/kg/day Therapeutic plasma concentration 15 to
40 micrograms/ml Indicated for All forms of seizures except absence
seizures 36
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- Common side effects Sedation (tolerance develops), headache,
hyperkinesia (old & young) slurred speech, skin reactions,
cognitive impairment Comments 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! 37
- Slide 38
- Dose Start 15 mg/kg/day Therapeutic plasma concentration 50 to
100 micrograms/ml Indicated for All forms of epilepsy 38
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- 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
39
- Slide 40
- 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) 40
- Slide 41
- Comments Watch for weight loss and depressive psychosis Ensure
adequate hydration; increased risk of kidney stones. Avoid carbonic
anhydrase inhibitors e.g. acetazolamide Half life 18 to 30 hours
reduced where given with enzyme inducing drugs 41
- Slide 42
- Rectal valium Syringes: 2.5 mg, 10 mg, 20 mg Locked to
prescribed dose by pharmacist Package of two syringes
- Slide 43
- USUALLY prescribed to be given once a seizure has lasted for
4-5 minutes Exceptions: Prolonged seizures Depending on patient,
perhaps 2-3 seizures within a certain period of time
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- Ages 2-5 years: 0.5 mg/kg Ages 6-11 years: 0.3 mg/kg Age 12 +
years: 0.2 mg/kg
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- Often used for seizure clusters Dosing 0.025-0.1 mg/kg May be
given orally in between seizures