Transcript Epilepsy Medications - Marshall University

Mitzi Payne, MD
Pediatric Neurology
Hoops Family Children’s Hospital at Cabell
Huntington Hospital
Marshall University Department of Neuroscience
 Fewest
possible seizures
 Limit side effects
 Monotherapy
 Minimal dosing schedules (once, twice,
three times a day)
 Limit need for blood tests
2
 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
 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
 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
 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
 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
7
 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 (AED’s, abx, etc)
8
 Blood
concentrations are guide only
 “Doctor
/ Mom / Patient: Don’t worry, the
level is in the NORMAL RANGE”, says the
physician / nurse / receptionist.
9
 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
 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
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


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
 Target
for many medications
 Sodium channels give way to the action
potential in excitatory neurons
Phenytoin
Carbamazepine
Oxcarbazepine
Lamotrigine
14
 End
neuronal excitability, but bring
neuron back to its normal resting
potential
 Involved in length of action potential
15
 Inhibitory neurotransmitters
 GABA A post -synaptic; 7 classes
• Dependent upon chloride and bicarbonate ions
 GABA B
pre- and post -synaptic
16
 Barbiturates
• phenobarbital
 Benzodiazepines
• Clobazam, clonazepam, diazapam
 Tiagabine
 Vigabatrin
17
 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
 Valproic
acid
 Gabapentin
 Piracetam
 Levetiracetam
19
 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
21
 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
Seizure type
Drug of choice
Alternatives
Carbamazepine Lamotrigine
Simple &
Phenytoin
Gabapentin
complex partial Valproate
Levetiracetam
Topiramate
Tiagabine
Oxcarbazepine
Phenobarbital
23
Seizure type
Drug of choice
Alternatives
Generalized
tonic clonic
Carbamazepine
Phenytoin
Valproate
Ethosuximide
Valproate
Lamotrigine
Topiramate
Phenobarbital
Lamotrigine
Clonazepam
Absence
Atypical absence Valproate
Atonic,
myoclonic
Clonazepam
24
 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
 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
 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
 Dose
• 0.5 to 8 mg a day
 Therapeutic
plasma concentration
 Indicated for
• Refractory absence and myoclonic seizures
• Sleep
• Irritability
28
 Common
side effects
• Sedation, ataxia, behaviour problems,
hyperactivity
 Comments
• Half life 18 to 50 hours
• Tolerance develops in 30%
29
 Dose
• 10 to 60mg a day
 Indicated
for
• Refractory seizures
• Cluster seizures
 Common
side effects
• As for clonazepam
30
 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
 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
 Dose
• Start 5 mg/kg/day
 Therapeutic
plasma concentration
• Not clinically relevant
 Indicated
for
• All forms of seizures
33
 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
 Dose
• Start 20-30 mg/kg/day
 Therapeutic
• Not relevant
plasma concentration
 Indicated
for
 Common
side effects
• Partial seizures, Generalized seizures
• Irritability, nausea, drowsiness, rash,
 Comments
• No drug interactions described
35
 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
 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
 Dose
• Start 15 mg/kg/day
 Therapeutic
plasma concentration
• 50 to 100 micrograms/ml
Indicated for
• All forms of epilepsy
38
 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
 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
 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
 Rectal
valium
 Syringes: 2.5 mg, 10 mg, 20 mg
 Locked to prescribed dose by
pharmacist
 Package of two syringes
 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
 Ages
2-5 years: 0.5 mg/kg
 Ages 6-11 years: 0.3 mg/kg
 Age 12 + years: 0.2 mg/kg
 Often
used for seizure clusters
 Dosing 0.025-0.1 mg/kg
 May be given orally – in between
seizures