P-Slide 1 Neuropharmacology of Antiepileptic Drugs American Epilepsy Society.
Medical Management of Seizures and Epilepsy · determine choice of antiepileptic medication therapy...
Transcript of Medical Management of Seizures and Epilepsy · determine choice of antiepileptic medication therapy...
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Medical Management of Seizures and Epilepsy
2019 Annual Epilepsy Pediatric Patient Care Conference
N a t h a n i e l H o d o b a , M DB a r r o w N e u r o l o g i c a l I n s t i t u t e a t P h o e n i x C h i l d r e n ’ s H o s p i t a l
C h i l d N e u r o l o g y C h i e f R e s i d e n t P G Y 5
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I have no disclosures or conflicts of interest.
Brand names of certain medications may be discussed;this is only for simplicity and clarification and does notconstitute an endorsement.
Off-label use of medication may be discussed in thislecture.
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Objectives
Discuss the rational for treatment of epilepsy
Understand the process by which physicians determine choice of antiepileptic medication therapy
Discuss the ways in which antiepileptic medications work to both stop and prevent seizures and review currently available antiepileptic medications
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The Problem
65 million people worldwide live with epilepsy 150,000 new cases each year Children and older adults are the most rapidly
growing segments Incidence 50 in 100,000 in childhood 20 in 100,000 in adolescence
3 million people in the United States Fourth most common neurologic disease Prevalence 5 in 1000 children in developed countries
Annual direct medical cost of $12.5 billion
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The Real Impacts of Epilepsy
Development and cognition Psychiatric illness Social stigma Safety Independent living Employment SUDEP Status epilepticus
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Which Medicine First?
Age
Cost
Availability
Administration
Ease of dosing
Balance of seizure control and side effects
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History of Anti-Epileptic Drugs
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Seizure
Epilepsy?
History, Physical Exam, Neuroimaging, EEG
Yes
No
Broad Spectrum AED
Onset?
No Preventative AED
Generalized Focal
UnknownEpilepsy Syndrome
Yes
Syndrome Specific AED
Narrow Spectrum AED
Epilepsy Syndrome
Yes
Syndrome Specific AED
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Form, Function and Other Considerations
Formulations Liquid
Elixir Suspension Solution
Tablet Tablet Chewable Disintegrating Extended release
Capsule Capsule Sprinkle Extended release
Other Nasal spray Rectal gel Intravenous
Urgency Loss of consciousness Risk of physical injury High seizure burden Active seizure Status epilepticus
Positive Effects Comorbidities
Trigeminal neuralgia Neuropathic pain Migraine Essential Tremor Anxiety Bipolar disorder
Adverse Effects Drug interactions Side effects
Drowsiness, dizziness, rash Depression and suicidality Pregnancy impact
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Mechanism of Action
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Seizures and Epilepsy
Disruption of normal balance of inhibition and excitation Inhibition GABA
Excitation AMPA NMDA Metabotropic Sodium Potassium Calcium
Synchronous electrical discharges
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Categorizing Anti-Epileptics
Broad Levetiracetam Lamotrigine Zonisamide Valproic acid Topiramate Felbamate Phenobarbital Tiagabine Benzodiazepines Vigabatrin
Narrow Perampanel Phenytoin Carbamazepine Oxcarbazepine Eslicarbazepine Lacosamide Rufinamide Ethosuximide Ezogabine
Sodium Channel Blockade Carbamazepine Oxcarbazepine Eslicarbazepine Felbamate Lamotrigine Lacosamide Phenytoin Rufinamide Topiramate Valproate Zonisamide
Calcium Channel Blockade Ethosuximde Gabapentin Lamotrigine Pregabalin Valproic acid Zonisamide
Spectrum Specific Receptors
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More Receptors
GABA modulation Benzodiazepines Phenobarbital Felbamate Topiramate Zonisamide
Increase GABA Tiagabine Vigabatrin
NMDA Receptor Perampanel Topiramate
Synaptic Vesicle Release Levetiracetam Brivaracetam
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Syndromes
Childhood absence epilepsy Ethosuximide Lamotrigine Valproic acid
Juvenile Myoclonic Valproate
Infantile spasms ACTH Vigabatrin (TSC)
SLC2A1 (GLUT-1) Ketogenic diet
Lennox-Gastaut Clobazam Rufinamide Felbamate
Dravet syndrome Epidiolex Stiripentol
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Low And Slow
Minimal effective dose Suppress seizures completely with no/minimal side effects Children often have long intervals between seizures Therapeutic range
Trial and error
Side effect monitoring
Adherence
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Note Worthy Side effects
Valproic acid Pancreatitis Liver failure Weight gain
Felbamate Aplastic anemia
Carbamazepine Aplastic anemia Hyponatremia
Phenytoin Liver injury Aplastic anemia
Keppra Behavioral changes
Ezogabine Blue pigmentation of skin
and retina Viagabatrin Visual field changes
Topiramate Weight loss Kidney Stone
Zonisamide Hyperthermia Decreased sweat production
Lamotrigine Steven Johnsons Syndrome
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When A Seizure Happens
Rescue At Home Clonazepam Midazolam Diazepam
Ongoing seizure in the Hospital 1s the line
Lorazepam 2nd line
Fosphenytoin Valproic acid Levetiracetam
3rd line Phenobarbital Midazolam
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When Seizures Stop
Medication discontinuation Two years seizure freedom Prognostic factors
Age at onset Type of seizure IQ Neurologic exam EEG
ILAE Definition 2014 Epilepsy resolved when: Seizure free for at least 10
years Most recent 5 years off
all anti-seizure medications
Expected age to have outgrown epilepsy syndrome.
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What If The Seizures Don’t Stop?
Rational polytherapy
Confirmation of diagnosis
Ketogenic diet
Epilepsy surgery Modulating devices Disconnection Resection Ablation
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QUESTIONS?
Thank You