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Flashcards in Seizure Tx: AED Deck (27):
1

Seizure Introduction

Seizures affect approx 40 million people worldwide and 2 million people in the US
1% of the US population is affected
20% - etiology known (brain trauma, tumor, stroke, infection)
80% - etiology unknown
Anti epileptic drugs (AEDs) are #1 treatment

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Types of partial seizures

Partial Seizures: Seizures begin locally

Simple: Without impairment in consciousness
Complex: With impairment in consciousness
Secondary generalized: Partial onset evolving into GTC

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Types of generalized seizures

Generalized Seizures: Bilaterally symmetrical and w/out local onset

Tonic-clonic: Grand mal
Absence: Petit mal
Myoclonic
Atonic

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Epilepsy syndromes

Infantile spasms: Occurs in infants <1yr old, often develop other seizure types later in life

Lennox-gastaut syndrome: Combo of generalized seizure types, cognitive dysfunction

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Status Epilepticus

Continuous seizure activity lasting >30 minutes OR two or more seizures w/out return of consciousness in between

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Epilepsy Pathophysiology

Sudden electrical disturbance of the cerebral cortex (CNS); Group of neurons fire rapidly and repeatedly for seconds or minutes; Likely related to excess excitatory neurotransmitters, failure of inhibitory neurotransmitters, or combo (imbalance between excitatory and inhibitory)

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Goals of therapy

Control or reduce the frequency of seizures
Ensure adherence
Optimize quality of life
Balance between seizure control and side effects

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General Treatment Approach

-Determine risk of subsequent seizure: Risk factors include structural CNS lesion, abnormal EEG, partial seizure type, positive family history, and postictal motor paralysis
-AED selection determined by seizure type, adverse effect profile and patient preference
-Begin w/monotherapy: 550-70% can be maintained on one AED
-Titrate dose as needed, depending on seizure control, AE
-Adherence is KEY: up to 60% of pts w/epilepsy are nonadherent-->treatment failure (AE, don't have seizures all the time; adolescents have the highest non-adherence)

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Non-pharmacologic Therapy

1. Surgery
-Temporal lobectomy
-Corpus Collosum section
-Hemispherctomy
2. Vagal nerve stimulator implantation: Regular pulses of electrical energy to prevent or interrupt electrical disturbances; Thin, round pulse generator implanted under the skin on the upper left side of the chest; Electrodes connect to the left vagus nerve on the left side of the neck; Costly ($15,000) but has "medication sparing" effect; Can cause hoarseness and cough
3. Ketogenic Diet: High fat, no carbs; Induces state of ketosis which decreases seizures
4. Modified Atkins Diet for kids

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AEDs Mechanism of Action

Effect sodium and calcium channels -->stabilization of neuronal membranes
Enhance inhibitory neurotransmission (GABA)
Decrease excitatory neurotransmission (Glutamate and Aspartate)
-->Increase seizure threshold
-->Inhibition of the spread of abnormal (seizure) discharges

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Therapeutic Range

Serum concentration that controls seizures w/out causing concentration-related AE
Population data used to determine range
Personal therapeutic range for each patient

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Concentration-Related AE

Most common
Increased drug levels results in increased side effects
Not permanent
See at "peak" concentration or throughout day
Management:
-Lower dose/level
-Change schedule or formulation of medication: take more often at lower dose or take ER form
-D/C med

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Idiosyncratic AE

More rare
Not related to dose/level
May be permanent
Seen throughout day
Management:
-D/C med
-Treat adverse reaction as needed

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Types of AE

Concentration-Related
Idiosyncratic

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AEDs and Suicide Risk

-Patients taking AEDs seem to have TWICE the risk of suicidal thoughts and behaviors as those not taking the drugs
-Reason for increased risk is unknown
-Relative risk appears higher in patients treated for seizure disorders compared to migraines, BDP, or other conditions
-Patients w/epilepsy already have a higher risk of depression and a THREE-fold higher risk of suicide
-Risk is small, but patients should be educated to seek help if suicidal thoughts or behavior occur

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Drug Interactions: Absorption

-Aluminum or magnesium containing antacids may decrease AED absorption
-Separate doses by 2 hours or more to prevent interaction

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Drug Interactions: Distribution

Protein Binding
-Highly protein bound drugs compete for protein binding sites
-Transient elevation in free drug
-Ex: Phenytoin and Valproic Acid

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Drug Interactions: Metabolic

CYP450 Enzyme System
-Substrates
-Inducers: Increase original med dose
-Inhibitors: Decrease original med dose

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AED Cost

The newer the med, the more expensive it is

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AED Dosing

Phenytoin (Dilantin): 300-400mg
Carbamazepine (Tegretol): 800-1600mg
Valproic Acid (Depakote): 1000-3000mg
Gabapentin (Neurontin): 1800-3600mg
Lamotrigine (Lamictal): 100-500mg

*Total daily doses
**If a patient uses a generic, keep them on the same generic; don't change

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AED Monitoring

Monitor therapeutic range: Check once steady state has been reached; MC to measure in the morning at the trough level
-On inducer: Reach steady state faster
-On inhibitor: Reach steady state slower

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Evaluation of Therapy

-Individual therapeutic range should be established
-Ongoing monitoring of seizure control, adverse effects, drug interactions, adherence, toxicity, and social adjustment
-Record severity and frequency of seizures in a seizure diary

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AED use in women of childbearing age

Interactions w/contraceptions:
-Enzyme inducers (PHT, CBZ, PB, PRM) -> decreased estrogen concentrations
-Either use higher dose OC or alt method of birth control
Teratogenic effects during pregnancy
-Fetal risk 2-4% w/out epilepsy, 4-6% w/epilepsy and 1 AED
-Goal: monotherapy w/lowest possible dose to control seizures
-Avoid VPA if possible
-Check levels throughout pregnancy
Breastfeeding
-Varies, most are safe

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Genetic testing recommendations

-Patients of Asian decent should be screened for the HLA-B*1502 gene before starting CBZ and PHT
-About 5% of pts who have it will develop Stevens-Johnson syndrome or TEN w/CBZ; FDA is working to evaluate the risk w/PHT
-Certain HLA subtypes will see a drug as harmful and mount an immune response that manifests as a hypersensitivity reaction

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Epilepsy Treatment Algorithm

See Handout for Algorithm

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Discontinuation of AEDs

All of the following criteria must be met before considering D/C:
-Seizure free for 2-5 yrs
-Normal neurologic exam
-Normal IQ
-Single type of partial or generalized seizure
-Normal EEG w/treatment

Slowly decrease polytherapy to monotherapy
W/monotherapy, slowly decrease AED over at least 1-3 months to prevent withdrawal seizures
Decrease dose by no more than 1/3 each time

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SUMMARY

-Seizures affect 1% of the US population
-The primary treatment for seizure disorders is AED therapy
-Pharmacologic therapy is based on seizure type
-Therapy requires ongoing monitoring of seizure control, adverse effects, drug interactions, adherence, toxicity and social adjustment