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Flashcards in Seizure Tx: AED Deck (27):

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


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


Types of generalized seizures

Generalized Seizures: Bilaterally symmetrical and w/out local onset

Tonic-clonic: Grand mal
Absence: Petit mal


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


Status Epilepticus

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


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)


Goals of therapy

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


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)


Non-pharmacologic Therapy

1. Surgery
-Temporal lobectomy
-Corpus Collosum section
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


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


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


Concentration-Related AE

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


Idiosyncratic AE

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


Types of AE



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


Drug Interactions: Absorption

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


Drug Interactions: Distribution

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


Drug Interactions: Metabolic

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


AED Cost

The newer the med, the more expensive it is


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


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


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


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
-Varies, most are safe


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


Epilepsy Treatment Algorithm

See Handout for Algorithm


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



-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