- Neurological disorder of brain resulting in 2 or more unprovoked seizures - Requires professional diagnosis from neurologist

- Exclusively in childhood and early adolescence - Brief LOC, higher frequency - Attacks last for a few seconds and often go unrecognized - Sometimes diagnosed by teachers with worsening grades

- Used for partial and generalized tonic-clonic (NOT absence seizures) - Na Channel blocker (blocks Na/Ca influx) - potent CYP inducer - Rarely used due to narrow therapeutic index (only in developmentally disabled) - PO/IV

Week 1 Flashcards by Chelsey Case

Epilepsy

Neurological disorder of brain resulting in 2 or more unprovoked seizures
Requires professional diagnosis from neurologist

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Simple Partial Seizure

NO loss of consciousness
Motor signs (jerking, lip smacking)
Parathesis (numbness)
Autonomic signs (sweating, flushing)

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Complex Partial Seizure

Impaired consciousness
Purposeless behavior, glassy stare
Hallucinations, aggressive behavior (sometimes appears psychiatric)

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Secondary Generalized Seizure

Partial onset which further evolves to generalized tonic-clonic seizures
Involves entire cerebral cortex (vs portion of brain in other partial-focal seizures)

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Absence Seizures

Exclusively in childhood and early adolescence
Brief LOC, higher frequency
Attacks last for a few seconds and often go unrecognized
Sometimes diagnosed by teachers with worsening grades

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Generalized tonic-clonic Seizures

“Grand Mal” seizure
- Sudden LOC
- Tonic: tensed up, loud noises, incontinence
- Clonic: convulsing/shaking

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Atonic Seizures

“Drop attack”
- Occurs mainly in children
- Associated with sudden loss of postural tone (falls to ground)

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Risk Factors (breakthrough seizures for pts with epilepsy)

Sleep deprivation
Missed doses of AEDs
Alcohol withdrawal
Physical/Mental exhaustion
Flickering lights
Intercurrent infections
Metabolic disturbances
Uncommon reasons (loud noise, hot bath, etc.)

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Should patients be treated with lifelong AEDs after 1 seizure? Or multiple seizures if provoked by external factors?

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Predictors of favorable outcomes

Seizure free >3 years (unless structural abnormality)
Monotherapy
Normal EEG (careful)
NO psychomotor retardation
No juvenile myoclonic epilepsy
**Longer seizure free = better prognosis

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EEG

Measure of electrical activity in brain (from far perspective)
- Abnormal ONLY DURING a seizure (not in between)
***EEGs are NOT indications for confirming NOR to stop AED therapy for seizure free pts

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Polytherapy considerations

Refractory pts
Inadequate response to 1st AED
Underlying structural abnormalities

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Goals of Antiepileptic therapy

To significantly limit the frequency of seizures and manageable side effects (NOT to eliminate any chance of seizure recurrence)

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When to consider AED withdrawal?

Normal neuro exam, IQ and EEG
Seizure free for at least 3 years
No juvenile myoclonic epilepsy
**Must still titrate down from medication to avoid abrupt withdrawal (may provoke seizure)

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Phenytoin (Dilantin)

Used for partial and generalized tonic-clonic (NOT absence seizures)
Na Channel blocker (blocks Na/Ca influx)
potent CYP inducer
*Rarely used due to narrow therapeutic index (only in developmentally disabled)
PO/IV

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Phenytoin ADEs

Dose related: GI upset, nystagmus (rapid eye movement), sedation, potential VTE (rate injection <50 mg/min)

Non-dose related: *Gingival hyperplasia, Hirsutism, Hydantoin syndrome

Carbamazepine (Tegretol)

MoA/clinical use similar to Phenytoin
*Additionally used for mania and trigeminal neuralgia
**Extremely potent CYP inducer of numerous drugs including autoinduction
200-800 mg/day given BID

Carbamazepine ADEs

**Hyponatremia and water intoxication (rare)
GI upset, drowsiness, ataxia and headache
Congenital deformations (avoid in pregnancy)
**Blood dyscrasias as fetal aplastic anemia (D/C)
**Mild leukopenia (Monitor dosing)

Carbamazepine affects on WBC

Transient DECREASE WBC count
- Baseline CBC required prior to initiation
- Repeat CBC in 6 weeks post-initiation
- Normal to see low WBC (monitor dose)
- **If decreased counts of other cells or labs including WBC - D/C STAT

Valproic Acid (Divalproex/Depakote)

Very effective in absence and myoclonic seizures (also gen tonic-clonic)
Less effective for partial seizures
**Beneficial for migraine ppx
Increases GABA content in brain
CYP inhibitor
PO (caps/syrup) or IV

Valproic Acid ADEs

GI issues (most common due to insolubility)
Increased appetite/Weight gain
Hepatotoxicity
**Neural Tube Defects (contraindicated in pregnancy) – pts on VPA must visit neurologist prior to pregnancy

Gabapentin (Neurontin)

Used in adjunct to other AED therapies
**Beneficial for pain due to diabetic neuropathy or postherpetic neuralgia
Increases GABA activity
Does not inhibit/induce CYP

Gabapentin ADEs

Somnolence, dizziness, ataxia, fatigue and nystagmus
**Concern for abuse potential

Lamotrigine (Lamictal)

Used as adjunct or monotherapy
**Beneficial for vertigo/chronic dizziness
Na channel blocker -> blocks excitatory neurons such as Glutamate (similar to Phenytoin)
**Requires SLOW titration
Does not inhibit/induce CYP
24 hour half life (long)

Lamotrigine ADEs

- **Skin rash (potential SJS/TEN) - **Somnolence (requires slow titration) - Blurred vision, ataxia, aggression, influenza-like syndrome

Topiramate (Topamax)

- Na channel blocker as well as potentiates inhibitory effect of GABA (increased levels) - **Beneficial for migraine ppx and mood - Good absorption (80%), food has no effect - 18-24 hour half life - **Requires SLOW titration

Topiramate ADEs

- **Psychological or cognitive dysfunction (constant feeling of intoxication) - **Weight loss - **Bilateral Paresthesia (numb/tingling) -- NOT unilateral (potential stroke) - Urolithiasis and retinal issues (increased risk with dehydration) - Sedation, dizziness, fatigue - Long flights pose potential issue...?

Levetiracetam (Keppra)

- Commonly used for most seizure types (typical drug of choice) - Non-competitive antagonist at AMPA glutamate receptor - Generally well tolerated with little ADEs (potential weight gain) - Enhances CNS depressants

Levetiracetam Dosing

IR (tabs, sol, susp): 500mg BID - increase every 2 weeks by 500mg based on tolerability to max dose 1.5g BID ER (*only approved for focal (partial) onset seizures): 1,000mg QD - increase every 2 weeks by 1g based on tolerability to max dose 3g QD

Oxcarbazepine (Trileptal)

- Very similar mechanism to CBZ (Na channel blocker) - **Good alternative for those on Carbamazepine and well controlled (encouraged transition) due to decreased ADEs

Vigabatrin (Sabril)

- Drug of choice for infantine spasms - Inhibits GABA metabolizing enzyme and increases GABA in brain (similar to VPA) - Alternative AED option (works well, significant ADE profile)

Vigabatrin ADEs

- **Visual field defects - **Psychosis and depression (continue to gradually worsen)

Zonisamide (Zonegran)

- Add on therapy for partial seizures - Prolongation of Na channel inactivation - No CYP enzyme affects - 50-68 hour half life - ADEs: Drowsiness, ataxia, loss of appetite, N/V, somnolence

Tiagabine (Gabitril)

- Adjunctive therapy in partial and generalized tonic-clonic seizures - Inhibits GABA uptake and increases levels of GABA in brain - ADEs: Asthenia (weakness/lack of energy), sedation, dizziness, mild memory impairment, abdominal pain

Clinical Advices for AED use in Epilepsy

1. Essential to have accurate and comprehensive diagnosis by neurologist 2. Must treat underlying causes of seizures (hypoglycemia, infection, tumors, etc.) 3. Description of symptoms from both patient and witness of seizure 4. EEG's are ONLY SUPPORTIVE (not for confirmation)

First Aid for Seizures

- **Record time of seizure onset (call 911) - Prevent pt from hurting themself (soft object under head) - Do not force objects in pt's mouth - Turn pt on side to allow saliva drainage - Do not pour liquid or offer any food/medications until pt is fully awake - Give CPR if pt does not begin breathing ~2mins after convulsions (common to stop breathing during tonic-clonic)