Seizure

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Pharmacokinetics (PK)

Non-linear PK

Type B

VPA (doses >2.5gm/day) Ethosuximide (dose >1.5gm) Gabapentin Pregabalin (GI absorption^) Carbamazepine (CBZ, auto-induction)

Type A

Phenytoin Ethotoin

Linear PK: dose/conc. proportional r/s

Phenobarbital Valproic acid (VPA dose <2.5) Mephenytoin Felbamate Levetiracetam Oxcarbazepine Lamotrigine Zonisamide Tiagabine Topiramate

When need to step up therapy/add another agent or just not sure of the specific seizure:

-Levetiracetam -Lamotrigine -Topiramate -Zonisamide -Valproate -Clobazam -Rufinamide -Felbamate -Perampanel -Phenobarbital -Primidone -Clonazepam

Therapy Map

Focal seizures

Simple partial Complex partial Secondary GTC

Narrow Spectrum: -Lacosamide -Pregabalin -Gabapentin -Carbamazepine -Oxcarbazepine -Eslicarbazepine -Phenytoin -Vigabatrin -Ezogabine -Tiagabine

Generalized/bihemispheric seizures

Myoclonic Primary GTC Absence

Ethosuxamide

Generalized/Multifocal onset

Tonic Atonic Atypical Absence GTC

Spasms?

Yes

Vigabatrin ACTH (ADRENOCORTICOTROPIC HORMONE)

No

Valproate Rufinamide Clobazam Lamotrigine

Anti-epileptic Therapy

Pharm: Start tx, most benefit w/ 1st or 2nd agents -Many guidelines -Focus on dosing and serum concentration ranges to adjust therapy

Carbamazepine (CBZ): toxicity can be fatal

Valproic acid (VPA): widest range (!50mcg/mL)

Phenytoin: total and unbound

Non-pharm

Ketogenic diet (high fat, low carb and protein Modified Atkins diet used in peds.

Surgery: refractory focal epilepsy

Nerve stimulators- Vegal Nerve Stimulation (VNS)

-Changes CSF Cpss of inhibitory and stimulatory NTs -Very safe: voice change, hoarse, coughing, nausea

Seizure

Neurotransmitters (NT) and ion channels involved:

Pathophys: -NT's move across the synaptic cleft

Ion Channels

GABA-B receptors activated by axon potential decrease Ca2+ influx and inhibit NT release

Axon potential at presynaptic nerve terminal (Ca2 channel) releases NT

Excitatory

Glutamate; assoc. w/ 3 receptor systems

Inhibitory

GABA; GABA-A receptor

Has binding site for BDZ + Barbiturates (Pb)

Agonists: diazepam, phenobarbital -enhance GABA binding to the receptor -membrane stabilization thru Cl ion influx = anti-epileptic action - seizure >30 sec. can dec by 10x by BDZ +Pb effects

-Paroxysmal discharge of neurons -imbalance b/w excitatory/inhibitory neurotransmission -neurons fire abnormally

SUDEP

Two highest risk factors are generalized seizures and >3 per year

Risk Factors: -Presence of generalized tonic-clonic seizures -Freq of ^: 3 or more per year -failure to + additional anti-epileptic med when pts are refractory

Generalized Seizures

Typically involves bilateral brain regions (tonic-clonic)

Atonic

Tonic-clonic

Absence

Drugs: -Ethosuxamide -Valproate

Partial Seizures

Complex

Simple

Myoclonic seizure causes:

Dravet syndrome

Fenfluramine

Progressive Myoclonic epilepsy

Rett syndrome

Lennox Gastaut syndrome (LGS)

Juvenile Myoclonic epilepsy (JME)